FitSugar

City Living and Breast Cancer

FitSugar — Thu, 29 Nov 2007 02:00:00 -0800

October might have been Breast Cancer Awareness Month, but the research is not limited to a month. Researchers are persistent, and a new study gives city living women a reason to stay vigilant too.

New research from the UK indicates that women living in cities have much denser breast tissue than their country living counterparts. Combine this data with the previous research that indicates women with the densest breasts are considered four times as likely to develop breast cancer. There is a relationship between breast cancer and breast tissue.

There are three pieces of information to consider here:

Particles commonly found in air pollution, which is more common in urban areas, often mimic hormones that can interfere with the make up of breast tissue, and create denser tissue.
The more dense the breast tissue is the more difficult to detect tumors and suspicious growths with X rays. Mammograms are a specialized form of X-ray and are considered the most effective way of detecting tumors. Early stage cancer is more difficult to detect in dense breast tissue.
This study was performed on women who reside in London, 972 of them, in fact. An English health survey found that women residing in London were the thinnest in the country. This is important since there is an inverse relationship between breast density and body weight: thinner women generally have less body fat and therefore denser breast tissue.

If you live in a city, take heed. Remember to perform your monthly breast exams and take cancer screening seriously. You should also read 5 Things to Reduce Your Risk of Breast Cancer.

Source

Breast cancer

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In September 2007, Evista (raloxifene) was approved for prevention of breast cancer in postmenopausal women with osteoporosis, and postmenopausal women at high risk for invasive breast cancer. Raloxifene and tamoxifen are the only two drugs approved for breast cancer prevention in high-risk women.
In March 2007, lapatinib (Tykerb) was approved in combination with capecitabine (Xeloda) for treatment of advanced HER2-positive breast cancer.
In November 2006, trastuzumab (Herceptin) was approved for treatment of early-stage HER2-positive breast cancer. Trastuzumab is also approved for advanced HER2-positive breast cancer.

Screening

The American College of Physicians’ 2007 guidelines recommend that women with a low risk for breast cancer talk to their doctor before starting to have mammogram screening at age 40. Other associations, including the American Cancer Society, continue to recommend annual mammograms for women age 40 and older.
Women at high risk for breast cancer should have an MRI scan along with their annual mammogram, according to 2007 guidelines from the American Cancer Society.
For women who have been diagnosed with cancer in one breast, an MRI can help detect tumors in the other breast, indicates a 2007 study in the New England Journal of Medicine.

Post-Treatment Guidelines

The American Society of Clinical Oncology (ASCO)’s 2006 post-treatment guidelines recommend regular physical exams, breast self-exam, mammograms, and genetic counseling. Know how to recognize the signs of breast cancer recurrence. ASCO does not recommend blood and imaging tests for routine recurrence screening.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Fewer women are using HRT, which may explain why new cases of breast cancer among postmenopausal women have declined, suggests a recent New England Journal of Medicine study.

Aromatase Inhibitors

Drug treatment with aromatase inhibitors is improving survival in women with hormone-sensitive advanced breast cancer, suggest recent studies. Switching from tamoxifen to an aromatase inhibitor may help improve the odds for survival.

Introduction

Breast cancers are potentially life-threatening malignancies that develop in one or both breasts. The structure of the female breast is important in understanding this cancer:

The interior of the female breast consists mostly of fatty and fibrous connective tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the milk through the breast and converge in a collecting chamber located just below the nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of origin) or invasive (spreading).

The female breast is either of two mammary glands (organs of milk secretion) on the chest.

Noninvasive breast cancers include:

Ductal carcinoma in situ (also called intraductal carcinoma or DCIS). DCIS consist of cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left untreated, it may sometimes progress to an invasive, infiltrating ductal breast cancer.
Lobular carcinoma in situ, or LCIS. Although noninvasive, lobular carcinoma in situ is a marker for an increased risk of invasive cancer in both breasts. (Some experts prefer to call this condition lobular neoplasia rather than refer to it as a cancer.) According to a 2001 report, for patients with LCIS the risk for developing invasive cancer in the same breast is about 18% -- and 14% in the other breast -- after 20 years. These invasive cancers can be either lobular or ductal.

At the time of diagnosis of these early cancers (DCIS and LCIS), there is no evidence of invasion.

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive breast cancers include the following:

Infiltrating ductal carcinoma. This is invasive breast cancer that penetrates the wall of a duct. It comprises between 70 - 80% of all breast cancer cases.
Infiltrating lobular carcinoma. This invasive cancer has spread through the wall of a lobule. It accounts for 10 - 15% of all breast cancers. It may sometimes appear in both breasts, sometimes in several separate locations.

Click the icon to see an image of the breast.

There are other less common breast cancers that are not discussed in this report.

Risk Factors

About 12 - 13% of women develop breast cancer in their lifetime. Experts estimate that about 178,480 women will be newly diagnosed with invasive breast cancer in the United States in 2007. Another 2,030 men will be diagnosed with breast cancer during the year. Although breast cancer in men is rare, the incidence has been increasing, and men are diagnosed at a later stage than women. An estimated 40,460 women and 450 men will die from breast cancer in 2007. The earlier breast cancer is diagnosed, the earlier the opportunity for treatment. According to the American Cancer Society, over 2 million women who have been treated for breast cancer are alive today.

Age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over age 50, and especially in women over age 65. The odds by age are as follows:

From ages 30 - 39, a woman’s chance for being diagnosed with breast cancer is 1 in 233
Ages 40 - 49, the odds are 1 in 69
Ages 50 - 59, the odds are 1 in 38
Ages 60 - 69, the odds are 1 in 27
Ages 70 - 79, the odds are 1 in 11
After age 80, the odds are 1 in 8

Breast cancer is more prevalent among Jewish women of Eastern European (Ashkenazi) descent. Meanwhile, African-American women tend to get breast cancer at an earlier age than Caucasians. Although African-American women have lower overall rates of breast cancer, they represent the highest proportion of women who are diagnosed with the disease before age 45. Comparative studies of breast cancer rates among sub-Saharan Africans suggest a genetic component, as African women are diagnosed most frequently between ages 35 - 45.

The mortality rate in African-Americans is twice that of Caucasians, although it is declining. Social and economic factors make it less likely that African-American women will be screened, so they are more likely to be diagnosed at a later stage. They are also less likely to have access to effective treatments. However, there also appears to be a biological basis for African-American women’s poorer prognosis. According to research presented at the 2007 Breast Cancer Symposium, African-American women are more likely to have estrogen receptor-negative tumors, a type of breast cancer that is more difficult to treat.

An estimated 10% of all women with breast cancer have a very strong family history of the disease. Inherited forms of breast cancer often appear in young women under the age of 50. In such families, some members may also be at higher risk for ovarian cancer. These mutations can be inherited from either a mother or father.

Prior to menopause, a mass on the ovary that is smaller than 2 centimeters is probably a follicle cyst that will go away on its own. However, if the growth is larger and doesn't go away over the course of a few menstrual cycles, then it may need to be removed.

BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for 30 - 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each gene carries is:

Between 25 - 35% of BRCA1 carriers develop breast cancer by age 70.
Between 35 - 50% of BRCA2 carriers develop the disease. BRCA2 genes also increase the lifetime risk of breast cancer in men.

These mutations are present in only about 0.5% of the overall population. However, certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -- have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also seen in some African-American and Hispanic women.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations).

ESR Genes. Genetic variations in estrogen receptor genes (ESRs) may increase the risk for some women but offer protection to others. Mutations in the ESR1 and ESR2 genes may be associated with breast cancer susceptibility for Ashkenazi women over age 50 years.

Other Genetic Factors. Mutations in the tumor suppressor gene p53 are more common in the breast cancer tumors of African-American women than in Caucasian women. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father), CHEK2, and ATM, a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy -- enough to increase the risk for breast cancer.) Cowden's syndrome is an inherited disorder caused by a defective PTEN gene that is associated with a higher risk of breast cancer.

Not all genetic mutations are inherited. In 2007, scientists announced they had located a genetic mutation found in as many as 30 - 40% of breast cancers. The IKBKE mutation appears to occur during the course of a women’s lifetime. It causes overproduction of a kinase protein (IKK-epsilon) that fuels cell growth and tumor development. By identifying this genetic mutation, scientists hope they can develop drugs that will target and block IKK-epsilon production.

Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman is exposed to over her lifetime, the higher her risk for breast cancer.

Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at menopause may slightly increase a women’s risk for breast cancer.

Pregnancy. Women who have never had children or who had their first child after age 30 may have a slightly increased breast cancer risk. Having children at an early age, and having multiple pregnancies, reduces breast cancer risk.

Although a few studies have suggested a slightly increased risk for breast cancer in women who have had abortions, the weight of evidence does not support an association between abortion and breast cancer. A large-scale 2007 study found that neither induced abortions nor spontaneous abortions (miscarriages) increases breast cancer risk. However, interrupting a pregnancy does reduce the protective features of a full-term pregnancy.

Studies have been mixed on whether breast-feeding decreases breast cancer risk. Breast-feeding reduces a woman’s total number of menstrual cycles, and thereby estrogen exposure, which may account for its possible protective effects. Some studies suggest that the longer a woman breast-feeds, the lower her risk.

Oral Contraception. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer. Some studies have found no evidence that oral contraceptive use increases the risk for breast cancer, even in women who have taken birth control pills for 15 years or more or had taken them at young ages. In contrast, other studies have reported a slightly higher risk in women who are current or recent users and in women who take them for more than 4 years before a first full-term pregnancy.

Hormone Replacement Therapy. Many studies have reported a higher risk for breast cancer in postmenopausal women who take hormone replacement therapy (HRT) that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take estrogen for 10 - 15 years or more do have an increased risk, especially women who are already at higher risk for breast cancer. In addition, HRT increases breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined. The decline in rates occurred among women over the age of 50 and was particularly associated with cancers that were estrogen receptor-positive. This type of cancer requires estrogen for growth. Experts think that postmenopausal women’s discontinuation of estrogen-containing HRT may explain the decrease in rates of new cases of estrogen receptor-positive cancer.

A 2007 position statement from the North American Menopause Society recommends that women who are at risk for breast cancer should avoid hormone therapy and try other options to manage menopausal symptoms such as hot flashes. At this time, most experts recommend that women use HRT only for short-term relief of menopausal symptoms. [See In-Depth Report #40: Menopause.]

Infertility and Infertility Treatments. There has been concern that infertility treatments using the drug clomiphene may increase the risk for breast cancer. A reassuring 2006 study indicated that ovulation induction with clomiphene does not increase breast cancer risk, and may actually decrease it. (Clomphine is related to tamoxifen, a drug that is used for breast cancer prevention in high-risk women.) The study also suggested that women who are infertile because of ovulatory dysfunction have a 25% lower risk for breast cancer than fertile women.

Abnormalities or Breast Conditions Suggesting a Higher Risk. Certain factors and breast conditions may increase the risk for breast cancer:

Dense breast tissue is associated with a higher risk for breast cancer. Studies suggest that women with highly dense tissue have 2 - 6 times the risk of women with the least dense tissue. Genetic factors play a large role in breast density. Hormone replacement therapy also increases breast density. In addition, dense breasts make mammograms more difficult to read, which increases the likelihood of missing early signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical hyperplasia, is a significant risk factor for breast cancer.

Some common benign breast abnormalities that pose few or no risks include the following:

Cysts. These mostly occur in women in their middle-to-late reproductive years and can be eliminated simply by aspirating fluid from them.

Click the icon to see an image of cysts in the breast.

Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breast-feeding.

Click the icon to see an image of a breast abscess.

Nipple discharge. Discharge from the nipple is worrisome to patients, but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.

Click the icon to see an image of nipple discharge.

Mastalgia. This is breast pain that occurs in association with, or independently from, the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.

The following physical characteristics have been associated with increased risk:

Obesity increases the risk for all types of estrogen receptor-positive breast cancers. Women who gain weight after menopause are most at risk. (On a positive note, losing weight after menopause decreases breast cancer risk.) In postmenopausal women, estrogen is produced in fat tissue. High amounts of fatty tissue increase levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at age 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.

Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. There has been particular concern with pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and pyrethroids (permethrin), but at this time evidence of any causal association is very weak.

Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. Recent studies also suggest a slightly increased risk for their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.

Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Girls who received high-dose radiation therapy face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations.

Researchers theorize that viruses may be involved in some types of breast cancers. A study of breast cancer samples taken from Tunisian women in North Africa found similarities with a virus known to cause breast cancer in mice. The samples were compared with those taken from women living in other global regions. The researchers suggested that a human breast cancer virus may be more prevalent in specific parts of the world.

Prevention and Lifestyle Factors

Evidence indicates that regular exercise, particularly vigorous exercise, may offer some modest protection against breast cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting hormones such as estrogen. In fact, a 2006 study suggested that physical activity may help women reduce the risk for developing estrogen receptor-positive tumors.

Exercise can also help women who have been diagnosed with breast cancer. Studies indicate that both aerobic and weight training exercises benefit the body and the mind, and improve quality of life for breast cancer survivors. Even moderate exercise can help improve survival. A 2005 study in the Journal of the American Medical Association reported survival benefits for women diagnosed with breast cancer who walked 3 – 5 hours per week at an average pace. The American Cancer Society recommends engaging in 45 - 60 minutes of physical activity at least 5 days a week. A recent study indicated that diet and exercise can reduce the risk of breast cancer recurrence.

Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing the amount of bone loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, thereby helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite, and helps in the reduction of body fat.

Despite much research on the association between diet and breast cancer, there is still little consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancer-fighting" food. The American Cancer Society’s dietary guidelines for cancer prevention recommend that people:

Choose foods and amounts that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for breast cancer should consider not drinking alcohol at all).

For breast cancer survivors, the American Cancer Society recommends diets that include lots of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy products), moderation in soy foods, and moderate or no alcohol consumption.

Here are results from recent studies evaluating diet and breast cancer, for preventing both the development of cancer and its recurrence:

Fats. Research is still mixed on the role that fats, and which specific types of fats, play in breast cancer risk and prevention. Several studies have indicated that red meat, which is high in saturated fat, may increase breast cancer risk when eaten in large quantities on a daily basis. (Red meat is also high in iron, which in itself may increase breast cancer risk.) According to results from the 2006 Women’s Health Initiative study of dietary fat and breast cancer, experts cannot yet definitely say that a low-fat diet will help prevent breast cancer. However, the study suggested that women who normally eat a very high-fat diet may benefit by reducing their fat intake. In the study, the low-fat diet reduced blood estrogen levels by 15%. The low-fat diet also appeared to reduce the risk for developing progesterone receptor-negative tumors.

Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants, which may help protect against the tissue damage linked to increased cancer risk. Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best sources for these nutrients. These fiber-rich foods are an essential part of a healthy diet. However, it is not clear whether fruits and vegetables can specifically prevent breast cancer development or recurrence. According to a 2007 study of women with early-stage breast cancer, a low-fat diet very high in vegetables, fruit, and fiber does not work any better in preventing breast cancer recurrence than the standard 5 servings a day of fruits and vegetables. (However, a combination of diet and exercise may help.)

Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal -- but not postmenopausal -- women, according to a 2007 study. Low-fat or non-fat dairy products are a healthier choice than high-fat ones.

Click the icon to see an image of vitamin D sources.

Soy. Soy is an excellent low-fat protein alternative to meat. Soy contains phytoestrogens, which are estrogen-like plant chemicals. In particular, soy contains a type of phytoestrogen called isoflavones. Because many soy foods (such as tofu) are eaten in Asian countries where women tend to have a lower incidence of breast cancer, research has focused on whether soy may have a protective effect. To date, the evidence does not indicate that soy foods or supplements can reduce breast cancer risk. In addition, some studies suggest that high intakes of soy may actually increase the risk of estrogen-responsive cancers such as breast cancer. Some animal studies have suggested that the isoflavone compound genistein may reduce the protective properties of tamoxifen, a drug used to prevent breast cancer in high-risk women. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy foods and avoid taking dietary supplements that contain high amounts of isoflavones.

Click the icon to see an image of phytochemicals.

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history, should take as many preventive measures as possible, starting at an early age. The following lifestyle choices may be beneficial:

Exercising and eating healthily is the first essential rule.
High-risk premenopausal women may choose alternatives to oral contraceptives and, if feasible, consider having children early in their life.
High-risk postmenopausal women may want to forego hormone replacement therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or drinking it very sparingly.

In spite of some rumors published in the popular press, antiperspirants or use of deodorants after shaving have not been linked with any higher risk for breast cancer.

Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs) act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others. Two SERMs -- tamoxifen (Nolvadex) and raloxifene (Evista) -- are approved for breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not recommended as prevention for women at low risk for breast cancer or its recurrence. Women at high risk for breast cancer should discuss with their doctors the risks and benefits of SERMs.

Tamoxifen (Nolvadex) is the most studied of these drugs. It is currently used to treat breast cancer and was the first drug approved for prevention. Evidence strongly suggests that it halves the risk for estrogen receptor-positive cancers in high-risk women, including those with BRCA2 mutations (although possibly not BRCA1). It also helps prevent recurrence in women who have been treated for breast cancers. However, it has no protective effects against estrogen receptor-negative (hormone-insensitive) cancers.

Tamoxifen can increase the risk for uterine (endometrial) cancers. It can also increase the risk for blood clots, strokes, and endometriosis. Less serious side effects include hot flashes and vaginal discharge.

Raloxifene (Evista) was approved in 2007 for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for invasive breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis in postmenopausal women. One of raloxifene’s main benefits is that it has a lower risk than tamoxifen of causing uterine cancer. However, raloxifene also has some serious risks.

According to the prescribing information from the Food and Drug Administration (FDA), raloxifene can increase the risk of blood clots. Women with a history of blood clots in the legs, lungs, or eyes should not take this medicine. Although studies indicate raloxifene does not increase the risk of stroke, it can increase the risk of dying from a stroke. Women with a history of stroke or current risk factors for stroke should discuss with their doctors whether raloxifene is an appropriate choice. Less serious side effects of raloxifene include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Raloxifene can cause birth defects and is approved only for postmenopausal women. It should not be taken with the cholesterol-lowering drug cholestyramine (Questran) or with estrogens.

The FDA based its approval of raloxifene on results from several major studies. The comparison trial Study of Tamoxifen and Raloxifene (STAR), published in 2006 in the Journal of the American Medical Association, indicated that raloxifene works as well as tamoxifen in reducing the risk of invasive breast cancer, and has a lower risk of causing blood clots. However, the Raloxifene Use for the Heart (RUTH) trial, published in 2006 in the New England Journal of Medicine, suggested that raloxifene carries its own risks for blood clots and fatal strokes and may not be a safe choice for women at high risk of heart disease.

Investigational Drugs for Breast Cancer Prevention.

Aromatase inhibitors. Aromatase inhibitors such as anastrazole (Armidex), letrozole (Femara), and exemestane (Aromasin) are effective treatments for hormone-receptor positive breast cancer. Like tamoxifen, they are also being investigated for protection in high-risk women. However, these drugs may decrease bone mineral density and cognitive function, and increase the risk for falls.
Retinoids. Analogues of vitamin A called retinoids are being studied for protection against breast cancer. One retinoid, fenretinide, appears to offer some protection against a second breast cancer in previously diagnosed, premenopausal women (but not in postmenopausal women). It can cause birth defects and should not be used during pregnancy.

Symptoms

Breast cancers in their early stages are usually painless. Often the first symptom is the discovery of a hard lump. Fifty percent of such masses are found in the upper outer quarter of the breast. The lump may make the affected breast appear elevated or asymmetric. The nipple may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an orange. In some cases there is a bloody or clear discharge from the nipple. Many cancers, however, produce no symptoms and cannot be felt on examination. They can be detected only with a mammogram.

Monthly breast self-exams should always include: visual inspection (with and without a mirror) to note any changes in contour or texture, and manual inspection in standing and reclining positions to note any unusual lumps or thicknesses.

Diagnosis

Breast Examination by a Health Professional. Early detection of breast cancer significantly reduces the risk of death. Women ages 20 - 49 should have a physical examination by a health professional every 1 - 2 years. Those over age 50 should be examined annually. A breast exam by a health professional can find 10 - 25% of breast cancers that are missed by mammograms. Between 6 - 46% of the lumps detected by examination are malignant. (The yield is lowest in younger women and highest in older women.)

Self-Examinations. Woman have been encouraged to perform a self-examination each month, but well-conducted studies in 2002 reported no difference in mortality rates between women who were intensively instructed in self-examination and those who were not. This does not mean women should stop attempting self-examinations, but they should not replace the annual examination done by a health professional, which evidence suggests is beneficial.

1. Pick a time of the month that is easy to remember and perform self-examination at that time each month. The breast has normal patterns of thickness and lumpiness that change within a monthly period, and a consistently scheduled examination will help differentiate between what is normal from abnormal.

2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly larger than the other). Check for changes or redness in the nipple area. Look for changes in the appearance of the skin. With hands on the hips, push the pelvis forward and pull the shoulders back and observe the breasts for irregularities. Repeat the observation with hands behind the head. Move each arm and shoulder forward.

3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over the breast area.

The finger action should be as follows: Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dime-sized circles. Press lightly first to feel the breast area, then press harder using a circular motion.

Using this motion, start from the collarbone and move downward to underneath the breast. Shift the fingers slightly over, slightly overlapping the previously checked region, and work upward back to the collarbone. Repeat this up-and-down examination until the entire breast area has been examined. Be sure to cover the entire area from the collarbone to the bottom of the breast area and from the middle of the chest to the armpits. Move the towel under the other shoulder and repeat the procedure.

Examine the nipple area, by gently lifting and squeezing it and checking for discharge.

4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of soap.)

Note: A lump can be any size or shape and can move around or remain fixed. Of special concern are specific or unusual lumps that appear to be different from the normal varying thicknesses in the breast.

Click the icon to see an image of a breast self-exam.

Current Recommendations for Screening. Mammograms are very effective low-radiation screening methods for breast cancer. At this time, the U.S. Preventive Services Task Force recommends screening mammograms, with or without breast examination, every 1 - 2 years for all women over age 40.

Guidelines from the American College of Physicians (ACP), however, debate whether women with a low risk for breast cancer should begin mammogram screening at age 40. The 2007 guidelines, instead, recommend that women in their 40s ask their doctor when they should begin having the test. In contrast, the American Cancer Society and the U.S. National Cancer Institute continue to endorse annual screening for women age 40 and older.

The ACP's guidelines have created controversy within the medical community. Supporters of the guidelines believe that these new recommendations reflect some of the risks involved in screening younger women. These risks include radiation exposure and unnecessary biopsies. Mammographies in younger women produce a relatively high rate of false-positive results (when the test falsely indicates breast cancer). Scientists are working on new technologies to improve mammography's accuracy, but more work is needed. For example, a 2007 New England Journal of Medicine study reported that computer-aided detection software, which is used to help radiologists interpret mammograms, may instead make readings less accurate.

Opponents of the ACP guidelines argue that mammograms help catch tumors while they are in their earliest and most treatable stages, and that the most deadly types of breast cancer tend to occur in women in their 40s.

In addition, according to a review in the American Cancer Society's journal, mammography rates have declined since 2000. In fact, while many experts believe that the recent decline in new cases of breast cancer is partially due to reduced use of hormone replacement therapy, other experts are concerned that fewer cases of breast cancer are being detected because fewer mammographies are being performed.

After age 50, all guidelines recommend annual screenings. The older a women gets, the greater her risk for developing breast cancer. (Women over age 65 account for most new cases of breast cancer.) Women with risk factors for breast cancer, including a close family member with the disease, should consider having annual mammograms starting 10 years earlier than the age at which the relative was diagnosed.

Click the icon to see an image of a mammogram.

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and ultrasound techniques can detect very small tumors (less than half an inch). However, they are expensive and time-consuming procedures. Nevertheless, some doctors believe they are important in identifying small tumors missed on mammography in women who are receiving lumpectomy or breast-conserving surgeries. Such findings would allow the surgeons to remove the optimal amount of abnormal tissue. Ultrasound may also be particularly important for women with dense breast tissue who show signs of breast cancer.

In a report published in 2007, the American Cancer Society recommended that high-risk women have an MRI of their breast with their annual mammogram, including those who have:

A BRCA1 or BRCA2 mutation
A first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation, even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or may have one of these genetic syndromes based on a history in a first-degree relative

For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for detecting hidden tumors in the other breast. A landmark 2007 study in the New England Journal of Medicine reported that MRI scans of women who were diagnosed with cancer in one breast detected over 90% of cancers in the other breast that had been previously missed by mammography or clinical breast exam. Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the other breast. Some experts advocate MRIs for all women newly diagnosed with breast cancer; others oppose this view. MRI scans may be most useful for younger women with breast cancer who have dense breast tissue that may obscure tumors from mammography readings. MRIs are less likely to be helpful for older women with early tumors in one breast and clear mammography readings in the other.

It is very important that women have MRIs at qualified centers that perform many of these procedures each year. MRI is a complicated procedure and requires special equipment and experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious findings are detected.

Scintimammography. In scintimammography, a radioactive chemical is injected into the circulatory system, which is then selectively taken up by the tumor and revealed on mammograms. This method is very accurate in detecting the presence or absence of breast cancer, and some doctors hope that it might eventually reduce the number of unnecessary invasive biopsies. It is used for women who have had abnormal mammograms or for women who have dense breast tissue. It is not used for regular screening or as an alternative to mammography.

A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic examination of a tissue sample of the suspicious area).

When a lump can be felt and is suspicious for cancer on mammography, an excisional biopsy may be recommended. This biopsy is a surgical procedure for removing the suspicious tissue and typically requires general anesthetic.

Click the icon to see an image of breast biopsy.

A core biopsy involves a small incision and the insertion of a spring-loaded hollow needle that removes several samples. The patient only requires local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities but there is no lump. With this procedure, using mammography as a guide, the doctor inserts a small wire hook through a hollow needle and into the suspicious tissue. The needle is withdrawn, and the hook is used by the surgeon to locate and remove the lesion. The patient may receive local or general anesthetic.
A new vacuum-assisted device may be useful for some biopsies. This uses a single probe through which a vacuum is used to draw out tissue. It allows several samples to be taken without having to remove and re-insert the probe.

Final analysis of the breast tissue may take several days.

If breast cancer has been determined, the next diagnostic step is to find out how far it has spread. To do this, the doctor performs a procedure called an axillary lymphadenectomy, which partially or completely removes the lymph nodes in the armpit beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2 days.

Click the icon to see an image of the axillary lymph nodes.

Once the lymph nodes are removed, they are analyzed to determine whether subsequent treatment needs to be more or less aggressive:

If no cancer is found in the lymph nodes, the condition is referred to as node negative breast cancer. The chances are good that the cancer has not spread and is still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive. Their presence increases the possibility that the cancer has spread microscopically to other areas of the body. In such cases, however, it is still not known if the cancer has metastasized beyond the lymph nodes or, if so, to what extent. The doctor may perform further tests to see if the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain (MRI or CT scan).

Side effects of the procedure include increased risk for infection and pain, swelling in the arm from fluid build-up, and impaired sensation and restricted movement in the affected arm. Patients might ask their doctor about the availability of physical therapy or upper-body exercises after treatment. In two studies, such programs resulted in quicker recovery and no fluid build-up in the arm.

A technique known as a sentinel node biopsy is a less invasive alternative to axillary lymph node dissection. This procedure can help determine if cancer has spread beyond the nodes. If the doctor finds no evidence of cancer, the patient may not need to have a complete axillary lymphadenectomy.

Click the icon to see an image of a sentinel node biopsy.

Sentinel node biopsy involves:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph nodes will be cancer free, making further surgery unnecessary.

Patients who have a sentinel node biopsy tend to have better arm function and a shorter hospital stay than those who have an axillary node biopsy. The American Society of Clinical Oncology's 2005 guidelines recommend sentinel node biopsy instead of axillary lymph node dissection for women with early stage breast cancer who do not have nodes that can be felt during a physical exam. It is still not known if the sentinel node biopsy has any survival advantages compared to standard lymph node removal procedures.

Women often have to wait several days for results of sentinel node biopsies to learn whether they will require another surgery to remove additional lymph nodes. In 2007, the Food and Drug Administration approved the GeneSearch BLN Assay to help speed sentinel node biopsy testing. This molecular-based lab test can detect within 40 minutes whether cancer has spread to nearby lymph nodes. Because the test delivers rapid results while the patient is still on the operating table, it may help spare women the discomforts of a second surgical procedure and help them get treatment earlier.

Prognosis

In the U.S., about 40,460 women will die from breast cancer this year, making it the second most lethal cancer in women. (Lung cancer is the leading cancer killer in women.) The good news is that early detection and new treatments have improved survival rates. The 5-year survival rate for women diagnosed with cancer is 80%. About 88% of women diagnosed with breast cancer will survive at least 10 years. Unfortunately, women in lower social and economic groups still have significantly lower survival rates than women in higher groups.

Several factors are used to determine successful treatment and the possibility for a cure. They include:

The location of the tumor and how far it has spread
Whether the tumor is hormone receptor-positive or -negative
Genetic factors
Tumor size and shape
Rate of cell division
Biologic markers

The good news is that women are living longer with breast cancer, and at this time more than 2 million American women are survivors. Due to better treatment options, from 1990 - 2003, breast cancer mortality rates declined by 24%. However, survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.

Recurrences of cancer usually develop within 5 years of treatment. However, 25% of recurrences and half of new cancers in the opposite breast occur after 5 years. One study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast. The outlook for such new cancers is independent from those of the first one.)

The location of the tumor is a major factor in outlook:

If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (is node-negative), the 5-year survival rates with treatment are up to 98%. However, cancer recurs in 9 - 30% of women with node-negative cancers. Recurrence is a potentially life-threatening problem, even if the disease relapses locally in the same breast. In one study of DCIS patients with locally invasive recurrence, 8-year mortality rates were only 12%.
If the lymph nodes contain cancer cells (are node positive) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, the cancer is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and bone), the average survival time is about 2 years (with some patients living for many years). New drug therapies, particularly aromatase inhibitors, have helped prolong survival for women with metastatic cancer.

The location of the tumor within the breast is an important predictor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.

Breast cancer cells may contain receptors, or binding sites, for the hormones estrogen and progesterone. Cells containing these binding sites are known as hormone receptor-positive cells. If cells lack these connectors, they are called hormone receptor-negative cells. About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.

Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to hormone therapy such as tamoxifen or aromatose inhibitors. Hormone receptor-negative tumors are referred to as "hormone insensitive" or "hormone resistant."

Women have a better prognosis if their tumors are hormone receptor-positive because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.) A 2007 study in the Journal of Clinical Oncology indicated that recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor-positive tumors, due in part to the widespread use of post-surgical tamoxifen therapy.

Determining a "genetic signature" for a tumor may prove to be a very powerful predictor of the aggressive nature of a breast cancer. Researchers have focused on 70 genes whose activity patterns may help make such predictions. In 2007, the Food and Drug Administration approved MammaPrint, a DNA microarray diagnostic test that profiles these 70 genes. The molecular test may help predict how likely it is that breast cancer will recur within 5 - 10 years. However, the accuracy of the test depends on a woman’s risk. It is more accurate when predicting a low risk for recurrence than a high risk.

The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage. Others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively.

Researchers are investigating numerous substances in tumor cells that may indicate whether or not a cancer is likely to spread. Such chemical markers may help doctors determine treatments, and some may even prove to be targets for future drugs. The following are only a few of the more well-researched markers.

HER2. The American Cancer Society recommends that all women newly diagnosed with breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Two types of tests are used to detect HER2:

Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)

Some doctors think that FISH is a more accurate test than IHC. According to 2006 HER2 testing guidelines from the American Society of Clinical Oncology and the College of American Pathologists, either test may be used as long as it is performed by an accredited laboratory. Tests that are not clearly positive or negative should be repeated. Treatment with trastuzumab (Herceptin) or lapatinib (Tykerb) may help women who test positive for HER2.

Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own supply of blood vessels, which enable the tumor to send colonies of cancer cells into the bloodstream and spread to other parts of the body. Specific angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), may turn out to be important markers for determining treatment and prognosis. The monoclonal antibody bevacizumab (Avastin) targets VEGF. The drug is showing promise in clinical trials for prolonging progression-free survival in women with metastatic breast cancer.

Others. Many other markers are being investigated, including p53, cathepsin-D, protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase, CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.

Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Another test measures cells at a certain phase of their division.

Recent evidence has not supported early reports of survival benefits for women with metastatic breast cancer who engage in support groups. However, some studies have suggested that psychotherapy, group support, or both may relieve pain and reduce stress, particularly in women who are suffering emotionally.

Stress has been ruled out as a risk factor either for breast cancer itself or for its recurrence.

Treatment

The three major treatments of breast cancer are surgery, radiation, and drug therapy. No one treatment fits every patient, and combination therapy is usually required. The choice is determined by many factors, including the age of the patient, menopausal status, the kind of cancer (ductal vs. lobular), its stage, and whether or not the tumor contains hormone-receptors.

Breast cancer treatments are defined as local or systemic:

Local Treatment. Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects the whole body.

Any or all of these therapies may be used separately or, most often, in different combinations. For example, radiation alone or with chemotherapy or hormone therapy may be beneficial before surgery, if the tumor is large or not easily removed at prevention. Surgery followed by radiation and hormone therapy is usually recommended for women with early-stage, hormone-sensitive cancer. There are numerous clinical trials investigating new treatments and treatment combinations. Patients, especially those with advanced stages of cancer, may wish to consider enrolling in a clinical trial.

Treatment strategies depend in part on the stage of the cancer.

Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (‘in situ"), meaning that the cancer is still confined within breast ducts or lobules and has not yet spread to surrounding tissues. Stage 0 cancer is classified as either:

Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast. LCIS rarely develops into invasive breast cancer, but having it in one breast increases the risk of developing cancer in the other breast.

Treatment options for DCIS include:

Breast-conserving surgery and radiation therapy (followed by hormone therapy for women with hormone-sensitive cancer)
Total mastectomy (followed by hormone therapy for women with hormone-sensitive cancer)
Breast-conserving surgery without radiation therapy

Treatment options for LCIS include:

Regular exams and mammograms to monitor any potential changes (observation treatment)
Hormone therapy to prevent development of breast cancer (for women with hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely recommended

Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.

Stage II cancer is classified as either stage IIA or stage IIb.

In stage IIA cancer the tumor is either:

No more than 2 centimeters and has spread to the underarm lymph nodes (axillary lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes

Treatment options for stage I and stage II breast cancer may include:

Breast-conserving surgery (such as lumpectomy) followed by radiation therapy
Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes, chemotherapy, or hormone therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for women with HER2-positive cancer

Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories: Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).

In stage IIIA breast cancer, the tumor is usually confined to the underarm lymph nodes. Treatment options for stage IIIA breast cancer are the same as those for stages I and II.

In stage IIIB breast cancer, the tumor has spread to either:

Tissues near the breast (including the skin or chest wall)
Lymph nodes within the breast or under the arm

Stage IIIB treatment options may include:

Chemotherapy, and possibly hormone therapy (sometimes in combination with chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy) with lymph node dissection followed by radiation therapy and possibly more chemotherapy or hormone therapy
Clinical trials

Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:

10 or more of the underarm lymph nodes
Lymph nodes beneath the collarbone and near the neck on the same side of the body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes

Treatment options for operable stage III breast cancer are the same as those for stage I and II breast cancers.

In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the collarbone and near the neck on the same side of the body as the affected breast. Treatment options are the same as those for stage IIIB.

Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone. The cancer at this stage is considered to be chronic and incurable, and the usefulness of treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease and slow its progression, as well as to reduce pain and discomfort.

Treatment options for stage IV cancer include:

Surgery or radiation for any localized tumors in the breast. A 2006 study indicated that surgical removal of the primary tumor immediately after metastatic cancer diagnosis can dramatically improve survival.
Chemotherapy, hormone therapy, or both. Targeted therapy with trastuzumab (Herceptin) or lapatinib (Tykerb) should be considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as high-dose chemotherapy with stem cell transplant.

In 2006, the American Society of Clinical Oncology (ASCO) released updated guidelines on follow-up care for patients who have been treated for breast cancer. ASCO recommends:

Visit your doctor every 3 - 6 months for the first 3 years after your first cancer treatment, every 6 - 12 months during the fourth and fifth year, and once a year thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule follow-up visits for re-evaluation of your treatment.

ASCO does not recommend the use of laboratory blood tests (complete blood counts, carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDG-PET scan, CT scan) for routine breast cancer follow-up.

Genetic counseling may be helpful if you have:

Ashkenazi Jewish heritage
Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed with breast cancer
History of breast cancer in a male relative

Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how long a woman should wait to become pregnant after breast cancer treatment. Because of the connection between estrogen levels and breast cancer cell growth, some experts recommend delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer recurrence and improve odds for survival. However, a 2007 study indicated that conceiving 6 months after treatment does not negatively affect survival. Discuss with your doctor your risk for recurrence, and when it may be safe to attempt pregnancy.

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years after treatment, but breast cancer can recur many years later. Treatment options are based on the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.

Because most breast cancer recurrences are discovered by patients in between doctor visits, it is important to notify your doctor if you experience any of the following symptoms. These symptoms may be signs of breast cancer recurrence:

New lumps in the breast
Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge

Surgery

Surgery forms a part of nearly every patient's treatment for breast cancer. The initial surgical intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy (the removal of the breast) was the standard treatment for nearly all breast cancers. Now, many patients with early-stage cancers can choose breast-conserving treatment, or lumpectomy followed by radiation, with or without chemotherapy.

For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined with radiation therapy works as well as a modified radical mastectomy.

Breast-conserving procedures are now appropriate and as successful as mastectomy in most women with early stage breast cancer. All women should discuss these options fully with their doctor. Recurrence rates with conservative surgery are highest in women under age 45. Some women choose mastectomy over breast-conserving treatment even if the latter is appropriate because it gives them a greater sense of security and allows them to avoid radiation therapy.

Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with breast radiation therapy, to remove additional tissue (should the margins of the specimen show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation therapy is appropriate and as effective as mastectomy in most women with Stage I or II breast cancers.

Click the icon to see an illustrated series detailing breast lump removal surgery.

Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes referred to as quadrantectomy) removes the cancer and a large area of breast tissue, occasionally including some of the lining over the chest muscles. It is less invasive than a full mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Excellent studies have found that breast-conserving surgeries plus postoperative radiotherapy offer the same survival rates as radical mastectomy in women with early breast cancer. A new technology called partial breast radiation (MammoSite), approved by the Food and Drug Administration in 2002, confines radiation to the tumor site rather than delivering it to the whole breast, and reduces treatment time from 5 weeks to 5 days in women who undergo breast conserving surgery.

Surgery to remove the breast (mastectomy) is important for women with operable breast cancer who are not candidates for breast conserving surgeries. There are different variations on the procedure:

A total mastectomy involves removal of the whole breast and sometimes lymph nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes under the arm, and some additional fat and skin. (A modified radical mastectomy removes the entire breast and armpit lymph nodes, with the underlying chest wall muscle.) A 25-year study supported other research that observed no survival advantages from radical mastectomy compared to the less invasive mastectomies for the great majority of patients. It is rarely used anymore except when cancer is very advanced.

Click the icon to see an illustrated series detailing mastectomy surgery.

Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area of the procedure, and pain relievers may be necessary.

The most frequent complication of extensive lymph node removal is edema, or swelling, of the arm, which is usually mild and rarely painful but does increase the risk for infection. The likelihood of edema can be lessened by removing only some of the lymph nodes instead of all of them.

Infrequent complications include poor wound healing, bleeding, or a reaction to the anesthesia.

After mastectomy and lymph node removal, women may experience numbness, tingling, and difficulty in extending the arm fully. These effects can last for months or years afterward.

After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction, which can be performed during the mastectomy itself, if desired. Several studies have indicated that women who take advantage of cosmetic surgery after breast cancer have a better sense of well-being and a higher quality of life than women who do not choose reconstructive surgery. The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is taken from elsewhere in the body. Muscle flap procedures are more complicated, however, and blood transfusions may be required. (It should be noted that implants, including silicone implants, do not appear to put a woman at risk for breast cancer recurrence.) If the nipple is removed, it is rebuilt from other body tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast that is identical to its partner, and additional operations may be necessary to achieve a desirable effect.

Click the icon to see an illustrated series detailing breast reconstruction surgery.

Numerous studies are investigating minimally invasive techniques that use lasers, deep-freezing of cancer cells (cryosurgery), high-intensity ultrasound, and other experimental approaches to kill cancer cells and reduce severe complications of surgery. Radiofrequency ablation, for example, is an approach that uses an electrode inserted into the tumor. It emits radio waves that produce enough heat to destroy cancer cells. Early trials are promising. These procedures, however, are not considered standard at the present time.

Radiation

Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor in the breast or surrounding tissue. It is used for several weeks following lumpectomy or partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce the chance of breast cancer recurrence in the breast and chest wall. Radiation is also important in advanced stages of cancer for relief of symptoms and to slow progression. Research shows that radiation therapy is helpful for women of all ages, including those over age 65.

Radiation is generally administered in the following ways:

External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and delivered externally by an x-ray machine that targets radiation to the whole breast. It may be delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or lymph node involvement). The treatment is generally given daily (except for weekends) for about 6 weeks. A follow-up boost of radiation therapy in patients with lumpectomies appears to reduce the risk for recurrence.

Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy). Implants are most often used as a radiation boost after whole breast radiation. Studies suggest they improve survival in patients at high risk for local recurrence. Some evidence suggests that implants alone can reduce treatment time and may be as effective as external beam radiation in some patients with early stage breast cancer. A new technology for breast brachytherapy (MammoSite) was approved in 2002. The technique provides 5-year local tumor control rates similar to those of whole-breast radiation for selected patients, with much shorter treatment time and good cosmetic results.

Investigators are also testing other approaches to radiation treatment. One uses a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard photon radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions. Such an approach may improve the coverage of breast cancers while reducing the toxic effects to the heart and lungs.

Side effects of radiation include:

Fatigue is very common and increases with subsequent treatments, but most women are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated sessions, the skin may become moist and "weepy." Exposing the treated skin to air as much as possible helps healing. (Washing the affected skin with soap and water does not seem to be harmful and in one study was associated with a lower risk for this side effect.)
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.

Future complications include:

Radiation to the left breast may increase the long-term risk for developing heart disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft tissue malignancies known as sarcomas.

Current advanced imaging techniques use precise radiation that reduces exposure. These newer techniques are likely to reduce the risks for heart disease and other serious complications.

Medications

The most important advances in the cure of breast cancer have come through the use of drug therapy, also called systemic therapy. Surgery and radiation therapy are effective for treating tumors confined to the breast but not for cancer cells that have spread or are at risk of spreading. In such cases, drug therapy is needed.

Drug treatments for breast cancer include:

Chemotherapy. Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by injection. They work systemically by killing cancer cells throughout the body. (Unfortunately, they also kill normal cells, which accounts for many of their side effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to treat types of early-stage breast cancer.
Hormone Therapy. The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is recommended for women whose breast cancers are hormone-receptor positive (either estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Targeted Therapy. Newer biologic drugs target specific proteins involved in cancer. Because they do not work as systemically as chemotherapy or hormone therapy drugs, they tend to cause fewer widespread side effects. Currently, the monoclonal antibody trastuzumab (Herceptin) and the kinase inhibitor lapatinib (Tykerb) are the two targeted therapies approved for breast cancer. These drugs target the HER2/neu protein and are used to treat HER2-positive breast cancers. Bevacizumab (Avastatin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein involved in tumor blood vessel formation (angiogenesis). It is being studied in clinical trials for treatment of metastatic breast cancer.

Drug therapy may be used as:

Primary therapy for patients for whom surgery or radiation therapy is not appropriate.
Neoadjuvant therapy (before surgery or radiation) to shrink tumors to a size that can be treated with local therapy.
Adjuvant therapy (following surgery or radiation) to reduce the risk of cancer recurrence.

For metastatic cancer, drugs are used not to cure but to improve quality of life and prolong survival.

Chemotherapy

Chemotherapy needs to be tailored to the type of cancer involved. Women require different treatments depending on whether the tumor is node-negative or -positive, hormone receptor-positive or -negative, or HER2-positive or -negative. Different treatment approaches are also used for early-stage cancer and advanced cancer.

A 2006 study in the Journal of the American Medical Association indicated that women with hormone receptor-negative cancers respond better to chemotherapy than women with hormone receptor-positive cancer. However, some women with hormone receptor-positive cancer do benefit from chemotherapy, as well as from hormone therapy.

Adjuvant chemotherapy is administered following surgery and before radiation therapy. A 2007 study in the Journal of Clinical Oncology suggested that women with early-stage breast cancer can safely wait for up to 12 weeks after surgery before beginning chemotherapy. However, delaying chemotherapy until more than 12 weeks after surgery significantly increases the risk for breast cancer recurrence and can reduce the odds for survival by as much as 60%.

Many different types of chemotherapy drugs are used to treat breast cancer. Common types of chemotherapy drug classes include:

Anthracyclines include doxorubicin (Adriamycin) and epirubicin (Ellence). Anthracycline-based combination regimens are often used to treat early-stage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Two 2003 studies suggested that taxane-based therapy is particularly helpful for node-positive breast cancer. A newer formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin) and carboplatin (Paraplatin). These drugs may be used in combination regiments for advanced cancer or for cancers associated with BRCA genes.

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug classes rather than drug names. For example, regimens that contain an anthracycline drug (such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy regimens.

Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months. Common chemotherapy regimens for early-stage breast cancer include:

AC (Doxorubicin and cyclophosphamide)
AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody that targets the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage breast cancer and are associated with more aggressive disease. Younger women tend to be most affected. In November 2006, the Food and Drug Administration approved trastuzumab for treatment of HER2-positive, early-stage breast cancer (cancer confined to the breasts or lymph nodes that has been surgically removed). Trastuzumab is given along with other chemotherapy drugs following lumpectomy or mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and death among women with early-stage breast cancer, but it increases the risk of heart problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to have regular heart monitoring, especially if they have already have heart problems.

Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. New advances in drug therapies, however, can help shrink tumors, prolong survival, and improve quality of life.

Chemotherapy regimens for advanced cancer may use a single drug or a combination of drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for advanced breast cancer. Some specific combinations for advanced cancer include:

Gemcitabine and paclitaxel. In 2004, the Food and Drug Administration approved the antimetabolite drug gemcitabine (Gemzar) for use in combination with paclitaxel (Taxol) as a first-line treatment option for women with metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere). Capecitabine is an oral drug that is chemically related to 5-FU. It is also being studied in combination with many other drugs.

Numerous chemotherapy drugs and drug combinations are being tested in clinical trials. Patients with advanced breast cancer may also receive other types of drug treatments. Bisphosphonate drugs, such as zoledronic acid (Zometa) and pamidronate (Aredia), are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones.

Two targeted therapy drugs are approved for the treatment of HER2-positive advanced breast cancer

Trastuzumab (Herceptin) was approved in 1998 for treatment of metastatic breast cancer. It is used in adjuvant chemotherapy, along with drugs such as paclitaxel.
Lapatinib (Tykerb) was approved in March 2007 for patients who have not been helped by other cancer drugs, including an anthracycline, a taxane, or trastuzumab. Lapatinib is used in combination with capecitabine (Xeloda). Research suggests it may have fewer risks for heart problems than trastuzumab.

Promising new treatments for advanced breast cancer include:

Ixabepilone (BMS-247550). Ixabepilone is the first of a new class of cancer drugs called epothilones. It is showing encouraging results when combined with capecitabine, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin). Bevacizumab is a targeted therapy anti-angiogenesis drug approved for treatment of colorectal and lung cancers. It is being studied in combination with various chemotherapy drugs for treatment of advanced cancer.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting. Aprepitant (Emend), a new drug for preventing chemotherapy-caused nausea and vomiting, was approved in 2006.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following:

Anemia. The erythropoietins epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) stimulate red blood cell production and can help reduce or prevent anemia, resulting in significant improvement in quality of life. Aranesp persists longer in the blood than epoetin alfa and may therefore require fewer injections.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause occurs in about 30% of women, particularly in those over 40. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women. Women may also wish to consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro fertilization and freezing of embryos for later use. The American Society of Clinical Oncology recommends that women being treated for cancer see a reproductive specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
A quarter to a third of women report problems in concentration, motor function, and memory, which can be long-term. In one study, women were having these symptoms 2 years after treatment, although by 4 years they had resolved.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure, particularly in women with pre-existing risk factors. Cumulative doses of anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur, more often in taxol than taxotere. Taking a steroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, relievable with corticosteroids.

High-dose chemotherapy along with peripheral-blood stem cell rescue or bone marrow transplantation procedures have been used for cancer that has metastasized and, in some cases, for earlier stages of breast cancer in high-risk patients. The objective of this treatment is to be able to give patients very high toxic doses of cell-killing drugs.

Transplantation procedures are based on stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments can harm these growing cells as well as cancer cells.

Despite the initial enthusiasm over the use of high-dose therapy for treatment of high risk breast cancer, this approach can no longer be generally recommended and should not be used outside of a clinical trial setting. The results of several randomized studies have failed to show a convincing advantage for the use of high-dose therapy. Nevertheless, some experts believe this approach can still be useful in selected patients, and studies continue. In general, however, transplantation has a limited role in breast cancer management, and its use should be restricted to clinical trials.

Hormone Therapy

Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for patients with hormone receptor-positive tumors. Different types of hormone therapy work in different ways by:

Blocking estrogen receptors in cancer cells (Tamoxifen)
Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)

Tamoxifen was the first widely used hormonal therapy drug, but it has been replaced by aromatase inhibitors for some women. Aromatase inhibitors are used only to treat postmenopausal women. Tamoxifen is mainly used as adjuvant therapy for premenopausal women with hormone-sensitive breast cancer.

Tamoxifen (Nolvadex) has been the standard hormonal drug used for breast cancer. It belongs to a class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Because SERMs block estrogen’s effects on cancer cells, they are sometimes referred to as "anti-estrogen" drugs.

Tamoxifen is used for all cancer stages in women of all ages with hormone receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women. Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer, but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is approved only for postmenopausal women with hormone-sensitive advanced breast cancer in which tamoxifen or aromatase inhibitors no longer work.

To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial) cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a symptom of uterine cancer.

Less serious, but discomforting, side effects include hot flashes and mood swings. According to a 2007 study, nearly 25% of women stop taking tamoxifen within 1 year because of these symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years, however, increases the risk for cancer recurrence and death. Talk with your doctor about antidepressants or other therapies that may help you cope with tamoxifen’s side effects.

Many doctors now recommend that postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen therapy. Several 2007 studies indicated that switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and reduces the risk of death from breast cancer as well as other causes.

Endometrial cancer is a cancerous growth of the endometrium (lining of the uterus). It is the most common uterine cancer.

Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work differently than tamoxifen. Tamoxifen interferes with tumors’ ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.

Because these drugs cannot stop the ovaries of premenopausal women from producing estrogen, they are recommended only for postmenopausal women.

There are currently three aromatase inhibitors approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:

Anastrazole (Armidex) for treatment after surgery
Exemestane (Aromasin) for women who have taken tamoxifen for 2 - 3 years
Letrozole (Femara) for treatment after surgery or for women who have completed 5 years of tamoxifen therapy

All of these drugs are also approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies indicate that the introduction of aromatase inhibitors has helped greatly in prolonging survival for women with advanced cancer.

Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone loss and fractures. In general, recent studies indicate that aromatase inhibitors are better than tamoxifen in improving survival and reducing the risk of cancer recurrence. Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.

Ovarian ablation literally shuts down estrogen production from the ovaries. Medications can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but several therapies are available to help prevent bone loss.)

Chemical Ovarian Ablation. Drug treatment (non-chemotherapy drugs) to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, therefore stopping ovulation and estrogen production.

Studies suggest that women with estrogen-positive early stage cancer who take goserelin have similar survival rates to those who take standard chemotherapy. They also experience fewer serious side effects. A major analysis of four trials using LHRH agonists plus tamoxifen suggested that this combination should be the standard for patients with advanced breast cancers that are hormone-receptor positive, although this is an area of controversy. (Chemotherapy is still more effective in women with estrogen-negative tumors.)

Ovariectomy. Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Ovariectomy does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on younger patients.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.oncolink.org -- Oncolink
www.womenshealth.gov -- National Women's Health Information Center
www.nccn.org -- National Comprehensive Cancer Network
www.plwc.org -- People Living With Cancer
www.cancer.gov/clinicaltrials -- Find clinical trials
www.breastcancer.org -- Find clinical trials

References

Bardia A, Hartmann LC, Vachon CM, Vierkant RA, Wang AH, Olson JE, et al. Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status. Arch Intern Med. 2006 Dec 11-25;166(22):2478-83.

Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007 Mar 1;109(5):832-9.

Boccardo F, Rubagotti A, Aldrighetti D, Buzzi F, Cruciani G, Farris A, et al. Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma: pooled analysis of 2 consecutive trials. Cancer. 2007 Mar 15;109(6):1060-7.

Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065-79.

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36.

Breen N, A Cronin K, Meissner HI, Taplin SH, Tangka FK, Tiro JA, et al. Reported drop in mammography : is this cause for concern? Cancer. 2007 Jun 15;109(12):2405-9.

Chia SK, Speers CH, D'Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Jul 23;110(5):973-979 [Epub ahead of print]

Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, et al. Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med. 2006 Nov 13;166(20):2253-9.

Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70.

Fenton JJ, Taplin SH, Carney PA, Abraham L, Sickles EA, D'Orsi C, et al. Influence of computer-aided detection on performance of screening mammography. N Engl J Med. 2007 Apr 5;356(14):1399-409.

Geiger AM, Thwin SS, Lash TL, Buist DS, Prout MN, Wei F, et al. Recurrences and second primary breast cancers in older women with initial early-stage disease. Cancer. 2007 Mar 1;109(5):966-74.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43.

Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. 2007 Jan 27;334(7586):194. Epub 2006 Dec 8.

Jatoi I, Chen BE, Anderson WF, Rosenberg PS. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007 May 1;25(13):1683-90. Epub 2007 Apr 2.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA; National Cancer Institute-Sponsored Breast Cancer Surveillance Consortium. Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst. 2007 Sep 5;99(17):1335-9. Epub 2007 Aug 14.

Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, et al.American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006 Nov 1;24(31):5091-7. Epub 2006 Oct 10.

Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.

Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007 May 28;167(10):1050-9.

Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006 Oct 20;24(30):4888-94. Epub 2006 Oct 2.

Michels KB, Xue F, Colditz GA, Willett WC. Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study. Arch Intern Med. 2007 Apr 23;167(:814-20.

Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet. 2006 Dec 9;368(9552):2053-60.

North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause. 2007 Mar-Apr;14(2):168-82.

Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. Epub 2007 Jul 2.

Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA. 2007 Jul 18;298(3):289-98.

Qaseem A, Snow V, Sherif K, Aronson M, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007 Apr 3;146(7):511-5.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007 Mar-Apr;57(2):75-89.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118-45. Epub 2006 Dec 11.

Review Date:
1/26/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (11/01/07).

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Endometriosis

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Lifestyle Changes
Medications
Conservative Surgery
Hysterectomy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Women with menstrual pain due to endometriosis have a new treatment option. In May 2007, the FDA approved Lybrel, a continuous-dose oral contraceptive that completely eliminates menstrual periods. Lybrel, which contains low doses of the estrogen estradiol and the progesterone levonorgestrol, is taken 365 days a year with active pills. Some women may, however, experience unscheduled bleeding or spotting.

Endometriosis and Adenomyosis

Women who continue to experience menstrual and pelvic pain after surgery for endometriosis may actually have adenomyosis, suggests a 2006 study in Fertility and Sterility. Adenomyosis occurs when knots of endometrial tissue develop within the muscles of the uterus. With endometriosis, endometrial tissue grows outside of the uterus.

Predictors of Hysterectomy

Three factors combined can predict whether a woman will decide to have a hysterectomy, according to a 2007 study published in the Journal of the American College of Surgeons. Women who met all three criteria had a 95% chance of having a hysterectomy:

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement despite treatment
Previous use of GnRH agonist drugs

Hysterectomy and Sexual Function

Women who have both their uterus and cervix removed (total hysterectomy) are no more likely to experience sexual problems than women who have only their uterus removed (subtotal hysterectomy), suggests a 2006 review in the Cochrane Database. The review also found no differences between total and subtotal hysterectomy for urinary and bowel problems. However, women who had subtotal hysterectomy were more likely to experience cyclical bleeding during the year after surgery than women who had a total hysterectomy.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Estrogen-only HRT after hysterectomy does not increase breast cancer risk in the short term (up to 20 years), according to several 2006 studies. Combination estrogen-progestin HRT does increase breast cancer risk.

Introduction

Endometriosis is a condition in which the cells that line the uterus grow outside of the uterus. The condition can interfere with a woman's fertility and ability to become pregnant. Endometriosis can also cause severe pelvic pain, especially during menstruation.

Endometriosis is a common gynecological condition. It was described in medical literature more than 300 years ago and has since been recognized as a chronic, painful, and often progressive disease in women. However, the causes of endometriosis are unknown, it is widely variable in symptoms and severity, and it is difficult to diagnose. In fact, some experts believe that endometriosis is actually several disorders, not just one.

Endometriosis. Endometriosis occurs when cells from the mucus membrane lining the uterus (endometrium) form implants that attach, grow, and function outside the uterus, generally in the pelvic region. Endometrial implants consist of both following cell types:

Gland cells. These cells secrete hormones and other fluids and are normally located in the uterine lining.
Stroma cells. These are the framework cells that build supportive tissue.

Endometrial cells contain receptors that bind to estrogen and progesterone, which promote uterine growth and thickening. During endometriosis these cells become implanted in organs and structures outside the uterus, where these hormonal activities continue to occur, causing bleeding and scarring.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body, causing pain and irregular bleeding.

Endometrial implants vary widely in size, shape, and color. Over the years, they may diminish in size or disappear, or they may grow.

Early implants are usually very small and look like clear pimples.
If they continue to grow they may form flat injured areas (lesions), small nodules, or cysts called endometriomas, which can range from sizes smaller than a pea to larger than a grapefruit.
Implants also vary in color; they may be colorless, red, or very dark brown. These so-called chocolate cysts are endometriomas filled with thick, old, dark brown blood that usually appear on the ovaries.

Implants can form in many areas, most commonly in the following:

The peritoneum. This is the smooth surface lining that covers the entire wall of the abdomen and folds over inner organs in the pelvic area.
On or next to the ovaries.

Less commonly they occur in other areas:

Cul-de-sac, an area between the uterus and rectum
Connective tissue that supports the uterus (called the uterosacral ligaments)
Vagina
Fallopian tube
Urinary tract (in about 20% of cases, usually without causing symptoms).
Gastrointestinal tract (in 12 - 37% of patients)

Click the icon to see an image of the female reproductive anatomy.

Very rarely, they appear in areas far from the pelvis, including the lungs and even the arms and thighs.

The process of endometriosis mimics menstruation at certain stages:

Each month, the exiled endometrial implants respond to the monthly cycle just as they would in the uterus. They fill with blood, thicken, break down and bleed.
Products of the endometrial process cannot be shed through the vagina as menstrual blood and debris are. Instead, the implants develop into collections of blood that form cysts, spots, or patches.
Lesions may grow or reseed as the cycle continues.

The lesions are not cancerous, but they can develop to the point that they cause obstruction or adhesions (web-like scar tissue) that attach to nearby organs, causing pain, inflammation, and sometimes infertility.

The primary structures in the reproductive system are as follows:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.

The inner lining of the uterus is called the endometrium, and during pregnancy it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones. The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

Causes

Endometriosis occurs among women all over the world, but researchers have been unable to determine its cause. A combination of genetic, biologic, and environmental factors appear to work together to trigger the initial process, to produce implantation, and to trigger subsequent reseeding and spreading of the implants.

Retrograde Menstruation. One explanation for the development of endometriosis implants involves retrograde menstruation. This occurs during a woman's period, when menstrual tissue flows backward through the fallopian tubes rather than out through the vagina. Early theorists suggested that, in some cases, the redistributed uterine tissue attached and grew in areas outside the uterus, forming endometriosis implants. This theory does not fully explain endometriosis, however. Many women experience some retrograde menstruation, but not all of them develop endometrial cysts. Consequently, other factors must explain why uterine tissue becomes implanted and grows in areas outside the uterus.

Lymphatic Transport. This theory suggests that endometriosis first develops when uterine tissue is separated and then is transported to other organs by way of the lymphatic system or the bloodstream.

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people refer to swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if they are enlarged, are: the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

Environmental Toxins. Other suspects for causing initial development of endometriosis are chemicals called organochlorines, which include dioxins (such as PCBs and furans). These chemicals have estrogen-like effects and are widely found in pesticides and other common products. The organochlorines have a particularly powerful impact on the ovary. Organochlorines have been associated with infertility, certain reproductive cancers, and autoimmune disorders, conditions that also occur with higher frequency in women with endometriosis.

Candida. There is absolutely no evidence that endometriosis is caused by candida (commonly called yeast infection), as claimed in some consumer publications.

There are two basic mysteries surrounding the persistence and growth of endometriosis:

Why do endometrial implants survive the attack by the immune system, which is typically launched against any foreign presence in the body?
How do these endometrial travelers develop new blood vessels and implant themselves in other locations?

Impaired Immune System.Some research is focused on possible immune disorders in women with endometriosis. One theory proposes that women with endometriosis have fewer natural killer (NK) cells, which are factors in the immune system important for surveillance. In their absence, the immune system is weakened and may allow endometrial tissue to invade and take root. A recent study suggests that other types of immune system cells are also underactive in women with endometriosis, allowing the woman's body to tolerate the implanted tissue.

Some evidence suggests that endometriosis represents an autoimmune condition, in which the immune system launches an attack on its own cells and tissue. Much of the evidence rests on the relatively high incidence of other inflammatory autoimmune disorders (multiple sclerosis, rheumatoid arthritis, lupus) that occur in women with endometriosis. It is unclear, however, how this response relates to endometriosis itself and whether endometriosis should be treated as an autoimmune condition.

Growth Factors and Angiogenesis. Macrophages also produce growth factors, which are of particular interest because they play important roles in angiogenesis, a natural process by which new blood vessels form.

Vascular endothelial growth factor (VEGF) is secreted by endometrial cells, and so is of special interest. Under normal conditions, VEGF is secreted within the uterus. When oxygen levels drop following menstruation and blood loss, VEGF levels rise and promote the growth of new blood vessels. This process is important for repairing the uterus following menstruation.

When endometrial cells land outside the uterus, however, investigators theorize that this same process occurs with unfortunate results. The cells secrete VEGF when they are deprived of blood and oxygen, which in turn stimulates blood vessel growth. In this case, however, blood vessel growth serves to promote implantation outside the womb.

Other growth factors involved in angiogenesis that may play a role in endometriosis include transforming growth factors (such as TGF-beta), platelet-derived endothelial growth factor (PD-ECGF), and tumor necrosis growth factors.

Inflammatory Response. The damage, infertility, and pain produced by endometriosis may be due to an overactive response by the immune system to the early presence of endometrial implants. The body, perceiving the implants as hostile, launches an attack. Levels of large white blood cells called macrophages are elevated in endometriosis. Macrophages produce very potent factors, which include cytokines (particularly those known as interleukins) and prostaglandins. Such factors are known to produce inflammation and damage in tissues and cells.

A major study is underway to uncover the genetic factors that predispose certain women to endometriosis. The incidence of endometriosis in women who have a mother or sister with the disorder may be up to 10 times higher than average.

Symptoms

Pain at the time of menstruation (dysmenorrhea ) is the primary symptom and occurs in nearly all girls and women with endometriosis. Studies suggest that endometriosis is the cause of about 15% of cases of pain in the pelvic region in women.

Timing of Pain. In addition to menstruation, endometrial pain can occur at other times of the month. A survey published by the Endometriosis Association reported the following findings on the timing of endometrial pain:

71% of women reported pain within 2 days after their periods started.
47% reported pain in the middle of a cycle. (A sharp pain during ovulation may be due to an endometrial cyst located in the fallopian tube that ruptures as the egg passes through.)
40% reported pain at other times of the month.
20% reported continual pain.
7% said there was no pattern.
Many women with endometriosis experience pain during intercourse.
Adolescents are more likely to experience pain that occurs both during their periods and at other times in the cycle, while in older women endometrial pain is more likely to occur during menstruation.

Location of Pain. Nearly all women with endometrial pain experience it in the pelvic area (the lower part of the trunk of the body). The pain is often a severe cramping that occurs on both sides of the pelvis, radiating to the lower back and rectal area and even down the legs.

Occasionally, however, pain may also occur in other regions if endometriosis affects other part of the pelvic area, such as the bladder or intestine.

Severity of Pain. The severity of the pain also varies widely and does not appear to be related to the extent of the endometriosis itself. In other words, a woman can have very small or few implants and have severe pain, while those with extensive endometriosis may have very few signs of the disorder except for infertility. Large cysts can rupture and cause very severe pain at any time.

Patients may experience additional symptoms, which include the following:

Joint and muscle aches
Fatigue
Bloating
Nausea
Dizziness
Heavy menstrual bleeding
Headaches
Depression and malaise (feeling generally low)
Sleep problems

Risk Factors

Endometriosis affects at least 5.5 million women in North America and millions more worldwide. An estimated 2 - 4% of all premenopausal adult women have detectable endometriosis, and over a third of these women experience noticeable pain. Because many women with endometriosis have no symptoms, the actual percentage of premenopausal women with the disorder may be as high as 15%. Some experts believe endometriosis may be responsible for between 45 - 70% of chronic menstrual pain in adolescence.

Age. Endometriosis can occur in women of all ages. It has been reported in girls as young as age 8 (and has been documented before the onset of menstruation), and in women over age 75, with the average age being between 25 - 29. About 40 - 60% of women with endometriosis report symptoms before age 25.

Ethnic Groups. Endometriosis is most common among Asian women, with Caucasians next. It is reported least frequently in African-American women.

Women at higher risk for endometriosis tend to have more problems with menstruation. Those at higher risk have a shorter than normal cycle, heavier periods, and longer periods. Heavier, more frequent periods, or longer exposure may simply make the risk for retrograde menstruation more likely. (This is the condition in which menstrual flows backward and is believed to be at least partially responsible for the initial development of endometriosis.) Menopause usually brings an end to mild-to-moderate endometriosis, although if women with a history of endometriosis take hormone replacement therapy (HRT), the condition may be reactivated.

Not having children has been associated with a greater risk for endometriosis. Some evidence suggests that early pregnancy may be protective against endometriosis because the cervix becomes dilated during labor, which reduces the risk for retrograde menstruation (menstrual backflow). On the other hand, endometriosis itself can increase the risk for infertility, so it may be a cause rather than a result of not having children. Some studies have found no protection against endometriosis with pregnancy, although women with the condition find relief from symptoms during pregnancy.

Some experts report that almost 7% of first-degree female relatives of endometriosis patients also develop it. A family history of endometriosis not only puts women at high risk for the condition but possibly a more severe manifestation of it as well.

Women may also be at higher risk for endometriosis if they were born with uterine abnormalities that obstruct the normal outflow of blood and cause retrograde menstruation.

There have been reports of endometriosis developing after cesarean sections, including implants developing in surgical scars and in the urinary tract. Some experts believe endometriosis should be suspected in women with urinary tract symptoms and a history of cesarean section.

Various disorders occur in greater rates in women who have endometriosis. In some cases, these disorders and endometriosis may be caused by common factors, but it is not clear what they are.

They include:

Certain cancers, particularly for early-onset breast and ovarian cancers, non-Hodgkin's lymphomas, and melanoma.
Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. In all of these diseases, the immune system launches a destructive inflammatory response against the body's own cells (which differ in location depending on the disease). These are uncommon disorders, but in a major 2002 survey of women with endometriosis, they occurred in 12% of these women. This provides some support to the theory that endometriosis, too, is an autoimmune condition.
Hypothyroidism. In the same 2002 survey mentioned above, 42% of women had low thyroid or some other hormonal disorder.
Fibromyalgia and chronic fatigue syndrome. In the same survey, 31% reported one of these conditions.
Diabetes.
Allergies and asthma. Endometriosis is more prevalent in women with a family history of asthma and allergies, including food and skin allergies and hay fever.
Migraine. A small 2006 study suggested that women who have migraine headaches are at increased risk of endometriosis.

Some studies have reported a higher incidence of certain factors in women with endometriosis:

Women with endometriosis tend to be taller and thinner than average.
Women with red hair have an increased risk for endometriosis. Experts guess that the gene determining red hair might be located near other genes that make such women susceptible to endometriosis.

Alcohol and caffeine use have been associated with a higher risk.

Complications

Endometriosis is a chronic disease that is difficult to diagnose and treat. Without treatment, endometriosis gets progressively worse in 65 - 80% of patients. Even with treatment, endometriosis continues to advance in 20% of patients. Cysts and implants may grow and spread to other parts of the pelvis, and in very severe cases, to the urinary or intestinal tracts. Eventually adhesions may form. These are dense, web-like structures of scar tissue that can attach to nearby organs and cause pain, infertility, and intestinal obstruction.

Pain is the most common complaint for women with endometriosis, and it can significantly impair the quality of life. The pain experienced around menstruation can be so debilitating that up to 25% of women with the condition are incapacitated for 2 - 6 days of each month. In severe cases, regular activities may be curtailed for up to 2 weeks per month. Sleeping problems have been reported in 75% of patients, mostly due to pain.

Endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30 - 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. In an attempt to determine the chances for infertility with endometriosis, researchers have come up with a staging system based on findings during diagnostic surgery.

Endometriosis rarely causes an absolute inability to conceive, but it can contribute to infertility both directly and indirectly.

Direct Effect of Endometrial Cysts. Endometrial cysts may directly prevent infertility in a number of ways:

If implants occur in the fallopian tubes, they may block the egg's passage.
Implants that occur in the ovaries prevent the release of the egg.
Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but also may cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity. It is possible that in such cases, the body perceives these foreign endometrial implants as hostile, and launches an attack.

In this process, the body overproduces specific immune factors that contribute to infertility:

Cytokines. Cytokines are very potent immune factors that, when overproduced, cause damage and inflammation in the very regions that are directed to protect. Such damage could produce scarring and obstructions that interfere with implantation and development of a fertilized egg. In severe endometriosis, there is inflammation in the fluid surrounding the uterus, which could create a hostile environment for the sperm.
Prostaglandins. Elevated levels of these hormone-like factors not only produce inflammation but also increase uterine contractions. (Women with endometriosis have a higher than average risk for miscarriage.)
Other Immune Factors. Growth factors, which stimulate growth of new blood vessels, and toxins produced by implants may impair fertility.

Other Conditions Linking Endometriosis and Infertility. Researchers have noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. Such abnormalities are more often a factor in infertility in women with mild-to-moderate endometriosis than in those with severe cases.

One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.

Implants can also occur in the bladder (although rare) and cause pain and even bleeding during urination. Implants also sometimes form in the intestine and cause painful bowel movements, constipation, or diarrhea. Hormonal treatments, the standard therapies for endometriosis, are not helpful in such cases, and surgery may be needed.

Endometriosis has characteristics that are similar to cancerous tumors, including cellular invasion of other tissues, unrestrained growth, development of new blood vessels, and impaired ability of cells to naturally self-destruct. It is not a malignant disease, however, but experts have been debating for years whether it represents any significant danger.

The possible risks for ovarian and endometrial cancers are of specific concern. Some researchers have identified certain genetic mutations that may transform endometrial cells into ovarian or endometrial cancers in rare cases. Some evidence suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases, and, in fact, have a better outlook.

Of additional concern are studies suggesting that women with endometriosis have a higher risk for other cancers, particularly for early-onset breast cancer and non-Hodgkin's lymphoma (NHL).

The emotional effect of severe endometriosis can be almost as devastating as the pain. It can affect marriage and work. In one survey conducted by the Endometriosis Association, patients reported the following emotional effects from this disease:

84% of patients reported feeling depressed during periods of pain
75% felt irritable
More than 50% reported feelings of anxiety and anger
About 20% said they felt hopeless

In one study, during the days around menstruation 30% of women with endometriosis increased their alcohol intake compared to 14% of women with other gynecological problems and only 9.5% of women with no gynecological disorders.

Diagnosis

Although endometriosis is the most commonly diagnosed uterine disorder, it is often misdiagnosed or missed altogether. In a study of women with proven endometriosis, more than half of them had been told by a doctor that nothing was wrong. In another study, half of women with endometriosis reported that they visited a doctor five or more times before they were diagnosed.

Endometriosis frequently begins to develop in adolescence, but it is not typically diagnosed until a woman is in her mid-20s or early 30s. There are a number of reasons for this:

The symptoms vary widely, and sometimes do not occur at all. Some women do not know they have endometriosis until they fail to become pregnant and seek help for infertility.
Pain in the pelvic or abdominal area can be caused by so many conditions that it is often difficult to pin down the precise cause.

Endometriosis should be highly suspected in women with severe menstrual cramps who are also infertile. Laparoscopy, an invasive diagnostic procedure, is the only definitive method for diagnosing endometriosis. However, a trial using one of several hormonal therapies is usually sufficient to confirm or rule out endometriosis. Such drugs include danazol, GnRH agonists, and progestins.

Many conditions cause pelvic pain. In many cases, the cause is unknown and it often resolves on its own. In one study, pelvic pain improved or resolved without treatment in 77% of women over a 15-month period. However, some causes of pelvic pain can be serious and should be ruled out during a work-up for endometriosis.

Primary Dysmenorrhea. Primary dysmenorrhea is recurrent pelvic pain associated with menstruation. Dysmenorrhea is common in many women. [See In-Depth Report #100: Menstrual disorders.]

Adenomyosis. A condition called adenomyosis occurs when nodules (knots) of endometrial tissue develop within the deep muscle layers of the uterus. This disorder is often classified with endometriosis, but adenomyosis is a different disease. (Endometriosis occurs when endometrial tissue grows and functions outside the uterus.) Adenomyosis is a significant cause of severe pelvic pain and menstrual irregularities. Until recently adenomyosis was diagnosed only after a hysterectomy, but advanced imaging techniques using ultrasound and magnetic resonance imaging scans may be able to detect it. A 2006 study indicated that women who have had surgery for endometriosis, yet continue to suffer from menstrual and pelvic pain, may actually have adenomyosis.

Adenomyosis typically occurs in women who have uterine fibroids, women age 40 - 50, and women who have had children. [See In-Depth Report #73: Uterine fibroids.]

Fibroid tumors may not need to be removed if they are not causing pain, bleeding excessively, or growing rapidly.

Other Causes of Pelvic Pain. Many conditions cause pelvic pain that may or may not be related to menstruation. Some causes of pelvic pain can be serious and should be ruled out:

Uterine fibroids
Pelvic inflammatory disease (which is a result of infections in the pelvic area)
Miscarriage
Ectopic pregnancy

Click the icon to see an image of an ectopic pregnancy.

Pelvic cancer (rare)
Uterine polyps
The use of an intrauterine device (IUD) for contraception

Conditions that may mimic symptoms of endometriosis but which are unrelated to problems in the reproductive organs include:

Severe kidney or urinary tract infections
Celiac disease
Appendicitis
Interstitial cystitis
Inflammatory bowel disease
Diverticulitis
Irritable bowel syndrome

The doctor may be able to feel tender masses or nodules during a pelvic examination, but these signs can indicate many conditions and do not necessarily mean endometriosis is present.

Laparoscopy. Diagnostic laparoscopy, an invasive surgical procedure, is currently the only definitive method for diagnosing endometriosis. Laparoscopy normally requires a general anesthetic, although the patient can go home the same day.

Click the icon to see an image of laparoscopy.

The procedure is as follows:

The surgeon makes tiny abdominal incisions through which a fiber optic tube, equipped with small camera lenses, is inserted. The doctor uses these devices to view the uterus, ovaries, tubes, and peritoneum (lining of the pelvis) on a video monitor.
Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away so that the doctor has a wider view.
A blue dye may be flushed through the fallopian tubes to determine blockage; if there is an obstruction, the dye will not flow through the tube.
If the surgeon needs to remove small endometrial cysts or other lesions during the procedure (operative laparoscopy), tiny surgical instruments are passed through a tube.

The procedure is used for detecting and staging endometriosis to determine its severity. In some cases, the procedure itself will restore fertility in women with endometriosis.

Transvaginal Hydrolaparoscopy. Transvaginal hydrolaparoscopy is a new and less invasive approach than laparoscopy, since the instruments are inserted through the vagina, not through incisions in the abdomen. It requires only sedation, does not use CO2 to distend the abdomen, and has a much shorter and easier recovery than with standard laparoscopy. When used by a skilled professional, it is as accurate as laparoscopy, but is not yet widely available.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of fibroids, polyps, or other causes of bleeding. (It may miss cases of uterine cancer, however, and is not substitute for more invasive procedures, such as D&C or endometrial biopsy, if cancer is suspected.)

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This can cause cramping.

Hysteroscopy is non-invasive, but 30% of women report severe pain with the procedure. The use of an anesthetic spray such as lidocaine may be highly effective in preventing pain from this procedure. Other complications include excessive fluid absorption, infection, and uterine perforation. Hysteroscopy is also used as part of surgical procedures.

An ultrasound is performed in cases where other conditions are suspected, such as uterine fibroids, ovarian cysts, or ectopic pregnancy. This non-invasive imaging technique can detect endometriomas, or cysts that are usually located on the ovaries and filled with thick dark blood. Ultrasound can also pick up cysts larger than 1 cm (about 1/3 inch), but will miss smaller cysts, or small and shallow endometrial implants on the surface of ovaries, or on the peritoneum (lining of the pelvis).

Once a diagnosis is made, more sophisticated imaging techniques, such as computed tomography (CT) scanning or magnetic resonance imaging (MRI), may be used to obtain a more accurate image of severe endometriosis.

Investigators are studying certain chemicals detected in blood tests that may prove to help diagnose endometriosis and so avoid invasive diagnostic procedures in many women. Among the most studied to date are CA-125 and CA19-9. Both are elevated in women with severe endometriosis. Higher levels of both chemicals occur in many other diseases, however, including ovarian cancer, so results using this test alone do not provide enough information for a definitive diagnosis of endometriosis.

During laparoscopy, the surgeon determines the number, size, and location of endometrial implants and adhesions. This information helps rank endometriosis by the extent of the disease and give the likelihood of infertility:

Minimal (stage I)
Mild (stage II)
Moderate (stage III)
Severe (stage IV)

A number of experts do not believe these categories are useful, because they often do not relate to the intensity of the pain, or to treatment success rates.

Some experts believe it is more accurate to further categorize endometriosis by the depth of penetration:

Superficial Endometriosis. Endometriosis that lies more on the surface is more highly associated with infertility than deep implants.
Infiltrative Endometriosis. Implants deeper than 5 - 6 mm; deep implants are believed to be the best indicator of progression and severe symptoms.

Treatment

There is no perfect way of managing endometriosis. The three basic treatment approaches are:

Watchful waiting (to relieve symptoms)
Hormonal therapy (to reduce endometrial implants)
Surgery (to reduce endometrial implants, restore fertility, or possibly cure the condition)

The choice depends on a number of factors, including the woman's symptoms, her age, whether fertility is a factor, and the severity of the disease.

In general, watchful waiting is a good initial choice for:

Women with mild pain who, if fertile, do not wish to become pregnant. If women with mild endometriosis wish to become pregnant, the doctor may recommend unprotected sex for 6 months to year. If pregnancy does not occur, then treatment may be started.
Women approaching menopause.

Some experts believe that early diagnosis and treatment in young women without symptoms might prevent some cases of infertility later on. Unfortunately, however, some treatments for endometriosis may actually trigger symptoms in those who do not yet experience them.

Hormone therapies are used to mimic states in which ovulation does not occur (such as pregnancy or menopause) or to directly block ovulation. Hormonal drugs include oral contraceptives, progestins, GnRH agonists, and danazol. They can be very effective in relieving endometriosis symptoms. Some of these drugs may also be used after surgery to help prevent recurrence of endometriosis. There is also some evidence that GnRH agonists and danazol may improve immune factors associated with endometriosis. But there are downsides:

None of these drugs can cure the problem. Symptoms recur in about half of patients within 5 years of treatment.
They do not improve fertility rates and may delay conception in women who use them.
Side effects of these drugs can be distressing. There is a high dropout rate with the use of nearly all these hormonal treatments.
Women who take GnRH agonists, danazol, or similar drugs should use non-hormonal birth control methods (such as the diaphragm, cervical cap, or condoms) because these drugs can increase the risk for birth defects.

Surgery is an option for the following women:

Women with severe pain that does not respond to watchful waiting and medical treatment.
Women who want to become pregnant and endometriosis is most likely the major contributor to infertility.

There are two basic surgical approaches for endometriosis:

Conservative Surgery (Laparoscopy or Laparotomy). Conservative surgery uses laparotomy or laparoscopy to remove the endometriosis implants without removing any other reproductive organs. It is a good option for women who wish to become pregnant or who cannot tolerate hormone therapy. Some experts believe that laparoscopy surgery should be the treatment of choice for women with endometriosis. Endometriosis often recurs after conservative surgery, however. Recurrence rates at 2 years range from 2 - 47%. The risk for recurrence or residual pain after any procedure increases with the severity of the condition, particularly if endometriosis has affected areas outside the uterus.
Radical Surgical Therapy (Hysterectomy). Hysterectomy with removal of ovaries (oophorectomy) along with all endometrial implants is the only potential cure for endometriosis. If endometriosis has developed outside the uterus than even this procedure is not curative. Removing only the uterus with hysterectomy, in any case, has the same risk for recurrence as conservative surgery.

Click the icon to see an illustrated series detailing hysterectomy.

In choosing between hysterectomy (with or without oophorectomy) and conservative surgeries, age and the desire for children are important factors. One study reported a greater sense of loss, more residual symptoms, and more pain in younger women (under age 30) who have undergone hysterectomy than in older women. In one study, 37% of such younger women regretted their decision to have a hysterectomy.

Once careful instruction is given for all the risks and benefits of the different surgical options, the doctor must respect any decision a patient makes to retain as much of her reproductive system as she wants, even if she is past menopause. Both the patient and the doctor should also be clear about the possibility of changing procedures once the operation has begun, depending on what the surgeon may observe. For example, the surgeon may find abnormalities that require more extensive surgery.

Much of the success of any procedure relies on the experience of the surgeon. A woman should always ask for a doctor's track record, or the number of times the doctor has performed the procedure in question. The more, the better. Asking for complication rates may be helpful, but a patient should realize that an experienced surgeon may have a higher number of high-risk patients, and therefore, a higher complication rate than a less experienced surgeon with fewer serious cases.

For women with severe endometriosis who want to become pregnant, conservative surgery (typically laparoscopy) is the appropriate approach for restoring fertility. Hormonal therapies that treat endometriosis itself, such as GnRH agonist or progestins, are generally considered not to help fertility. However, a 2002 study suggested that the use of the GnRH agonists after surgery helped improve conception rates in women who subsequently undergo assisted reproductive techniques (ART), such as in vitro fertilization (IVF). A 2006 study indicated that GnRH agonists given along with infertility treatments may help improve a woman's chance of becoming pregnant. This research is still preliminary.

In any case, ART and hyperstimulation of the ovary using fertility drugs to produce eggs are the standard fertility treatments available to women if surgery fails. ART includes techniques such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Hyperstimulation is the less expensive approach. In a 2003 study, however, ART achieved much greater conception rates in women with endometriosis, particularly those with late-stage disease.

It is not clear whether women with early -stage endometriosis do any better with fertility treatment than simply trying to become pregnant through non-aggressive means. Women with endometriosis who are trying to conceive should discuss all treatment options with a specialist. [See In-Depth Report #22: Infertility in women.]

Lifestyle Changes

Some women report relief by avoiding dairy products and having a diet rich in fiber and low in saturated (animal) fats. Fiber-rich foods (such as fruits and vegetables) along with plenty of fluids (water or juice, not caffeine) are not only healthy but help prevent constipation, which can intensify symptoms. If women choose a diet that limits dairy products, they should be sure to have sufficient calcium from other sources.

A 2005 study involving over 500 women reported that red meat and ham consumption increased the risk for endometriosis. Diets high in green vegetables and fresh fruit appeared to protect against it.

Fat compounds called omega-3 fatty acids may have specific anti-inflammatory effects. They are found in certain oily fish (sardines, mackerel) and can be obtained in supplements. Supplements may be labeled either omega-3 fatty acids or EPA-DHA (which are the important compounds). Evening primrose oil and black currant oil, found in health food stores, contain similar fatty acids that may be helpful. However, food sources are the healthier choice.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people who have IBD (inflammatory bowel disease).

Drinking alcohol and and smoking cigarettes may increase endometriosis risk. It is unclear whether caffeine is a significant risk factor.

A sitz bath is simply sitting in a basin of water. Some people report relief by alternating between sitting 3 minutes in a hot water basin and then 1 minute in a cold water basin. This is repeated three times. The procedure is performed twice a day 3 - 4 days a week, except during menstruation.

A warm bath or application of heated abdominal pad may help relieve painful menstrual cramps.

Kegel exercises are designed to strengthen the muscles of the pelvic floor that both support the bladder and close the sphincters. Some people find they help endometriosis. The exercises consist of tightening and releasing the pelvic muscle. Since the muscle is internal and sometimes difficult to isolate, doctors often recommend practicing while urinating on the toilet. The patient tries to contract the muscle until the flow of urine is slowed or stopped and then releases it. (However, once learned, Kegel exercises should not be regularly performed while urinating as this practice may eventually weaken the muscles.)

Exercise may be very helpful for women with endometriosis. It relieves stress and tension and may reduce hormonal levels that can contribute to endometrial growth.

Acupuncture and Acupressure. Some studies have reported relief from pelvic pain after acupuncture or acupressure, a technique that applies small pins or pressure to specific points on the body. Some women report relief with reflexology, a technique that uses manual pressure on acupuncture points on the ears, hands, and feet.

Click the icon to see an image of acupuncture.

Transcutaneous Electrical Nerve Stimulation. Transcutaneous electric nerve stimulation (TENS) applies electrodes to certain parts of the body and administers low-level electrical pulses to those locations. Research suggests that it works by altering the body's ability to receive pain signals. The standard approach is to give 80 - 100 pulses per second, for 45 minutes, three times a day. TENS is painless and patients are barely aware of the sensation. A 2002 analysis suggested that this approach may help some women with dysmenorrhea.

Yoga and Meditative Techniques. Yoga and meditative techniques that promote relaxation may also be helpful for menstrual cramps.

Chiropractic. Some women with primary dysmenorrhea have sought help from chiropractors trained in spinal manipulation. One study compared a high-force spinal manipulation technique with a low-force maneuver used as a placebo technique. Both showed lower scores on tests that measure pain, perhaps indicating that a simple back rub by a sympathetic partner or friend may be helpful.

Herbal and Other So-Called Natural Remedies for Cramp Relief. Researchers have not conducted many rigorous studies on herbal remedies for menstrual and pelvic pain. Small studies have suggested that pycnogenol, a plant extract derived from the bark of the French maritime pine tree, may help reduce endometriosis symptoms. Some patients have reported relief from menstrual cramps with aromatherapy using lavender, sage, and rose oils.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Medications

The basic approach in hormonal treatments for endometriosis is to block production of female hormones (estrogen and progesterone) or to prevent ovulation. Hormonal drugs are used for pain relief only. None have been proven to improve fertility rates and in some cases may delay conception. Specific hormonal drugs may have different effects for women with endometriosis.

Inducing Pseudopregnancy. Oral contraceptives that contain estrogen and progestins mimic a pregnant state and block ovulation. (Progestins are natural or synthetic forms of progesterone). Progestins may also be used alone, since they have specific effects that can cause the endometrial tissue itself to atrophy.
Inducing Pseudomenopause. Gonadotropin-releasing hormone (GnRH) agonists or gestrinone, an anti-progesterone that mimic menopause. They reduce estrogen and progesterone to their lowest level.
Inducing On-going Blockage of Ovulation. Danazol, a derivative of male hormones, is a powerful ovulation blocker.

Studies report that around 80% of women achieve pain relief after taking these drugs. To date, comparison studies have found few differences in effectiveness among the major hormonal treatments. Differences occur mostly in their side effects. Women should discuss the effects of particular medications with their doctors to determine the best choice.

Oral contraceptives (OCs), commonly called "the Pill," contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestin). For some patients, OCs may provide better endometriosis pain relief than gonadotropin releasing hormone agonist drugs. OCs may reduce the risk of ovarian cancer by 30 - 50% and of endometrial cancer by 50%, a potentially important benefit in women with endometriosis. Patch contraceptives are available, but they may increase the risk for menstrual cramping.

Click the icon to see an illustrated series detailing the birth control pill.

When used throughout a menstrual cycle, OCs suppress the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevent ovulation. There are many brands available. The estrogen compound used in most oral contraceptives is estradiol. Many different progestins are used, and there are many brands. None to date have proven to be superior over others. Women should discuss the best options for their individual situations with their doctor.

Standard OCs come in a 28-pill pack that contains 21 active pills and 7 inactive pills. Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These OCs contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.

Seasonale, the first continuous-dosing contraceptive, was approved in 2003. It contains 81 days of active pills followed by 7 days of inactive pills. Women who take Seasonale have on average a period every 3 months. Seasonique, a follow-up to Seasonale, was approved in 2006. As with Seasonale, it produces about 4 periods a year. With Seasonique, a woman takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.

In 2007, the FDA approved Lybrel, which supplies a daily low dose of levonorgestrel and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Estrogen and progestin each cause different side effects. The most serious side effects are due to the estrogen in the combined pill. Uncommon but more dangerous complications of OCs include high blood pressure and deep-vein blood clots (thrombosis), which may contribute to heart attack or stroke. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer and, if it does, which women are at risk.

Progestins alone may be helpful and are the oldest drugs used for endometriosis. Progestins can prevent ovulation and reduce the risk for endometriosis in the following ways:

They block luteinizing hormone (LH), one of the reproductive hormones important in ovulation.
They change the lining of the uterus and eventually cause it to atrophy.
They may provide pain relief equivalent to the more powerful hormone drugs. Some experts recommend them as the first choice for women with endometriosis who do not want to become pregnant.

Specific Progestins. Progestins are available in pill or injectable form, or as a progestin-releasing intrauterine device (IUD). Medroxyprogesterone (Depo-Provera), which is administered by injection every 3 months, is one of the standard progestins used. A new low-dose formulation, Depo-subQ Provera 104, was approved in 2005. Oral progestins include norethindrone (Micronor, Aygestin, Norlutate). Norethindrone is also known as norethisterone.

A 2006 study compared low-dose depot medroxyprogesterone with the gonadotropin releasing hormone (GnRH) agonist leuprolide (Lupron). The two drugs worked equally well in controlling endometriosis pain. However, leuprolide caused more loss of bone mineral density, a condition associated with osteoporosis. Patients who received medroxyprogesterone injections had fewer hot flashes than those who received leuprolide, but they had more episodes of bleeding and spotting.

Progestin-releasing IUDs can be very helpful for many women with endometriosis, particularly an advanced version called the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena). Studies suggest that the LNG-IUS reduces endometrial cell proliferation and increases cell self-destruction. Progestin released by the IUD mainly affects the uterus and cervix and causes fewer widespread side effects than other forms of progestins.

The LNG-IUS has proved effective for heavy bleeding (menorrhagia), and studies indicate that it helps control the symptoms of minimal-to-moderate endometriosis. Studies indicate that the LNG-IUS works as well as GnRH agonists in managing endometriosis pain, and causes less loss of estrogen. Some experts think that the LNG-IUS could become the treatment of choice for women with endometriosis pelvic pain who do not wish to become pregnant.

Click the icon to see an image of an IUD.

Side Effects of Progestins. Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that uses only progestin, although they may be less or more severe depending on the form and dosage of the contraceptive. Side effects may include:

Changes in uterine bleeding, such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods
Unexpected flow of breast milk
Abdominal pain or cramps
Diarrhea
Fatigue, unusual tiredness, weakness
Hot flashes
Decreased sex drive
Nausea
Trouble sleeping
Acne or skin rash (although low-dose OCs actually improve acne)
Depression, irritability, or other mood changes
Swelling in the face, ankles, or feet
Weight gain

Newer formulations of combination pills that use low-dose estrogen and newer progestins may reduce and even avoid many of these side effects. Progestins used in non-oral contraceptives, such as the LNG-IUS IUD, also may not pose as high a risk for these side effects. If side effects persist or are severe, a woman should always talk to her doctor. Many women do not experience these side effects, or if they do, their bodies eventually adjust.

Gonadotropin releasing hormone (GnRH) agonists are effective hormone treatments for endometriosis. They are able to block the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen. Ovulation and menstruation resume around 4 - 10 weeks after stopping the drug. The specific length of time depends on the type of GnRH agonist used.

Women with endometriosis often have a difficult time getting pregnant. A 2006 review suggested that GnRH agonists may help women with endometriosis become pregnant when the drug is given along with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). (IVF and ICSI are standard infertility treatments.) The review found that 3 - 6 months of GnRH therapy in combination with infertility treatment quadrupled the pregnancy rate. However, the study did not supply data on how many women actually gave birth. In addition, there is not enough information on whether these drugs may adversely affect a woman or her fetus.

Specific GnRH Agonists. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, Nafarelin (Synarel). Studies have reported that nafarelin shrank all implants and significantly relieved symptoms in 85% of patients, delayed recurrence of endometriosis after surgery, and in comparison with leuprolide, was less expensive, had fewer side effects, and a provided better quality of life.

Side Effects and Complications. Commonly reported side effects (which can be severe in some women) include menopause-like symptoms that include hot flashes, night sweat, and changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

The most important concern is possible osteoporosis from estrogen loss. Women ordinarily should not take GnRH agonists for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Add-back therapy provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist. Studies suggest this is safe and effective for protecting bone.
Intermittent leuprolide uses repeated 6-month courses of GnRH agonists followed by an average of 9 months of symptom control only.
Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
Adding bone-protective drugs may be helpful. The standard ones are bisphosphonates and include alendronate (Fosamax), risedronate (Actonel), and etidronate (Didronel). Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include the parathyroid hormone teriparatide (Forteo) and selective estrogen-receptor modulators (SERMs), such as raloxifene (Evista).

GnRH treatments used alone do not prevent pregnancy. Furthermore, if a woman becomes pregnant during their use, there is some risk for birth defects. Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Danazol (Danocrine) is a synthetic drug that resembles a male hormone (androgen). It suppresses the pathway leading to ovulation. Studies have shown symptomatic improvement in 90% of women, although in one study, only about 58% of women expressed satisfaction with this therapy. A high drop-out rate occurs, most often because of adverse side effects, particularly male characteristics, such as growth of facial hair, acne, weight gain, dandruff and deepening of the voice.

Danazol may increase the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have also been reported, as well as rare cases of liver damage. One study reported that taking a low dose may relieve endometrial symptoms and reduce the risk for these side effects. Exercise may also help reduce side effects. As with GnRH drugs, pregnant women or those trying to become pregnant should not take this drug because it may cause birth defects.

Antiprogestins are promising drugs for endometriosis because they reduce both estrogen and progesterone receptors.

Gestrinone. Gestrinone is the most studied antiprogestin and appears comparable to GnRH agonists in reducing pain and while causing fewer menopausal symptoms. In one study, bone density even increased slightly. Adverse effects of gestrinone include male hormone symptoms, such as acne, and possibly the development of unhealthy cholesterol levels.

Mifepristone. Mifepristone (Mifeprex) is another antiprogestin that may be helpful for treating endometriosis. In one 6-month study, mifepristone improved symptoms and reduced endometrial implants without causing menopausal side effects. Long-term use, however, may cause changes in the uterine tissue and cell proliferation.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Over-the-counter NSAIDs may be sufficient for about 75% of women with endometrial pain. NSAIDs block prostaglandins (the substances that increase uterine contractions). They are effective painkillers and also have other properties that act against inflammatory factors. Aspirin is the most common NSAID, but there are dozens of others available over the counter or by prescription. Among the most effective NSAIDs for menstrual disorders are ibuprofen (Advil, Motrin, Midol PMS), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and mefenamic acid (Ponstel). For maximum benefit, they should be taken 7 - 10 days before a period is expected. However, long-term use of NSAIDs can increase the risk for gastrointestinal bleeding and ulcers. One study of women with iron deficiency anemia reported that overuse of NSAIDs for menstrual disorders contributes to anemia.

Acetaminophen. Acetaminophen (Tylenol) reduces levels of female hormones (gonadotropins and estradiol, an estrogen), which may have some beneficial effect on menstrual disorders. A combination of acetaminophen and pamabrom (Women's Tylenol Menstrual Relief) is specifically aimed at treating menstrual pain and bloating. (Pamabrom is a diuretic, a drug used to reduce fluid build-up and bloating.)

Opioids. Drugs containing codeine should not generally be used for endometriosis pain management. They can cause pelvic congestion and constipation, which can worsen symptoms in patients with gastrointestinal distress.

GnRH Antagonists. GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). These newer drugs differ from GnRH agonists in that they have a direct effect on the pituitary gland. The result is quicker action. They also pose a lower risk for complications and side effects.

Aromatase Inhibitors.Drugs that inhibit aromatase, an enzyme that is a major source of estrogen, are being studied for effects against endometriosis. Such drugs include anastrozole, letrozole, exemestane, and vorozole. Aromatase levels may be abnormal in women with endometriosis. A 2004 pilot study of letrozole combined with a progestin showed reduction of endometriosis as well as decrease in pelvic pain, suggesting that this treatment holds promise.

Selective Estrogen-Receptor Modulators (SERMs). Drugs known as selective estrogen-receptor modulators (SERMs) are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. They have not been widely studied for endometriosis since tamoxifen (Nolvadex), the most commonly used SERM, may worsen endometriosis. However, the actions of other SERMs, such as raloxifene (Evista) or tibolone (only available in Europe), may be beneficial and warrant more research.

Selective Progesterone Receptor Modulators (SPRMs). SPRMs, also called mesoprogestins, have both agonist and antagonist properties. This new class of drugs may be effective for suppressing endometrial growth.

Other investigational drugs for treatment of endometriosis include tumor necrosis factor alpha (TNF-alpha) inhibitors, angiogenesis inhibitors, and various immune modulators.

Conservative Surgery

The goal of conservative surgery is to aggressively remove as many endometrial implants and cysts as possible without causing surgical scarring and subsequent adhesions that could cause fertility problems. The two conservative procedures used are either laparoscopy or laparotomy.

Improving Fertility. Surgery has been shown to improve infertility rates in women with severe endometriosis (stages III and IV). Whether it offers any advantage in pregnancy rates in women with mild-to-moderate endometriosis (stage I or II) is unclear. Nevertheless, some doctors recommend conservative surgery even in early-stage endometriosis, because of the progressive nature of the disorder some evidence suggests it improves fertility. Fertility can often be restored even if the surgery does not remove all the endometrial implants. However, the best fertility rates in such cases occur in the early postoperative period. They decline over time if implants have not been completely eliminated. Subsequent surgeries become less effective in restoring fertility.

Reducing Pain and its Recurrence. Studies report pain reduction after surgery in more than 60% of women. Conservative surgery, however, can miss microscopic implants that may continue to cause pain and other symptoms after the procedure.

Even with very successful surgery, endometriosis usually recurs within a period of between 2 months and several years. In one study, the risk for recurrence after conservative surgery was highest in women who have had previous surgery or who have stage IV disease (large endometriotic cysts). Other factors including age, pregnancy, or the number of cysts, did not seem to influence the degree of risk. An earlier study indicated that women who became pregnant after surgery for endometriosis had a lower risk for recurrence, but pregnancy itself does not cure endometriosis. The use of GnRH agonists after surgery may delay recurrence without affecting fertility.

Both laparoscopy and laparotomy are effective, but there are differences. Some experts believe that laparoscopy surgery should be the treatment of choice for women with endometriosis.

Laparoscopy is currently the gold standard treatment for endometriosis. It is usually done under general anesthetic and involves the following:

Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away so that the doctor has a wider view.
The procedure requires making small incisions at the navel and above the pubic bone.
The laparoscope (a hollow tube equipped with camera lenses and a fiber optic light source) is inserted through the incision at the navel (the umbilical incision).
A probe is then inserted through the second incision, allowing the doctor to directly view the outside surface of the uterus, fallopian tubes, and ovaries.
One or two additional small incisions can be made on either side of the lower abdomen through these incisions. Surgical instruments or other devices are passed through these accessory incisions to destroy or remove abnormal tissue. Implants can be removed by excision (surgical removal) using a laser or scissors or by destroying the area with lasers or with electricity (or electrocautery).

In one study, laparoscopy achieved pain relief in over 62% of women. A more recent study conducted 3 - 12 months post-surgery in women with severe (stage III/IV) endometriosis suggested 88% of patients were satisfied with the procedure.

In addition, pregnancy rates can range from 20% to over 50% after laparoscopy. (The procedure does not reduce the chances for pregnancy in women who must still undergo assisted reproductive techniques to conceive.) Still, recurrence rates for laparoscopy are no better than those with laparotomy -- the more invasive procedure.

Laparotomy uses a wide abdominal incision and conventional surgical instruments. It is more invasive and requires a longer recovery time. In some severe cases, the doctor may need a wider view of the pelvic area and will perform this procedure. Laparotomy is typically used for infiltrating endometriosis, although the less invasive laparoscopy is showing increasing effectiveness, even for deep implants.

Complications after Surgery. Many patients experience temporary but severe discomfort in the shoulders after laparoscopy due to residual carbon dioxide gas that puts pressure on the diaphragm. The incisions, even with laparoscopy, may cause pain afterward, which can usually be treated effectively with mild pain relievers. There are small risks for bleeding, infection, and reaction to anesthesia. Surgery in the pelvic area may also cause scarring, which may cause pain and interfere with fertility.

Preoperative Drug Treatment. Hormonal drugs administered before laparoscopy and laparotomy are being investigated to reduce the size of endometrial cysts and so perhaps to improve outlook. A 2000 study, for example, reported that the GnRH agonist goserelin injected monthly 12 weeks before laparoscopy resulted in much smaller implants and better treatment of the disease than treatment with surgery alone.

Postoperative Drug Treatment. A number of studies have also been conducted to determine if taking hormonal drugs after surgery can provide further pain relief. Results have been mixed, and the benefits, if any, are probably slight.

Some evidence suggests that surgically cutting the pain-conducting nerve fibers leading from the uterus diminishes the pain from dysmenorrhea. Two procedures, uterine nerve ablation and laparoscopic presacral neurectomy, can block such nerves. Small studies have shown benefits from these procedures, but stronger evidence is needed before they can be recommended for women with severe primary dysmenorrhea.

Laparoscopic Uterosacral Nerve Ablation (LUNA). LUNA is a recent approach that uses either laser or cauterization to destroy nerves in a small segment of the ligaments that connect the cervix with the lower back. The ligaments do not appear to provide any structural support. There are few side effects from the procedure. The patient does not lose any sensations associated with sexual activity.

Laparoscopic Presacral Neurectomy (LPSN). LPSN uses laser techniques to sever a web of nerves between the lower spine and tail bone that transmit pain from the uterus. The procedure does not affect fertility. Studies suggest that it may work better than LUNA in the long term, but it also poses a higher risk of complications. These complications include constipation, diarrhea, and urinary problems. However, many women find that these symptoms eventually improve.

Hysterectomy

Hysterectomy, the surgical removal of the uterus, is the second most frequently performed surgery in premenopausal women (Cesarean sections are first). About 600,000 hysterectomies are performed each year in the U.S., which is among the highest rate of all countries. By age 60, about a third of American women have had this procedure. The highest hysterectomy rates are in women age 40 - 44. Women in the southern and midwestern areas of the United States are more likely to have the operation than those in the northeast and west.

A 2007 study suggested that a combination of factors predicts whether a woman will decide to have a hysterectomy. A woman who meets all three of these factors has a 95% chance of having a hysterectomy:

Presence of symptoms (pelvic pain, bleeding, symptomatic fibroids)
Lack of symptom improvement or resolution despite treatment
Previous use of GnRH agonist drugs

The number of procedures has continued to increase, but only slightly in recent years. Endometriosis accounts for 18% of these procedures, but the rates vary widely by ethnic group, with the great majority of endometriosis-related hysterectomies performed in Caucasian women.

Hysterectomy does not necessarily cure endometriosis. One study reported that endometriosis reappeared in 13% of women within 3 years of a hysterectomy and in 40% after 5 years.

Most women are satisfied with the procedure. A major analysis of evidence on hysterectomies reported that symptoms related to menstrual problems decline significantly in most women, although none completely disappear for all women. The majority of women also experience improved quality of life and emotional functioning. Women who have a hysterectomy are less likely to experience hot flashes than women who have a natural menopause.

Still, one study suggested that 70% of recommendations for hysterectomies did not meet the standard of care as determined by expert groups. In such cases, patients were not given alternative choices or adequate diagnostic evaluations. Any woman, even one who has reached menopause, who is uncertain about a recommendation for a hysterectomy should certainly seek a second opinion.

Once a decision for a hysterectomy has been made, the patient should discuss with her doctor what will be removed. The common choices are:

Total Hysterectomy (Removal of uterus and cervix). Removing only the uterus with hysterectomy has the same risk for recurrence as conservative surgery.
Supracervical Hysterectomy (Removal of uterus and preservation of the cervix). Procedure is performed in about 20 - 25% of cases.
Bilateral Salpingo-Oophorectomy (Removal of the fallopian tubes and ovaries). It can be used with either total or supracervical hysterectomy. This is the only potential cure for endometriosis. If endometriosis has developed outside the uterus then even this procedure is not curative.

Hysterectomy is surgical removal of the uterus, resulting in inability to become pregnant. This surgery may be done for a variety of reasons including, but not restricted to, chronic pelvic inflammatory disease, uterine fibroids and cancer. A hysterectomy may be done through an abdominal or a vaginal incision.

Total Hysterectomy. In a total hysterectomy the uterus and cervix are removed; this eliminates the risk of uterine and cervical cancer. (Given technical advances and growing surgical experience, a total hysterectomy may eventually be unnecessary except in special circumstances, such as when cancer is present.)

Supracervical Hysterectomy. In a supracervical hysterectomy (also called subtotal hysterectomy), only the uterus is removed. Retaining the cervix helps support the pelvic floor and may help maintain full sexual sensation, but the risk for cervical cancer remains. Women may experience cyclical bleeding for up to a year after surgery.

Bilateral Oophorectomy. Bilateral oophorectomy is the removal of both ovaries. (When only one ovary is removed, the procedure is called oophorectomy.) Bilatera salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. These procedures may be performed with either total or supracervical hysterectomy. When a woman decides to have her ovaries removed, she should be aware of both the positive and negative consequences.

Oophorectomy significantly reduces the rates of re-operation and endometrial pain recurrence compared to hysterectomy alone. By removing the ovaries, oophorectomy causes estrogen loss and helps to reduce the risk for ovarian cancer and breast cancer. Premenopausal women should realize, however, that oophorectomy causes immediate menopause, which poses a risk for a number of health problems. These problems include osteoporosis, heart disease, skin wrinkling, and reduction in muscle tone. Estrogen replacement can help offset them. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.

There is still a further choice, which is whether the hysterectomy should be performed through an incision in the abdomen or through the vagina. A variant of vaginal hysterectomy, called laparoscopic-assisted vaginal hysterectomy (LAVH), is yet another option.

Abdominal Hysterectomy. Abdominal hysterectomy is the most common procedure and is used in over 80% of hysterectomies in African-American women and about 60% in Caucasian and other ethnic groups. With the abdominal procedure, a wide incision is required to open the abdominal area, from which the surgeon removes the uterus. If possible, the incision should cut horizontally across the top of the pubic hairline (called a bikini incision). This incision heals faster and is less noticeable than a vertical incision, which is used in more complicated cases. The patient may need to remain in the hospital for 3 - 4 days, and recuperation at home takes about 4 - 6 weeks.

Vaginal Hysterectomy. Vaginal hysterectomy requires only a vaginal incision through which the uterus is removed. It is used in less than 20% of cases in African-American women and slightly under 40% among Caucasian and other groups.

A variation of the vaginal approach is called laparoscopic-assisted vaginal hysterectomy (LAVH). It uses several small abdominal incisions through which the surgeon severs the attachments to the uterus and ovaries. They can then be removed through the vaginal incision, as in the standard approach. Hospitalization stays may be longer and costs are greater than with standard vaginal hysterectomy. The use of LAVH has risen significantly and is now employed in over a quarter of vaginal procedures. LAVH is very costly, however, and some experts question whether it adds any significant benefits compared to the standard vaginal procedure.

If possible, a patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:

For a day or two after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and to hasten recovery.
Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
Patients are advised not to lift heavy objects, not to douche or take baths, and not to climb stairs or drive for several weeks.
For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and form abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should discuss with the doctor when they can start exercise programs that more intense than walking. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year; others may recover in only a few weeks.

Minor complications after hysterectomy are very common. About half of women develop minor and treatable urinary tract infections. There is usually mild pain and light vaginal bleeding post operation. The infrequent occurrence of severe bleeding or hemorrhaging after vaginal hysterectomy, or laparoscopic-assisted vaginal hysterectomy, may be promptly treated by laparoscopy.

More serious complications, such as those described below, are uncommon, but patients should be aware of their symptoms and call the doctor immediately if they occur.

Among the three procedures, a 2001 study reported that complication rates were 44% for abdominal hysterectomy, 24% for vaginal hysterectomy, and only 2% for LAVH. (LAVH is used in less than 4% of hysterectomies, however.)

Infection. Infection occurs in 10 - 15% of patients, the risk being higher with abdominal than with vaginal surgery. Risk factors for infection appear to be obesity, a longer than normal operative time, and low socioeconomic status. Patients should be aware of any symptoms and call the doctor immediately if they occur:

Continuing or increasingly severe pain
Fever
Heavy discharge
Bleeding (antibiotics given at the time of surgery help to reduce this risk)

Blood Clots. There is a slight risk for small blood clots, usually in veins of the legs (thrombophlebitis). A sudden swelling or discoloration in the leg can indicate this condition and require immediate medical attention.

Click the icon to see an image of thrombophlebitis.

Other Serious Complications. Other serious and even life-threatening complications are rare but can include:

Pulmonary embolism (blood clots that travel to the lung)

Click the icon to see an image of a pulmonary embolism.

Surgical injury of the urinary or intestinal tracts.
Abscesses.
Perforation of the bowel.
Fistulas (a passage that bores from an organ to the skin or to another organ).
Dehiscence (opening of the surgical wound).

Long-Term Complications. Women who have had a total hysterectomy are at higher risk for the following long-term complications:

Muscle weakness in the pelvic area.
Prolapse (descent) of the bladder, vagina, and rectum if the muscle’s walls are overly weakened; may require further surgery.
Bowel problems may develop if adhesions (extensive scarring) have formed and obstruct the intestines, sometimes requiring additional surgery.
Shortening of the vagina is a possible complication specific to vaginal hysterectomy. It can cause pain during intercourse.

Such complications are uncommon.

After hysterectomy, women may experience hot flashes, a symptom of menopause, even if they retain their ovaries. However, women who have a hysterectomy are less likely to experience hot flashes than women who have a natural menopause. Surgery may have temporarily blocked blood flow to the ovaries, therefore suppressing estrogen release. If both ovaries have been removed in premenopausal women, the procedure causes premature menopause. Other menopausal symptoms include vaginal dryness and irritation, insomnia, and weight gain.

The most important complications occur in women who have had their ovaries removed. This causes estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease and stroke. A number of drugs are available that can help protect both bones and heart.

Women have typically taken hormone replacement therapy (HRT) after surgery if their ovaries have been removed. HRT can help prevent hot flashes. There have been concerns about HRT-related health risks, including the risk for breast cancer. However, several 2006 studies of postmenopausal women who had hysterectomy indicated that estrogen-only HRT does not increase the risk for breast cancer, except if it is taken for many decades. (Two studies showed no increased risk for breast cancer after 7 years and 15 years, respectively. Women who took estrogen-only HRT for more than 20 years after hysterectomy had only a moderately increased risk.) Combination estrogen-progestin HRT does increase breast cancer risk.

In premenopausal women, such preventive measures are not needed if the ovaries are left intact. The ovaries will usually continue to function and secrete hormones even after the uterus is removed, but the lifespan of the ovaries is reduced by an average of 3 - 5 years. In rare cases, complete ovarian failure occurs right after hysterectomy, presumably because the surgery has permanently cut off the blood supply to the ovaries.

Sexual intercourse may resume 4 - 6 weeks following surgery. The effect of hysterectomy on sexuality is unclear. Studies have reported that up to 25% of women experience increased sexual drive. Nevertheless, some women report no change, and other women develop problems related to sexual function. For example, around 10% of women experience vaginal dryness, about 2% of women develop pain during sex, and another 2% also appear to lose capacity for orgasm.

Two procedures associated with hysterectomy may affect sexuality directly.

Although the clitoris can trigger orgasm even if the cervix is removed, some experts believe that uterine contractions stimulated by sexual intercourse also cause a so-called “deep orgasm.” Retaining the cervix may help to retain this sensation. However, a 2006 review found that women who undergo a total hysterectomy (removal of both uterus and cervix) are no more likely to have sexual difficulties or problems with urinary and bowel function than women who have only their uterus removed.
Patients who have both ovaries removed may be at higher risk for loss of sexuality. Ovaries produce small amounts of testosterone (the male hormone responsible for sexual drive) even after menopause.

Testosterone Replacement. Testosterone replacement therapy may restore sexuality in women who experience a decline in sexual drive. Occasionally, oral or injection treatments can produce male characteristics such as facial hair and voice change. A slow-release pellet inserted every 6 months under the skin in the hip appears to reduce these side effects. Taking hormones long-term almost always carries some risk, and it is not yet known what danger testosterone replacement may pose in women.

Annual Pap smears are recommended for all women with an intact cervix who are 18 years or older or who have become sexually active. After a total hysterectomy, in which the cervix has been removed, a woman does not need annual Pap smears of the cervix. However, she still should get regular pelvic and breast exams. Also, women with a history of abnormal Pap smears usually require annual screening.

Resources

www.asrm.com -- American Society for Reproductive Medicine
www.acog.com -- American College of Obstetricians and Gynecologists
www.endometriosisassn.org -- The Endometriosis Association
www.nichd.nih.gov -- National Institute of Child Health and Human Development
www.endozone.org -- Endometriosis Zone
www.pelvicpain.org -- International Pelvic Pain Society
www.endocenter.org -- Endometriosis Research Center
www.resolve.org -- National Infertility Association

References

Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. Epub 2006 Sep 18.

Chen WY, Manson JE, Hankinson SE, Rosner B, Holmes MD, Willett WC, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med. 2006 May 8;166(9):1027-32.

Han SH, Hur MH, Buckle J, Choi J, Lee MS. Effect of aromatherapy on symptoms of dysmenorrhea in college students: A randomized placebo-controlled clinical trial. J Altern Complement Med. 2006 Jul-Aug;12(6):535-41.

Learman LA, Kuppermann M, Gates E, Gregorich SE, Lewis J, Washington AE. Predictors of hysterectomy in women with common pelvic problems: a uterine survival analysis. J Am Coll Surg. 2007 Apr;204(4):633-41. Epub 2007 Feb 23.

Lethaby A, Ivanova V, Johnson NP. Total versus subtotal hysterectomy for benign gynaecological conditions. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004993.

Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril. 2006 Sep;86(3):711-5. Epub 2006 Jun 16.

Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA. 2006 Apr 12;295(14):1647-57.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Fibrocystic breast disease

admin — Wed, 03 Sep 2008 17:52:59 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention

Illustrations

Female Breast

Fibrocystic breast disease

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Fibrocystic breast disease refers to benign (noncancerous) changes in the tissues of the breast. The term "disease" in this case is misleading, and many health care providers prefer the term "change."

The condition is so common that it is believed to be a variation of normal. It may also be called mammary dysplasia, benign breast disease, and diffuse cystic mastopathy.

Alternative Names

Mammary dysplasia; Benign breast disease

Causes, incidence, and risk factors

The cause is not completely understood. The changes are believed to be associated with hormones produced by the ovaries because the condition usually subsides with menopause, when ovary function changes. The changes also may vary during the menstrual cycle.

Fibrocystic breast disease is estimated to affect over 60% of all women. It is common in women between the ages of 30 and 50, and rare in women who have go through menopause. It is less common in women who take birth control pills.

Risk factors include a family history of the condition, a high fat diet, and excess caffeine intake, although these are controversial.

Symptoms

Symptoms may range from mild to severe. They typically peak before each menstrual period and improve immediately afterwards.

Symptoms include:

Dense, irregular and bumpy "cobblestone" consistency in the breast tissue
- Usually more noticeable in the outer upper part of the breast
Breast discomfort
- Usually in both breasts
- May be persistent or it may come and go
Breast(s) feel full
Dull, heavy pain and tenderness
Premenstrual tenderness and swelling
Occasional nipple discharge

Signs and tests

The health care provider will perform a breast exam. A breast exam will reveal breast "masses" that move and change shape. The masses are usually rounded with smooth borders and may feel rubbery.

Mammograms may be difficult to interpret because of dense breast tissue. A breast ultrasound can help identify cystic changes in the breast. A biopsy of the breast may be necessary to rule out other problems.

Aspiration of the breast with a fine needle can often diagnose and treat larger cysts.

Treatment

Self care may include restricting dietary fat to approximately 25% of the total daily calorie intake, and eliminating caffeine.

Performing a breast self-examination monthly, and wearing a well-fitting bra to provide good breast support are important.

The effectiveness of vitamin E, vitamin B6, and herbal preparations, such as evening primrose oil are somewhat controversial. Discuss their use with your health care provider.

Birth control pills may be prescribed because they often decrease the symptoms. In severe cases, a medicine called danazol may be prescribed if the potential benefit is thought to outweigh the potential negative effects. Tamoxifen is occasionally used in severe cases.

Expectations (prognosis)

If dietary changes decrease the symptoms, and are maintained, the benefit most likely will persist. A combination of treatment and use of medications may be necessary to obtain relief for severe cases.

Women with fibrocystic breast disease do not have an increased cancer risk.

Complications

Because fibrocystic changes may make breast examination and mammography more difficult to interpret, early cancerous lesions may occasionally be overlooked.

Calling your health care provider

Call your health care provider if you feel a new, unusual, or "dominant" lump during a breast self-examination.

Call for an appointment with your health care provider if you are a woman, aged 20 or older, who has never been taught, or does not currently know how, to perform breast self-examination. Also call if you are a woman, aged 40 or older, who has not had a screening mammogram.

Prevention

Reducing the amount of fat and caffeine in your diet may help reduce symptoms, although studies have questioned their role in the disease.

Review Date: 5/26/2008

Reviewed By: Susan Storck, MD, FACOG, Clinical Teaching Faculty, Department of Obstetrics and Gynecology, University of Washington School of Medicine; Chief, Eastside Department of Obstetrics and Gynecology, Group Health Cooperative of Puget Sound, Redmond, Washington. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Source Doc: 1_000912

Breast - premenstrual tenderness and swelling

admin — Thu, 04 Sep 2008 19:06:23 -0700

Overview

Definition
Alternative Names
Considerations
Common Causes
Home Care
Call your health care provider if
What to expect at your health care provider's office

Illustrations

Female Breast

Breast self-exam

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Premenstrual swelling and tenderness of both breasts occurs during the second half of the menstrual cycle.

Alternative Names

Premenstrual tenderness and swelling of the breasts

Considerations

Symptoms of premenstrual breast tenderness may range from mild to severe. Symptoms typically peak just before each menstrual period and improve immediately after or during the menstrual period. Breast tissue may have dense, rough, "cobblestone" feel to the fingers -- usually more marked in the outer areas. There may also be an intermittent or persistent sense of breast fullness with dull, heavy pain, and tenderness.

During the menstrual cycle, estrogen production increases and peaks just prior to midcycle. This causes enlargement of the breast ducts. Premenstrually, progesterone peaks near the 21st day (in a 28-day cycle) and causes growth of the breast lobules (milk glands).

Premenstrual swelling and tenderness of the breasts is commonly associated with premenstrual syndrome (PMS) and fibrocystic breast disease (benign breast changes). The cause of fibrocystic breast disease is not completely understood, but is believed to be associated with ovarian hormones since the condition usually gets better with menopause.

Premenstrual breast tenderness and swelling probably occur to some degree in nearly all women. Symptoms severe enough to cause concern or limit function may occur in as many as 60% to 70% of women during their childbearing years. The incidence may be lower in women taking oral contraceptives (birth control pills). Risk factors may include family history and diet (excessive dietary fat or caffeine intake).

Common Causes

Menstrual cycle
Estrogen medications
Adolescent pregnancy
First-trimester pregnancy

Home Care

Self-care may include restricting dietary fat to approximately 25% of total daily calorie intake and eliminating caffeine. Breast self-examination should be performed monthly.

A well-fitting bra should be worn to provide good breast support.

The effectiveness of vitamin E, vitamin B6, and herbal preparations such as evening primrose oil are somewhat controversial and should be discussed with your health care provider.

Oral contraceptives may be prescribed to decrease symptoms.

Depo-Provera, a long-acting injection of medroxyprogesterone acetate used as a contraceptive, is also available for those who experience premenstrual breast swelling and tenderness. Depo-Provera relieves symptoms by eliminating menstrual periods.

Danazol, a synthetic androgen (male hormone), may be used in severe cases when the potential benefit is thought to outweigh the potential bad side effects.

Call your health care provider if

You have unilateral (one-sided), new, unusual, or changing lumps in breast tissue.
You do not know how to properly perform a breast self-examination.
You are a woman, age 40 or older, and have never had a screening mammogram.

What to expect at your health care provider's office

The medical history will be obtained and a physical examination performed. Medical history questions documenting premenstrual breast tenderness may include:

Does the tenderness occur with every menstrual period?
Do you know how to do breast self-examination?
Have you noticed any breast lumps?
What other symptoms are also present?

Your health care provider will check for breast lumps, and note the qualities of the lump (firm or soft, smooth or bumpy, and so on).

Diagnostic tests:

A mammogram or breast ultrasound may be performed to evaluate any abnormalities found in a breast exam. If a lump is found that is not clearly benign, a breast biopsy may be necessary.

Review Date: 5/23/2006

Reviewed By: Audra Robertson, MD, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA. Review provided by VeriMed Healthcare Network

A.D.A.M. Copyright

adam.com

Source Doc: 1_003153

Breast ultrasound

admin — Thu, 04 Sep 2008 19:09:32 -0700

Overview

Definition
Alternative Names
How the test is performed
How to prepare for the test
How the test will feel
Why the test is performed
Normal Values
What abnormal results mean
What the risks are

Illustrations

Female Breast

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Breast ultrasound is the use of ultrasonic sound waves (sounds that cannot be heard by humans) to produce an image of breast tissue.

Alternative Names

Ultrasonography of the breast

How the test is performed

You will be asked to undress from the waist up and put on a medical gown during the test. During the test, you will lie on your back on the examining table.

A water-soluble gel is placed on the breast and a hand-held device (transducer) that directs the sound waves to the breast tissue. The transducer is moved over the surface of the breast to create a picture.

The test is then repeated for the other breast, if necessary.

How to prepare for the test

Since you need to remove your clothing from the waist up, it may be helpful to wear a two-piece outfit. On the day of the test, do not use any lotions or powders on your breasts.

How the test will feel

The number of people involved in the test will be limited to protect your privacy.

You will be asked to raise your arms above your head and turn to the left or right as needed.

There is no discomfort from the ultrasound device.

Why the test is performed

Breast ultrasonography may be used with mammography or by itself.

Ultrasonography may be used to detect and classify breast lesions in the following types of women:

Women with dense breasts
Women with fibrocystic breast disease
Women with a lesion that cannot be well classified with mammography alone
Young women with masses
Pregnant women with masses
Women with silicon breast implants
Women who refuse exposure to x-rays (mammography)

Normal Values

Normally, the breast tissue will appear uniform and without masses.

What abnormal results mean

Distinctive patterns may indicate:

Cysts
Benign lesions
Malignant lesions (breast cancer)

What the risks are

There are no risks associated with breast ultrasonography.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003379

Osteoarthritis

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Conditions with Similar Sym...
Risk Factors
Diagnosis
Prognosis
Lifestyle Changes
Medications
Alternative and Complementa...
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Pain Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors work equally well for pain management, but both types of drugs increase the risk for heart attacks, according to an important report from the U.S. Agency for Healthcare Quality and Research.
The prescription NSAID diclofenac (Voltaren, Cataflam) may present a higher risk for heart attack than other NSAIDs, suggests a 2006 Journal of the American Medical Association study.
Standard osteoarthritis medications provide moderate pain relief for only 2 - 3 weeks, suggests a 2007 review in the European Journal of Pain.

Acupuncture

Acupuncture may be helpful for people with knee and hip osteoarthritis, according to several 2006 studies:

An Annals of Internal Medicine study of 1,007 people with chronic osteoarthritis knee pain indicated that patients who received acupuncture plus standard care had greater improvement than those who received only physical therapy and anti-inflammatory drugs.
An Arthritis and Rheumatism study of 3,663 patients with chronic osteoarthritis knee or hip pain suggested that acupuncture plus routine care can provide significant improvements in pain relief and quality of life. In both studies, the benefits of acupuncture were sustained for up to 6 months after treatment completion.

Exercise and Knee Osteoarthritis

Weight-bearing exercise (walking, jogging) neither prevents nor increases the risk of knee osteoarthritis in healthy middle-aged and elderly people, suggests a 2007 study in Arthritis and Rheumatism.

Risk of Hip Osteoarthritis

About 1 in 4 Americans can expect to develop osteoarthritis of the hip at some point in life, according to research presented at the 2006 American College of Rheumatology annual meeting. Body weight is a factor. People who are normal weight have a 20% risk, compared to those who are overweight (25%) or obese (39%).

Introduction

Osteoarthritis, also known as degenerative joint disease, is the most common form of arthritis. Scientists now believe osteoarthritis results from a combination of genetic abnormalities and joint injuries. In this disorder, an affected joint experiences a progressive loss of cartilage, the slippery material that cushions the ends of bones.

Osteoarthritis is a chronic disease of the joint cartilage and bone, often thought to result from "wear and tear" on a joint, although there are other causes such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse with increased use throughout the day.

As a result, the bone beneath the cartilage undergoes changes that lead to bony overgrowth. The tissue that lines the joint can become inflamed, the ligaments can loosen, and the associated muscles can weaken. The patient experiences pain when using the joint. In addition to humans, nearly all vertebrates suffer from osteoarthritis, including porpoises and whales, as did long-extinct terrestrial travelers such as dinosaurs.

Click the icon to see an animation about osteoarthritis.

Joints are designed to provide flexibility, support, stability, and protection. These functions, essential for normal and painless movement, are primarily supplied by specific parts of the joint: the synovium and cartilage.

Synovium. The synovium is a membrane that surrounds the entire joint. It is filled with synovial fluid, a lubricating liquid that supplies nutrients and oxygen to cartilage.

Cartilage. The cartilage is a slippery tissue that coats the ends of the bones. Cartilage is one of the few tissues in the body that does not have its own blood supply. It has a number of essential components:

Click the icon to see an image of the synovial membrane and cartilage in the knee joint.

Chondrocytes. Chondrocytes, the basic cartilage cells, are critical for balance and function.
Water. Cartilage contains a high percentage of water, although it decreases with age. About 85% of cartilage is water in young people, and about 70% is water in older individuals.
Proteoglycans. These are large molecules that help make up cartilage. Their important value is their capacity to bond to water, which ensures the high-fluid content in cartilage.
Collagen. This is the critical protein in cartilage. It forms a mesh to give support and flexibility to the joint. Collagen is the main protein found in all the connective tissues of the body, including the muscles, ligaments, and tendons.

The combination of the collagen meshwork and the high water content, tightly bound by proteoglycans, creates a resilient and slippery pad in the joint, which resists the compression between bones during muscle movement. The synovial fluid lubricates and provides oxygen and nutrients to the bloodless cartilage.

Deterioration of Cartilage. Osteoarthritis develops when cartilage in a joint deteriorates. The process is usually slow.

In the early stages of the disease the surface of the cartilage, or even the synovium in some people, becomes inflamed and swollen. There is a loss of proteoglycan molecules and other tissue components that cause water loss. Fissures and pits appear in the cartilage.
As the disease progresses and more tissue is lost, the cartilage loses elasticity and fluid. It becomes increasingly prone to damage due to repetitive use and injury.
Eventually large amounts of cartilage are destroyed, leaving the ends of the bone within the joint unprotected.

To compound the process, bone around arthritic joints is not structurally normal. As the body tries to repair damage to the cartilage, problems can develop:

Clusters of damaged cells or fluid-filled cysts may form around the bony areas or near the fissures.
Fluid pockets may also form within the bone marrow itself, causing swelling. The marrow, which runs up through the center of bone, is rich in nerve fibers, and such injuries may be an important source of pain in many patients with osteoarthritis.
Bone cells may respond to damage by multiplying, growing, and forming dense, misshapen plates around exposed areas.
At the margins of the joint, the bone may produce outcroppings, on which new cartilage cells (chondrocytes) proliferate and grow abnormally.

Unlike some other types of arthritis, such as rheumatoid arthritis, osteoarthritis does not spread through the entire body. (In other words, it is not systemic.) Rather, it affects one or several joints. Osteoarthritis affects joints differently depending on their location in the body.

Osteoarthritis is commonly found in joints of the fingers, feet, knees, hips, and spine.
It sometimes occurs in the wrist, elbows, shoulders, and jaw, but is not common in these locations.

Causes

The biologic factors leading to the deterioration of cartilage in osteoarthritis are not entirely understood. Many experts believe that osteoarthritis results from a genetic susceptibility that causes some biologic response to injuries to the joint, which in turn leads to progressive deterioration of cartilage. In addition, the ability to make repairs becomes progressively limited as cartilage cells age.

Although osteoarthritis generally accompanies aging, osteoarthritic cartilage is chemically different from normal aged cartilage. As chondrocytes (the cells that make up cartilage) age, they lose their ability to make repairs and produce more cartilage. This process may play an important role in the development and progression of osteoarthritis.

Researchers report a high correlation of osteoarthritis between parents and children or between siblings. Genetic factors are thought to be involved in about half of osteoarthritis cases in the hands and hips and a somewhat lower percentage of cases in the knee. A number of genes are under investigation that might contribute to an inherited risk.

For example, mutations in the ank gene may be important in some cases. The ank gene regulates pyrophosphate, a chemical that inhibits the formation of mineral deposits, and may protect the cartilage in joints. Mutations in the ank gene then may result in lower pyrophosphate levels in the joint, leading to accumulation of mineral deposits and arthritis. (About 60% of people with osteoarthritis have mineral deposits in their cartilage.)

Another gene, called the osteoprotegerin gene, is important in regulating bone and cartilage formation. Mutations in this gene may play a role in osteoarthritis.

The inflammatory response is an overreaction of the immune system to an injury or other assault in the body, such as an infection. This response causes specific immune factors, called cytokines, to gather in injured areas and cause inflammation and damage to body tissue and cells. The inflammatory response plays an important role in rheumatoid arthritis and other muscle and joint problems associated with autoimmune diseases. It has generally been believed that inflammation plays at most a minor role in osteoarthritis and is more likely to be a result -- not a cause -- of the disease.

However, recent studies suggest that inflammation may play an important role in the progression of osteoarthritis and its chronic nature. For example, a 2003 study found evidence of severe inflammation in the lining of the joints in 30% of patients with osteoarthritis. Still, the effects of the inflammatory response in osteoarthritis are likely to be different from those in rheumatoid arthritis and less severe.

Some theories on how this response may contribute to osteoarthritis involve overproduction of enzymes called matrix metalloproteinases or MMPs (also called collagenases). In large amounts they break down collagen, the building blocks of cartilage. Some studies suggest that immune factors called vascular endothelial growth factor (VEGF) are overproduced during the inflammatory response and in turn increase production of MMPs.

Another theory suggests that the inflammatory response is triggered by the changes and injuries in the bone that occur during osteoarthritis. According to this theory, immune factors released in this process diffuse into the cartilage, where they suppress cartilage cell growth and activate MMPs.

Joint injuries are the starting point in the disease process. Osteoarthritis sometimes develops years after a single traumatic injury to or near a joint. One large study found that by age 65, osteoarthritis developed in almost 14% of those who had joint injuries as young adults, compared to just 6% in those without earlier injuries. Patients with knee injuries were five times more likely to have osteoarthritis in the injured knee than those without injuries, and patients with hip injuries were more than three times more likely to develop arthritis in the injured hip. Proper treatment of injuries, such as surgical repair of ligament tears in the knee with a strong rehabilitation approach, may help to prevent the development of osteoarthritis.

Other causes of osteoarthritis include:

Bleeding disorders such as hemophilia that cause bleeding to occur in the joint
Disorders such as avascular necrosis that block the blood supply near the joint
Complications of persistent, inflammatory arthritic conditions, particularly chronic gout, pseudogout, or rheumatoid arthritis
Conditions that cause iron build-up in the joints such as hemochromatosis

Symptoms

The pain of osteoarthritis typically begins gradually and progresses slowly over many years. People under age 40 may have the condition with no symptoms at all. Osteoarthritis is commonly identified by the following symptoms:

The most common symptom of osteoarthritis in any joint is pain that worsens during activity and gets better during rest. As the disease advances, the pain may occur even when the joint is at rest.
Pain is generally described as aching, stiffness, and loss of mobility.
The pain may behave like a roller coaster, with bad spells followed by periods of relative relief.
Pain seems to increase in humid weather.
Some people experience muscle spasm and contractions in the tendons.
Osteoarthritis in the knee may cause a crackling-like noise (called crepitus) when moved.

Hand. Osteoarthritis of the hand occurs most often in older women and may be inherited within families. The following joints are most frequently affected:

Distal interphalangeal (DIP) joint. The first joint below the fingertips is the most common location of osteoarthritis of the hand. These joints can develop bony growths known as Heberden's nodes.
Carpometacarpal (CMC) joint. The joint at the base of the thumb, where the thumb joint connects with the wrist, is the second most common location.
Proximal interphalangeal (PIP) joint. The middle joints of the fingers can also develop osteoarthritis. These joints may develop small, solid lumps (nodules) known as Bouchard's nodes.

Click the icon to see an image of osteoarthritis.

Recent studies suggest that osteoarthritis of the hand may predict the later development of osteoarthritis in the hip or knee. A 2005 study found that patients with hand osteoarthritis were three times more likely to develop hip arthritis. Osteoarthritis of the hand also slightly increased the risk for knee osteoarthritis.

Knee. Osteoarthritis is particularly debilitating in the weight-bearing joints of the knees. The joint is usually stable until the disease reaches an advanced stage when the knee becomes enlarged and swollen. Although painful, the arthritic knee usually retains reasonable flexibility.

Osteoarthritis can cause loss of cartilage in the knee. The meniscus, the cartilage pad between the joint formed by the thighbone and the shinbone, plays an important role in protecting the joint. It acts as a shock absorber. In knee surgery called meniscectomy, the doctor removes the damaged cartilage. However, a 2006 study suggested that preserving the meniscus, even if it is damaged, is better than removing it. Researchers showed that even a small amount of meniscus helps protect the joint and prevent osteoarthritis from worsening. Experts recommend that patients try lifestyle changes (exercise and weight loss), braces, and medication before undergoing knee surgery.

Click the icon to see an image of the knee joint.

Hips. About 1 in 4 people will develop hip arthritis over the course of their lifetime. Being obese increases the risk. Osteoarthritis frequently strikes the weight-bearing joints in one or both hips. Pain develops slowly, usually in the groin and on the outside of the hips, or sometimes in the buttocks. The pain also may radiate to the knee, confusing the diagnosis. Those with osteoarthritis of the hip often have a restricted range of motion (particularly when trying to rotate the hip) and walk with a limp, because they slightly turn the affected leg to avoid pain.

Click the icon to see an image of the hip joint.

Spine. Osteoarthritis may affect the cartilage in the disks that form cushions between the bones of the spine, the moving joints of the spine itself, or both. Osteoarthritis in any of these locations can cause pain, muscle spasms, and diminished mobility. In some cases, the nerves may become pinched, which also produces pain. Advanced disease may result in numbness and muscle weakness. Osteoarthritis of the spine is most troublesome when it occurs in the lower back or in the neck, where it can cause difficulty in swallowing.

Click the icon to see an image of the spine.

Shoulder. Osteoarthritis is less common in the shoulder area than in other joints, but it may develop in the shoulder joint (the glenohumeral joint). In such cases, it is most often associated with a previous injury, and patients gradually develop pain and stiffness in the back of the shoulder. Osteoarthritis also can develop in the acromioclavicular (AC) joint, which is between the shoulder blade and the collarbone. However, it rarely causes symptoms in this location.

Conditions with Similar Symptoms

Numerous conditions have symptoms of joint aches and pains. Something as benign as sleeping on a bad mattress to the serious afflictions associated with cancer can mirror symptoms of osteoarthritis. Other problems that can cause aches and pains in the joints include physical injuries, infections, tendinitis, and poor circulation. A number of rare genetic diseases attack the joints.

Osteoarthritis can generally be distinguished from other joint diseases by considering several factors together:

Osteoarthritis usually occurs in older people and is located in only one or a few joints
The joints are less inflamed than in other arthritic conditions
Progression of pain is usually gradual.

A few of the most common disorders that can be confused with, or may even accompany, osteoarthritis are discussed below.

Osteoarthritis may be confused with rheumatoid arthritis, particularly when osteoarthritis affects multiple joints in the body. Rheumatoid arthritis begins in the synovial membrane rather than the cartilage. It normally occurs earlier in life than osteoarthritis, often striking people in their 30s and 40s. Rheumatoid arthritis affects many joints, and often occurs symmetrically on both sides of the body. People generally have morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis usually clears up within half an hour.)

X-rays show changes in the bones that differ from those occurring in osteoarthritis. In rheumatoid arthritis, blood tests often show a specific antibody, known as rheumatoid factor, which is not present with osteoarthritis. In another blood test, levels of a factor called erythrocyte sedimentation rate (ESR) are often elevated in rheumatoid arthritis, but they are generally normal in osteoarthritis. Rheumatoid arthritis also does not usually show up in the fingertips where osteoarthritis is common.

Rheumatoid arthritis is a body-wide (systemic) autoimmune disease that initially attacks the synovium, a connective tissue membrane that lines the cavity between joints and secretes a lubricating fluid.

Click the icon to see an image of osteoarthritis vs. rheumatoid arthritis.

Chondrocalcinosis is a disease in which certain calcium crystals known as CPPD (calcium pyrophosphate dihydrate) are deposited in the joints. It affects about 25% of the population and can accompany and even worsen osteoarthritis. The problem has been called pseudogout or pseudo-osteoarthritis, in the latter case particularly when it affects the knees. A doctor can usually differentiate between the two disorders, however, because chondrocalcinosis usually damages other joints (such as wrists, elbows, and shoulders) that are not usually affected by osteoarthritis. The condition may explain why some patients with osteoarthritis receive benefit from colchicine, a drug used for gout and other crystal-induced joint diseases.

Charcot's joint occurs when an underlying disease, usually diabetes, causes nerve damage in the joint, which leads to swelling, bleeding, increased temperature, and changes in bone. There may be a loss of sensation that leads to an increased risk for injury from overuse.

Risk Factors

Osteoarthritis is the most common type of arthritis. In the U.S., about 12.1% of Americans (21 million people) age 25 and older have osteoarthritis. The prevalence in osteoarthritis increases as people age. Experts estimate that by 2030, 20% of Americans (72 million people) age 65 years and older will be at risk for developing osteoarthritis.

Before age 45, osteoarthritis occurs more frequently in males (although it is not common in younger adults). After age 55, it develops more often in females. In a 2000 study, 33% of women had osteoarthritis compared to 25% of men. Some research suggests that women may also experience greater muscle and joint pain, in general, than men. And, women also tend to be undertreated for pain compared to men. The causes of such differences in pain sensitivity and treatment are largely unknown and most likely are due to a complicated mix of biologic, psychologic, and social factors.

The incidence is highest in lower educational levels. In a 2000 study, 41% of adults with less than a high school education had arthritis compared to 21% of college graduates.

Although the average rate of osteoarthritis among older adults in the U.S. is 60%, it can vary widely in certain geographical regions. In the U.S., the rates in older adults are lowest (34%) in Hawaii and highest (70%) in Alabama. In general, the highest prevalence of arthritis in America occurs in the central and northwestern states.

The rate of osteoarthritis varies by ethnic group. In the U.S., Caucasians and African-Americans have higher rates of arthritis than Hispanics or other ethnic groups. Osteoarthritis also tends to favor specific joints over others in certain ethnic groups. The following are some examples:

Older African-American men are about 33% more likely than Caucasian men to have hip osteoarthritis. In one study, although men in both groups had equal risks for arthritic knees, African-American men were more likely to have arthritis in both knees and to have more severe cases. Although comparable disparities in knee arthritis were observed between African-American and Caucasian women, they might be explained by greater average weight among African-American women. The study could not account for the differences among men, however.
Asians appear to have a higher incidence of osteoarthritis in the knee, an equal risk for osteoarthritis in the spine, and a lower risk for osteoarthritis in the hips than Caucasians.

Genes that determine the angles, amount of force, and other structural factors in the hip joints, or genes that regulate the chemistry in the joints, may account for ethnic differences.

Some researchers suggest that a number of people have anatomical abnormalities, such as mismatched surfaces on the joints, which could be damaged over time by abnormal stress. Legs of unequal length or skewed feet can cause jerky movement and may cause osteoarthritis. One study reported that those whose knees bent inward ("knock-kneed") or outward ("bow-legged"), for example, were more likely to have progressive osteoarthritis of the knee.

Obesity, defined as being 20% over one's healthy weight, places people (particularly women) at increased risk for osteoarthritis. It also worsens osteoarthritis once deterioration begins. This higher risk is due to increased weight on the joints. However, being obese also increases the risk for osteoarthritis in the fingers as well as the knees and hips, suggesting that being overweight may contribute to osteoarthritis in other ways. Some research indicates that obesity may produce an inflammatory response, which is now a major suspect in age-related diseases -- not only osteoarthritis but also heart disease. [See In-Depth Report #53: Weight control and diet.]

Because injuries can trigger the disease process, people whose work or leisure activities place them at risk for muscle and joint injuries may face a higher risk for osteoarthritis later on.

Workers at Higher Risk. Certain occupations that require repeated stressful motions (such as squatting or kneeling with heavy lifting) can contribute to deterioration of cartilage. One study suggested that workers whose jobs require kneeling or squatting for more than an hour a day are at high risk for knee osteoarthritis. (In the study, jobs that involved heaving lifting, climbing stairs, or walking also posed some, but not as high, a risk. Being heavier compounded the chances for osteoarthritis.)

Exercise. There has been some question about the role of strenuous exercise in osteoarthritis. Sports that definitely pose a higher risk for osteoarthritis are those that require repetitive or direct joint impact (such as football), twisting, or both (baseball pitching, soccer).

Marathon runners, however, have a relatively low rate of osteoarthritis. Some scientists speculate that running enhances cartilage health because the rhythmical compression of cartilage expels wastes and promotes absorption of nutrients.

In any case, regular and moderate exercise is important for everyone and does not increase the risk for osteoarthritis. In fact, a 2006 study of middle-aged and elderly people found that recreational weight-bearing exercise (walking, jogging) neither protects against nor increases the risk for osteoarthritis. Furthermore, many factors associated with a sedentary life (muscle weakness, obesity) are associated with a higher risk for osteoarthritis.

Diagnosis

Osteoarthritis is often visible in x-rays. Cartilage loss is indicated by certain images:

If the normal space between the bones in a joint is narrowed.
If there is an abnormal increase in bone density.
If bony projections, cysts, or erosions are evident.
X-rays can also reveal any cysts that might develop in osteoarthritic joints. If other conditions are suspected or if the diagnosis is uncertain, additional tests are necessary.
An MRI may show evidence of osteoarthritis that x-rays miss.

X-rays are a form of electromagnetic radiation (like light); they are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

Blood test results may help diagnose or rule out osteoarthritis. Some examples include:

Elevated levels of rheumatoid factor (specific antibodies in the synovium) and so-called erythrocyte sedimentation rates (ESR or sed rate) indicate rheumatoid arthritis.
Hyaluronic acid (HA), a joint lubricant, is being tested as a potential biomarker for osteoarthritis. High levels of HA may indicate increased risk for osteoarthritis.
Elevated levels of a factor called C-reactive protein, which is produced by the liver in response to inflammation, are proving to be good predictors of osteoarthritic progression in the knee.

If the diagnosis is uncertain or infection is suspected, a doctor may attempt to withdraw synovial fluid from the joint using a needle. There will not be enough fluid to withdraw if the joint is normal. If the doctor can withdraw fluid, problems are likely, and the fluid will be tested for factors that might confirm or rule out osteoarthritis:

Cartilage cells in the fluid are signs of osteoarthritis.
A high white blood cell count is a sign of infection.
High uric acid in the fluid is an indication of gout.

Click the icon to see an animation on gout.

Other factors may be present that suggest different arthritic conditions, including Lyme disease and rheumatoid arthritis.
In people with known osteoarthritis, researchers may look for certain factors in synovial fluid (sulfated glycosaminoglycan, keratin sulfate, and link protein) that can suggest a more or less severe condition.

Prognosis

Osteoarthritis itself is not life-threatening, but a person's quality of life can significantly deteriorate from pain and loss of mobility. The negative effects on activities and physical and mental health are significant regardless of age, educational level, or gender. Only heart disease has a greater impact on work. Five percent of those who leave the work force do so because of osteoarthritis. Unless alleviated by medication or corrected by surgery, advanced osteoarthritis can force the patient to forgo even relatively low-impact activities, such as walking. No treatment can cure osteoarthritis, and none can alter its progression with certainty, but many available therapies can relieve symptoms and significantly improve the quality of life.

Lifestyle Changes

Many doctors suggest first trying lifestyle changes to reduce stress on affected joints. Physical therapy and supportive devices can be helpful. Intensive education on how to protect and care for an osteoarthritic joint may help patients avoid multiple visits to their doctor.

Once osteoarthritis has been diagnosed, patients should reduce shock to the affected joint. Hammering away at deteriorating cartilage is likely to speed up the degeneration. People in occupations requiring repetitive and stressful movement should explore ways to reduce trauma. Adjusting the work area or substituting tasks that produce less stress on joints helps reduce shock.

Joints require motion to stay healthy. Long periods of inactivity cause the arthritic joint to stiffen and the adjoining tissue to atrophy. A moderate exercise program that includes low-impact aerobics and power and strength training has benefits for osteoarthritic patients, even if exercise does not slow down the disease progression. Exercise helps:

Reduce stiffness and increase flexibility. It may also help improve the strength and elasticity of knee cartilage.
Promote weight loss.
Improve strength, which in turn improves balance and endurance.
Reduce stress and improve feelings of well being, which helps patients cope with the emotional burden of pain.

Exercise especially helps patients with mild-to-moderate osteoarthritis in the hip or in the knee. Many patients who begin an aerobic or resistance exercise program report less disability and pain. They are better able to perform daily chores and remain more independent than their inactive peers. Older patients and those with medical problems should always check with their doctor before embarking on an exercise program.

Three types of exercise are best for people with osteoarthritis:

Strengthening exercise
Range-of-motion exercise
Aerobic, or endurance, exercise

Strengthening Exercise. Strengthening exercises include isometric exercises (pushing or pulling against static resistance). Isometric training builds muscle strength while burning fat, helps maintain bone density, and improves digestion.

Some experts encourage patients to emphasize strengthening leg muscles as a first treatment step, before using pain relievers. Patients who rely on painkilling drugs may overuse knees, which do not have muscle tissue sufficiently strong enough to protect the joints from further damage. However, some studies suggest that building up thigh muscles may worsen osteoarthritis in people whose knees are misaligned (for instance those who are "bow-legged" or "knock-kneed"). Such individuals should check with a physical therapist for the best options. Strengthening the thigh muscles is certainly protective for people who have not yet developed osteoarthritis.

Exercise, such as weightlifting, helps build muscle that is usually lost with age and puts stress on bones, helping keep them strong and healthy.

Range-of-Motion Exercise. These exercises increase the amount of movement in a joint and muscle. In general, they are stretching exercises. The best examples are yoga and tai chi, which focus on flexibility, balance, and proper breathing. In one study, older adults who practiced the gentle movement, breathing, and meditation exercises of tai chi for 10 weeks reported less pain than their peers who did not learn the technique.

Click the icon to see an image of cholesterol.

Aerobic (Endurance) Exercise. These exercises help control weight and may reduce inflammation in some joints. Low-impact workouts also help stabilize and support the joint. Cycling and walking are beneficial, and swimming or exercising in water is highly recommended for people with arthritis. (Patients with osteoarthritis should avoid high-impact sports, such as jogging, tennis, and racquetball.)

Click the icon to see an image of exercise.

In addition to exercise, manipulation of muscles and joints by a trained therapist may be helpful. In one study, patients who had a combination of physical therapy and an exercise program reported 30 - 40% improvement after only two to four visits.

Overweight patients with osteoarthritis can lessen the shock on their joints by losing weight. Knees, for example, sustain an impact three to five times the body weight when descending stairs. Losing 5 pounds of weight can eliminate 20 pounds of stress on the knee. The greater the weight loss, the greater the benefit. [See In-Depth Report #53:Weight loss and diet.]

Plant Chemicals. A large study reported significant improvement in symptoms when patients took extracts from avocados and soybeans called saponins. Another study noted that although these substances did not relieve hip pain, they did slow progression of joint deterioration. Soy has chemicals called isoflavones that may have additional benefits, such as preventing bone loss.

Fish Oil and Omega-3 Fatty Acids. Omega-3 fatty acids, which are found in fish oil, canola oil, black currant or primrose seed oils, and flax seeds, have anti-inflammatory properties and may help protect against cartilage deterioration. Supplements of omega-3 fatty acids, such as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids that are found in fish oil, are available.

Vitamin B3 (Niacin). Some research suggests that vitamin B3 may have some benefits for people with osteoarthritis.

Click the icon to see an image of the benefits of vitamin B3.

Click the icon to see an image of the sources of vitamin B3.

Calcium and Vitamin D. Calcium and vitamin D are important for strong bones. Although osteoarthritis is primarily a disease of joints, bone strength is also important, particularly in older people.

Click the icon to see an image of osteoporosis.

Many experts now recommend 1,000 mg of calcium a day for most adults and 1,200 - 1,500 mg for adolescents. Pregnant women, postmenopausal women not on estrogen therapy, and those on corticosteroids should get 1,500 mg per day; breast feeding women should get 2,000 mg/day. Because calcium supplements increase the risk for kidney stones, an upper limit of 2,500 mg is recommended.

Current guidelines recommend 400 IU of vitamin D per day and 600 IU per day after age 60. Lack of sunlight and unhealthy diets contribute to deficiencies in vitamin D. Good dietary sources include fortified milk, sardines, herring, salmon, tuna, liver, dairy products, and egg yolks. Although supplements are often necessary, vitamin D can be toxic in high doses, and no one should take more than 1,200 IU per day.

Selenium. Selenium is a trace mineral found in grains, nuts, vegetables, and some meats and seafood. Preliminary research suggests that people who do not get enough selenium in their diet may be more likely to develop knee osteoarthritis. Researchers are investigating whether selenium supplements may help protect against osteoarthritis and prevent it from worsening.

Ice. When a joint is inflamed (particularly in the knee) applying ice for 20 - 30 minutes can be effective. If an ice pack is not available, a package of frozen vegetables works just as well.

Heat Treatments. Patients afflicted with osteoarthritis of the hands can relieve pain with hot soaks and warm paraffin application. Osteoarthritis of the hip can be treated with heating pads.

Interestingly, moving to a warm climate does not seem to make much difference. According to one study, people who live in warmer places are actually more sensitive to small shifts in temperature than people who live in cold damp climates, and they experience pain as readily as their northern peers do in response to larger temperature shifts.

A wide variety of devices are available to help support and protect joints:

Splints or braces, worn while the joint is at rest or in use, help align joints and properly distribute weight. They are used most frequently to treat arthritic hands, wrists, knees, ankles, and feet. Many of these devices allow some movement within the affected joint and do not restrict nearby joints. They are usually made from lightweight metal, leather, elastic, foam, and moldable plastic with easy-to-use Velcro straps. Any brace, splint, or other device for joint protection should be custom-fitted by a physical or occupational therapist, or an orthotist. Poorly fitting or improperly used orthoses can cause more harm than good.
Using elastic supports on affected joints may benefit some people. For example, in one study, wearing insoles plus elastic straps supporting the ankle joint helped overweight women with osteoarthritis in the knee. It is important to consult with a doctor about how to use elastic supports.
Wrapping the knee with special therapeutic tape that provides support to specific parts of the joint may be effective. In one trial, patients experienced a 40% reduction in pain within a few days. They wore the tape for 3 weeks, and pain relief continued for 3 more weeks following treatment. The tape should be applied by physical therapists or other trained health professionals. Longer-term studies are needed to determine any continuous benefits.
Wearing shock-absorbing soles in shoes or orthopedic shoes can help in daily activities and during gentle exercise. Heel wedges in the shoes can sometimes help patients avoid knee replacement surgery.
A neck brace or corset may relieve back pain.
A firm mattress also often proves beneficial.
In extreme cases of back pain, lying in traction might be necessary.
Canes, crutches, or walkers offer benefits to patients with advanced arthritis.
Specially designed hip protectors, worn under the clothes, can also protect against hip fractures in elderly patients with impaired mobility who are apt to fall.

Medications

Many medications are available for relieving the symptoms of osteoarthritis. A major analysis indicated that drug therapy is generally more effective than non-drug treatments (surgery, acupuncture). However, a 2006 review of knee osteoarthritis studies found that pain-relief medications generally help only for the first 2 - 3 weeks of treatment. The following are some of the medications used in mild-to-severe cases:

Acetaminophen
Nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors
Capsaicin
Tramadol
Narcotic pain relievers (oxycodone, oxymorphone, or morphine)
Glucosamine and chondroitin (see Alternative and Complementary Medicine section)

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and others) is currently the first choice for treating osteoarthritis. However, several major analyses report that acetaminophen is less effective than NSAIDs in reducing moderate-to-severe pain. Because acetaminophen has fewer side effects, most experts suggest trying this drug first, then switching to an NSAID if acetaminophen does not provide sufficient pain relief.

Side Effects. Acetaminophen is inexpensive and generally safe. It poses far less of a risk for gastrointestinal problems than NSAIDs and does not appear to increase the risk for miscarriage (as NSAIDs do), even when used regularly.

It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and the stimulation of red blood cell production.

Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve, Naprosyn), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren, Cataflam), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), nabumetone (Relafen), dexibuprofen (Seractil), indomethacin (Indocin), meloxicam (Mobic, generic).
Topical NSAIDs delivered in gels, creams, or patches do not appear to provide any long-term benefits in reducing arthritic pain. A review of clinical trial data, published in 2004, suggested that guidelines that recommend topical NSAIDs for treatment of osteoarthritis should be revised.

Many experts now recommend that patients use oral NSAIDs for only a short period of time. A 2004 review, published in the British Medical Journal, suggested that long-term use of NSAIDs does not actually reduce osteoarthritis pain and may increase patients’ risk of experiencing side effects. High dosages of NSAIDs can cause heart problems (such as increased blood pressure), kidney problems, and stomach bleeding.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

A 2006 comprehensive report from the U.S. Agency for Healthcare Quality and Research indicated that both NSAIDs and COX-2 inhibitors are equally effective for pain relief and pose similar risks for heart attacks. The report found that one particular NSAID, naproxen (Aleve, Naprosyn), presents less risk of heart attack for some patients. A 2006 Journal of the American Medical Association study suggested that diclofenac (Voltaren, Cataflam) may pose a higher risk for heart attack than other NSAIDs. All patients should talk to their doctors before switching any medications.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. Such ulcers are also more likely to bleed than those caused by the bacteria H. pylori. NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Because there are usually no gastrointestinal symptoms from NSAIDs until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding.

Among the groups at high risk for bleeding are elderly people, anyone with a history of ulcers of GI bleeding, patients with serious heart conditions, alcohol abusers, and those on certain medications, such anticoagulants ("blood thinners"), corticosteroids, or bisphosphonates (drugs used for osteoporosis). Proton-pump inhibitors may help to prevent and heal ulcers caused by NSAIDs. Proton-pump inhibitors include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid)

Click the icon to see an image of a gastric ulcer.

Drugs for Prevention NSAID-Induced Ulcers. If you have NSAID-induced ulcers, follow these steps:

Switch to alternative pain relievers. This is the first step in preventing or healing ulcers caused by NSAIDs. If people cannot change drugs, they should use the lowest NSAID dose possible.
Try proton-pump inhibitors (PPIs). These drugs help reduce NSAID-ulcer rates by as much as 80% compared with no treatment. Brands include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).
Try misoprostol or Arthrotec. If other drugs are inappropriate, misoprostol protects against the major intestinal toxicity of NSAIDs. It was the first drug approved for preventing NSAID-induced ulcers. It is equally, or even more, effective than some of the PPIs, but it does not heal existing ulcers and has more side effects than PPIs. Patients tend to stop using it. Arthrotec is a combination of an ulcer protective drug called misoprostol and the NSAID diclofenac. One study found that patients taking Arthrotec had 65 - 80% fewer ulcers than those who took NSAIDs alone.

Healing Existing Ulcers. A number of drugs are available to heal NSAID-induced ulcers. Treatment takes about 2 - 6 weeks. Proton-pump inhibitors are the most effective drugs. Others that may be beneficial include sucralfate or H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac).

Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of cardiovascular events, as well as skin rashes and other adverse effects, the FDA has been re-evaluating the relative risks and benefits of this drug class. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the United States market. Celecoxib (Celebrex) is still available, but patients should discuss with their doctors whether this drug is appropriate and safe for them.

A newer COX-2 inhibitor, etoricoxib (Arcoxia) is approved in 60 countries but not the United States. A 2006 Lancet study indicated that etoricoxib is similar to the NSAID diclofenac in risks for heart attack and stroke. (However, diclofenac has already been shown to have a higher risk of heart attack than any other NSAID, so some experts do not find this study result reassuring.) Etoricoxib caused more high blood pressure and fluid retention (edema) than diclofenac. Etoricoxib appeared to pose a lower risk than diclofenac for uncomplicated upper gastrointestinal problems, (obstruction, perforation, bleeding, ulcers), but there was little difference between the two drugs for more serious gastrointestinal complications. In 2007, the FDA rejected an application to market etoricoxib in the U.S.

Capsaicin is a component of hot red peppers and may bring pain relief when used as a skin cream (Zostrix). This is the only skin preparation that does more than just mask pain or reduce it temporarily. Capsaicin seems to reduce a substance in the body, known as substance P, which contributes both to inflammation and the delivery of pain impulses from the central nervous system. A small amount of capsaicin must be applied to the area of inflammation about four times a day. During the first few days of use, the patient will experience a warm, stinging sensation when the cream is applied. This sensation goes away, and pain relief usually begins within 1 - 2 weeks.

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone with more long-lasting benefits than acetaminophen. Side effects are the same as for each of these drugs.

Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system, are the most powerful medications available for the management of moderate to severe pain. There are two types of narcotics:

Opiates, which are derived from natural opium (morphine and codeine).
Opioids, which are synthetic drugs. They include oxycodone (Percodan, Percocet, Roxicodone, Oxycontin), hydrocodone (Vicodin), oxymorphone (Numorphan), and fentanyl (Duragesic).

Although the use of narcotics for arthritic pain is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse. Some experts believe that opioids have a place in osteoarthritis treatment when milder drugs are not effective or appropriate. For example, a 2006 study suggested that a fentanyl skin patch may offer pain relief and improved function to some patients with severe knee or hip osteoarthritis who have not been helped by, or who cannot tolerate, NSAIDs or weaker opioids.

The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects. Common side effects include anxiety, constipation, nausea and vomiting, dizziness, drowsiness, paranoia, urinary retention, restlessness, and labored or slow breathing. Unfortunately, opioid abuse among young people is a major concern.

When pain becomes a major problem and less potent pain relievers are ineffective, doctors may resort to corticosteroid (steroid) injections, usually by administering a shot into the affected joint every 3 months. Corticosteroid shots are useful only if inflammation is present in the joint. Relief from pain and inflammation is of short duration, and this treatment is rarely used for chronic osteoarthritis. These drugs may not be as effective for women as for men.

Corticosteroids mask pain, and the patient must be very careful to avoid over-use of the affected joints. Patients are usually advised not to have more than two or three injections a year, since there is some concern that repeated injections over the long term may be harmful. A reassuring study found no greater disease progression in people who had injections every 3 months for 2 years compared to those who were given sham injections on the same schedule. Because long-term use of corticosteroids has many potentially serious side effects, steroid medications are never given orally or systemically for the treatment of osteoarthritis.

Injections of hyaluronic acid (Hyalgan, Synvisc, Artzal, Nuflexxa) into the joint -- a procedure called viscosupplementation -- is now recommended as one of the treatments for osteoarthritis. Hyaluronic acid is a naturally occurring substance in joints that acts as a lubricant for slow movements and a shock absorber for fast motions. In high amounts, it also may have anti-inflammatory effects.

Patients receive a series of three to five injections once a week.
The drug is injected into the joint.
A health care worker will apply local anesthetic because these viscous (sticky) injections require a large needle.
Patients need to avoid weight-bearing activities for about 48 hours after each shot.

Hyaluronic injections appear to be about as effective as NSAIDs and corticosteroid injections for relieving pain, at least in men, and they have no adverse effects in the stomach or intestines. One study reported that between 39 - 56% of patients were at least nearly free of weight-bearing pain up to 24 weeks after the final injection. In another study, response was judged better or much better for 87% of knees after a second course, which was administered about 8 months later. Nevertheless, a number of studies on viscosupplementation have shown little or no benefits, particularly in women, and more research is needed to determine if they are useful. Injections are also expensive. Accurate placement of the needle directly into the knee joint space is important and may be difficult, even for experienced doctors, if there is no fluid build-up in the joint. Best success rates are with a specific approach into the kneecap called the lateral midpatellar.

Side Effects. Serious adverse reactions are rare. The most common side effects, pain at the injection site and knee pain and swelling, are usually mild and temporary. More research is needed to confirm benefits and long-term risks.

Researchers are studying various drugs that may provide pain relief or stop the disease process itself:

Bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) help prevent bone loss in people with osteoporosis. They are currently being investigated for osteoarthritis as well. A 2005 study reported that risedronate may delay joint destruction in patients with knee osteoarthritis.
Lidocaine, a local anesthetic, is available in patch form (Lidoderm) and has been used specifically for herpes zoster pain. Early studies indicate that it may provide significant pain relief for osteoarthritis.
Tetracycline antibiotics, such as doxycycline, may have a role to play in treating osteoarthritis. At low concentrations, the drug reduces the production of collagenases, which are enzymes critical to disease development and progression. Initial results from clinical trials suggest that doxycycline may help delay joint space narrowing.
Licofelone is a drug that inhibits both the COX enzyme plus an inflammatory substance called lipoxygenase 5. Early trials indicate it may be effective and safer than either NSAIDs or COX-2 inhibitors.
Diacerein inhibits an inflammatory substance in arthritic joints called interleukin-1b. It has shown promise in clinical trials. A 2006 review indicated that diacerein may be slightly better than NSAIDs for pain relief.
Botulinum toxin type A (Botox) injections may provide sustained pain relief for patients with knee osteoarthritis according to research presented at the 2006 American College of Rheumatology annual meeting.
Nitric oxide increases blood flow in the mucous lining and secretions of mucus and bicarbonate. Combining nitric oxide with NSAIDs may reduce the adverse effects on the gastrointestinal tract.
Trials of gene therapies that either fight joint degradation or strengthen cartilage are in very early stages.

Alternative and Complementary Medicine

Glucosamine hydrochloride and chondroitin sulfate are natural substances that are part of the building blocks found in and around cartilage. Extracts have been used in Europe for more than a decade to reduce pain and improve mobility in patients with osteoarthritis. For many years, researchers in the U.S. have been studying whether these dietary supplements really work for relieving osteoarthritis pain.

In 2006, the New England Journal of Medicine published the results from a major trial sponsored by the U.S. National Institutes of Health. Researchers compared the effects of glucosamine and chondroitin, alone and in combination, with the COX-2 inhibitor celecoxib (Celebrex) in nearly 1,600 patients with knee osteoarthritis. The dietary supplements were also compared with placebo (an inactive substance). Patients took the assigned substance once a day for 6 months.

The results indicated that, for most patients, neither glucosamine nor chondroitin were better than placebo in relieving knee pain. However, for patients with moderate-to-severe pain, a combination of glucosamine and chondroitin was significantly more effective than the other remedies. Celebrex worked best for patients with mild pain.

The next stage of the study will evaluate whether glucosamine and chondroitin, alone and in combination, can halt the progression of knee osteoarthritis.

Research presented at the 2006 American College of Rheumatology annual meeting suggested that chondroitin may prevent joint narrowing in patients with knee osteoarthritis.

Dosage. There are no current standard recommended dosages. Patients in the GAIT trial took 1,500 mg of glucosamine and 1,200 mg of chondroitin.

Side Effects. The safety records of both substances appear excellent. Long-term effects are still unknown, but studies of up to 3 years have reported no significant side effects. However, there are some concerns that glucosamine may affect insulin and blood sugar (glucose) metabolism. Patients with diabetes should not take glucosamine without first talking to their doctors.

Oral Enzymes. People in Europe have used natural enzymes -- including bromelain, trypsin, papain, and rutin -- to treat arthritic pain. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). They are not painkillers, and any benefits derived from them may take several weeks.

Ginger (Zingiberaceae). A 2001 study of patients with knee arthritis found that an extract of ginger reduced pain while standing and after walking. By using ginger, patients were able to reduce their pain medications after 6 weeks. Side effects included mild digestive upset.

S-adenosylmethionine (SAMe). S-adenosylmethionine (SAMe, pronounced "Sammy") is a synthetic form of a natural byproduct of the amino acid methionine. It has been marketed as a remedy for both depression and arthritis. Some research suggests that it may work as well as NSAIDs for short-term treatment of osteoarthritis. Other studies suggest that it may help rebuild damaged cartilage.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Acupuncture is being increasingly used to reduce osteoarthritis pain. The technique is painless and involves the insertion of small fine needles at select points in the body. Several study reviews have found that acupuncture provides at least short-term pain relief for osteoarthritis of the knee. Other studies have suggested that acupuncture’s benefits are mainly due to a strong placebo effect, or to the psychologically beneficial effects of close contact with health care providers.

In 2004, researchers published results from an important clinical trial that studied the effects of acupuncture on nearly 600 people with osteoarthritis of the knee. The results indicated that acupuncture can relieve pain and improve function. Several 2006 studies of thousands of patients with chronic osteoarthritis pain compared acupuncture to conventional treatment (physical therapy, anti-inflammatory drugs). These studies showed positive results and suggested that acupuncture’s benefits may be sustained for up to 6 months after treatment. In any case, acupuncture appears to be a safe and beneficial addition to standard therapy for certain patients, such as pregnant women, who cannot take most pain medications.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Transcutaneous electric nerve stimulation (TENS) uses low-level electrical pulses to suppress pain. Patients are barely aware of the sensation. According to one study, the optimal treatment length is 40 minutes. A variant (sometimes called percutaneous electrical nerve stimulation, or PENS) applies these pulses through a small needle to acupuncture points. A review of trials reported that both methods were better than placebo (sham treatments) in treating osteoarthritis of the knee, although additional well-designed studies are needed.

Low-level laser therapy (LLLT) generates extremely pure light in a single wavelength. It does not produce heat and is painless. Some researchers are combining LLLT with transcutaneous electric nerve stimulation (TENS). Studies report widely varying results, with some showing significant reductions in pain and others reporting no effect. The differences may be due to different approaches, and standardized methods are needed to determine any benefits.

Hydrotherapy, also called spa therapy or balneotherapy, is an ancient therapy that uses bathing in mineral baths for soothing pain. Although many studies report positive results, including improved quality of life, very few have been rigorously conducted. A major analysis reported weak evidence on any real effect on pain or quality of life, but some patients may find comfort from this pleasant therapy.

Surgery

Different surgical procedures are available as a final measure to relieve pain and increase function in patients with osteoarthritis. Certain surgical procedures can help relieve pain if medications fail. Even with these procedures, however, joint replacement may still be needed later on.

Arthroscopy is performed to clean out bone and cartilage fragments that, in theory at least, may cause pain and inflammation. More than 650,000 of these procedures are done on arthritic knees each year in the U.S., and about half of patients report less pain after the procedure.

A rigorous 2002 trial, however, found that arthroscopic knee surgery was no more effective than sham surgery, (in which surgeons only pretended to operate on the knee), for relief of osteoarthritic pain or stiffness. The study, which followed patients at a Veterans Affairs hospital for 2 years, has called into serious question whether the popular procedure has any real benefits for osteoarthritis beyond what might be achieved by a placebo response. Research and debate continues on whether arthroscopy provides true benefits for those with osteoarthritis and, if so, which patients it may most help.

Click the icon to see an illustrated series detailing knee arthroscopy surgery.

When osteoarthritis becomes so severe that pain and immobility make normal functioning impossible, many people become candidates for artificial (prosthetic) joint implants using a procedure called arthroplasty. Hip replacement is the most established and successful replacement procedure, followed by knee replacement. Knee replacement, in fact, has a slightly better long-term success rate than hip replacement. Other joint surgeries (shoulders, elbows, wrists, fingers) are less common, and some arthritic joints (in the spine, for instance) cannot yet be treated in this manner. When two joints, such as both knees, need to be replaced, having the operations done sequentially rather than at the same time may result in fewer complications.

Click the icon to see an illustrated series detailing knee joint replacement surgery.

Candidates. The primary indications for surgery are pain and significant limitations of movement, including walking, that cannot be treated by less invasive therapies. Some experts suggest, however, that joint replacement should be considered earlier rather than as a last resort. They argue that patients who wait until they are severely disabled do not recover as completely as those who have the procedure earlier.

Patients who may not be good candidates are those with the following conditions:

Severe neurologic, emotional, or mental disorders
Severe osteoporosis
Other chronic medical conditions
Obesity

Surgeons often prefer to delay prosthetic implantation in younger patients, because implants wear out and they will require at least one revision procedure later on. Newer, more long-lasting materials, however, may help reduce the rate of re-operations.

Procedure Description. Although the following is mostly a description of hip replacement surgery, the principles are similar for other arthroplasties.

The surgeon removes the ball and socket joint that joins the pelvis and thigh bone (femur) and replaces it with an artificial joint (a prosthesis). It is composed of two pieces:

A cup-like device fits in the hip socket (called the acetabula), which has been hollowed out. This ball-and-socket cup is positioned to form the new joint.
A metal shaft, or stem, with a polished metal ball at the top, is inserted into the narrow center of the femur.

The prosthesis is usually made of a metal alloy and plastic. A ceramic implant may prove to last longer than other materials and be a safe option for younger patients.

There are different options available for attaching it to the adjoining bones:

A cement made of polymethylmethacrylate (usually preferred for older patients who generally have thinner bones).
So-called cementless implants, in which the prosthesis is coated with a porous material that allows bone to grow into and eventually adhere to the device. These implants are usually used for patients younger than age 65, who are likely to need repeat surgery in their lifetime.

Click the icon to see an illustrated series detailing hip joint replacement surgery.

Complications. Complications can occur, and, although uncommon, some can be life-threatening. There is a 1% chance of death within 3 months of an initial procedure and a 2.6% risk after a repeat procedure. The risks are highest in the first 3 months. Those at highest risks for complications are elderly adults, men (compared to women), African-Americans, and those with serious medical conditions.

Specific complications include the following:

Deep blood clots (known as deep vein thrombosis) and pulmonary embolism. Deep blood clots can develop in the legs after this surgery. This poses a very small risk (0.9%) for pulmonary embolism -- a dangerous condition in which the clot travels to the lungs. Anticoagulants (blood thinners) are important for preventing blood clots. These drugs include warfarin and low-molecular weight heparin. Anticoagulant therapy is given during the hospital stay and continued for several weeks at home. The patient also wears specially fitted elastic stockings to help prevent clots. Patients who are overweight are at higher than average risk for post-operative blood clots
Infection. Wound infection occurs in about 0.2% of joint replacements and requires prompt removal of the implant to treat the infection. A new prosthesis must be re-implanted at a later time. Any pre-existing infection must be treated and cured before surgery is performed. (Older women should be aware of urinary tract infections, which may require postponing surgery.) After surgery, patients should take certain precautions. For example, they should take antibiotics before invasive dental procedures or other surgery because bacteria can be introduced into the bloodstream and infect the areas around the artificial joints.
Hip dislocation. Occurs in about 3.1% of first hip procedures. The rate is much higher (14.4%) in revision operations.

Click the icon to see an image of a dislocated hip.

Pain. Thigh pain can occur after hip replacement. Porous hip prostheses are more likely to produce thigh pain than cement implants, although advanced techniques using a tapered shaft are reducing this complication.
Failure. The primary reason for implant failure is osteolysis (bone destruction) caused by long-term wear. The main source of wear is from tiny particles released from the prosthesis.
Other complications. These include uneven leg lengths, nerve damage that can cause numbness or weakness, urinary tract infections, delayed healing, and allergic reactions to the metal. Long-term, there have been rare reports of a possible autoimmune response, in which loose particles released from the prosthetic device trick certain immune system factors into attacking healthy cells. Any incidence of unexplained weight loss and fatigue may be symptoms of this uncommon event.

Rehabilitation. Aside from the surgeon's skill and the patient's underlying condition, the success rate depends on the kind and degree of activity the joint receives following replacement surgery.

The patient is urged and aided into getting out of bed and walking the day after surgery. Most hip replacement patients leave the hospital within a week and can walk with crutches within 2 - 4 weeks, recovering fully in about 3 months.

Physical therapy takes about 6 weeks to rebuild adjoining muscle and strengthen surrounding ligaments. Studies suggest that an exercise program started before surgery and resumed afterward can improve recovery. Continuous passive motion (CPM) is an effective regimen for knee replacement patients. It uses a mechanical device that slowly moves the joint through an arc of motion for an extended period of time. It is used to prevent scar tissue from developing. In one review, a combination of physical therapy and CPM were more beneficial than physical therapy alone.

Limitations After Surgery. While many patients find that joint replacement provides remarkable pain relief and restores some mobility, they need time to adjust to the artificial joint.

Limitations after hip surgery include:

Usually patients with new hips are able to walk several miles a day and climb stairs, but they cannot run.
Prosthetic hips should not be flexed beyond 90 degrees, so patients must learn new ways to perform activities requiring bending down (like tying a shoe).

Limitations after knee surgery include:

Walking distance improves in 80% of patients after knee replacement surgery, but patients still cannot run.
Only slightly more than half of patients report improvement in stair climbing. (Artificial knee joints generally have a range of motion of just 110 degrees.)

Failure Rates. Infection is a major cause of early failure and always requires revision. Improper balancing of the ligaments and other tissues surrounding the joint and resulting poor joint stability is also a common reason for failure of arthroplasties. Surgical expertise is important for avoiding this complication.

Older cement prostheses have a particularly high rate of bone loss and loosening due to cement deterioration. In general, studies report reoperation rates of over 30% after 10 years. Fortunately, advances in cement and prosthetic implants are improving the implant survival rates and reducing the need for revision procedures.

Uncemented arthroplasty using porous material has shown good results for the hip, although it may be less successful for knee replacement. In spite of short-term success, longer experience with this method suggests it may not be superior to cement prostheses. Failure of bone to grow into the porous material is a relatively common event, a problem that does not occur with cement prostheses. Some experts recommend cement implants over cementless ones for total knee arthroplasty.

A repair procedure called arthroplasty revision may be used in cases where the original transplant fails. The specific procedure depends on whether the bone defects that occurred are contained or uncontained.

Contained defects can be repaired with small bone grafts, the use of cement, or oversized cementless implants as required.
Uncontained defects are more severe and may require a large bone graft or specially constructed implants to restore bone.

If a second arthroplasty is required, the potential for complications is magnified: more bone is cut, more blood is lost, and the operation takes longer. Patients are also generally older and more vulnerable to complications.

Resection Arthroplasty. In resection arthroplasty, a false joint of scar tissue is created. This procedure is used most often in treating arthritis of the foot.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed by osteoarthritis, the surgeon may choose to perform osteotomy:

A surgeon opens the knee.
The surgeon performs a debridement (removal of damaged tissue) in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.
The procedure may ease symptoms and slow disease progression. It is best used in heavier adults who are under 60 years old.

Hemicallotasis. Hemicallotasis is a procedure for the knee that may be a less invasive alternative to osteotomy. The surgeon attaches the knee with pins to an external frame-like device that lengthens the deformed part of the knee over several weeks. The patient is mobile during this period. Infections at the pin site are the most common complications.

Arthrodesis. If the affected joint cannot be replaced, surgeons can perform a procedure called arthrodesis that eliminates pain by fusing the bones together. The patient must understand, however, that fusing the bones makes movement of the joint impossible. Bone fusion is most often done in the spine and in the small joints of the hands and feet.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in cases of limited knee damage. It is recommended for relatively sedentary patients who are 60 years or older and not obese. It may relieve pain and delay the need for a total knee replacement. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which preserve more movement than a total knee replacement.

Cartilage Transplants. Autologous chondrocyte implantation, also called chondroplasty or the Carticel approach, is used for knees damaged by injuries. In this procedure, arthroscopy is used to first remove cartilage in eroded areas. The results have been good to excellent, although long-term benefits are questionable. Whether it has any benefit for older patients with osteoarthritis is not yet known. Other cartilage transplant procedures are also under study.

Hip Resurfacing. Hip resurfacing is a surgical alternative to total hip replacement. It involves scraping the surfaces of the hip joint and femur and placing a metal cap over the bone. The procedure preserves much of the bone, so that a standard hip replacement can be done years later if needed. It may provide more stability, a faster recovery, and greater range of motion, making it a potentially good option for young, physically active patients.

Resources

www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- Arthritis Foundation
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.fda.gov/cder/drug/infopage/cox2 -- FDA NSAID and COX-2 Inhibitor Information

References

Bjordal JM, Klovning A, Ljunggren AE, Slordal L. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomised placebo-controlled trials. Eur J Pain. 2007 Feb;11(2):125-38.

Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006 Nov 18;368(9549):1771-81.

Chou R, Helfland M, Peterson K, Dana T, Roberts C. Comparative Effectiveness and Safety of Analgesics for Osteoarthritis. Comparative Effectiveness Review No. 4. (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-02-0024.) Rockville, MD: Agency for Healthcare Quality and Research. September 2006.

Felson DT, Niu J, Clancy M, Sack B, Aliabadi P, Zhang Y. Effect of recreational physical activities on the development of knee osteoarthritis in older adults of different weights: the Framingham Study. Arthritis Rheum. 2007 Feb 15;57(1):6-12.

Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP; MEDAL Steering Committee. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomized comparison. Lancet. 2007 Feb 10;369(9560):465-73.

Langford R, McKenna F, Ratcliffe S, Vojtassak J, Richarz U. Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial. Arthritis Rheum. 2006 Jun;54(6):1829-37.

McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase2. JAMA. 2006 Oct 4;296(13):1633-44.

Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006 Sep 25;166(17):1899-906.

Scharf HP, Mansmann U, Streitberger K, Witte S, Kramer J, Maier C, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. 2006 Jul 4;145(1):12-20.

Witt CM, Jena S, Brinkhaus B, Liecker B, Wegscheider K, Willich SN. Acupuncture in patients with osteoarthritis of the knee or hip: a randomized, controlled trial with an additional nonrandomized arm. Arthritis Rheum. 2006 Nov;54(11):3485-93.

Review Date:
3/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Pneumonia

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Prognosis
Risk Factors
Diagnosis
Treatment
Medications
Surgery
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosis:

Diagnosing pneumonia may be difficult, since lab tests to grow the bacteria from samples can take many days to process, and chest x-rays cannot always distinguish between pneumonia and other conditions. New tests have the potential to make diagnosis easier and quicker. One is a blood test that identifies a marker of severe inflammation in the body. A new 15-minute urine test shows promise in identifying Legionella pneumophila and Streptococcus pneumoniae in patients on ventilators. Physicians may now sample fluid from the trachea or lungs to identify the pneumonia-causing bacteria.

Treatment:

Treating pneumonia has become increasingly complex as bacteria develop resistance to widely used antibiotics. New antibiotics and combinations of older antibiotics are proving effective against many hardy strains of bacteria. Moreover, guidelines for the appropriate treatment of patients at high risk for pneumonia -- those with heart disease, diabetes, asthma, HIV infection, leukemia, and other lung diseases, for example -- are improving the ability to prevent pneumonia and reduce deaths from the disease.

Drug Warning:

In February 2007, the Food and Drug Administration (FDA) announced that the antibiotic telithromycin (Ketek) would no longer be approved for acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis, but it would remain on the market for the treatment of mild-to-moderate pneumonia acquired outside of hospitals or long-term care facilities (community-acquired pneumonia, or CAP). In addition to warnings for liver damage, Ketek will now carry warnings of additional drug-related adverse events, including visual disturbances and loss of consciousness.

Introduction

Pneumonia is an inflammation of the lung that is most often caused by infection with bacteria, viruses, or other organisms. Occasionally, inhaled chemicals that irritate the lungs can cause pneumonia. Healthy people can usually fight off pneumonia infections. However, people who are sick, including those who are recovering from the flu (influenza) or an upper respiratory illness, have weakened immune systems that make it easier for bacteria to grow in their lungs.

When air is inhaled through the nose or mouth, it travels down the trachea to the bronchus, where it first enters the lung. From the bronchus, air goes through the bronchi, into the even smaller bronchioles and lastly into the alveoli.

Pneumonia may be defined according to its location in the lung:

Lobar pneumonia occurs in one part, or lobe, of the lung.
Bronchopneumonia tends to be scattered throughout the lung.

Doctors often classify pneumonia based on where the disease is contracted. This helps predict which organisms are most likely responsible for the illness and, therefore, which treatment is most likely to be effective.

Community-Acquired Pneumonia (CAP). People with this type of pneumonia contracted the infection outside a hospital setting. It is one of the most common infectious diseases. It often follows a viral respiratory infection, such as the flu.

One of the most common causes of bacterial CAP is Streptococcus pneumoniae. Other causes include Haemophilus influenzae, mycoplasma, and Chlamydia.

Hospital-Acquired Pneumonia. Hospital-acquired pneumonia is an infection of the lungs contracted during a hospital stay. This type of pneumonia tends to be more serious, because hospital patients already have weakened defense mechanisms, and the infecting organisms are usually more dangerous than those encountered in the community. Hospital patients are particularly vulnerable to Gram-negative bacteria and staphylococci. Hospital-acquired pneumonia is also called nosocomial pneumonia.

A subgroup of hospital-acquired pneumonia is ventilator-associated pneumonia (VAP), a highly lethal form contracted by patients on ventilators in hospitals and long-term nursing facilities.

Click the icon to see an image of hospital-acquired pneumonia.

Pneumonia-causing agents reach the lungs through different routes:

In most cases, a person breathes in the infectious organism, which then travels through the airways to the lungs.
Sometimes, the normally harmless bacteria in the mouth, or on items placed in the mouth, can enter the lungs. This usually happens if the body's "gag reflex," an extreme throat contraction that keeps substances out of the lungs, is not working properly.
Infections can spread through the bloodstream from other organs to the lungs.

However, in normal situations, the airways protect the lungs from substances that can cause infection.

The nose filters out large particles.
If smaller particles pass through, sensors along the airway prompt a cough or sneeze. This forces many particles back out of the body.
Tiny particles that reach the small tubes in the lungs (bronchioles) are trapped in a thick, sticky substance called mucus. The mucus and particles are pushed up and out of the lungs by tiny hair-like cells called cilia, which beat like a drum. This action is called the "mucociliary escalator."

Click the icon to see an image of respiratory cilia.

If bacteria or other infectious organisms manage to avoid the airway's defenses, the body's immune system attacks them. Large white blood cells called macrophages destroy the foreign particles.

Click the icon to see an image of a macrophage.

The above-mentioned defense systems normally keep the lung healthy. If these defenses are weakened or damaged, however, bacteria, viruses, fungi, and parasites can easily infect the lung, producing pneumonia.

The lungs are two spongy organs in the chest surrounded by a thin, moist membrane called the pleura. Each lung is composed of smooth, shiny lobes; the right lung has three lobes and the left has two. Approximately 90% of the lung is filled with air. Only 10% is solid tissue. There are several parts to each lung.

When a person takes a breath (inhales), air travels from the trachea (windpipe) into the lung through the main bronchus, which branches into tiny flexible tubes called bronchi.

The bronchi divide, like the branches of a tree, into smaller airways called bronchioles.

The bronchioles lead to a group of microscopic sacs called alveoli, which look like clusters of grapes. Each healthy adult lung contains millions of tiny alveoli. (Note: The singular of alveoli is alveolus.)

Click the icon to see an image of the lungs.

Each alveolus has a thin membrane that allows oxygen and carbon dioxide to pass in and out of the capillaries, the smallest of the blood vessels. When you take a deep breath, the membrane unfolds and expands. Fresh oxygen moves into the capillaries, and carbon dioxide passes from the capillaries into the bloodstream, where it is carried out of the body through the lungs.

Blood vessels carry the oxygen-rich blood to the heart, where it is pumped throughout the body.

Causes

Bacteria are the most common cause of pneumonia. However, pneumonia can also be caused by viruses, fungi, and other agents. It is often impossible to identify the specific culprit.

Many bacteria are grouped into one of two large categories by the laboratory procedure used to look at them under a microscope. The procedure is known as Gram staining. Bacteria are stained with special dyes, then washed in a special solution. The color of the bacteria after washing determines whether they are Gram-negative or Gram-positive. Knowing which group the bacteria belong to helps determine the severity of the disease, and how to treat it. Different bacteria are treated with different drugs.

Gram-Positive Bacteria. These bacteria appear blue on the stain and are the most common organisms that cause pneumonia. They include:

Streptococcus (S.) pneumoniae (also called pneumococcus), the most common cause of pneumonia. This Gram-positive bacterium causes 20 - 60% of all community-acquired bacterial pneumonia (CAP) in adults. Studies also suggest it causes 13 - 38% of CAP in children.
Staphylococcus (S.) aureus, the other major Gram-positive bacterium responsible for pneumonia, causes about 2% of CAP and 10 - 15% of hospital-acquired pneumonias. It is the organism most often associated with viral influenza, and can develop about five days after the onset of flu symptoms. Pneumonia from S. aureus most often occurs in people with weakened immune systems, very young children, hospitalized patients, and drug abusers who use needles. It is uncommon in healthy adults.
Streptococcus pyogenes or Group A streptococcus.

Gram-Negative Bacteria. These bacteria stain pink. Gram-negative bacteria commonly cause infections in hospitalized or nursing home patients, children with cystic fibrosis, and people with chronic lung conditions.

Haemophilus (H.) influenzae is the second most common organism causing community acquired pneumonia, accounting for 3 - 10% of all cases. It generally occurs in patients with chronic lung disease, older people, and alcoholics.
Klebsiella (K.) pneumoniae may be responsible for pneumonia in alcoholics and other people who are physically debilitated. It is also associated with recent use of potent antibiotics.
Pseudomonas (P.) aeruginosa is a major cause of hospital-acquired pneumonia (nosocomial pneumonia). It is a common cause of pneumonia in patients with chronic or severe lung disease.
Moraxella (M.) catarrhalis is found in everyone's nose and mouth. Experts have identified this bacterium as an uncommon cause of certain pneumonias, particularly in people with lung problems such as asthma or emphysema.
Neisseria (N.) meningitidis is one of the most common causes of meningitis (central nervous system infection), but the organism has been reported in pneumonia, particularly in epidemics of military recruits.
Other Gram-negative bacteria that cause pneumonia include E. coli, proteus (found in damaged lung tissue), enterobacter and acetinobacter.

Atypical pneumonias produce mild symptoms and a dry cough. Organisms that cause atypical pneumonias include:

Mycoplasma (M.) pneumoniae, the most common atypical pneumonia organism. Mycoplasma is a very small bacterium that lacks a cell wall. Pneumonia caused by M. pneumoniae spreads when someone carrying the infection comes in close contact with others for a long period of time. It is most often found in school-aged children and young adults. The condition, commonly called "walking pneumonia," is usually mild.
Chlamydia (C.) pneumoniae is now thought to cause 10% of all CAP cases. This atypical pneumonia is most common in young adults and children, and is usually mild. It is less common, but usually more severe, in the elderly.
Legionella pneumophila causes Legionnaire disease. It is contracted by breathing in drops of contaminated water. Outbreaks are often been reported in hotels, cruise ships, and office buildings, where people are exposed to contaminated droplets from cooling towers and evaporative condensers. They have also been reported in people who have been near whirlpools and saunas. Legionella pneumophila is not passed from person to person. Some experts believe the organism causes 29 - 47% of all pneumonia cases.

Legionnaire disease was first described in 1976 after an outbreak of fatal pneumonia at an American Legion convention. The newly described organism that caused the disease was named Legionella pneumophila, shown in this picture. (Courtesy of the Centers for Disease Control.)

A number of viruses can cause pneumonia either directly or indirectly. They include:

Influenza (Flu). Pneumonia is a major complication of the flu and can be very serious. It can develop about 5 days after flu symptoms start. The flu weakens the body's defense systems, making it easier for bacteria to grow in the lungs.
Respiratory syncytial virus (RSV). Most infants are infected with RSV at some point, but it is most often mild. However, RSV is a major cause of pneumonia in infants as well as adults with damaged immune systems. Studies indicate that RSV pneumonia may be more common in adults, especially the elderly, than previously thought.
Severe acute respiratory syndrome (SARS). SARS is a respiratory infection caused by a newly-described coronavirus, which appears to have jumped from animals to humans. The disease was first reported in China in 2003.
Human parainfluenza virus. This virus is a leading cause of pneumonia and bronchitis in children, the elderly, and patients with damaged immune systems.
Adenoviruses. Adenoviruses are common and usually are not problematic, although they have been linked to about 10% of childhood pneumonia.
Herpesviruses. In adults, herpes simplex virus and varicella zoster (the cause of chickenpox) can cause pneumonia in people with impaired immune systems.
Avian influenza. Type A influenza subtype H5N1 in birds is spreading around the globe. Fortunately, only a few hundred human cases have been identified. Most have resulted from close contact with infected birds. Person-to-person contact is rare. All patients diagnosed with "bird flu" show signs of pneumonia, although symptoms may be mild. Oseltamivir (Tamiflu) is the most effective treatment for this type of influenza, which can be fatal.

The mouth contains a mixture of bacteria that is normally harmless. However, if this mixture reaches the lungs, it can cause a serious condition called aspiration pneumonia. This may happen after head a injury or general anesthesia, or when a patient takes drugs or alcohol. In such cases, the gag reflex doesn't work as well as it should, so bacteria can enter the airways. Unlike other organisms that are inhaled, bacteria that cause aspiration pneumonia do not need oxygen to live. These bacteria are called anaerobic bacteria.

Impaired immunity leaves patients vulnerable to serious, life-threatening pneumonias known as opportunistic pneumonias. They are caused by organisms that are harmless to people with healthy immune systems. Infecting organisms include:

Pneumocystis carinii, renamed Pneumocystis jiroveci in 2002, is an atypical organism. Originally thought to be protozoa, it is now classified as a fungus. P. jiroveci is very common and generally harmless in people with healthy immune systems. It is the most common cause of pneumonia in AIDS patients.

Click the icon to see an image of pneumocystis carinii.

Fungi, such as Mycobacterium avium
Viruses, such as cytomegalovirus (CMV)

Click the icon to see an image of CMV.

In addition to AIDS, other conditions also put patients at risk for opportunistic pneumonia. They include cancers such as lymphoma and leukemia. Long-term use of corticosteroids and drugs known as immunosuppressants also increase the risk for these pneumonias.

Exposure to chemicals can also cause inflammation and pneumonia. Where you work and live can put you at higher risk for exposure to pneumonia-causing organisms.

Workers exposed to cattle, pigs, sheep, and horses are at risk for pneumonia caused by anthrax, brucella, and Coxiella burnetii, which causes Q fever.

Click the icon to see an image of inhalation anthrax.

Agricultural and construction workers in the Southwest are at risk for coccidoidomycosis (Valley fever). The disease is caused by the spores of the fungus Coccidioides immitis.
Those working in Ohio and the Mississippi Valley are at risk for histoplasmosis, a lung disease caused by the fungus Histoplasma capsulatum.

Click the icon to see an image of coccidoidomycosis.

Workers exposed to pigeons, parrots, parakeets, and turkeys are at risk for psittacosis, a lung disease caused by the bacteria Chlamydia psittaci.
Hantavirus, a rare virus carried by rodents, causes a dangerous form of lung disease. It does not spread from person to person. Cases have occurred in New Mexico, Arizona, California, Washington, and Mexico.

Click the icon to see an image of the hantavirus.

Severe acute respiratory syndrome (SARS) is a contagious respiratory infection that was recognized as a worldwide threat in 2003. It was first identified as a new disease by World Health Organization (WHO) physician Dr. Carlo Urbani. Urbani diagnosed SARS in a 48-year-old American businessman, who had traveled from the Guangdong province of China through Hong Kong to Hanoi, Vietnam. The businessman died from the illness. Dr. Urbani died from SARS just a month later, on March 29, 2003 at the age of 46. SARS spread fast. Within 6 weeks of Urbani's discovery, the disease had infected thousands of people around the world on every continent except Antarctica. Schools closed throughout Hong Kong and Singapore, and national economies were affected. The WHO officially identified SARS as a global health threat, and issued an unprecedented travel advisory. It wasn't clear at the time whether SARS would become a global pandemic or settle into a less aggressive pattern. The latter seems to have happened. As of a May 2005, there was no known SARS transmission anywhere in the world, according to the U.S. Centers for Disease Control and Prevention (CDC). The SARS outbreak is a dramatic example of how quickly world travel can spread a disease. According to reports from the CDC and WHO, more than 8,000 people became sick with SARS during the outbreak. Of that group, 774 died. The outbreak is also an example of how quickly a networked health monitoring system can respond to an emerging threat

Causes And Risk Factors. SARS is a serious form of atypical pneumonia that causes acute respiratory distress and sometimes death. It is caused by a new member of the coronavirus family, the family that includes the virus that causes the common cold). The discovery of the SARS-related virus represents one of the fastest identifications of a new organism in history.

SARS is spread by droplet contact. When someone with SARS coughs or sneezes, infected droplets are sprayed into the air. Like other coronaviruses, the SARS virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets and up to 3 hours after the droplets have dried. While droplet transmission through close contact has been responsible for most cases of SARS, there is evidence that SARS might also spread by infected droplets carried on hands and other objects the droplets had touched. Airborne transmission was a real possibility in some cases. Live virus had even been found in the stool of people with SARS, where it has been shown to survive for up to 4 days. And the virus may be able to live for months or years when the temperature is below freezing.

With other coronaviruses, re-infection (contracting the same disease after recovery or during initial illness) is common. Preliminary reports suggest that this may also be the case with SARS.

The estimated incubation period is 2 - 10 days, although there have been documented cases where the onset of illness was considerably faster or slower. People with active symptoms of illness are clearly contagious. It is not known, however, how early contagion begins before symptoms appear, or how long contagion might linger after the symptoms have disappeared.

Prevention. The best way to prevent SARS is to avoid direct contact with people who have SARS until 10 days after their fever and other symptoms are gone. Reduce travel to locations where there is an uncontrolled SARS outbreak. The CDC has identified hand hygiene as the cornerstone of SARS prevention. Wash your hands often with soap and water, or use an alcohol-based instant hand sanitizer. Cover your mouth and nose when sneezing or coughing. Consider respiratory secretions infectious. Clean commonly touched surfaces with an EPA-approved disinfectant. In some situations, masks, and goggles may be useful for preventing the spread of airborne or droplet infection. Gloves should be used in handling potentially infectious secretions.

Vaccine. In December 2004, the U.S. National Institutes of Health began a small clinical trial to test a preventive SARS vaccine. Interim results showed the vaccine to be safe and well tolerated. Chinese researchers began testing a SARS vaccine in May 2004.

Symptoms. The hallmark symptoms of SARS are fever of 100.4° F (38.0° C) or higher and a dry cough, with difficulty breathing or other respiratory symptoms. The following symptoms, listed in order of how often they appeared, were found in more than half of the first SARS patients:

Fever
Chills and shaking
Muscle aches
Cough
Headache

Less common symptoms (also in order) include:

Dizziness
Cough that produces mucus (sputum)
Sore throat
Runny nose
Nausea and vomiting
Diarrhea

Signs and Tests. Listening to the chest with a stethoscope (auscultation ) may reveal abnormal lung sounds. In most people with SARS, progressive chest x-ray changes or chest CT changes reveal the presence of pneumonia.

Much attention was given early in the outbreak to the development of a quick, sensitive test for SARS. Specific tests for the SARS virus include the PCR for SARS virus, antibody tests to SARS (such as ELISA or IFA), and direct SARS virus isolation. All current tests have some limitations. General tests used in the diagnosis of SARS might include:

Chest x-ray or chest CT is abnormal.
CBC. People with SARS tend to have a low white blood cell count (leukopenia), a low lymphocyte count (lymphopenia), or a low platelet count (thrombocytopenia).
Clotting profiles. SARS patients often have prolonged blood clotting times.
Metabolic blood tests. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) levels are often high. ALT and LDH are most often measured to evaluate the presence of tissue damage.
CPK blood test. Creatine phosphokinase (CPK) is an enzyme found predominantly in the heart, brain, and skeletal muscle. Levels of the CPK enzyme are sometimes elevated in patients with SARS.
Sodium and potassium blood tests are sometimes below normal levels.

Treatment. People suspected of having SARS should be evaluated immediately by a physician. Antibiotics are sometimes given in an attempt to treat bacterial causes of atypical pneumonia. Antiviral medications have also been used. High doses of steroids have been employed to reduce lung inflammation. In some serious cases, serum from people who have already gotten well from SARS (convalescent serum) has been given. Evidence of general benefit of these treatments has been inconclusive.

Other supportive care such as supplemental oxygen, chest physiotherapy, or mechanical ventilation is sometimes needed.

Prognosis. The overall worldwide death rate due to SARS at the end of the outbreaks was 14 - 15%, although it was up to 50% in infected people over age 65. Many more were sick enough to require breathing assistance from a machine (mechanical ventilation). Many others required ICU care.

Today, intensive public health policies are proving to be effective in controlling outbreaks. Many nations have stopped the epidemic within their own countries. All nations must be vigilant, however, to keep this disease under control.

Complications.

Respiratory failure
Liver failure
Heart failure
Myelodysplastic syndromes (bone marrow abnormalities leading to anemia, low platelet counts, and low white blood cell counts)

Call Health Care Provider. Call your health care provider if you suspect you or someone you have had close contact with has SARS.

Symptoms

General Symptoms. The symptoms of bacterial pneumonia develop very quickly and typically include:

A single episode of shaking chills followed by fever
Chest pain on the side of the infected lung. Severe abdominal pain sometimes occurs in people with pneumonia in the lower lobes of the lung.
Shortness of breath
Rapid breathing and heart beat
Cough, which may be initially dry, but eventually produces sputum
Nausea, vomiting, and muscle aches

Emergency Symptoms. Symptoms of pneumonia indicating a medical emergency include the following:

High fever
Rapid heart rate
Bluish-toned (cyanotic) skin
Labored and heavy breathing.
Mental confusion
Coughing up mucus (sputum) containing pus or blood

Symptoms in the Elderly. It is important to note that older people may have fewer or different symptoms than younger people. Symptoms may come on much more slowly. An elderly person who experiences even a minor cough and weakness for more than a day should seek medical help. Some elderly people may exhibit confusion, lethargy, and general deterioration.

Pneumonia caused by anaerobic bacteria such as prevotella (formerly called bacteroides) can produce dangerous abscesses in the lungs. People with such pneumonias may have prolonged fever and a productive cough. There is frequently blood in the mucus that is coughed up. Blood may indicate dead lung tissue. About a third of these patients experience weight loss.

General Symptoms for Atypical Pneumonias. Atypical pneumonia is most commonly caused by mycoplasma and usually appears in children and young adults.

The disease progresses gradually.

General flu-like symptoms often occur first. They may include fatigue, fever, weakness, headache, nasal discharge, sore throat, earache, and stomach and intestinal distress.
Vague pain under and around the breastbone may occur, but the severe chest pain associated with typical bacterial pneumonia is uncommon.
Patients may have a severe hacking cough, but it usually does not produce sputum.

Symptoms of Legionnaire Disease. Symptoms of Legionnaire disease usually occur more rapidly and include high fever, a dry cough, and shortness of breath. These symptoms are often accompanied by headache, muscle pains, fatigue, gastrointestinal problems, and mental confusion.

Prognosis

More than a million people are hospitalized each year for pneumonia, making it the third most frequent cause of hospitalizations (births are first, and heart disease is second). Although the majority of pneumonias respond well to treatment, the infection kills 40,000 - 70,000 people each year.

Hospitalized Patients. For patients who require hospitalization for pneumonia, the death rate is 10 - 25%. If pneumonia develops in patients already hospitalized for other conditions, death rates range from 50 - 70%, and are higher in women than in men.

Older Adults. Community-acquired pneumonia is responsible for 350,000 - 620,000 hospitalizations in the elderly every year. Older adults have lower survival rates than younger people. Even when older individuals recover from CAP, they have higher-than-normal death rates over the next several years. Elderly people who live in nursing homes or who are already sick are at particular risk.

Very Young Children. About 20% of deaths in stillborn and very young infants are due to pneumonia. Small children who develop pneumonia and survive are at risk for developing lung problems in adulthood.

Pregnant Women. Pneumonia poses a special hazard for pregnant women, possibly due to changes in a pregnant woman's immune system. This complication can lead to premature labor and increases the risk of death during pregnancy.

Patients With Impaired Immune Systems. Pneumonia is particularly serious in people with impaired immune systems. This is particularly true for AIDS patients, in whom pneumonia causes about half of all deaths.

Patients With Serious Medical Conditions. Pneumonia is also very dangerous in people with diabetes, cirrhosis, sickle cell disease, cancer, and in those whose spleens have been removed.

Specific organisms vary in their effects. Mild pneumonia is usually associated with the atypical organisms mycoplasma and chlamydia. Severe pneumonia is most often associated with a wide range of organisms. Some are very virulent (potent) but are extremely curable, while others are difficult to treat.

Mycoplasma and chlamydia are the most common causes of mild pneumonias and are most likely to occur in children and young adults. They rarely require hospitalization when they are appropriately treated, although recovery may still be prolonged. Severe and life-threatening cases are more likely to occur in elderly people with other medical conditions.
Streptococcus pneumoniae is the most common cause of pneumonia and, in fact, all bacterial upper respiratory infections. It can produce severe pneumonia, with mortality rates of 10%. Nevertheless, pneumococcal pneumonia is very responsive to many antibiotics.
Staphylococcus aureus is a Gram-positive bacterium that often causes severe pneumonia in hospitalized and high-risk patients and following influenza A and B. People who get this form of pneumonia may develop pockets of infection in their lungs (abscesses) that are difficult to treat and can cause the death of lung tissue (necrosis). Mortality rates are 30 - 40%, in part because the patients who develop this infection are generally very ill or vulnerable.
Pseudomonas aeruginosa and Klebsiella pneumoniae are Gram-negative bacteria that pose a risk for abscesses and severe lung tissue damage.
Legionella pneumophila is very virulent and can cause widespread damage. Treatments have improved dramatically since it was first identified. However, a 2002 study suggested that many patients experience long-term problems, including coughing, shortness of breath, fatigue, and neurological and muscular complications.
Viral pneumonia is usually very mild, but there are exceptions. Respiratory syncytial virus (RSV) pneumonia rarely poses a danger for healthy young adults, but it can be life-threatening in infants and serious in the elderly.

Abscess. An abscess in the lung is a thick-walled, pus-filled cavity that forms when infection has destroyed lung tissue. It typically occurs as a result of aspiration pneumonia, when a mixture of organisms is carried into the lung. Untreated abscesses can cause hemorrhage (bleeding) in the lung, but targeted antibiotic therapy significantly reduces their danger. Abscesses are more common with Staphylococcus aureus, Pseudomonas aeruginosa, or Klebsiella pneumoniae, and uncommon with Streptococcus pneumoniae.

Respiratory Failure. Respiratory failure is one of the top causes of death in patients with pneumococcal pneumonia. Acute respiratory distress syndrome (ARDS) is the specific condition that occurs when the lungs are unable to function and oxygen is so severely reduced that the patient's life is at risk. Failure can occur if pneumonia leads to mechanical changes in the lungs (ventilatory failure) or oxygen loss in the arteries (hypoxemic respiratory failure).

Bacteremia. Bacteremia, bacteria in the blood, is the most common complication of pneumococcus infection, although it rarely spreads to others sites. Bacteremia is a frequent complication of infection from Gram-negative organisms, including Haemophilus influenzae.

Pleural Effusions and Empyema. The pleura are two thin membranes that line the chest and lungs:

The visceral pleura cover the lungs.
The parietal pleura cover the chest wall.

In some cases of pneumonia the pleura become inflamed, which can result in breathlessness and acute chest pain when breathing.

In about 20% of pneumonia cases fluid builds up between the pleural membranes, a condition known as pleural effusion. Ordinarily, the narrow zone between the two membranes contains only a tiny amount of fluid, which lubricates the lungs.

In most cases, particularly in Streptococcus pneumoniae, the fluid remains sterile (no bacteria are present), but occasionally it can become infected and even filled with pus, a condition called empyema. Empyema is more likely to occur with specific organisms such as Staphylococcus aureus or Klebsiella pneumoniae infections. The condition can cause permanent scarring.

Collapsed Lung. In some cases, air may fill up the area between the pleural membranes, causing the lungs to collapse. This is called pneumothorax. It may be a complication of pneumonia (particularly Streptococcus pneumoniae ) or of the invasive procedures used to treat pleural effusion.

Pneumothorax occurs when air leaks from inside of the lung to the space between the lung and the chest wall. The lung then collapses. The dark side of the chest (right side of the picture) fills with air from outside of the lung tissue.

Other Complications of Pneumonia. In rare cases, infection may spread from the lungs to the heart and possibly throughout the body. This can cause abscesses in the brain and other organs. Severe hemoptysis (coughing up blood) is another potentially serious complication of pneumonia, particularly in patients with lung problems such as cystic fibrosis.

Kidney complications and electrolyte imbalances are common in patients admitted to the hospital with pneumonia. If not treated, these problems cause more severe illness and increase the risk of death. Treatment with intravenous saline can usually resolve the problem.

The pneumonias cased by the atypical organisms mycoplasma and chlamydia are usually mild. Some research suggests, however, that chlamydia may have powerful inflammatory effects in the blood vessels. This effect may have certain adverse long-term consequences even in healthy younger individuals.

Heart Disease and Stroke. Research has suggested that chlamydia may trigger the immune system to react, causing inflammation in the coronary arteries. Over time, this can cause hardening of the arteries (atherosclerosis). Atherosclerosis can lead to heart attacks and strokes. Studies on a causal relationship between chlamydia and heart disease have been mixed.

Click the icon to see an image of arterial plaque.

Chylamydia pneumoniae has been associated with a thickening in the carotid arteries that lead to the brain -- a risk factor for stroke. It is not clear whether the organism poses any significant risk for stroke.

Click the icon to see an image of atherosclerosis of the internal carotid artery.

Asthma. Chlamydia pneumoniae, Mycoplasma pneumoniae, and RSV are becoming suspects in many cases of severe adult asthma. One small Australian study found evidence of previous chlamydia infection in 64% of the asthmatic patients tested.

Risk Factors

Risk factors for pneumonia often depend on the specific type of disease.

CAP is the most common type of pneumonia. It develops outside of the hospital. Each year 2 - 4 million people in the US develop CAP, and 600,000 are hospitalized. The elderly, infants, and young children are at greatest risk for the disease.

Pneumonia that is contracted in the hospital is called hospital-acquired or nosocomial pneumonia. It affects an estimated 5 -10 of every 1,000 hospitalized patients every year. More than half these cases may be due to strains of bacteria that have developed resistance to antibiotics. In fact, methicillin-resistant Staphyllococcus aureus and multidrug-resistant Pseudomonas aeruginosa are leading causes of death from hospital-acquired pneumonia. The elderly, the very young, and those with chronic or severe medical conditions, are at highest risk.

In addition, the following conditions within the hospital put patients at higher risk:

Surgery, particularly in people over the age of 80. Among the surgical procedures that pose a particular risk are splenectomy (removal of the spleen), abdominal aortic aneurysm repair, or operations that impair coughing.
Being in the intensive care unit (ICU). This is particularly true for newborns or patients on breathing machines (mechanical ventilators). In one study, 10% of ICU patients on a breathing machine developed pneumonia. Such patients who lie flat on their backs are at particular risk for aspiration pneumonia. Raising the patient up may reduce this risk.
Sedation. Hospital patients who receive sedatives also have a higher risk of developing nosocomial pneumonia.
Previous use of antibiotics, particularly within 6 months.

Hospitalized patients are particularly vulnerable to Gram-negative bacteria and staphylococci, which can be especially dangerous in people who are already ill.

Chronic Lung Disease. Chronic obstructive lung diseases (COPD), which include chronic bronchitis and emphysema, affect 15 million people in the U.S. This condition is a major risk factor for pneumonia. In patients with COPD, vaccination with the pneumococcal vaccine can substantially reduce the risk of developing pneumonia or decrease its severity.

Bronchitis is the inflammation of the bronchi, the main air passages to the lungs. It generally follows a viral respiratory infection. Symptoms include coughing, shortness of breath, wheezing, and fatigue.

Click the icon to see an image of emphysema.

People With Compromised Immune Systems. People with impaired immune systems are extremely susceptible to pneumonia. It is a common problem in people with HIV and AIDS. In one study, the primary bacteria were found to be Legionella pneumophilia and Streptococcus pneumoniae. Smoking and chemotherapy for cancer were more common in those with legionella pneumonia. The patients tended to have a higher CD4 count, undetectable viral load, and more frequent need for antiretroviral therapy. Their pneumonia was more severe than in HIV patients diagnosed with pneumococcal pneumonia. Those with legionell were more likely to have respiratory failure, need ventilation, have pneumonia in both lungs, and were more likely to die. However, AIDS was more common in the patients with pneumococcal pneumonia.

In addition to AIDS, other conditions that compromise the immune system include organ transplantation, chemotherapy, and adult and pediatric cancers, especially leukemia and Hodgkin's lymphoma. Patients who are on corticosteroids or other medications that suppress the immune system are also prone to infection.

Gastroesophageal Reflux Disease. Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move up into the esophagus. This is called reflux. Current studies indicate an association between GERD and various problems that occur in the sinuses, ears, nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid (aspirates) from the esophagus into the lungs, serious pneumonia can occur. GERD may contribute to these conditions by triggering inflammation in these upper passages.

However, GERD drugs may increase one's risk. Patients at high risk for pneumonia should take gastric acid-suppressing drugs only when necessary and at the lowest possible dose. A 2004 study found that the use of gastric acid-suppressing drugs raises the risk of developing CAP. The highest risks were associated with proton pump inhibitors (PPIs) such as Prilosec and Nexium, but H2-receptor antagonists such as Tagamet and Pepcid also elevated risk. The researchers theorize that reducing levels of germ-killing stomach acid allow germs to spread in the upper gastrointestinal tract and move into the respiratory tract. The risk posed by these medications is highest in the elderly, children, and patients with asthma, COPD, and compromised immune systems.

Acute stroke. Acute stroke is a risk factor for developing pneumonia. In one German study, the incidence of stroke-associated pneumonia (SAP) was 22% in patients admitted to the intensive care following a stroke. Dysphagia, non-lacunal basal-ganglia infarction, or any infection present on admission, and National Institutes of Health Stroke Scale score greater than or equal to 10 were found to be independent risk factors for the development of SAP. Other risk factors included combined brainstem and cerebellar infarction, infarction affecting more than 66% of the middle cerebral arterial territory, hemispheric infarction exceeding middle cerebral artery territory, impaired vigilance, mechanical ventilation, age of 73 or greater, and cardioembolic stroke. Patients with lacunal strokes were found to be at less risk of SAP.

Click the icon to see an image of gastric reflux.

Dormitory or Barrack Conditions. Recruits on military bases and college students living in dormitories are at higher than average risk for Mycoplasma pneumonia. These groups are at lower risk, however, for more serious types of pneumonia.

Smoke and Environmental Pollutants. The risk for pneumonia in people who smoke more than a pack a day is three times that of nonsmokers. Those who are chronically exposed to secondhand cigarette smoke, which can injure airways and damage the cilia, are also at risk. Quitting smoking reduces the risk of dying from pneumonia to normal, but the full benefit takes 10 years to be realized. Toxic fumes, industrial smoke, and other air pollutants may also damage cilia function, which is a defense against bacteria in the lungs.

Drugs and Alcohol. Alcohol or drug abuse is strongly associated with pneumonia. These substances act as sedatives and can diminish the reflexes that trigger coughing and sneezing. Alcohol also interferes with the actions of macrophages, the white blood cells that destroy bacteria and other microbes. Intravenous drug abusers are at risk for pneumonia from infections that originate at the injection site and spread through the bloodstream to the lungs.

Fatty Diet: A diet high in fatty acids such as palm oils appears to increase the risk of CAP in young and middle-aged women by as much as 54%. Higher intake of monosaturated fats appears to decrease the risk of pneumonia.

Certain children have a higher-than-normal risk for pneumonia and recurrence. Conditions that predispose infants and small children to pneumonia include:

Impaired immune system
Leukemia
Infection with the respiratory syncytial virus (RSV)
Gastroesophageal reflux disorder
Inborn lung or heart defects
Abnormalities in muscle coordination of the mouth and throat
Asthma
Certain genetic disorders such as sickle-cell disease, cystic fibrosis, and Kartagener's syndrome, which result in poorly functioning cilia, the hair-like cells lining the airways

Diagnosis

Diagnostic Difficulties in Community-Acquired Pneumonia (CAP). It is important to determine whether the cause of CAP is a bacterium, atypical bacterium, or virus, since they require different treatments. In children, for example, S. pneumonia is the most common cause of pneumonia, but respiratory syncytial virus may also cause the disease. Although symptoms may differ, they often overlap, which can make it difficult to identify the organism by symptoms alone.

Nevertheless, in many cases of mild-to-moderate CAP, the physician is able to diagnose and treat pneumonia based solely on a history and physical examination.

Diagnostic Difficulties with Hospital-Acquired (Nosocomial) Pneumonia. Diagnosing pneumonia is particularly difficult in hospitalized patients for a number of reasons:

Many hospitalized patients have similar symptoms, including fever or signs of lung infiltration on x-rays.
In hospitalized patients, sputum or blood tests often indicate the presence of bacteria or other organisms, but such agents do not necessarily indicate pneumonia.

Doctors making a diagnosis of pneumonia should rule out other conditions, using a chest x-ray, two sets of blood cultures, a urine analysis for legionella, and a lung fluid sample, among other tests.

The patient's history is an important part of making a pneumonia diagnosis. Patients should be sure to report any of the following:

Recent or chronic respiratory infection
Exposure to people with pneumonia or other respiratory illnesses (such as tuberculosis)
History of smoking
Alcohol or drug abuse
Recent travel
Occupational risks

Use of the Stethoscope. The most important diagnostic tool for pneumonia is the stethoscope. Sounds in the chest that may indicate pneumonia include:

Rales, a bubbling or crackling sound. Rales on one side of the chest or heard while the patient is lying down are strongly suggestive of pneumonia.
Rhonchi, abnormal rumblings indicating the presence of thick fluid.
A dull thud obtained by percussion. The physician will also use a test called percussion, in which the chest is tapped lightly. A dull thud, instead of a hollow drum-like sound, indicates certain conditions suggestive of pneumonia. These conditions include including consolidation (a condition in which the lung becomes firm and inelastic), and pleural effusion (fluid build-up in the space between the lungs and the lining around it).

Although current antibiotics can destroy a wide spectrum of organisms, it is best to use an antibiotic that targets the specific one making a person sick. Unfortunately, people carry many bacteria, and sputum and blood tests are not always effective in distinguishing between harmless and harmful kinds.

In severe cases, a doctor needs to use invasive diagnostic measures to identify cause of the infection. Standard lab tests used to help diagnose pneumonia include:

Sputum Tests. The color of the mucus (sputum) sample coughed up from the lungs can reveal the severity of the disease. Only a sputum sample will reveal the infecting organism.

The patient coughs as deeply as possible to bring up mucus from the lungs, since a shallow cough produces a sample that usually only contains normal mouth bacteria. Some people may need to inhale a saline spray to produce an adequate sample. In some cases, a tube will be inserted through the nose into the lower respiratory tract to induce a deeper cough.

The physician will check the sputum for:

Blood, which means an infection is present
Color and consistency: If it is yellow, green, or brown, an infection is likely.

The sputum sample is sent to the laboratory, where it is analyzed for the presence of bacteria and to determine whether the bacteria are gram-negative or Gram-positive.

Blood Tests. The following blood tests may be performed:

White blood cell count (WBC). High levels indicate infection.
Blood cultures. Cultures are done to determine the specific organism causing the pneumonia, but they usually can not distinguish between harmless and dangerous organisms. They are accurate in only 10 - 30% of cases. Their use is generally limited to severe cases.
Detection of antibodies to S. pneumoniae. Antibodies are immune factors that target specific foreign invaders. One type of immunohistochemical test for S. pneumoniae is showing tremendous promise.
Polymerase Chain Reaction (PCR). In some difficult cases, PCR may be performed. A test makes multiple copies of the genetic material (RNA) of a virus or bacteria to make it detectable.
Procalcitonin test. This marker of systemic inflammatory response to infection is increasingly recognized as a valuable method of determining which patients need antibiotics, and when antibiotic therapy can be safely stopped. Such information is critical to preventing the development of antibiotic-resistant bacteria.

Urine Tests. Urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae may be performed in patients with severe CAP. The S. pneumoniae test takes only 15 minutes and may identify up to 77% of pneumonia cases and rule out S. pneumoniae infection in 98% of patients. It may not be useful in children.

Invasive Tests. In critically-ill patients with ventilator-associated pneumonia, physicians have tried sampling fluid taken from the lungs or trachea. The techniques enabled the physicians to identify the pneumonia-causing bacteria and start the appropriate antibiotics. However, this made no difference in the length of stay in the ICU or hospital, and there was no significant difference in outcome.

Laboratory Tests for Less Common Organisms

If uncommon organisms -- such as legionella, mycoplasma, and chlamydia -- are strongly suspected, more advanced laboratory tests may be used:

Specialized techniques can detect antibodies to the organisms in blood samples, but these antibodies, such as those responding to mycoplasma or chlamydia, are not present early enough in the course of pneumonia to permit prompt diagnosis and treatment.
PCR is useful for identifying certain atypical strains, including mycoplasma and Chlamydiapneumoniae and, possibly, Haemophilus influenzae type b, but it is expensive.
A urine test can be used to diagnose some cases of Legionnaire disease.
Specialized tests called DNA probes are being developed to detect these organisms in respiratory secretions.

X-Rays. A chest x-ray is nearly always taken to confirm a diagnosis of pneumonia.

X-rays are a form of electromagnetic radiation (like light). They are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

A chest x-ray may reveal the following:

White areas in the lung called infiltrates, which indicate infection
Complications of pneumonia, including pleural effusions and abscesses

Other Imaging Tests. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans may be useful in some circumstances, especially when:

X-ray results are unclear
Patients do not respond to antibiotics
Complications occur
Patients have other serious health problems

Click the icon to see an image of a CT scan.

CT and MRI can help detect the presence of tissue damage, abscesses, and enlarged lymph nodes. They can also detect some tumors that block bronchial tubes. No imaging technique can determine the actual organism causing the infection. However, features on CT scan of patients with certain forms of pneumonia -- for example, that caused by Legionella pneumophila -- are usually different from features produced by other bacteria in the lungs.

Invasive diagnostic procedures may be required when:

Patients have life-threatening complications
Standard treatments have failed for no known reason
AIDS or other immune problems are present

Invasive procedures include:

Thoracentesis. If a doctor detects pleural effusion during the physical exam or on an imaging study, and suspects that empyema (pus) is present, a thoracentesis is performed.

Fluid in the pleura is withdrawn using a long thin needle inserted between the ribs.
The fluid is then sent to the lab for multiple tests.

Complications of this procedure are rare, but can include collapsed lung, bleeding, and introduction of infection.

Bronchoscopy. A bronchoscopy is done in the following way:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The physician inserts a fiber optic tube into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the physician to view the windpipe and major airways and look for pus, abnormal mucus, or other problems.
The doctor removes specimens for analysis and can also treat the patient by removing any foreign bodies or infected tissue encountered during the process.

Click the icon to see an image of bronchoscopy.

Bronchoalveolar lavage (BAL) may be done at the same time as bronchoscopy. This involves injecting high amounts of saline through the bronchoscope into the lung and then immediately sucking the fluid out. The fluid is then analyzed in the laboratory. Studies find BAL to be an effective method for detecting specific infection-causing organisms.

The procedure is usually very safe, but complications can occur. They include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Lung Biopsy. In very severe cases of pneumonia or when the diagnosis is unclear, particularly in patients with damaged immune systems, a lung biopsy may be required. A lung biopsy involves taking some tissue from the lungs and examining it under a microscope.

Lung Tap. This procedure typically uses a needle inserted between the ribs to draw fluid out of the lung for analysis. It is known by a number of names including lung aspiration, lung puncture, thoracic puncture, transthoracic needle aspiration, percutaneous needle aspiration, and needle aspiration. It is a very old procedure that is not done often any more, since it is invasive and poses a slight risk for collapsed lung. Some experts argue, however, that a lung tap is more accurate than other methods for identifying bacteria, and the risk it poses is slight. Given the increase in resistant bacteria, they believe its use should be reconsidered in young people.

Common Causes of Persistent Coughing. Over 30 million people seek medical help each year for persistent coughing, which is nearly always temporary and harmless when other symptoms, such as fever, are not present. The four most common causes of persistent coughing are asthma, postnasal drip, gastroesophageal reflux disease (GERD), and chronic bronchitis. Other obvious common causes of chronic cough include heavy smoking or the use of heart drugs known as ACE inhibitors.

Acute Bronchitis. Acute bronchitis is an infection in the passages that carry air from the throat to the lung. The infection causes a cough that produces phlegm. Acute bronchitis is almost always caused by a virus and usually clears up on its own within a few days. In some cases, acute bronchitis caused by a cold can last for several weeks.

Chronic Bronchitis. Chronic bronchitis causes shortness of breath and is often accompanied by infection, mucus production, and coughing, but it is a long-term and irreversible condition. The same microbes that cause pneumonia can cause chronic bronchitis, and symptoms of the two disorders are often similar. They include fatigue, coughing, fever, and production of sputum. There are significant differences between chronic bronchitis and pneumonia:

Patients with bronchitis are less likely to have wheezing, shortness of breath, chills, very high fevers, and other signs of severe illness.
Those with pneumonia usually cough up heavy sputum, which is also more likely to contain blood.
X-rays of patients with bronchitis do not show fluid or consolidation in the lung.

Asthma. In asthma, the cough is accompanied by wheezing and occurs mostly at night or during activity. Fever is rarely present (unless the patient also has an infection). Asthmatic symptoms from occupational causes can cause persistent coughing, which is usually worse during the work week. Tests -- the methacholine inhalation challenge and pulmonary function studies -- may be effective in diagnosing asthma.

Anthrax. Because of current terrorist concerns, it is important to differentiate between anthrax and community-acquired pneumonia. According to one study, people with inhalation anthrax are more likely to have rapid heart rate and less likely to have headache, nasal symptoms, and muscle aches than those with pneumonia. Blood tests with anthrax also show high hematocrit and low albumin and sodium levels. Certain chest x-ray findings also raise the likelihood of anthrax.

Other Disorders that Affect the Lung. Many conditions mimic pneumonia, particularly in hospitalized patients. They include:

Tuberculosis
Bronchial asthma
Bronchiectasis, an irreversible widening of the airways usually associated with birth defects, chronic sinus or bronchial infection, or blockage
Atelectasis, a collapse of lung tissue
Heart failure. If it affects the left side of the heart, fluid build-up can occur in the lungs and cause persistent cough, shortness of breath, and wheezing.
Severe allergic reactions, such as reactions to drugs
Acute respiratory distress syndrome (ARDS)
Lung cancer
Interstitial pulmonary fibrosis, a non-infectious inflammation of the lung marked by progressive damage and scarring

Ruling Out Causes in Children. Important causes of coughing in children at different ages include:

Asthma
Physical abnormalities in infants under 18 months
Sinusitis in children 18 months to 6 years
Psychologic causes in older children and adolescents

Acute bronchitis is an infection in the passages that carry air from the throat to the lung. In such cases, the airway tubes become inflamed and collect mucus, causing a cough that produces phlegm. In 95% of cases, acute bronchitis is caused by a virus and is spread from person to person through coughing. In some cases, mycoplasma or chlamydia may be responsible.

Symptoms. The cough in acute bronchitis usually lasts for 7 - 10 days. In about half of patients, coughing can last for up to 3 weeks, and 25% of patients continue to cough for more than one month.

Complications. Acute bronchitis is usually temporary. It can last for weeks to months if the airways are not healing properly. Pneumonia should be suspected if coughing is continuous and hacking, if blood appears in the sputum, and if the patient has a high fever and signs of severe illness. These signs include shortness of breath or extreme weakness and fatigue. [See In-Depth Report #94: Colds and the flu. ]

Of particular interest and some concern are the roles of mycoplasma and chlamydia, two of the infectious organisms that cause acute bronchitis. These agents are being investigated for their roles as possible causes of asthma. Chlamydia is also being investigated as a trigger for coronary artery disease.

Treatments.

Bronchodilators. For some patients with acute bronchitis, inhaled medications called bronchodilators may be effective. These drugs relax and open the airways and may relieve symptoms and reduce the duration of the coughing. The most common bronchodilator used for acute bronchitis is albuterol (Proventil, Ventolin). It is called salbutamol outside the US. The drug is a short-acting beta-2 agonist.
Antibiotics. Acute bronchitis almost never warrants antibiotics. (Coughing caused by pneumonia, however, does require antibiotics.) A 5-year study of more than 800 patients found that those with uncomplicated acute bronchitis all recovered within the same time period, regardless of whether or not they received antibiotics. For most patients, coughing lasted an average of 12 days. For a quarter of the patients, coughing lasted 17 days.

Treatment

Patients with pneumonia are generally treated with:

Antibiotics
Respiratory support with oxygen, if needed

Up to 10% of all adult hospitalizations in the U.S. are due to pneumonia. Studies indicate that many patients are hospitalized unnecessarily for pneumonia, and those patients could be released sooner. A number of strategies are being devised to determine when and which patients can be safely discharged. Studies have shown that low-risk patients with mild-to-moderate pneumonia do just as well when treated as outpatients and return to work and normal activities faster than those treated in the hospital.

One approach for determining whether a patient should be hospitalized categorizes patients into 5 classes depending on risk factors for severity, with class 1 being the least severe (having less than a 0.5% risk for death) and class 5 being the most severe (having at least a 10% risk of death).

Ruling out the Least Severe Cases. The procedure for determining the need for hospitalization starts by selecting patients in the lowest risk groups (classes 1 and 2) who can be discharged with outpatient care only. This can often be done with a simple physical examination, which can rule out a severe condition. Patients in low-risk categories have the following characteristics:

Under age 50 and not a patient in a nursing home
No other major illnesses
No serious symptoms such as altered mental state, breathing problems, bluish skin, very low blood pressure, or very high fever

Even these criteria, however, are flexible. Physicians must use their own judgment and take all factors into consideration. As examples, the following young people with signs of pneumonia should be hospitalized, even if they otherwise fit low-risk (class 1) categories:

Any infant under the age of one month
Young adults with alcoholism or severe psychiatric condition
Young adults or children with abnormal heart rhythm
Young adults or children who are vomiting heavily
Children who are dehydrated

Determining The Next Levels of Severity. If a patient is not in a class 1 category or does not appear to need hospitalization, the next step is to determine which of the other 4 higher classes the patient fits into. This step involves assigning points to other findings, including:

Laboratory test results
X-ray findings
Demographics (Is the patient male or female? Does the patient live in a nursing home?)

The points are added and the patients are scored:

Patients who score the lowest are assigned class 2 and 3. They can usually be treated at home or need only to be hospitalized for 24 hours for observation.
Patients with higher scores are placed in classes 4 and 5, and are hospitalized.

Home care may be possible even in severe cases when there is good support and available home nursing services. Often, caregivers can even be trained to administer intravenous antibiotics and chest therapy to patients at home.

Joint guidelines issued in 2007 by the Infectious Disease Society of America and the American Thoracic Society (ITSA/ATS) recommend that mild CAP in otherwise healthy patients be treated with oral macrolide antibiotics (azithromycin, clarithromycin, or erythromycin).

Many patients with heart disease, kidney disease, diabetes, or other comorbid conditions may still be treated as outpatients. However, they should be given a fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin) or a beta-lactam (preferably high-dose amoxicillin or amoxicillin-clavulanate), plus a macrolide, unless they live in an area with high S. pneumoniae resistance to macrolides.

The following tips are also suggested:

Drink plenty of liquids.
Do not suppress a cough. Coughing is an important reflex for clearing the lungs. Some doctors advise taking expectorants, such as guaifenesin (Breonesin, Glycotuss, Glytuss, Hytuss, Naldecon Senior EX, Robitussin) to loosen mucus. However, there is no proof that any of these products make much difference in outcome.
Mild pain can be treated with aspirin (in adults only), acetaminophen (Tylenol), or ibuprofen (Advil, Motrin).
For severe pain, codeine or other stronger pain reliever may be prescribed. It should be noted, however, that codeine and other narcotics suppress coughing, so they should be used with care in pneumonia. Such pain relievers often require monitoring.
A laboratory study reported that aromatic oils containing oregano, thyme, and rosewood destroyed S. pneumoniae. It is not known whether they have any effect on pneumonia in people.
Patients should practice chest therapy.

Treatment. If the pneumonia is severe enough for hospitalization, the standard treatment is intravenous administration of antibiotics for 5 - 8 days. In cases of uncomplicated pneumonia, many patients may require only 2 or 3 days of intravenous antibiotics followed by oral therapy. Antibiotics taken by mouth are prescribed when the patient has improved substantially or leaves the hospital.

ITSA/ATS guidelines recommend patients admitted to the hospital (but not the ICU) be treated with fluoroquinolones or a beta-lactam plus a macrolide (preferably cefotaxime or ceftriaxone and ampicillin).

Duration of Stay. Patients should remain in hospital until all their vital signs are stable. Most patients become stabilized in 3 days. Many experts use 7 variables to measure stability and to determine whether the patient can go home:

Temperature. (Some experts believe that patients can go home when their temperature drops to 101° F. Stricter criteria require that it be at or close to 98.6° F.)
Respiration rate. (Goal is a normal breathing rate, although expert opinion differs on the degree of normality required to be discharged.)
Heart rate. (Goal is 100 beats per minute or less.)
Blood pressure. (Goal is systolic blood pressure of 90 mmHg or greater.)
Oxygenation. (Goal is determined by the physician.)
The ability to eat. (Goal is regular appetite.)
Mental function. (Goal is normal.)

Patients or their families should discuss these criteria with their doctor. In a 2002 study, 42% of patients who had 2 or more signs of instability when they left the hospital were either readmitted or died within 30 days, compared with 10.5% of completely stabilized patients.

Chest therapy using incentive spirometry, rhythmic inhalation and coughing, and chest tapping are all important techniques to loosen the mucus and move it out of the lungs. It should be used both in the hospital and during recovery at home.

Incentive Spirometry. The patient uses an incentive spirometer at regular intervals to improve breathing and loosen sputum. The spirometer is a hand-held clear plastic device that includes a breathing tube and a container with a movable gauge. The patient exhales and then inhales forcefully through the tube, using the pressure of the inhalation to raise the gauge to the highest level possible.

Rhythmic Breathing and Coughing. During recovery, the patient performs rhythmic breathing and coughing every 4 hours:

Before starting the breathing exercise, the patient should tap lightly on the chest to loosen mucus within the lung. If available, a caregiver should also tap on the patient's back.
The patient inhales rhythmically and deeply 3 or 4 times.
The patient then coughs as deeply as possible with the goal of producing sputum.

Medications

Dozens of antibiotics are available for treating pneumonia, but selecting the best drug is sometimes difficult. Patients with pneumonia need an antibiotic that is effective against the organism causing the disease. When the organism is unknown, "empiric therapy" is given, meaning the doctor guesses which antibiotic is likely to work based on factors such as the patients' age, health, and severity of the illness.

In determining the appropriate antibiotic, the physician must first answer a number of questions:

How severe is the pneumonia? Mild-to-moderate cases can be treated at home with oral antibiotics, while severe pneumonia usually requires intravenous antibiotics administered in the hospital.
If the organism causing the pneumonia is not known, was the disorder community- or hospital-acquired? Different organisms are usually involved in each setting, and the physician can use this information to guess the most likely organism causing the pneumonia.
If the organism is known, is it typical or atypical? Community-acquired pneumonias, for example, are usually caused by the typical bacteria Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which have traditionally been treated with penicillin or other standard antibiotics. These antibiotics do not affect atypical organisms, such as legionella, mycoplasma, or chlamydia. These organisms are generally treated with a macrolide or possibly a newer quinolone.
Does the patient have an impaired immune system? Antibiotics used to treat such patients may differ from those used in patients with healthy immune systems.

Once an antibiotic has been chosen, there are still difficulties:

Individuals respond differently to the same antibiotic, depending on age, health, size, and other factors.
Patients can be allergic to certain antibiotics, thus requiring alternatives.
Patients may harbor strains of bacteria that are resistant to certain antibiotics.

For a more detailed discussion of the different types of antibiotics, see the "Antibiotic Classes" section below.

Many cases of community-acquired pneumonia are caused by S. pneumoniae, Gram-positive bacteria that usually respond to antibiotics known as beta-lactams (which include penicillin,) and to macrolides. However, resistant strains of S. pneumoniae are increasingly common. Most resistant strains respond to fluoroquinolines such as levofloxacin (Levaquin), gemifloxacin (Factive) or moxifloxacin (Avelox), or to ketolides (telithromycin).

In addition, other important causes of CAP, particularly in younger people, are atypical bacteria, which respond to macrolides (erythromycin, clarithromycin, or azithromycin), to ketolides, or to newer fluoroquinolones.

Antibiotic treatment for CAP is determined by a number of factors, including the patient's history of antibiotic therapy, co-existing diseases (such as COPD, diabetes, and heart failure), and whether the patient is well enough to be treated at home or requires hospitalization or nursing home care. Treatment options can include a single drug, such as levofloxacin or doxycycline, or combination treatment, such as a macrolide administered with a beta-lactam.

Antibiotics taken by mouth are generally sufficient for patients whose CAP is mild enough to be treated at home. Intravenous antibiotics are required for hospitalized patients with CAP. Antibiotic therapy should be given for a minimum of 5 days -- longer if the patient still has a fever and more than one sign of clinical instability.

Gram-Positive Pneumonia. S. aureus is a common cause of hospital-acquired pneumonia and is a potentially life-threatening infection. Resistance to penicillin is the rule in these cases, but certain specialized penicillins such as nafcillin may be effective. The alternatives to penicillins are first- or second generation cephalosporins. Unfortunately, resistance to these agents is increasing as well. Vancomycin is used for highly resistant bacteria.

Gram-Negative Pneumonia. Patients with hospital-acquired pneumonia are at high risk for infection from Gram-negative organisms such as Pseudomonas aeruginosa and Klebsiella pneumonia, which require aggressive therapy. Powerful antibiotics used against these organisms include the fourth-generation cephalosporins, carbapenems, or ciprofloxacin alone or in combination with an aminoglycoside (entamicin or tobramycin). A pilot study of inhaled (aerosol) tobramycin showed the novel form of this aminoglycoside to be as effective against P. aeruginosa as its intravenous formulation. Multidrug therapy may be necessary, particularly for patients on mechanical ventilators, who are at very high risk for multiple dangerous organisms. A 2006 study of high-dose ampicillin-sulbactam for multidrug-resistant (MDR) Acinetobacter baumannii pneumonia showed the combination to be 66.7 - 77.8% successful in curing critically ill, ventilator-dependent patients of the bacterial infection.

Trimethoprim-sulfamethoxazole is the first choice for both preventing and treating P. Jiroveci (formerly called P. carinii) pneumonia in HIV-positive patients. Clindamycin-primaquine may be used in patients who do not respond to standard therapies.

A study of children with leukemia found atovaquone to be an excellent alternative for preventing P. jiroveci pneumonia in children who cannot tolerate trimethoprim-sulfamethoxazole, the current standard preventing therapy.

Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones).

The most common side effect for nearly all antibiotics is stomach problems.
Antibiotics raise the risk of vaginal infections. Taking acidophilus supplements or eating yogurt with active acidophilius cultures may help restore healthy bacteria that offset the risk for such infections.
Overuse of antibiotics can cause infection with Clostridium difficile, a pathogen responsible for causing severe diarrhea, colitis, and abdominal pain. It can be fatal.
Allergic reactions can occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe -- even life-threatening -- anaphylactic shock.
Certain drugs, including some over-the-counter (OTC) medications, interact with antibiotics. Patients should inform the physician of all medications and OTC preparations they are taking and of any drug allergies they might have.

Beta-Lactams

Beta-lactam antibiotics share common chemical features. They include penicillins, cephalosporins, and some newer similar agents. They interfere with bacterial cell walls.

Penicillins. Penicillin was the first antibiotic. There are many forms to this still-important agent:

Natural penicillins include penicillin G (for intravenous use) and V (for oral use).
Penicillin derivatives called aminopenicillins, particularly amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation), are now the most common penicillins used. Amoxicillin is inexpensive and, at one time, was highly effective against S. pneumoniae. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar and is an alternative to amoxicillin, but requires more doses and has more severe gastrointestinal side effects.
Amoxicillin-clavulanate (Augmentin) is an augmented penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with community-acquired pneumonia caused by bacterial strains that have become resistant to penicillin.
Antistaphylococcal penicillins were developed to treat Staphylococcus aureus. The standard drug was methicillin, but it is no longer used routinely due to very high rates of resistance in hospital-acquired pneumonias. Resistance in community-acquired Staphylococcus aureus is also increasing. Alternatives include vancomycin and linezolid.
Certain penicillins used against Pseudomonas aeruginosa include ticarcillin and piperacillin. Piperacillin is more effective that ticarcillin.

Many people have a history of an allergic reaction to penicillin, but research suggests that the allergy may not recur in a significant number of adults. Skin tests are available to help determine if those with a history of penicillin allergies could use these important antibiotics.

Cephalosporins. Most of these agents are not very effective against bacteria that have developed resistance to penicillin. They are classed according to their generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation includes cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid),
Third generation includes cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria. Cefditoren has also been shown to be 85% effective against Haemophilus influenzae and 90% effective against penicillin-resistant strains of S. pneumoniae.

Other Beta-Lactam Agents. Carbapenems include meropenem (Merrem), biapenem, faropenem, ertapenem (Invanz) and combinations (imipenem/cilastatin [Primaxin]). These agents cover a wide spectrum of bacteria. They are now used for serious hospital-acquired infection and for bacteria that have become resistant to other beta-lactams. Imipenem has serious side effects when used alone, so it is given in combination with cilastatin to offset these adverse effects. The newer agents are less toxic, although they may not be as potent.

Sanfetrinem, a novel beta-lactam antibiotic known as a trinem is proving to be effective against S. pneumoniae,H. influenzae, and M. catarrhalis.

Ceftobiprole is an investigational beta-lactam in phase III clinical trials for methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and other Gram-negative pathogens. Other anti-MRSA beta-lactams in clinical development include CS-023/RO-4908463, a carbapenem, and ceftaroline, a cephalosporin (PPI-0903).

Fluoroquinolones

Fluoroquinolones (quinolones) interfere with the bacteria's genetic material to prevent reproduction.

Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent quinolone against Pseudomonas aeruginosa. It is not very effective for Gram-positive bacteria such as Streptococcus pneumoniae.
"Respiratory" quinolones are currently the most effective drugs available for a wide range of bacteria. Such drugs include levofloxacin (Levaquin), sparfloxacin (Zagam), and gemifloxacin (Factive). Some of the newer fluoroquinolones only need to be taken once a day.
The fourth generation quinolones Moxifloxacin (Avelox) and clinafloxacin, which is still under development, are proving to be effective against anaerobic bacteria.

S. pneumoniae -- strains resistant to the "respiratory" quinolones are uncommon in the U.S., but resistance is dramatically increasing.

Many quinolones cause side effects, including sensitivity to light and neurologic, psychiatric, and heart problems. Pregnant women should not take these agents. The drugs also enhance the potency of oral anti-clotting agents.

Macrolides, Azalides, and Ketolides

Macrolides and azalides also affect the genetics of bacteria. They include:

Erythromycin
Azithromycin (Zithromax, Zmax)
Clarithromycin (Biaxin)
Roxithromycin (Rulid)

These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. They are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these agents. All but erythromycin are effective against H. influenzae. Macrolide-resistance rates doubled between 1995 and 1999 as more and more children were being treated with these antibiotics. Some research suggests these agents may reduce the risk of a first heart attack in some patients by reducing inflammation in the blood vessels.

Extended-release (ER) azithromycin (Zmax) is the first anti-pneumonia antibiotic that can be given in a single dose. It is effective against Gram-positive, Gram-negative, and atypical pathogens. Studies have shown the results to be equal (noninferior) to that acheived with 7 days of levofloxacin or clarithromycin ER in patients wtih CAP. A single-dose antibiotic decreases the likelihood that a patient will discontinue taking the antibiotic early, which rapidly contributes to the development of drug-resistant bacteria.

Ketolides. Ketolides are a new class of antibiotic drugs. They are derived from erythromycin and were developed to combat organisms that have become resistant to macrolides. Telithromycin (Ketek), the first antibiotic in the ketolide class, was approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP).

In February 2007, the FDA withdrew approval of Ketek for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is approved for treatment only of CAP. The drug carries a black box warning noting the potentially serious side effects, including liver failure, vision problems, loss of consciousness, and neuromuscular problems.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. The side effects of tetracyclines include skin reactions to sunlight, burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Some are available in inhaled forms or by applying a solution directly to mucous membranes, skin, or body cavities. They can have very serious side effects, including hearing damage, balance problems, and kidney damage.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against S. pneumoniae and S. aureus, but not against H. influenzae.

Glycopeptides

Glycopeptides (vancomycin, teicoplanin) are used for Staphylococcus aureus infections that have become resistant to standard antibiotics. The drug can be taken by mouth or given intravenously. The latest generation of glycopeptides, a derivative of vancomycin, is called telavancin. Currently in phase III studies of hospital-acquired pneumonia, it looks positive for the treatment of Gram-positive pneumonia.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is less expensive than amoxicillin. It is particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. The drug is no longer effective against certain streptococcal strains. It should not be used in patients whose infections occur after dental work, or in people allergic to sulfa drugs. Allergic reactions can be very serious.

Oxazolidinone

Linezolid (Zyvox) is the first antibacterial drug in a new class of synthetic antibiotics called oxazolidinones. It has been shown to work against certain aerobic Gram-positive bacteria.

Other Agents

Inhaled polymyxin, a drug used in cystic fibrosis patients, is showing efficacy against pneumonia caused by multidrug-resistant Gram-negative bacteria, including pseudomonas and klebsiella.

Prevention of RSV. Two agents have been approved for protecting high-risk infants against RSV pneumonia:

Palivizumab (Synagis) is known as a monoclonal antibody, a genetically engineered antibody that targets the RSV virus. It is given by an injection into the muscle. Early studies of motavizumab, another monoclonal antibody in development, also show potent protection against RSV.
RSV immune globulin (RespiGam) is made up of antibodies to RSV that are obtained from the blood of healthy infants. RespiGam is given as a shot.

Treatment of RSV. Ribavirin is the first treatment approved for RSV pneumonia, although it has only modest benefits. The American Academy of Pediatrics recommends it for children at high risk for serious complications of RSV. In one study, a combination of ribavirin with RSV immune globulin was more effective than either drug used alone.

Drugs called bronchodilators, which open up the airways, are sometimes used to treat RSV infection. However, evidence is conflicting. One study involving albuterol, a common bronchodilator, found that epinephrine may be more effective.

Surgery

Although most patients with pneumonia do not require invasive therapy, it may be necessary in patients with abscesses, empyema, or certain other complications.

Thoracotomy is the standard surgery for pneumonia. It requires general anesthesia and an incision to open the chest and view the lungs. This procedure allows the surgeon to remove dead or damaged lung tissue. In severe cases, the entire lobe of the lung is removed. This is calledalobectomy. Remaining healthy lung tissue re-expands after surgery to make up for tissue that has been removed.

Chest tubes are used to drain infected pleural fluid. Tubes are not typically required for pneumonia or abscesses. The tubes are inserted after the patient is given a local anesthetic. They remain in place for 2 - 4 days, and are removed in one quick movement. This can be very distressing, although some patients experience no discomfort. Complications of chest tubes include infection, accidental injury of the lung, perforation of the diaphragm, and fluid build-up within the lung if the pleural fluid is removed too rapidly. Removing the chest tubes may cause the lung to collapse, requiring the reintroduction of a chest tube to inflate the lung.

Click the icon to see an illustrated series detailing chest tube insertion.

Prevention

The best way to prevent serious respiratory infections such as pneumonia is to avoid those who are sick (if possible), and to practice good hygiene. [See In-Depth Report #94: Colds and influenza.]

Colds and flu are spread primarily from infected persons who cough or sneeze. A very common method for transmitting a cold is by shaking hands. Hands should always be washed before eating and after going outside. Using ordinary soap is sufficient. Alcohol-based gels are also effective for every day use, and may even kill cold viruses. If extreme hygiene is required, alcohol-based rinses are needed.

Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV). Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Bacteria abound in hospitals and long-term care facilities, and are particularly virulent in areas with the sickest patients, such as intensive care units. Health care facilities are revising many of their practices and educating physicians, nurses, and therapists how to reduce the likelihood of transmitting bacteria.

A Swiss study found that coating endotracheal tubes with a solution of silver chloride and silver salts inhibited the growth of bacteria and reduced the transmission of Pseudomonas aeruginosa.
Another more widely adopted method involves the daily use of oral antibiotics to clean the mouths of patients on ventilators. This practice has been shown to lower the incidence of ventilator-associated pneumonia.

Foods Containing Lactobacilli (Good Bacteria). Friendly bacteria inside the intestines may help keep you healthy. Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. One such strain is acidophilus, which is used to make yogurt. According to a Finnish study, children attending day care who drank milk containing the strain lactobacilli GG reduced their risk of respiratory infections by 10 - 20%. More research is needed. (The strain used in the Finnish study was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed when it comes to whether or not vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

A review of more than 134,000 Swiss patients found that use of cholesterol-lowering statin drugs was associated with a significantly lower risk of fatal pneumonia and a somewhat lower risk of less-severe pneumonia.

Breast-feeding. Some evidence suggests that women who breast-feed reduce the risk of respiratory infections in their children.

Low Stress and Active Social Life. Several studies have reported that socially active people with low stress have fewer colds than people who have high stress levels or those who have low stress and few social connections.

Zinc appears to have certain important effects on the immune system, and it may have a direct effect on viruses. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. However, research findings regarding the benefits of zinc have varied. (The differing results may be due to different zinc preparations.)

A nasal gel containomg zinc gluconate has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, patients who took the nasal gel within 14 - 48 hours of getting sick had less severe symptoms and felt better faster than those who took a placebo. The finding supports earlier studies reporting that Zicam shortened the duration of a cold by about two days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges (e.g., Fast-Dry, Galzin) may be more effective and have a better taste than other formulations, such as zinc gluconate (Cold-Eeze, Orazinc). On the other hand, a 2002 study reported that zinc gluconate reduced the duration of colds significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective. The reasons for these conflicting results are not clear.
A small 2001 study on a nasal spray preparation found no benefits. The spray preparation had less zinc than the nasal gel.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds.

Side Effects of Zinc. Side effects include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a physician if any of these symptoms occur.
In rare cases, an allergic response may occur.

Food and Drug Interactions. Zinc may also interact with drugs or other elements.

It may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
Used in high doses for long periods of time, zinc can cause copper deficiencies.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for colds:

Echinacea. The herbal remedy echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. Studies have been mixed on its effectiveness. It is difficult to test, however, since it is available in different species (notably, E. purpurea and E. augustifolia ), and preparations vary from using extracts to dried forms of the root, the herb, or the whole plant. If echinacea is helpful at all, it may be more effective taken before symptoms develop than during the cold or flu. However, evidence suggests that it is not helpful at all. In addition, allergic reactions have been reported. People with autoimmune diseases or who have plant allergies should avoid taking it. There have also been some reports of a reaction called erythema nodosum associated with echinacea. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal cold and allergy medications may contain trace amounts of aristolochic acid, a chemical that is toxic to the kidneys and considered a carcinogen. Products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China having been laced with potent pharmaceuticals such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals.

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are called neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme called neuraminidase, which helps viruses spread (replicate).

Both zanamivir and oseltamivir have the following benefits:

Neuraminidase inhibitors are effective for treating both A and B strains of influenza. M2 inhibitors, which prevent the virus from reproducing, are only effective against type A.
They shorten the duration of the flu by 1 - 3 days.
They may help reduce transmission of the virus, although evidence is needed to confirm these findings.
They may have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. In January 2006, the Centers for Disease Control and Prevention (CDC) released a Heath Alert (the highest level of importance) regarding the use of M2 inhibitors (amantadine and rimantadine) for the prevention or treatment of flu. Due to significant increase in influenza A resistance to this class of antiviral medication, the CDC recommended against its use for the remainder of the 2005 - 2006 flu season.
Oseltamivir has been shown to prevent influenza from progressing to pneumonia in 50% of children who were given the drug within 1 day of being diagnosed with the flu.
They have fewer serious side effects than the M2 inhibitors.
Both have some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over age 13.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, they are much more expensive. They also need to be taken within 2 days of symptoms to be effective. There are also some differences between the two agents that could be significant for some individuals:

Zanamivir (Relenza) is administered as a nasal spray or inhaler. People with asthma or other lung disorders may experience airway spasms and should use this drug with caution. Side effects are minor in most patients. Of concern, however, was a 2001 British study, which found that a majority of elderly patients were not able to properly use the zanamivir (Relenza) inhaler device, rendering the medicine virtually ineffective. The study was small, however, and other reports suggest that zanamivir is sill effective in this older group.
Oseltamivir comes in capsule and liquid form. Side effects are also minor, but about 10 - 15% of patients experience nausea and vomiting. Patients with kidney dysfunction should take lower doses.

To date both M2 inhibitors and oseltamivir have been approved for prevention of influenza.

M2 inhibitors. Amantadine and rimantadine protect against the influenza A infection itself in about half of individuals. Rimantadine is preferred for prevention during outbreaks of influenza A because it has fewer adverse side effects. Unfortunately, a majority of influenza A strains are now resistant to both M2 inhibitors.
Neuraminidase Inhibitors. Both zanamivir (Relenza) and oseltamivir (Tamiflu) help prevent both influenza A and B. Only oseltamivir has been approved for this purpose, however, and only in people over 13. Both appear to be very effective in preventing influenza in people who have been exposed to family members with the flu.

Antiviral drugs are not a substitute for vaccines, but they are extremely important add-on therapy for people in certain high-risk groups. They may also be used:

In combination with the flu vaccine during seasons where there is a poor match between the virus and vaccine.
In high-risk individuals who are vaccinated after the flu season has started. In such cases, it takes about 2 weeks (or longer in children) for the vaccine to take effect. The anti-viral drugs offer protection during that period.
As supplementary protection for vaccinated people in high-risk groups, such as the elderly or people with compromised immune systems.
In people who cannot have vaccinations for whatever reason.
For people who provide care for high-risk individuals.
For high-risk individuals who cannot or will not be vaccinated.

Viral Influenza Vaccines (Flu Shot)

Description of Vaccines. Vaccines against the flu (or a "flu shot") use inactivated (not live) viruses. They are designed to provoke the immune system to attack antigens contained on the surface of the virus. Antigens are foreign molecules that the immune system specifically recognizes and targets for attack.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy them.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines must be redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem because it can infect other species, such as pigs or chickens, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they too vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children who have not developed immunity to the virus will experience severe flu if they are exposed to type B.

A live but weakened intranasal vaccine (FluMist) for healthy people aged 5 - 49 years is approved by the FDA. It is known as a live, attenuated, trivalent, intranasal influenza vaccine (LAIV). The vaccine is engineered to grow only in the cooler temperatures of the nasal passages, not in the warmer lungs and lower airways. It boosts the specific immune factors in the mucous membranes of the nose that fight off the actual viral infections. FluMist is a nasal spray. In one study it protected up to 93% of children against the flu.

Timing and Effectiveness of the Vaccine. Ideally, people should get a flu shot every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the influenza virus usually develop within 2 weeks of vaccination. Immunity peaks within 4 - 6 weeks, then gradually wears off. That is why most people should get a flu shot every year.

In healthy adults, the flu shot reduces the chance of illness by 70 - 90%. The current flu vaccines may be slightly less effective in the elderly and those with certain chronic diseases. Even in people with weak immune systems, however, the vaccine usually protects against serious flu complications, particularly pneumonia. In fact, among the elderly, interesting studies are now suggesting that influenza vaccination may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated.The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children 6 - 23 months of age. The flu shot is not approved for children less than 6 months of age.

In addition, any child over the age of 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell anemia, or immune deficiencies) should also receive a flu shot. Children who are receiving long-term aspirin therapy should also be immunized against the flu, because they are at higher risk for Reye syndrome, a life-threatening disease, if they get the flu.

Children with Asthma. Recent and major studies have found that the flu shot is safe for children with asthma. It is very important for these patients to reduce their risk for respiratory diseases. Unfortunately, 90% of asthma patients remain unvaccinated.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first two groups have the highest need for influenza vaccinations and are given top priority:

All adults age 65 and older. Older adults who receive a flu shot have lower hospitalization rates than those who don't. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from influenza. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. While there have been concerns about the safety of the vaccinations in certain high-risk patients, such as those with HIV or asthma, studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from influenza outweighs any potential adverse effects from the vaccines.
Adults ages 50 - 64 with chronic medical conditions. The US Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 be vaccinated, although this is not recommendation of the CDC.

Other adults who should consider influenza vaccinations include:

People at risk for flu complications who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for flu complications who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester.)
Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.

Side Effects. Possible side effects include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two-thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 - 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include cough, wheezing, tightness in the chest, and sore throat. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last up to 2 days. These symptoms are not the flu itself, but are an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Isolated cases of Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, but it has not been a problem with subsequent vaccines. Guillain-Barre disease can cause paralysis.

The pneumococcal vaccine protects against S. pneumoniae bacteria, the most common cause of respiratory infections. There are two effective vaccines available: One called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults, and another called 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

Click the icon to see an image of pneumococcal pneumonia.

Pneumococcal Vaccine in Young Children. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Evidence suggests that this vaccination, plus the vaccination against Haemophilus influenzae (an important cause of meningitis), has led to 25,000 fewer cases of serious bacterial infections each year.

The pneumococcal vaccine is now recommended by many experts for the following groups:

All children up to age 2. The pneumococcal vaccine (Prevnar or PCV7) has now been added to the Recommended Childhood Immunization Schedule. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Studies are suggesting that it prevents common ear infections as well as serious infections such as pneumonia. In one study, a similar vaccine under investigation protected not only children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
Children up to age 5 who are at risk for pneumonia or complications of influenza, such as those with sickle-cell disease, immune deficiencies, or chronic medical conditions.
Other children aged 2 - 5 who are higher risk for serious pneumococcal infections should be considered for vaccinations. They include African-Americans, Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year. (In one study, the vaccine reduced the number of ear infections episodes by 6%.)

The recommended schedule of immunization for Prevnar (PCV7) is four doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have three doses. Children starting their vaccinations between 12 and 23 months only need 2 doses. Those who are over 2 years old need only 1 dose.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to help reduce the rate of pneumonia in young adults, although not to the degree that it protects young children. Its benefits for the elderly, other than protection against bloodstream infection, are unclear. Still, pneumonia is declining among adults, which may be due to fewer infections transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

All people over age 65. (Anyone vaccinated more than 5 years previously should be revaccinated.) The vaccination is protective against pneumococcal bacteremia (blood infection) in this group, but it does not appear to protect against community-acquired pneumonia itself.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease, chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies, such as HIV, or those undergoing treatments to suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies suggest the vaccine may not be as effective in these patients as it is in those with healthy immune systems. Nevertheless they are at high risk for serious respiratory infections and should be vaccinated.
Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after 6 years.
Patients with problems in the spleen.
Alcoholics (especially those with cirrhosis).
People living in long-term care facilities.
Alaska Natives or Native Americans who may be at increased risk for pneumonia.

Because the vaccine is inactive, it is safe for pregnant women and people with immune deficiencies. In fact, when the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for more than 6 years in most people, although it may wear off faster in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated 6 years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

Side Effects. Pain and redness at the injection site, fever, and joint aches are possible with the pneumococcal vaccine. Children are more likely to have fever side effects within 48 hours if they receive other vaccines at the same time. They are also likely to have fewer side effects after the second dose. In rare cases, such local reactions can be severe. Even if a person is mistakenly re-vaccinated before the effects of the first vaccination have worn off, the risk for severe side effects is very low. Allergic reactions are very rare.

Resources

www.lungusa.org -- American Lung Association
www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov -- Centers for Disease Control and Prevention

References

Alperovich M, Neuman MI, Willett WC, Curhan GC. Fatty acid intake and the risk of community-acquired pneumonia in U.S. women. Nutrition. 2007;23(3):196-202.

Barr CE, Schulman K, Iacuzio D, Bradley JS. Effect of oseltamivir on the risk of pneumonia and use of health care services in chidlren with clinically diagnosed influenza. Curr Med Res Opin. 2007;23(3):523-531.

Bast DJ, Dresser L, Duncan CL, et al. Short-course therapy of gemifloxacin effective against against pneumococcal pneumonia in mice. Chemother. 2006;18(6):634-640.

Betrosian AP, Franzeskaki AF, Xanthaki A, Georgiadis G. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multi-drug resistant Acetinobacter baumannii. Scand J Infect Dis. 2007;39:38043.

Bush K, Heep M, Macielag MJ, Noel GJ. Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demontrate clinical efficacy. Expert Opin Investig Drugs. 2007;16(4):419-429.

Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med.2006;355(25):2619-2630.

Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ. 2007. Mar 26; [Epub ahead of print].

Christ-Crain M, Soltz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia. Am J Respir Crit Care Med. 2006;174:84-93.

Digiandomenico A, Rao J, Harcher K, et al. Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections. Proc Nat Acad SciUSA. 2007;104(11):4624-4629.

Gastmeier P, Sohr D, Geffers C, Behnke M, Ruden H. Risk factors for death due to nosocomial infection in intensive care unit patients: findings from the krankenhaus infektions surveillance system. Infect Control Hosp Epidemiol. 2007;28(4):466-472.

Granizo JJ, Gimenez MJ, Barbarean J, Coronel P, Gimeno M, Aguilar L. The efficacy of cediftoren pivoxil in the treatment of lower respiratory tract infections, with a focus on the per-pathogen bacteriologic response in infections caused by Streptococcus pneumoniae and Haemophilus influenzae: a pooled analysis of seven clinical trials. Clin Ther. 2006;28(12):2061-2069.

Guarner J, Packard MM, Nolte KB, et al. Usefulness of immunohistochemical diagnosis of Streptococcus pneumoniae in formalin-fixed, paraffin-embedded specimens compared with culture and Gram stain techniques. Am J Clin Pathol. 2007;127(4):612-618.

Hallal A, Cohn SM, Namias N, et al. Aerosol tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect (Larchmt ). 2007;8(1):73-82.

Labarere J, Stone RA, Obrosky DS, et al. Comparisons of outcomes for low-risk outpatients and inpatients with pneumonia: a propensity-adjusted analysis. Chest. 2007;131(2):480-488.

Laohavaleeson S, Kuti JL, Nicolau DP. Telavancin, a novel lipoglycopeptide for serious Gram-positive infections. Expert Opin Investig Drugs. 2007;16(3):347-357.

Lawrence SJ, Puzniak LA, Shadel BN, Gillespie KN, Kollef MH, Mundy LM. Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure. Infect Control Hosp Epidemiol. 2007;28(2):123-130.

Lee TA, Weaver FM, Weiss KB. Impact of pneumococcal vaccination on pneumonia rates in patients with COPD and asthma. J Gen Intern Med. 2007;22(1):62-67.

Lodise TP Jr, Pypstra R, Kahn JB. Probability of target attainment for ceftobiprole as derived from a population pharmacokinetic analysis of 150 subjects. Antimicrob Agents Chemother. 2007. Mar 26; [Epub ahead of print].

Madden RM, Pui CH, Hughes WT, Flynn PM, Leung W. Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia. Cancer. 2007. Mar 7; [Epub ahead of print].

Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27-S72.

Mesaros N, Nordmann P, Plesiat P, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect. 2007. Jan 31; [Epub ahead of print].

Muller B, Harbath S, Stolz D, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10.

Nair V, Niederman MS, Masani N, Fishbane S. Hyponatremia in community-acquired pneumonia. Am J Nephrol. 2007;29(2):184-190.

Nisar N, Guleria R, Kuman S, Chand Chawla T, Ranjan Biswas N. Mycoplasma pneumoniae and its role in asthma. Postgrad Med J. 2007;83:100-104.

Oosterhuis-Kafeja F, Beutels P, Van Damme P. Immunogenicity, efficacy, safety and effectiveness of penumococcal conjugate vaccines (1998-2006). Vaccine. 2007;25(12):2194-2212.

Pedro-Botet ML, Sopena N, Garcia-Cruz A, et al. Streptococcus pneumoniae and Legionella pneumophila pneumonia in HIV-infected patients. Scand J Infect Dis. 2007;39(2):122-128.

Pereira GH, Muller PR, Levin AS. Salvage treatment of pneumonia and initial treatment of tracheobronchitis caused by multidrug-resistant Gram-negative bacilli with inhaled polymyxin B. Diagn Microbiol Infect Dis. 2007. Mar 8; [Epub ahead of print].

Ramstedt M, Houriet R, Mossialos D, Haas D, Mathieu HJ. Wet chemical silver treatment of endotracheal tubes to produce antibacterial surfaces. J Biomed Mater Res B Appl Biomater. 2007. Mar 23; [Epub ahead of print].

Sakai F, Tokuda H, Goto H, et al. Computed tomographic features of Legionella pneumophila pneumonia in 28 cases. Comput Assist Tomogr. 2007;31(1):125-131.

Schlienger RG, Fedson DS, Jick SS, Jick H, Meier CR. Statins and the risk of pneumonia: a population-based, nested case-control study. Pharmacotherapy. 2007;27(3):325-332.

Spaude KA, Abrutyn E, Kirchner C, Kim A, Daley J, Fisman DN. Influenza vaccination and risk of mortality among adults hospitalized with community-acquired pneumonia. Arch Intern Med 2007;167(1):53-59.

Swainston HT, Keam SJ. Azithromycin extended-release: a review of its use in acute bacterial sinusitis and community-acquired pneumonia in the U.S. Drugs. 2007;65(5):773-792.

Thorpe C, Edwards L, Snelgrove R, et al. Discovery of a vaccine antigen that protects mice from Chlamydia pneumoniae infection. Vaccine. 2007;25(1):2252-2260.

Tolentino-Delos Reyes AF, Ruppert SD, Shiao SY. Evidence-based practice: use of the ventilator bundle to prevent ventilator-associated pneumonia. Am J Crit Care. 2007;16(1):20-27.

Verhamme KM, DeCoster W, DeRoo L, et al. Pathogens in early-onset and late-onset intensive care unit-acquired pneumonia. Infect Control Hosp Epidemiol. 2007;28(4):389-397.

Viejo Banuelos JL. Respiratory manifestations of avian influenza. Arch Bronchoneumol. 2006;42(Suppl 2):12-18.

Walter U, Knoblich R, Steinhagen C, Donat M, Benecke R, Kloth A. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. J Neurol. 2007. Mar 14; [Epub ahead of print].

Wu H, Pfarr DS, Johnson S, et al. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol. 2007. Feb 20; [Epub ahead of print].

Review Date:
4/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Review provided by VeriMed Health Network.

A.D.A.M. Copyright

adam.com

Benign prostatic hyperplasia

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Symptoms
Causes of Benign Prostatic ...
Causes of Lower Urinary Tra...
Risk Factors
Complications
Diagnostic Tests
Treatment
Lifestyle Changes
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Self-Management for Benign Prostatic Hyperplasia (BPH)

Men who receive training in lifestyle and behavioral approaches may be able to successfully manage BPH without drugs or surgery, suggests a 2007 study in the British Medical Journal. Men in the study were trained to self-manage their lower urinary tract symptoms (LUTS), a condition that often accompanies BPH. Self-management approaches included limiting daily fluid intake, avoiding caffeine and alcohol, and urinating at least once every 3 hours.

Diet and BPH

Eating lots of fruits and vegetables, especially those high in beta-carotene and vitamin C, may help protect against BPH, suggests a 2007 study in the American Journal of Clinical Nutrition. Another study, published in Urology, indicated that high consumption of cereal, bread, eggs, and poultry may increase the risk of BPH.

High Intake of Zinc Increases BPH Risk

High doses of zinc supplements may increase the risk for urinary problems, especially for men, indicates a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc. In general, the upper limit for zinc supplements should not exceed 40 mg/day.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe LUTS, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Botox for BPH?

Botulinum toxin A (Botox) is being investigated as a treatment for BPH. In research presented at the 2007 meeting of the American Urological Association, men who had Botox injected into their prostate glands experienced symptom relief and improved quality of life for up to a year after treatment.

Introduction

Hyperplasia is a general medical term referring to excess cell replication. Benign prostatic hyperplasia (BPH), also called benign prostate hyperplasia, is a noncancerous growth of the prostate gland. It is the most common noncancerous form of cell growth in men and usually begins with microscopic nodules in younger men. BPH, however, is not a precancerous condition. Prostate cancer usually occurs in the outer area of the prostate, called the peripheral zone.

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid that mixes with sperm to make semen. The urethra carries urine from the bladder and sperm from the testes to the penis.

As BPH progresses, overgrowth occurs in the central area of the prostate, called the transition zone, which wraps around the urethra (the tube that carries urine through the penis). This pressure on the urethra can cause lower urinary symptoms that have been the basis for diagnosing BPH. In 2000, an expert committee suggested that the impact of such symptoms on quality of life, including sexual activity, is also important in assessment of the disease.

Click the icon to see an image of BPH.

Description of the Prostate Gland. The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Glandular cells, which produce a milky fluid that liquefies semen.
Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen. Molecules called alpha adrenergic receptors stimulate the muscle cells.
Stromal cells (which form the structure of the prostate).

Click the icon to see an image of the male reproductive anatomy.

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland. The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate also secretes another substance that may have antibacterial properties.
The prostate gland also contains an enzyme called 5 alpha-reductase that converts testosterone to dihydrotestosterone, another male hormone with a major impact on the prostate.

Changes During the Lifespan. The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly. It reaches normal adult size and shape, about that of a walnut, when a man is in his early 20s. The gland generally remains stable until about the mid-40s, when, in most men, the prostate begins to grow again through a process of cell multiplication.

Hormonal changes also occur in the prostate gland. Testosterone levels fall while dihydrotestosterone remain at normal levels.

Symptoms

The symptoms commonly associated with BPH are collectively called lower urinary tract symptoms (LUTS). BPH is not always the cause of these symptoms. An enlarged prostate may be accompanied by few symptoms, while severe LUTS may be present with normal or even small prostates and are most likely due to other conditions. Many experts are now categorizing LUTS as either voiding or storage symptoms to help define the source of the problem.

Voiding symptoms, also referred to as obstructive symptoms, can be caused by an obstruction in the urinary tract. They are often due to BPH. Obstruction is the most serious complication of BPH and requires medical attention. Voiding symptoms include:

Weak or intermittent urinary stream
Straining when urinating
A hesitation before urine flow starts
A sense that the bladder has not emptied completely
Dribbling at the end of urination or leakage afterward
Painful urination
Hematuria (blood in the urine)

Storage symptoms, also referred to as irritative symptoms, include:

An increased frequency of urination, particularly at night
An urgent need to urinate
Bladder pain or irritation when urinating

Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

The process of urination is more complicated than it appears:

It begins when waste fluids flow out of the kidneys into two long tubes called ureters.
The ureters empty into the bladder, which rests on top of the pelvic floor, a muscular structure similar to a sling running between the pubic bone and the base of the spine.
The brain regulates muscles in the urinary tract through a pathway of nerves. As the bladder fills to its capacity of 8 - 16 oz of fluid, the nerves send signals from the bladder to the brain that indicate how full the bladder is.
As the bladder swells, the muscles contract to prevent urination.
At the time of urination, the spinal cord initiates the voiding reflex. The detrusor muscles (which surround the bladder) contract, while the internal sphincter (a strong muscle encircling the neck of the bladder) relaxes.
When the internal sphincter is open, urine flows out of the bladder into the urethra (the tube that carries urine from the bladder out through the penis).

Causes of Benign Prostatic Hyperplasia

The causes of benign prostatic hyperplasia are not fully known. Several theories have been proposed to explain benign cell growth in older men.

Male Hormones. Androgens (male hormones) most likely play a role in prostate growth. The most important androgen is testosterone, which is produced throughout a man's lifetime. The prostate converts testosterone to a more powerful androgen, dihydrotestosterone (DHT). DHT stimulates cell growth in the tissue that lines the prostate gland (the glandular epithelium) and is the major cause of the rapid prostate enlargement that occurs between puberty and young adulthood. DHT is a prime suspect in prostate enlargement in later adulthood.

Estrogen. Some authorities believe that the female hormone estrogen may also play a role in BPH. (Some estrogen is always present in men.) As men age, testosterone levels drop, and the proportion of estrogen increases, possibly triggering prostate growth.

Another theory focuses on cells in a certain section of the gland that may become active late in life, signaling other prostate cells to replicate or causing them to be sensitive to growth-stimulating hormones.

This theory suggests that a process known as apoptosis, in which cells naturally self-destruct, goes awry and results in cell proliferation.

Some experts theorize that the blood vessels in the prostate gland may deteriorate as men age, causing abnormal blood flow and oxygen loss, which would stimulate cell growth. Such a theory is supported by the presence of heart and circulatory problems in many men with BPH.

Causes of Lower Urinary Tract Symptoms

Several structural or medical conditions, either independently or in conjunction with BPH, can cause lower urinary tract symptoms. In addition, prostate growth does not always explain symptoms normally attributed to BPH. Men with large prostates do not always have symptoms, and men with small or normal-sized prostates sometimes have symptoms that are more severe than in those with enlarged glands.

Abnormalities in the urinary tract can cause BPH-like symptoms in men with or without enlarged prostate glands. Such conditions can produce obstruction, impair or weaken the detrusor muscles surrounding the bladder, or cause other damage that impacts the urinary tract. They include:

Muscle contractions in the area where the bladder and urethra meet
A narrowing of the urethra
A weakened bladder
Overactivity in prostate muscles

The male and female urinary tracts are relatively the same except for the length of the urethra.

The process of aging weakens the detrusor muscles that surround the bladder, which causes the bladder to become unstable and lose capacity. Unstable detrusor muscles may also impair bladder storage capacity, which then produce irritative or storage symptoms. Studies also indicate that as men get older they may produce more urine at night, although the total daily output of urine is similar to that in middle-aged men. It is not fully known why this occurs.

Prostatitis is an inflammation of the prostate gland. It can be caused by bacterial infection, which is the easiest cause to diagnose. However, the most common form of prostatitis is nonbacterial.

Bacterial Prostatitis. A prostatitis infection can occur abruptly (acute) or be long-term (chronic). Chronic bacterial prostatitis (CBP) is often subtle and may persist for weeks or months with low-grade symptoms, including an urgent need to urinate, frequent urination, and the need to urinate at night. Pain may occur in the lower back or rectum, or it may develop after ejaculation. Because the prostate isn't swollen, doctors may mistake chronic prostatitis for BPH. A urine culture should always be taken, which, in the case of both acute and chronic bacterial prostatitis, will reveal bacteria and confirm a diagnosis. Antibiotics are required to treat CBP. Fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim, Septra) are particularly effective, but prolonged treatment may be necessary.

Nonbacterial Prostatitis. In nonbacterial prostatitis, inflammation occurs, but no bacteria are present. It is 8 times more common than bacterial prostatitis. The causes of nonbacterial prostatitis have not been determined. In one study, alfuzosin, an alpha-blocker drug that is used for BPH, provided some modest relief in patients with prostatitis and chronic pain. The routine use of drug therapy does not seem to help this condition. More research is needed.

Prostatodynia. Although it is considered a form of prostatitis, prostatodynia is a noninflammatory disorder characterized by prostate pain, but neither inflammation nor bacteria are present. The causes of prostatodynia are unknown.

Congestion of the prostate, sometimes called prostatosis, is a benign condition in which the prostate seems to be swollen by excess fluid. It can cause frequent, slow, or uncomfortable urination, but it responds well to a program of frequent ejaculation and sitz baths.

On occasion, prostate cancer can mimic BPH, since both conditions may cause obstruction of the urethra. Bladder cancer can sometimes cause urinary bleeding, frequency of urination, or a sense of urgency, also symptoms of BPH.

Click the icon to see an image of prostate cancer.

Several other conditions can impair the lower urinary tract, including tumors, reactions to medications, and spinal cord injuries. Diseases that affect the nervous system, such as diabetes, multiple sclerosis, and shingles, can desensitize the nerves so that they fail to sense fullness and do not trigger the contraction of the bladder.

Risk Factors

About 5.5 million American men have benign prostatic hyperplasia (BPH) that could warrant medical attention. Age is the major risk factor. BPH occurs in about 60% of men over 60 years of age and over 80% of men over age 80.

A family history of BPH appears to increase a man's chance of developing the condition. One study reported that men with BPH who had three or more family members with the condition had much larger prostate glands than men with BPH without such a family history.

Some evidence suggests a higher incidence of benign prostatic hyperplasia -- particularly fast-growing BPH -- in men with obesity, heart and circulatory diseases, and type 2 diabetes. Diabetes and hypertension, in any case, worsen urinary tract symptoms in men with BPH. In one study, diabetes adversely affected flow rates, although residual urine volumes were not significantly greater.

Complications

The progression of symptoms in benign prostatic hyperplasia (BPH) is typically very slow, and additional symptoms, when they occur, often come and go. Individual response to these symptoms also varies widely. Some men can tolerate very uncomfortable sensations of abnormal urination, while other men seek relief from mild symptoms. BPH does not appear to impair sexual function. Problems with urination, however, can be very distressing and severely affect quality of life in some cases.

Click the icon to see an animation about BPH.

Men are more apt to tolerate voiding symptoms (intermittent flow, hesitancy before urinating) and seek help for storage symptoms (urgency, frequency, urination at night). Voiding symptoms, however, may indicate an obstruction blocking the bladder, which if extensive can severely reduce urine flow and cause other complications, some serious.

Acute Urinary Retention. Sometimes a man is unaware of an obstruction until he suddenly cannot urinate at all. This condition is called acute urinary retention. It is a dangerous complication that can damage the kidneys and may require emergency surgery. In general, BPH progresses very slowly, and long-term urinary retention is very uncommon. Men with BPH at highest risk for this problem tend to be elderly and to have moderate-to-severe lower voiding symptoms. Taking anti-hypertensive drugs (except for diuretics) or antiarrhythmic drugs may also increase the risk.

Other Complications. Bladder obstruction can also cause bladder stones, blood in the urine, urinary tract infection, and incontinence. It may also increase the risk for chronic kidney disease. Unfortunately, no current tests can accurately predict which men are at higher risk for complications, although men with a weak urine stream and larger prostates are at higher risk for urinary retention.

Click the icon to see an image of prostate cancer.

Debate is ongoing over whether BPH and prostate cancer have any association. Both occur in men in the same age groups, and BPH causes prostate enlargement. Most evidence finds no significantly higher risk for prostate cancer in men with BPH. For one reason, the two conditions develop in different parts of the prostate:

BPH occurs in the inner transition zone, while
Cancer tends to develop in the peripheral outer zone

A 10-year study found no higher risk for prostate cancer in men with BPH. Unsuspected prostate cancer is detected during surgery in about 15% of BPH patients, but the risk of this slow-growing cancer is high in all older men. Some estimates suggest that up to a third of men over age 50 have at least microscopic prostate cancer.

Still, there is some evidence that men with fast-growing BPH may be at higher than average risk for prostate cancer. This prostate condition is also associated with obesity, heart disease, and diabetes. Some experts suspect that insulin resistance may be the common factor in all of these conditions, including prostate cancer.

Diagnostic Tests

An indexing tool called the International Prostate Symptoms Score (IPSS) can help evaluate the key lower urinary tract symptoms. As opposed to laboratory tests or other objective tests, this scoring system measures the patient's own experience. The higher the score, the more severe the conditions. It is useful for many reasons:

The patient's score on this test gives a highly accurate assessment of the effect of lower urinary tract symptoms on the quality of a man's life.
It is a reasonable basis from which the patient and doctor can discuss treatment options.
The index is also often used to gauge treatment outcomes and may be a better indicator of success than objective tests, such as the measurement of the prostate gland or the rate of urine flow.

Limitations. The IPSS is useful only as a measure of symptom severity, and has the following limitations:

Other conditions can produce similar scores, so the test is not used as a diagnostic tool for BPH.
The index does not include other urinary symptoms, such as dribbling and incontinence or sexual health, that are important for quality of life. At the very least, the patient should have a frank discussion with his doctor if such symptoms are present and affect his life.
It also does not reflect regional or ethnic differences that can vary the responses to these symptoms.


Symptoms over past month	Never	Less than 1 time in 5	Less than half the time	About half the time	More than half	Almost always
Sensation that the bladder is not empty after urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to urinate within two hours of a previous urination	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to stop and start again several times while urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Have a weak urinary stream	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to strain to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Number of times during the night awakened by the need to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Circle appropriate number. Totals of 7 or less = mild symptoms; 8-19 = moderate; 20-35 = severe.

Other indexing systems, such as Symptom Problem Index (SPI) and the BPH Impact Index (BII), which gauge different quality-of-life and disease issues, are being used in addition to the IPSS to help assess the patient.

Digital Rectal Exam. The digital rectal exam is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate to estimate its size and to detect nodules or tenderness. The exam is quick and painless, but embarrassing for some, and far from infallible. The test helps rule out prostate cancer or problems with the muscles in the rectum that might be causing symptoms, but it generally underestimates the prostate's size. It is never the sole diagnostic tool for either BPH or prostate cancer.

Other Physical Examinations. The doctor will usually press on and manipulate (palpate) the abdomen and sides to detect signs of kidney or bladder abnormalities. The doctor will also check for signs of anemia or swelling in the legs and arms. Certain procedures that test reflexes, sensations, and motor response may be performed in the lower extremities to rule out possible neurologic causes of bladder dysfunction.

To determine whether the bladder is obstructed, an electronic test called uroflowmetry measures the speed of urine flow. The test cannot determine the cause of obstruction, which can be due not only to BPH but possibly also to problems in the urethra, weak bladder muscles, or other causes.

The patient is instructed not to urinate for several hours before the test and to drink plenty of fluids so he has a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that the patient remains still while urinating to help ensure accuracy, and that he urinates normally and does not exert strain to empty his bladder or attempt to retard his urine flow.
Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend then that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for several reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.
The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

A urinalysis can detect signs of bleeding or infection. A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. Although urinary infection is uncommon in younger men, it occurs more frequently in older men, particularly those with BPH. A urinalysis also helps rule out bladder cancer.

To rule out prostatitis (infection or inflammation of the prostate gland), a simple test called the Pre and Post Massage Test (PPMT) is about 90% accurate. This test requires two cultures and microscopic examinations of urine samples, taken before and after massage of the prostate gland. To massage the prostate the doctor simply inserts a gloved finger into the rectum and presses several times on the prostate. The following results are indicated by findings on cultures after massage:

Category II prostatitis (Chronic bacterial). Bacteria are found on post-massage.
Category IIIA prostatitis (Inflammatory chronic pelvic pain syndrome). Leukocytes or other cells are found that indicate inflammation.
Category IIIB prostatitis (Noninflammatory chronic pelvic pain syndrome). No signs of inflammation or bacteria.

In men with symptoms, blood tests can measure a substance called serum creatinine, which is a marker for kidney trouble. Kidney problems exist in an average of 13.6% of BPH patients. Studies have reported rates as high as 30% and as low as 0.3%.

A PSA test measures the level of prostate-specific antigen (PSA) in the patient's blood. It is the standard screening test for prostate cancer. A PSA is recommended annually for all men over 50 years old and for men over age 40 who are at high risk for prostate cancer.

BPH itself can also raise PSA levels, but the test has generally been optional for men with suspected BPH. One 2000 study indicated that PSA levels may be good predictors of future prostate growth in men with BPH. In the study, men with the lowest PSA level groups (0.2 - 1.3 ng/mL) had prostate growth rates of only 0.7 mL per year while those in the high PSA groups (3.3 - 9.9) had growth rates of 3.3. mL per year. Other research has detected a specific molecular form of PSA, called BPSA because it may be a specific marker for BPH. Such findings could eventually lead to a shift from focusing on symptoms and flow rates for diagnosis to a more specific and possibly preventive approach.

Certain treatments for BPH, including the drug finasteride (Proscar) and the surgical procedure transurethral resection of the prostate (TURP), can reduce PSA levels and possibly mask the existence of prostate cancer.

A more recent test identifies so-called free PSA, which is found in lower levels when prostate cancer is present and in higher levels with benign prostate hyperplasia. This may be more accurate than total PSA, regardless of whether a man is taking finasteride or not.

One of the important tests for urinary incontinence is the postvoid residual urine volume (PVR), the amount of urine left after urination. Normally, about 50 mL or less of urine is left; more than 200 mL is a definite sign of abnormalities. Measurements in between require further tests. The most common method for measuring PVR is with a catheter, a soft tube that is inserted into the urethra within a few minutes of urination. PVR can also be measured using transabdominal ultrasonography.

Ultrasound of the prostate does not require a catheter and gives an accurate picture of the size and shape of the prostate gland. Ultrasound is very beneficial when planning surgery and determining treatment options and gauging their effectiveness. Ultrasound may also be used for detecting kidney damage, tumors, and bladder stones. Ultrasound tests of the prostate generally use one of two methods:

Transrectal ultrasonography (TRUS) uses a rectal probe for assessing the prostate. TRUS is significantly more accurate for determining prostate volume. It can sometimes detect cancer.
Transabdominal ultrasonography uses a device placed over the abdomen. It can give an accurate measure of postvoid residual urine and is less invasive and expensive than TRUS.

Filling cystometry, also called cystometrography, is usually used for patients who cannot urinate and in whom nerve damage or injury of the bladder is suspected. The test is used to determine the absence or presence of a condition called uninhibited detrusor contractions (UDC), which often occurs in men with storage urinary tract symptoms. The detrusor is the group of muscle fibers that cover the outside of the bladder. The test does not add much information to results from less invasive tests and is not used routinely.

A urethrocystoscopy, also called cystourethroscopy, may be performed in men diagnosed with BPH, particularly if they are surgical candidates or if other urinary tract problems are suspected. Such problems include blood in the urine, infection, interstitial cystitis, bladder cancer, or prior surgery or injury. The doctor can determine the presence of a number of structural problems, including enlargement of the prostate, obstruction of the urethra or neck of the bladder, anatomical abnormalities, or the presence of stones.

Procedure. In this procedure, a flexible or rigid fiberoptic tube (an endoscope) is inserted into the urethra to allow doctors to view the lower urinary tract.

Complication. The procedure is not without risks. Complications are uncommon but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

An x-ray called an intravenous excretory urography (IVU) is an invasive test that is used only when complications in the upper urinary tract, particularly in the kidney, are suspected. Alternatively, an abdominal ultrasound plus a normal x-ray may be as useful as IVU for most patients with suspected upper urinary tract problems.

Complications and Side Effects. If there is any danger of kidney failure, the test should not be performed, since it can exacerbate the condition. Severe side effects of the test occur in 0.1% of patients.

Some doctors believe that a number of men may be incorrectly diagnosed with BPH when they have interstitial cystitis (an inflammation of the bladder that may be associated with allergic or autoimmune response). The potassium sensitivity test is sometimes used to diagnose IC. Some experts believe this test missed too many IC patients, although a 2001 study concluded that a combination of potassium sensitivity and urodynamic tests is useful in distinguishing between BPH and interstitial cystitis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also known as active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

The choice between watchful waiting and treatment usually depends on a number of factors, such as urine flow rates, prostate size, and PSA levels. Men with BPH who develop symptoms at around age 50 are more likely to need treatment within their lifetimes than older men. Unfortunately, there is no current way to determine who specifically might be at risk for serious problems and need early treatment.

The development of the International Prostate Symptoms Score (IPSS) has made the evaluation of symptoms somewhat easier. This scoring service serves as a benchmark for determining severity. The decision to treat or not to treat is typically based on the guidelines described below, but the ultimate choice is often guided primarily by a man's perception of his own symptoms.

Mild, or No, Symptoms. Men with mild, or no, symptoms (IPSS scores of 7 or below) usually choose watchful waiting even if their prostates are enlarged. BPH eventually progresses to the point of needing treatment in about 15% of men with mild symptoms who wait.

Moderate Symptoms. The choice is most difficult for men with moderate symptoms (scores between 8 - 19) and may simply depend on a man's ability to tolerate them. Some studies have reported that up to 40% of men with moderate symptoms eventually seek treatment, and a quarter require surgery. In a small percentage of patients, symptoms improve.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-Severe-Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery is also typically a reasonable option when BPH is clearly related to one or more of the following conditions:

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

The greatest improvements resulting from surgery are usually increased urinary flow and reduced urine retention. In one study, men who chose surgery reported more worry and depression before the procedure, but afterward they had less depression and anxiety than those who had chosen medication. Often, however, the benefits of surgery are not permanent.

Lifestyle Changes

Certain lifestyle changes can help relieve symptoms and are particularly important for men who choose to avoid surgery or drug therapy. A 2007 study found that men who were educated on behavioral and lifestyle management of BPH were less likely to require surgery or drug therapy. Men should limit daily fluid intake to less than 2,000 mL (about 2 quarts) and, in particular, avoid alcohol and caffeine intake. Men should try to urinate at least once every 3 hours. “Double-voiding” may also be helpful -- after urinating, wait and try to urinate again. Cold weather and immobility may increase the risk for urine retention. Keeping warm and exercising may be useful. Stress reduction techniques may also help.

Studies have suggested the following:

Avoid fluids after your evening meal.
Coffee has been associated with a higher risk for BPH. Some evidence suggests that drinking green tea, however, may benefit the prostate.
Moderate alcohol consumption may be protective. (Heavy alcohol consumption, however, may increase the risk for lower urinary tract symptoms, and, in any case, is harmful.)
Genistein, a chemical found in soy, reduced the growth of BPH tissue in the laboratory. Although Asians have a low incidence of BPH and prostate cancer and also have diets rich in soy, it is not yet known if eating soy products will reduce the risk of BPH or improve any symptoms.
Fruits and vegetables rich in beta-carotene and vitamin C may help protect against BPH. Conversely, high consumption of cereals, bread, eggs, and poultry may increase the risk for BPH.
High doses of zinc supplements may increase the risk of BPH.

Decongestants and Antihistamines. Men with BPH should avoid, if possible, the many medications for colds and allergies that contain decongestants, such as pseudoephedrine (Sudafed). Such drugs, known as adrenergics, can exacerbate urinary symptoms by preventing muscles in the prostate and bladder neck from relaxing to allow urine to flow freely. Antihistamines, such as diphenhydramine (Benadryl), can also slow urine flow in some men with BPH.

Diuretics. Men who are taking diuretics, which increase urination, may want to talk to their doctor about reducing the dosage or switching to another drug. These are important drugs for many people with high blood pressure, with a proven track record for saving lives. No one should go off these medications without medical supervision.

Other Drugs. Other drugs that may worsen symptoms are certain antidepressants and drugs used to treat spasticity.

Some, but not all, research suggests that moderate exercise can reduce urinary tract problems associated with BPH.

Kegel (pelvic floor muscle) exercises, first developed to help women with childbirth, can also help men prevent urine leakage. They strengthen the pelvic floor muscles that both support the bladder and close the sphincter.

Performing the Exercises. Since the muscle is internal and sometimes hard to isolate, doctors often recommend practicing while urinating:

The patient is asked to contract the muscle until the flow of urine is slowed or stopped. He attempts to hold each contraction for 20 seconds.
He then releases the contraction.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Medications

The two primary drug classes used for BPH are:

Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Uroxatral). Alpha-blockers help relieve BPH symptoms, but they do not reduce the size of the prostate. The can help improve urine flow and reduce risk of bladder obstruction. They are often the first choice, especially for men with smaller prostates.
5-alpha-reductase inhibitors. Finasteride (Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs are better for men with significantly enlarged prostates. In addition to relieving symptoms, they increase urinary flow and may even help shrink the prostate. However, patients may have to take these drugs for up to 6 - 12 months to achieve full benefits.

Because these two types of drugs work in different ways, researchers are investigating combinations of the two for selected patients. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, published in 2003, reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. The combination treatment may work best for high-risk patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.

General Guidelines for Alpha-Blockers.Alpha-adrenergic antagonists, commonly called alpha-blockers, were originally used to treat high blood pressure. They are prescribed for BPH to relax smooth muscles in the prostate. The muscle cells in the prostate are stimulated by molecules called alpha adrenergic receptors. This can cause lower urinary tract symptoms.

Drugs that block these receptors relax the muscles in and around the prostate, increase urinary flow and improve symptoms, sometimes significantly. Improvement occurs within days to weeks. Because these drugs are short-acting, symptoms return very quickly once a man stops taking the medication. They neither affect PSA levels nor shrink the size of the prostate. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct. Investigators are studying whether these drugs may help prevent the development of prostate cancer.

Alpha-blockers are prescribed for most men with BPH symptoms whose prostates are not significantly enlarged. Even men with moderately enlarged prostates might try alpha-blockers before more intense treatments because these drugs work fairly quickly, have no effect on sexual drive, and are the least expensive treatment for BPH. Some experts now recommend alpha-blockers as first-line treatment for patients with moderate-to-severe symptoms.

These drugs are generally referred to as either nonselective or selective alpha-blockers. Drugs in both categories are similar in effectiveness for reducing symptoms and improving urinary flow. There are some differences, however. Patients should discuss the appropriate alpha-blocker for their individual condition with their doctors.

Nonselective Alpha-Blockers. Nonselective alpha-blockers (also referred to as alpha-specific antagonists) include terazosin (Hytrin), doxazosin (Cardura), and alfuzosin (Uroxatral). Alfuzosin is the newest drug and can be taken once a day. They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These drugs work within a few weeks, are inexpensive, and produce long-lasting benefits. Alfuzosin begins to improve urine flow within hours.

Side Effects. Nonselective alpha-blockers can reduce blood pressure, which may cause dizziness, headache, rapid heartbeat, and fatigue. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects. (Alfuzosin's extended-release formulation appears to pose a much lower risk than the other drugs.) Alpha-blockers can also cause headache, sore throat, and weakness. Nasal congestion occurs in about 2% of cases. Men may also experience a decreased ejaculate. (Impotence is not a common side effect of alpha-blockers, as it is with finasteride.)
Long-Term Effects. These drugs slow the progression of BPH but do not help prevent urinary retention.
Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems and especially those with hypertension, high cholesterol levels, or both. However, alpha-blockers can exacerbate heart failure symptoms in men with this condition.

Selective Alpha-Blockers. Tamsulosin (Flomax) is the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved for treatment of BPH. Naftopidil is a similar drug under investigation. These drugs target receptors that affect only the smooth muscles of the prostate. Tamsulosin seems to work as well as nonselective alpha-blockers. It is not clear if it reduces long-term complications of BPH.

Selective alpha-blockers appear to be very safe, even for years. Side effects are minimal. Most common ones include nasal congestion. The risk for low blood pressure and dizziness is lower than with the nonselective alpha-blockers. They may pose a higher risk for problems in ejaculation than nonselective alpha-blockers, but do not appear to cause impotence or reduce sexual drive as finasteride does. These drugs can interact with certain medications, including calcium channel blockers (particularly verapamil).

Researchers are studying the combination of tamsulosin and tolteridine (Detrol). Tolteridine is an anticholinerogic medication used to treat urinary incontinence. Tamsulosin targets the prostate while tamsulosin helps inhibit involuntary contractions of the bladder. A 2006 study in the Journal of the American Medical Association found that a combination of tolterodine and tamsulosin worked better than either drug alone for men with lower urinary tract symptoms (LUTS), including overactive bladder.

Specific Benefits. The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Finasteride (Proscar) and dutasteride (Avodart), known as a 5-alpha-reductase inhibitors, block this enzyme and thus reduce dihydrotestosterone in the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but it can be helpful. Follow-up studies have reported that the drug is safe and effective over the long-term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing symptoms in men with large prostates. (Men with larger prostates and high PSA values may also benefit from combination therapy of finasteride and the alpha-blocker doxazosin.) In such cases, studies on finasteride also suggest it reduces the risk of acute urinary retention and the need for surgery. It also helps control bleeding in the urine that is related to BPH. A side benefit of finasteride is reduction of hair loss related to male hormones and in some cases hair growth in men with mild-to-moderate male pattern baldness.

Dutasteride (Avodart) is a newer drug that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. A 4-year study reported sustained improvements in urinary symptoms and prostate volume reduction. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride. Researchers are also investigating whether dutasteride can help prevent the development of prostate cancer.

Candidates. Some experts recommend 5-alpha-reductase inhibitors for men of any age who have all three of the following conditions:

Very large prostates (40 mL or larger)
Low urinary flow rates
Prostate enlargement related primarily to hormone-stimulated overgrowth of glandular tissue

Finasteride is also proving to be helpful for patients who have hematuria (blood in the urine) related to BPH.

Dosing. Finasteride and dutasteride are taken once a day. It may take as long as 6 - 12 months for a man to notice a change in symptoms.

Effects on PSA. Finasteride and dutasteride decrease prostate-specific antigen (PSA) levels, which are measured for screening prostate cancer. Lower PSA levels may mask the presence of the cancer. Doctors calculate PSA levels in men taking these drugs by doubling the PSA values. Studies confirm that this doubling equation helps provide an accurate measurement.

Side Effects. Finasteride has been associated with:

Sexual dysfunction, including low sexual drive and impotence, in about 6 - 19% of patients. Such problems appear to occur only during the first year of use and diminish over time in most men who take finasteride.
Reductions in energy.
Breast tenderness.
Possible weight loss in some men.

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but they can reduce sexual drive and are much more likely to cause impotence. Flutamide is an anti-androgen that may be an alternative to surgery in certain patients with BPH who have physical or mental disorders.

Popular herbal treatments for BPH include:

Saw Palmetto. Saw palmetto is one of the most popular herbal remedies for BPH. It comes from the berry of the plant Serenoa repens. A major 2006 study in the New England Journal of Medicine found that saw palmetto had no benefit for treating BPH. The study enrolled 225 men with moderate-to-severe BPH. The men received either placebo or 160 mg of saw palmetto twice daily. After 1 year, there were no differences in symptom improvement between the placebo and saw palmetto groups.

Beta-Sitosterol. Beta-sitosterol preparations come from South African star grass, Hypoxis rooperi, and other plant species. Some studies have shown beta-sitosterol to improve urinary symptoms and flow. They may increase the risk for impotence, however.

Pygeum Africanum. The herbal Pygeum africanum is an extract from the bark of an African plum tree. In an analysis of 18 trials, the herb provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were short in length, however.

Cernilton. Cernilton is prepared from rye grass pollen. Studies have been limited, but some suggest it may help improve symptoms, including nighttime urinary problems. Other studies have found no benefit.

Other popular herbs include nettle root extract (Urtica dioica) and pumpkin seed oil (Cucurbita peponis). There is no scientific evidence that any of these remedies help treat BPH.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including BPH. Preliminary studies are showing promising results in improving urine flow and reducing urinary retention. Research, presented at the 2007 annual meeting of the American Urological Association, reported that men with BPH who had Botox injected directly into their prostate gland had symptom relief and improved quality of life for up to a year after treatment.

PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors can treat erectile dysfunction (ED). They include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Because lower urinary tract symptoms (LUTS) and ED often occur together in older men, researchers are investigating whether PDE5 inhibitors may help improve BPH symptoms. Research presented at the 2006 American Urological Association meeting suggested that sildenafil improves urinary symptoms in men who have both ED and LUTS. Another study indicated that a combination of sildenafil and the alpha-blocker alfusozin (Uroxatral) worked better for treating LUTS and ED than either drug alone.

Other Areas of Investigation. Researchers are looking at several different drugs for future BPH therapies. Most drugs being researched for BPH, such as arylpiperazines, target molecules in the prostate that may help suppress cell growth. Some efforts are focusing on drugs that affect the central nervous system or nerve fibers in the bladder and urethra to reduce urinary tract symptoms.

Other Treatments

Several surgical approaches are now available for treating BPH.

Invasive Procedures. The most effective surgical procedures, transurethral resection of the prostate (TURP) and open prostatectomy, are also the most invasive. They carry the highest risks for significant complications, including impotence and incontinence. Greater surgeon experience with TURP, however, has reduced complications and hospital stays. Because it is more effective than less invasive procedures, TURP remains the procedure of choice for many doctors. When considering invasive surgery, the patient should be sure his surgeon performs at least 50 of these procedures each year. The complication rates of the surgeon should be no higher than 1% for incontinence and 4% for impotence. Transurethral incision of the prostate (TUIP) is an alternative to TURP for men with smaller prostate glands.

Less Invasive Procedures. Minimally invasive procedures use some form of heat to destroy excess prostate tissue. The heat may be delivered by:

Radio frequency: transurethral needle ablation (TUNA)
Microwave: transurethral microwave thermotherapy (TUMT)
Electrical current: transurethral electrovaporization (TUVP)
Ultrasound: high-intensity focus ultrasound (HIFU)
Hot water: water-induced thermotherapy (WIT)
Laser: interstitial laser coagulation (ILC) and holmium laser enucleation of the prostate (HoLEP)

One laser procedure, photoselective vaporization (PVP), is typically done as an outpatient procedure. The patient goes home on the same day. However, there is no long-term data for this procedure.

None of the other minimally invasive procedures have proven superior to TURP to date, but they vary by complications. Some may be appropriate for certain patients, such as the following:

Younger men. (Many of the less invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk for TURP is not high.)
Debilitated elderly patients
Patients with severe medical conditions, including uncontrolled diabetes, cirrhosis, active alcoholism, psychosis, and serious lung, kidney, or heart disease
Men who are on blood-thinning drugs

Transurethral resection of the prostate (TURP) involves surgical removal of the inner portion of the prostate where BPH develops. It is the most common surgical procedure for BPH, although the number of procedures has dropped significantly over the past decades because of the availability of effective medications.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

Procedure. TURP usually requires a 1 - 3 day hospital stay. The surgeon inserts a fiberoptic endoscope, which is a thin tube, into the urethra. No incision is needed. The surgeon uses the endoscope to cut away excess prostatic tissue, and water solutions are used to flush away the excised matter.

Risk of Water Intoxication. If the fluids used during TURP build up, water intoxication can develop, which can be serious. This condition is referred to as the transurethral resection (TUR) syndrome and includes abdominal cramps, nausea, vomiting, lethargy, and dizziness. Patients who undergo TURP for longer than 1 hour and those with larger prostate glands seem to be at greater risk for this complication. An irrigation system that uses a mechanical valve may reduce the risk.

Postoperative Catheterization. A Foley catheter generally remains in place for 3 - 5 days after surgery to allow urination. This device is a tube inserted through the opening of the penis to drain the urine into a bag. The catheter can cause bladder spasms that can be painful, but they eventually cease.

Some studies have suggested that in selected patients the catheter can safely be removed within 24 - 48 hours, allowing patients to go home earlier. Early catheter removal is not appropriate for patients with intense urine retention, signs of infection, bleeding, or other complications.

Recuperation. Urine flow is stronger almost immediately after most TURP procedures. After the catheter is removed, patients often experience some pain or sense of urgency as the urine passes over the surgical wound. These sensations gradually subside. Complete healing takes about 2 months. The following are some tips for hastening recovery and avoiding complications:

During recuperation at home, the patient should avoid driving, operating heavy equipment, lifting, sudden movements, and straining the muscles in the lower tracts, such as during a bowel movement.
Drinking 8 glasses of water a day after surgery is important to flush the bladder and help healing.
Foods that help prevent constipation, such as fruits and vegetables, are important. A laxative may be needed if constipation occurs.
Kegel exercises can help reduce incontinence. Performing three to four sets of 30 contractions daily is recommended. In one study, improvement due to Kegel exercises was significant within a month after surgery.

Postoperative Complications. Complications after TURP can be high, depending on the skill of the surgeon and other factors, but their incidence has decreased considerably over the past decades because of advances in surgical technique and more widespread expertise.

Bleeding. Some blood and small clots appear in the urine after surgery, and if the bladder is flushed with water, the urine may turn red. Such bleeding is normal. Occasionally, the scab on the surgical wound loosens, causing a sudden appearance of blood in the urine that can be alarming. Usually this stops after a rest, but the patient should notify the doctor at once if he is concerned about abnormal bleeding or clotting or has unusual feelings of discomfort. Rarely, hemorrhage may occur, requiring a transfusion.
Infection. Urinary tract infections occur in 5 - 10% of TURP patients. The risk is particularly high if a catheter is required. Antibiotics may be given to prevent infections, although often a doctor will choose to monitor a patient and administer antibiotics only if an infection is evident.
Incontinence. Temporary stress incontinence (urine leakage after activities such as sneezing, coughing, or lifting) occurs in most surgical patients. Urge incontinence is the involuntary loss of urine following an uncontrollable urge to urinate. About 2.1% of TURP patients experience stress incontinence, and nearly 2% have urge incontinence. In general, however, there is no significant risk for incontinence. [See In-Depth Report #50: Urinary incontinence.]
Sexual Dysfunction. Some men report certain sexual differences after the procedure, particularly low volume of fluid at ejaculation. Studies, however, do not report any significant risk for impotence. For most men who report this complication, sexual function returns in short order. (In some men it may take up to a year for complete recovery.) If potency was diminished before the operation, the procedure will not restore it. [See In-Depth Report #15: Erectile dysfunction.]
Retrograde Ejaculation and Low Semen. Many TURP patients report a lower volume of semen after the procedure. Between 66 - 75% of these patients experience retrograde ejaculation, in which semen is forced backward into the bladder instead of forward out of the urethra during orgasm. During most invasive procedures, the muscle that blocks off the bladder may be cut in order to widen the outlet. In such cases, the semen flows back through the wider opening rather than out of the penis. This condition can impair fertility and is of particular concern in younger men. Neither retrograde ejaculation nor the operation itself typically affects orgasm, although it takes many men some time to emotionally adjust to these conditions.
Low PSA Levels. PSA levels may be lowered after TURP, which might cause a doctor to miss a diagnosis of prostate cancer during routine screening.

Repeat Operations. Symptomatic relief is usually maintained for at least 15 years after surgery, but BPH may return or patients may need a second operation for other reasons. Up to 10% of TURP patients require a repeat operation within 10 years. In some cases, scarring in the bladder severe enough to cause obstruction occurs within a year of the procedure and may require transurethral incision (TUIP). More often, the urethra is scarred and narrows, but usually this condition can be corrected by a simple stretching procedure performed in the doctor's office.

In transurethral incision of the prostate (TUIP), the surgeon makes only one or two incisions in the prostate, causing the bladder neck and the prostate to spring open and reduce pressure on the urethra.

Candidates. TUIP is generally used only for men with minimally enlarged prostates (30 grams or less) who have obstruction of the neck of the bladder. Some experts believe TUIP is not performed enough and could benefit many patients, particularly those with severe medical conditions who are not good candidates for more invasive surgeries and men who want to lessen their risk for sterility.

Postoperative Complications. TUIP is less invasive than TURP, has a lower rate of the same complications, particularly retrograde ejaculation, and usually does not require a hospital stay. More studies are still needed, however, to determine whether they are comparative in long-term effectiveness.

In open prostatectomy, the enlarged prostate is removed through an open incision in the abdomen using standard surgical techniques. This is major surgery and requires a hospital stay of several days. Open prostatectomy is used only for severe cases, about 2 - 3% of BPH patients, when the prostate is severely enlarged, the bladder is damaged, or other serious problems exist. Up to 14% of patients require a second operation because of scarring. In making a decision about prostatectomy, it is essential that the doctor explains the consequences of a diminished sexual capacity that occurs after this procedure. When the situation of the patient does not constitute an emergency, prostatectomy should be considered a last resort if the patient still has an active sex life. Other complications are similar to those of TURP.

Click the icon to see an illustrated series detailing prostatectomy surgery.

Procedures. Laser technology is used for removal of prostate tissue. Laser procedures can usually be done as an outpatient procedure, and there is little risk for bleeding. Different procedures are used to provide different degrees of thermal cell destruction that range from coagulation to complete vaporization:

Interstitial laser coagulation (ILC) involves insertion of a scope through the prostate. A fiberoptic tip is threaded through the scope to direct a diode laser emission to targeted areas of the prostate. The coagulated tissue is naturally absorbed back into the body. Approved in 1998, this procedure is being performed less frequently as urologists turn to newer laser technologies (HoLEP, PVP).
Holmium laser enucleation of the prostate (HoLEP) is a newer technique that can actually cut and vaporize the tissue. Vaporization is effective immediately and also may pose lower risks for prolonged urinary retention and reoperation rates than coagulation. The Holmium laser is showing very good results with low complication rates in small studies, and trials have reported benefits lasting more than four years. (HoLEP is actually proving to be better than TURP or even open prostatectomy for removing very large prostate glands.)
Photoselective vaporization of the prostate (PVP) uses a potassium-titanyl-phosphate (KTP) laser ("green-light" laser) to vaporize prostate tissue. The procedure is virtually bloodless and may be a better option for men taking anticoagulant medication. Results from several recent clinical trials report sustained improvement up to 1 year after the procedure. More studies are needed to confirm long-term efficacy.

Complications. The laser procedure carries a lower risk for incontinence than TURP or TUVP, another minimally invasive procedure. Studies have been mixed on whether laser surgery poses any risk for sexual dysfunction. In one study, TURP had a lower risk for sexual dysfunction, although the risk from either procedure was very low and it wasn't clear that lasers had even been responsible for this complication. After laser procedures, and especially after coagulation, the prostate often temporarily enlarged and caused obstruction and irritation. Sometimes these symptoms were severe. Most men require a temporary catheter to drain urine after laser procedures. Newer laser procedures may significantly reduce these adverse effects.

Transurethral Microwave Thermotherapy (TUMT). Transurethral microwave thermotherapy (TUMT) delivers heat using microwave pulses to destroy prostate tissue. Studies have found that between 60 - 80% of men respond favorably to the treatment and the benefits seem to last. A 2001 study reported that it remained effective for at least 18 months and was superior over the long-term to the alpha-blocker drug terazosin. Improvement is not as complete as with TURP, but TUMT has fewer complications.

Candidates. TUMT may be beneficial for men with larger prostates and moderate to severe bladder obstruction, including those who require indwelling catheters. A 2000 study, for example, concluded that is was a safe and effective therapy for treatment of urinary retention. In general, the procedure should not be performed on men who have pacemakers, defibrillators, or any metal implants. One possible exception, the Targis System, was approved for use for patients with hip or penile implants that are located at least 1.5 inches from the urethra. Men who have had previous radiation therapy to the pelvic area are at higher risk for injuries from this procedure.
Procedure. A microwave antenna is inserted through the urethra with ultrasound used to position it accurately. The antenna is enclosed in a cooling tube to protect the lining of the urethra. Computer-generated microwaves pulse through the antenna to heat and destroy prostate tissue. When the temperature becomes too high, the computer shuts down the heat and resumes treatment when a safe level has been reached. The procedure takes 30 minutes to 2 hours, and the patient can go home immediately afterward. About 30% of patients experience some pain during the procedure. The patient should report any pain that appears to be unusually severe, however, since this could indicate improper application.
Complications. Swelling in the urinary tract often occurs later, which prevents urination and requires the use of a temporary catheter for about 3 days until the swelling subsides. There have also been reports of serious injuries to the penis and urethra from overheating due to improper application. It is important to note that TUMT does not significantly affect sexuality or cause incontinence or retrograde ejaculation, which are risks with some other prostate procedures.

Transurethral Needle Ablation. Transurethral needle ablation (TUNA) is a simple, safe, and relatively inexpensive procedure using needles to deliver high-frequency radio waves that heat and destroy prostate tissue. The procedure usually requires only a local anesthetic. One study reported that improvement was maintained in most patients after 2 years, although older men (over 70) had slightly worse symptoms and quality-of-life scores. Although small clinical studies have reported that TUNA is as effective as TURP, some experts believe that in actual medical practice TURP is still more effective.

Some studies have reported urinary retention, blood in the urine, retrograde ejaculation, and painful urination after the procedure, although in general TUNA has few or none of TURP's severe side effects. TUNA poses a very low to no risk for incontinence and impotence, and may be a good option for younger men.

Transurethral Electrovaporization. Transurethral electrovaporization (TUVP) uses high voltage electrical current delivered through a resectoscope to combine vaporization of prostate tissue and coagulation that seals the blood and lymph vessels around the area. Deprived of blood, the excess tissue dies and is sloughed off over time. Patients who have TUVP may be able to have their catheter removed within hours after the procedure compared to normal removal time of 3 - 5 days after TURP. A 5-year study reported that it was as effective as TURP over the long-term and had a similar complication rate.

Ultrasound. High-intensity focus ultrasound (HIFU) is a heat procedure under investigation that uses ultrasound to destroy specific prostate tissue. The principles are similar to transurethral microwave thermotherapy, but ultrasound techniques may destroy excess tissue without damaging other parts of the urethra.

Water-Induced Thermotherapy. A device called Thermoflex, which circulates heated water through a catheter to destroy prostatic tissue, has been approved for treating BPH. Another technique uses a balloon filled with hot water to destroy tissue around the urethra. Water-induced thermotherapy (WIT) does not require anesthesia and can be completed during a single outpatient visit.

Prostatic stents used for BPH are flexible mesh tubes that are inserted into the urethra. They are made of special alloys that do not cause reactions in the body. Typically, the insertion procedure takes only 15 minutes and requires only regional anesthetic and mild sedation. It usually requires minimal recuperation and no overnight hospital stay. Unfortunately, long-term studies are reporting high rates of dissatisfaction. Between 8 - 37% of the stents need to be removed later because of poor placement or complications, including irritation when urinating, urinary tract infections, and treatment failure. At this point stents seem to be best suited for high-risk surgical patients and those with a limited life expectancy. Stents composed of new materials and properties may increase their role.

Resources

www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.urologyhealth.org -- American Urological Association

References

Bravi F, Bosetti C, Dal Maso L, Talamini R, Montella M, Negri E, et al. Food groups and risk of benign prostatic hyperplasia. Urology. 2006 Jan;67(1):73-9.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Rohrmann S, Giovannucci E, Willett WC, Platz EA. Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am. J. Clin. Nutr. 2007 Feb;85(2):523-9.

van der Meulen J, Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, et al. Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ. 2007 Jan 6;334(7583):25. Epub 2006 Nov 21.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Exercise

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Recommended Exercise Method...
Exercise's Effects on the H...
Exercise's Effects on Diabe...
Exercise's Effects on Bones...
Exercise's Effects on the L...
Exercise's Effects on Weigh...
Exercise's Effects on Other...
Complications
Motivation
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Chronic Conditions and Exercise:

A new study found that aerobic and resistance training significantly reduced fatigue in men undergoing radiation treatments for prostate cancer. Fatigue is a common side effect of such treatments.
Doctors at the Mayo Clinic found that exercise improves the physical and emotional well-being of patients with Alzheimer's disease. The patients exercised for as little as 60 minutes each week. Doctors noted improvements in areas ranging from depression to wandering.

Exercise and Smoking:

A 2007 review of existing studies found that moderate exercise, for as little as 5 minutes, can help combat the nicotine withdrawal symptoms people experience when they try to stop smoking.

Exercise and Aging:

A 2006 report found that older and elderly adults who exercised twice a week for 4 months significantly increased their body strength, flexibility, balance, and agility. The average age of the study participants was 83.5.

Before and After Exercising:

You should do warm-up exercises for 5 - 10 minutes at the beginning of an exercise session. Low-level aerobic exercise is the best warm-up.
To cool down, you should walk slowly until your heart rate is 10 - 15 beats above your resting heart rate. Stopping too suddenly may sharply reduce blood pressure or cause muscle cramping.
You must be careful when stretching during your warm-up to avoid injuring cold muscles.

Definitions:

Aerobic exercise: Aerobic exercise forces the heart and lungs to work harder for longer periods. It builds endurance, improves blood flow throughout the body, and increases the levels of "good" cholesterol.
Resistance Training: Resistance training works muscles against a force (usually weights). It burns fat and builds muscle.

Introduction

Everyone's goal of living a long and healthy life should include a healthy diet, regular exercise, and maintaining normal weight. The combination of inactivity and eating the wrong foods is the second most common preventable cause of death in the United States (smoking is the first).

Most research on the benefits of exercise focuses on heart protection. Studies clearly show that exercise helps the heart. In addition, new studies are reporting that even people at higher risk for heart disease may lower their risk of dying from it if they exercise.

Evidence suggests that our genes evolved to favor exercise. In other words, during prehistoric times, if a person couldn't move quickly and wasn't strong, he or she died. Those who were fit survived to reproduce and pass on these "fitter" genes. Some researchers believe that with our current inactive lifestyle, these genes produce a number of bad effects, which can lead to many chronic illnesses.

The benefits of exercise include:

Improved oxygen delivery throughout the body
Improved metabolic processes - the way the body breaks down and builds necessary substances
Improved strength and endurance
Decreased body fat
Improved movement of joints and muscles
Improved sense of well-being

In addition, exercise can help change other dangerous lifestyle habits. A 2007 review of existing studies found that moderate exercise, for as little as 5 minutes at a time, can help combat the nicotine withdrawal symptoms people experience when they try to stop smoking.

No one is too young or too old to exercise. The United States Surgeon General recommends at least 30 minutes of moderate exercise, such as brisk walking, nearly every day. However, vigorous exercise carries risks that people should discuss with a doctor. You should always check with your doctor before starting a new exercise program, especially if you have any of the following risk factors:

History of smoking
Obesity
Family history of a long-term disease
A symptom you haven’t told your doctor about
Chest pain
Shortness of breath
Heart palpitations
Blood clots
Infections
Fever
Unexplained weight loss
Foot or ankle sores that won’t heal
Joint swelling
Pain or trouble walking after a fall
Eye injury or eye surgery
Hernia
Hip surgery

Fifty percent of all people who begin a vigorous training program drop out within a year. The key to reaching and maintaining physical fitness is to find activities that are exciting, challenging, and satisfying.

Recommended Exercise Methods

A few simple rules are helpful as you develop your own routine.

Don't eat for 2 hours before vigorous exercise.
Drink plenty of fluids before, during, and after a workout.
Adjust your activity level according to the weather, and reduce it when you are fatigued or ill.
When exercising, listen to the body's warning symptoms, and consult a doctor if exercise causes chest pain, irregular heartbeat, undue fatigue, nausea, unexpected breathlessness, or light-headedness.

Heart rate is the standard guide for determining aerobic exercise intensity. It can be determined by counting one's own pulse or with the use of a heart rate monitor. To feel your own pulse, press the first two fingers of one hand gently down on the inside of the wrist or under the jaw on the right or left side of the front of the neck. You should feel a faint pounding as blood passes through the artery. Each pounding is a beat.

Click the icon to see how to take a radial pulse

Click the icon to see how to take a carotid pulse.

There are different types of heart rates.

Resting heart rate. The average heart rate for a person at rest is 60 - 80 beats per minute. It is usually lower for people who are physically fit, and often rises as you get older. You can determine your resting heart rate by counting how many times your heart beats in one minute. The best time to do this is in the morning after a good night’s sleep before you get out of bed.

Maximum heart rate. To determine your own maximum heart rate per minute subtract your age from 220. For example, if you are 45, you would calculate your maximum heart rate as follows: 220 - 45= 175.

Target heart rate. Your target rate is 50 - 75% of your maximum heart rate. You should measure your pulse off and on while your exercise to make sure you stay within this range. After about 6 months of regular exercise, you may be able to increase your target heart rate to 85% (but only if you can comfortably do so).

Certain heart medications may lower your maximum and target heart rates. Always check with your doctor before starting an exercise program.

Note: Swimmers should use a heart rate target of 75% of the maximum and then subtract 12 beats per minute. The reason for this is that swimming will not raise the heart rate quite as much as other sports because of the so-called "diving reflex," which causes the heart to slow down automatically when the body is immersed in water.


Age	Low	High
	(50% max.)	(75% max.)
20	100	150
30	95	142
40	90	135
50	85	127
60	80	120
Source: American Heart Association

VO2 Max. Serious exercisers may use a VO2 max calculation, which measures the amount of oxygen consumed during intensive, all-out exercise. The most accurate testing method uses computers, but anyone can estimate V02 without instrumentation (with an accuracy of about 95%):

After running at top pace for 15 minutes, round off the distance run to the nearest 25 meters.
Divide that number by 15.
Subtract 133.
Multiply the total by 0.172, then add 33.3.

Olympic and professional athletes train for VO2 max levels above 80. But for the average person interested in fitness, a VO2 max equaling between 50 and 80 is considered an excellent score for overall fitness.

Click the icon to see an image on exercise and heart rate.

Warming up and cooling down are important parts of every exercise routine. They help the body make the transition from rest to activity and back again, and can help prevent soreness or injury, especially in older people.

Warm-up exercises should be practiced for 5 - 10 minutes at the beginning of an exercise session. Older people need a longer period to warm up their muscles. Low-level aerobic exercise such as brisk walking, swinging the arms, or jogging in place, is the best approach.
To cool down, you should walk slowly until the heart rate is 10 - 15 beats above your resting heart rate. Stopping too suddenly can sharply reduce blood pressure, and is dangerous for older people. It may also cause muscle cramping.
Stretching may be appropriate for the cooling down period, but it must be done carefully for warming up because it can injure cold muscles. (There is no clear evidence, however, that stretching reduces muscle injuries.)

Warming up before exercise and cooling down after is just as important as the exercise itself. By properly warming up the muscles and joints with low-level aerobic movement for 5 - 10 minutes, one may avoid injury and build endurance over time. Cooling down after exercise by walking slowly, then stretching muscles, may also prevent strains and blood pressure fluctuation.

For most people, exercise may be divided into three general categories:

Aerobic or endurance
Strength or resistance
Flexibility

A balanced program should include all three. Speed training is also a major category, but generally only competitive athletes practice it.

Benefits of Aerobic Exercise. Regular aerobic exercise provides the following benefits:

Builds endurance
Keeps the heart pumping at a steady and high rate for a long time
Boosts HDL ("good") cholesterol levels
Helps control blood pressure
Strengthens the bones in the spine
Helps maintain normal weight
Improves one's sense of well-being

Types of Aerobic Exercise. Aerobic exercise is usually categorized as high or low impact. Examples of each include the following:

Low- to moderate-impact exercises: Walking, swimming, stair climbing, step classes, rowing, and cross-country skiing. Nearly anyone in reasonable health can engage in some low- to moderate-impact exercise. Brisk walking burns as many calories as jogging for the same distance and poses less risk for injury to muscle and bone.
High-impact exercises: Running, dance exercise, tennis, racquetball, squash. High-impact exercises should be performed no more than every other day, and less often for those who are overweight, elderly, out of condition, or have an injury or other medical problem that would rule out high-impact.

Click the icon to see an image of aerobic exercise.

Aerobic Regimens. As little as one hour a week of aerobic exercises is helpful, but 3 - 4 hours per week are best. Some research indicates that simply walking briskly for 3 or more hours a week reduces the risk for coronary heart disease by 65%. In general, the following guidelines are useful for most individuals:

For most healthy young adults, the best approach is a mix of low- and higher-impact exercise. Two weekly workouts will maintain fitness, but three to five sessions a week are better.
People who are out of shape or elderly should start aerobic training gradually. For example, they may start with 5 - 10 minutes of low-impact aerobic activity every other day and build toward a goal of 30 minutes per day, three to seven times a week. (For heart protection, frequency of exercises may be more important than duration.)
Swimming is an ideal exercise for many elderly and certain people with physical limitations, including pregnant women, individuals with muscle, joint, or bone problems, and those who suffer from exercise-induced asthma.
People who seek to lose weight should aim for six to seven low-impact workouts a week.

One way of gauging the optimal intensity of exercise is to aim for a "talking pace," which is enough to work up a sweat and still be able to converse with a friend without gasping for breath. As fitness increases, the "talking pace" will become faster and faster.

Shoes. All that's really necessary for a workout is a good pair of shoes that are made well and fit well. They should be broken in, but not worn down. They should support the ankle and provide cushioning for impact sports such as running or aerobic dancing. Airing out the shoes and feet after exercising reduces chances for skin conditions such as athlete's foot.

Clothing. Comfort and safety are the key words for workout clothing. For outdoor nighttime exercise, a reflective vest and light-colored clothing must be worn. Bikers, roller bladers, and equestrians should always wear safety devices such as helmets, wrist guards, and knee and elbow pads. Goggles are mandatory for indoor racquet sports. For vigorous athletic activities, such as football, ankle braces may be more effective than tape in preventing ankle injuries.

Aerobic-Exercise Equipment. Home aerobic exercise machines can be adapted to any fitness level and used day or night. Before investing in any exercise machine, however, it is wise to first test it at a gym. In addition, initial supervised training when using these machines can reduce the risk of injury that might occur with self-instruction.

Very inexpensive exercise machines tend to be flimsy and hard to adjust, but many sturdy machines are available at moderate prices. The higher-end models may utilize computers to record calories burned, speed, and mileage. While their readouts may provide motivation and gauge the intensity of a workout, however, they are not always accurate.

The following are a few observations on specific equipment:

A good floor mat is important to provide cushioning for all home exercises.
A simple jump rope improves aerobic endurance for people who are able to perform high-impact exercise. Jumping rope should be done on a floor mat plus a surface that has some give to avoid joint injury.
For burning calories, the treadmill has been ranked best, followed by stair climbers, the rowing machine, cross-country ski machine, and stationary bicycle. (Elliptical trainers, however, may be even better than treadmills for increasing heart rate, calorie expenditure, and oxygen consumption.)
Stationary bikes condition leg muscles and are fairly economical and easy to use safely. The pedals should turn smoothly, the seat height should adjust easily, and the bike's computer should be able to adjust intensity.
Stair machines also condition leg muscles. They offer very intense, low-impact workouts and may be as effective as running with less chance of injury.
Rowing and cross-country ski machines exercise both the upper and lower body.


Aerobic dancing	Sufficient cushioning to absorb shock and pressure that are many times greater than ordinary walking. Arches that maintain side-to-side stability. Thick upper leather support. Toe-box. Orthotics may be required for people with ankles that over-turn inward or outward. Soles should allow for twisting and turning.
Cycling	Rigid support across the arch to prevent collapse during pedaling. Heel lift. Cross-training or combination hiking/cycling shoes may be sufficient for casual bikers. Toe clips or specially designed shoe cleats for serious cyclers. In some cases, orthotics may be needed to control arch and heel and balance forefoot.
Running	Sufficient cushioning to absorb shock and pressure. Fully bendable at the ball of the foot. Sufficient traction on sole to prevent slipping. Consider insoles or orthotics with arch support for problem feet.
Tennis	Allow side-to-side sliding. Low-traction soles. Snug fitting heels with cushioning. Padded toe box with adequate depth. Soft-support arch.
Walking	Lightweight. Breathable upper material (leather or mesh). Wide enough to accommodate ball of the foot. Firm padded heel counter that does not bite into heel or touch ankle bone. Low heel close to ground for stability. Good arch support. Front provides support and flexibility.

Benefits of Strength Exercise. While aerobic exercise increases endurance and helps the heart, it does not build upper body strength or tone muscles. Strength-training exercises provide the following benefits:

Build muscle strength while burning fat
Help maintain bone density
Improve digestion

It is also associated with a lower risk for heart disease, possibly because it lowers LDL (the so-called "bad") cholesterol levels.

Click the icon to see an image of cholesterol.

Strength exercise is beneficial for everyone, even people in their 90s. It is the only form of exercise that can slow and even reverse the decline in muscle mass, bone density, and strength that occurs with aging. Please note: People at risk for cardiovascular disease should not perform strength exercises without checking with a doctor.

Types of Muscle Contractions. There are three types of muscle contractions involved in strength training:

Isometric contractions do not change the length of the muscle. An example is pushing against a wall.
Concentric contractions shorten muscles. An example is the "up" phase of a bicep curl.
Eccentric contractions lengthen muscles. An example is the "down" phase as weights are lowered.

Click the icon to see an image of isometric exercise.

Strength-Training Regimens. Strength training involves intense and short-duration activities. For beginners, adding 10 - 20 minutes of modest strength training two to three times a week may be appropriate. The following are some guidelines for starting a strength regimen:

The sequence of a strength training session should begin with training large muscles and multiple joints at higher intensity and end with small muscle and single joint exercises at lower intensities.
Both shortening and lengthening muscle actions should be performed. Emphasizing the movements that lengthen muscles is of increasing interest. This approach involves slowing and increasing the duration of these "down" movements. It appears to significantly increase blood flow, and some evidence suggests it may achieve stronger muscles more quickly. It may also improve heart function compared to standard movements. Exercises that lengthen muscles may be particularly beneficial for older people and some people with chronic health problems. This type of training increases the risk for muscle soreness and injury, however, and this approach is still controversial.
Strength training involves moving specific muscles in the same pattern against a resisting force (such as a weight) for a preset number of times. This is called a repetition. Students should first choose a weight that is about half of what would require a maximum effort in one repetition. In other words, if it would take maximum effort to do a single repetition with a 10-pound dumbbell, the person would start with a five-pound dumbbell. In the beginning, most people can start with one set of 8 - 15 repetitions per muscle group with low weights. As individuals are able to perform one or two repetitions over their routine, weights can be increased by 2 - 10%.
Breathe slowly and rhythmically. Exhale as the movement begins. Inhale when returning to the starting point.
The first half of each repetition typically lasts 2 - 3 seconds. The return to the original position lasts 4 seconds.
An alternative technique called "super slow" training stretches out one repetition to a 14-second count. This method places far more stress on the muscle group, so fewer repetitions are needed. A full week of recovery is required before repeating this workout. The goal is to initiate changes in the muscles so that the body continues to burn calories after the exercise. Some people report dramatic results from this approach, but scientific proof of these claims is not available. It is a very tedious workout, and people have a hard time sticking with it. People with high blood pressure should not use this approach.
Joints should be moved rhythmically through their full range of motion during a repetition. Do not lock up the joint while exercising it.
For maximum benefit, one should allow 48 hours between workouts for full muscle recovery.

Click the icon to see the proper way to breathe during exercise.

Strength-Training Equipment. Unlike aerobic exercise, strength training almost always requires some equipment. Strength-training equipment does not, however, have to cost anything.

Any heavy object that can be held in the hand, such as a plastic bottle filled with sand or water, can serve as a weight.
Dumbbells (1 - 10 pounds) and resistance bands are inexpensive, portable, and effective.
Wearable weights help strengthen and tone the upper body.
Ankle weights strengthen and tone muscles in the lower body. Wearable ankle weights should not be worn during high-impact aerobics or jumping.
Hand grips strengthen arms and are good for relieving tension.
A pull-up bar can be mounted in a doorway for chin-ups and pull-ups.

More elaborate and expensive home equipment for working body muscles is also available, costing from $100 to over $1,000. No one should purchase or use strength-training equipment without instruction from a professional.

Benefits of Flexibility Training. Flexibility training uses stretching exercises. Many stretching exercises are particularly beneficial for the back. In general, flexibility training provides the following benefits:

Prevents cramps, stiffness, and injuries
Improves joint and muscle movement (improved range of motion)

Certain flexibility practices, such as yoga and tai chi, also involve meditation and breathing techniques that reduce stress. Such practices appear to have many health and mental benefits. They may be very suitable and highly beneficial for older people, and for patients with certain chronic diseases.

Click the icon to see an image of flexibility exercise.

Flexibility Training Regiments. Doctors recommend performing stretching exercises for 10 to 12 minutes at least three times a week. The following are some general guidelines:

When stretching, exhale and extend the muscles to the point of tension, not pain, and hold for 20 - 60 seconds. (Beginners may need to start with a 5- to 10-second stretch.)
Breathe evenly and constantly while holding the stretch.
Inhale when returning to a relaxed position. Holding your breath defeats the purpose; it causes muscle contraction and raises blood pressure.
When doing stretches that involve the back, relax the spine to keep the lower back flush with the mat, and to work only the muscles required for changing position (often these are only the abdominal muscles).

Studies continue to show that it is never too late to start exercising. A report published in the February 2006 Journal of Aging and Health found that elderly adults who exercised twice a week for four months significantly increased their body strength, flexibility, balance, and agility. The exercise program included walking and lifting weights. The average age of the study participants was 83.5. The study adds further evidence that even small improvements in physical fitness and activity can prolong life and independent living.

Still, about half of Americans over 60 describe themselves as sedentary (inactive). According to a 2004 report by the Centers for Disease Control and Prevention, approximately 12% of people aged 65 - 75 years and 10% of people aged 75 years or older meet current recommendations for strength training.

The following tips for exercising may be helpful:

Any older person should have a complete physical and medical examination, as well as professional instruction, before starting an exercise program.
Start low and go slow. For sedentary, older people, one or more of the following programs may be helpful and safe: Low-impact aerobics, gait (step) training, balance exercises, tai chi, self-paced walking, and lower legs resistance training, using elastic tubing or ankle weights. Even in the nursing home, programs aimed at improving strength, balance, gait, and flexibility have significant benefits.
Strength training assumes even more importance as one ages, because after age 30 everyone undergoes a slow process of muscular erosion. The effect can be reduced or even reversed by adding resistance training to an exercise program. As little as one day a week of resistance training improves overall strength and agility. Strength training also improves heart and blood vessel health.
Power training, which aims for the fastest rate at which a muscle or muscle group can perform work, may be particularly helpful for older women in strengthening muscles and preventing falls.
Flexibility exercises promote healthy muscle growth and help reduce the stiffness and loss of balance that accompanies aging.
Chair exercises may be performed by people who are unable to walk.
Older women are at risk for incontinence accidents during exercise. This can be reduced or prevented by performing Kegel exercises, limiting fluids (without risking dehydration), going to the bathroom frequently, and using leakage prevention pads or insertable devices.

Exercise's Effects on the Heart

Inactivity is one of the major risk factors for heart disease. However, exercise helps improve heart health, and can even reverse some heart disease risk factors.

Like all muscles, the heart becomes stronger as a result of exercise, so it can pump more blood through the body with every beat and continue working at maximum level, if need be, with less strain. The resting heart rate of those who exercise is also slower, because less effort is needed to pump blood.

A person who exercises often and vigorously has the lowest risk for heart disease, but any amount of exercise is beneficial. Studies consistently find that light-to-moderate exercise is even beneficial in people with existing heart disease. Note, however, that anyone with heart disease should seek medical advice before beginning a workout program.

The heart is a large muscular organ that pumps blood throughout the body. Valves inside the heart open and close. This controls how much blood enters or leaves the heart.

Exercise has a number of effects that benefit the heart and circulation (blood flow throughout the body). These benefits include improving cholesterol and fat levels, reducing inflammation in the arteries, assisting weight loss programs, and helping to keep blood vessels flexible and open. Studies continue to show that physical activity and avoiding high-fat foods are the two most successful means of reaching and maintaining heart-healthy levels of fitness and weight.

The American Heart Association recommends that individuals perform moderately-intense exercise for at least 30 minutes on most days of the week. This recommendation supports similar exercise guidelines issued by the Centers for Disease Control and Prevention, and the American College of Sports Medicine.

Coronary Artery Disease. People who maintain an active lifestyle have a 45% lower risk of developing heart disease than do sedentary people. Experts have been attempting to define how much exercise is needed to produce heart benefits. In 2002, a well-conducted study on overweight adults confirmed previous research that reported beneficial changes in cholesterol and lipid levels, including lower LDL levels (bad cholesterol), even when people performed low amounts of moderate- or high-intensity exercise such as walking or jogging 12 miles a week. However, more intense exercise is required to significantly change cholesterol levels, notably increasing HDL (good cholesterol). An example of this kind of program would be jogging about 20 miles a week. Such benefits in the study occurred even with very modest weight loss, suggesting that overweight people who have trouble losing pounds can still achieve considerable heart benefits by exercising.

Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise, which can be particularly helpful for older people.

Resistance (weight) training has also been associated with heart protection. It may offer a complementary benefit to aerobics by reducing LDL levels. Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Effects of Exercise on Blood Pressure. Regular exercise helps keep arteries elastic (flexible), even in older people. This, in turn, ensures good blood flow and normal blood pressure. Sedentary people have a 35% greater risk of developing high blood pressure than athletes do.

Click the icon to see the risks associated with untreated hypertension.

It should be noted that high-intensity exercise may not lower blood pressure as effectively as moderate-intensity exercise. In one study, moderate exercise (jogging 2 miles a day) controlled high blood pressure so well that more than half the patients who had been taking drugs for the condition were able to discontinue their medication. However, a small study published in 2005 suggests that moderate exercise does not have a significant impact on systolic blood pressure (the top number) in older adults. While those who exercised did have notable drops in both the top and lower (diastolic) blood pressure levels, the only statistically significant change was the decrease in the lower number.

Experts recommend at least 30 minutes of exercise on most -- if not all -- days. Studies show that yoga and tai chi, an ancient Chinese exercise involving slow, relaxing movements, may lower blood pressure almost as well as moderate-intensity aerobic exercises.

Click the icon to see an image of someone practicing yoga.

Anyone with existing high blood pressure should discuss an exercise program with their doctor. Before starting to exercise, people with moderate-to-severe high blood pressure should lower their pressure, and be able to control it with medications. Everyone, and especially people with high blood pressure, should breathe as normally as possible through each exercise. Holding the breath increases blood pressure.

Effects of Exercise on Heart Failure. Traditionally, heart failure patients have been discouraged from exercising. Now, exercise performed under medical supervision is proving to be helpful for select patients with stable heart failure.

Studies continue to report benefits from exercise training. In one study, heart failure patients as old as 91 years old increased their oxygen use significantly, after 6 months of supervised treadmill and stationary bicycle exercises.
Progressive resistance training may be particularly useful for heart failure patients, since it strengthens muscles, which commonly weaken in this disorder. Even simply performing daily handgrip exercises can improve blood flow through the arteries.

Experts warn, however, that exercise is not appropriate for all heart failure patients.

All stroke survivors should have a pre-exercise evaluation done by their doctor before starting an exercise program.

The effects of exercise on stroke are less established than those on heart disease, but most studies show benefits. The following are some examples:

According to one major analysis, men cut their risk for stroke in half if their exercise program was roughly equivalent to about an hour of brisk daily walking 5 days a week. In the same study, exercise that involved recreation was more protective against stroke than exercise routines consisting simply of walking or climbing.
A 2000 study of women also found substantial protection from stroke in brisk walking or striding (rather than casual walking).

Anyone with heart disease or risk factors for developing heart disease or stroke should seek medical advice before beginning a workout program. Patients with heart disease can nearly always exercise safely as long as they work out under medical supervision. Still, it is often difficult for a doctor to predict health problems that might arise as the result of an exercise program. At-risk individuals should be very aware of any symptoms warning of harmful complications while they exercise.

Some experts believe that anyone over 40 years old, whether or not they are at risk for heart disease, should have a complete physical examination before starting or intensifying an exercise program. Some doctors use a questionnaire for people over 40 to help determine whether they require such an examination. The questions they use are as follows:

Has any doctor previously recommended medically supervised activity because of a heart condition?
Is chest pain brought on by physical activity?
Has chest pain occurred during the previous month?
Does the person faint or fall over from dizziness?
Is bone or joint pain intensified by exercise?
Has medication been prescribed for hypertension (high blood pressure) or heart problems?
Is the person aware of or has a doctor suggested any physical reason for not exercising without medical supervision?

Those who answer "yes" to any of the above questions should have a complete medical examination before developing an exercise program.

Stress Test. A stress test helps determine the risk for a heart problem resulting from exercise. Anyone with a heart condition or history of heart disease should have a stress test before starting an exercise program. Experts currently also recommend this test before a vigorous exercise program for older persons who are sedentary, even in the absence of known or suspected heart disease. The test is expensive, however, and some experts believe that it may not be necessary for many older people with no evident health problems or risk factors.

A small percentage of heart attacks occur after heavy physical work.

High-Risk Individuals. In general, the following people should avoid intense exercise or start it only with careful monitoring:

People who have certain medical conditions: These conditions include uncontrolled diabetes, uncontrolled seizures, uncontrolled high blood pressure, a heart attack within the previous 6 months, heart failure, unstable angina, significant aortic valve disease, or aortic aneurysm.
People with moderate-to-severe hypertension: Experts generally recommend that moderate or severe high blood pressure (systolic blood pressure over 160 mm Hg or diastolic (bottom number) pressure over 100 mm Hg) should be brought to lower levels before a person starts a vigorous exercise program.
Sedentary people should be cautious. One major study found that sedentary people who throw themselves into a grueling workout significantly increase their risk of heart attack.
Episodes of exercise-related sudden death in young people are rare but of great concern. Some are preceded by fainting, which is due to a sudden and severe drop in blood pressure. It should be noted that fainting is relatively common in athletes, and is dangerous only in people with existing heart conditions. Young people with genetic or congenital (present at birth) heart disorders should avoid intensive competitive sports.
Anabolic steroids or products containing ephedra have been associated with cases of stroke, heart attack, and even death.

The risk for heart attack from exercise should be kept in perspective, however. Some form of exercise, carefully personalized, has benefits for most of the individuals mentioned above. In many cases, particularly when the only risk factors are a sedentary lifestyle and older age, exercise can often be increased over time until it is intense.

Hazardous Activities for High-Risk Individuals. The following activities may pose particular dangers for high-risk individuals:

Intense workouts (snow shoveling, slow jogging, speed walking, tennis, heavy lifting, heavy gardening) may be particularly hazardous for people with risk factors for heart disease, especially older people. They tend to stress the heart, raise blood pressure for a brief period, and may cause spasms in the arteries leading to the heart. (See image: Coronary Artery Spasm)
Some studies suggest that competitive sports, which couple intense activity with aggressive emotions, are more likely to trigger a heart attack than other forms of exercise.

Listening for Warning Signs. It should be noted that according to one study, at least 40% of young men who die suddenly during a workout have previously experienced, and ignored, warning signs of heart disease. In addition to avoiding risky activities, the best preventive tactic is simply to listen to the body and seek medical help at the first sign of symptoms during or following exercise. These symptoms include the following:

Irregular heartbeat
Shortness of breath
Chest pain

Click the icon to see an image of a coronary artery spasm.

Click the icon to see an image of stable angina.

Exercise's Effects on Diabetes

Moderate aerobic exercise can lower your risk for type 2 diabetes. An important study found that adults who worked out 2 and 1/2 hours a week cut their risk by 58%.

Exercise has positive benefits for those who have diabetes. It can lower blood sugar, improve insulin sensitivity, and strengthen the heart. Strength training, which increases muscle and reduces fat, may be particularly helpful for people with diabetes, but more evidence is needed to confirm this theory. One study reported that yoga helped patients with type 2 diabetes reduce their need for oral medications.

In 2005, researchers found that people with type 2 diabetes who walked a minimum of 3 miles every day were in better health, and had lower medical expenses, after 2 years of such exercise. Those who remained sedentary for that time period experienced a decline in their overall health and higher health care-related expenses. Study participants who worked out for an average of 38 minutes per day lowered their blood pressure, cholesterol ,and A1C levels (glucose concentration over time). These participants also had lower heart disease risk, even if they didn't lose weight. The increase in the study participants' activity equaled about 2,200 extra steps a day. The findings were reported in the journal Diabetes Care.

An earlier study found that healthy lifestyle changes may work better than the prescription medication metformin (Glucophage), when it comes to preventing metabolic syndrome. Metabolic syndrome is a combination of risk factors including abdominal obesity, insulin resistance, high triglycerides, and hypertension.

The following are precautions for all people with diabetes, whether type 1 or 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before starting a demanding exercise program. For best and fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctor. For people who have been sedentary, or have other medical problems, lower-intensity exercises are recommended, using programs the patients designed with their doctors.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy (a common diabetic complication). High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before starting a workout program.

Glucose levels swing dramatically during exercise. People with diabetes should monitor their levels carefully before, during, and after workouts.
Patients should probably avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
To avoid hypoglycemia (low blood sugar), people with diabetes should inject insulin in sites away from the muscles they use the most during exercise.
People with diabetes should drink plenty of fluids. Before exercising, they should avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses, or take in more carbohydrates, prior to exercise. However, they may need to take an extra dose of insulin after exercise. Stress hormones released during exercise may increase blood glucose level (in people without diabetes, insulin is released to control this increase). People with diabetes must regularly test their blood sugar, and take any medications as instructed by their doctor.

A person with diabetes must regularly check their blood sugar (glucose) level.

Exercise's Effects on Bones and Muscles

Exercise is critical for strong muscles and bones. Muscle strength declines as people age, but studies report that when people exercise they are stronger and leaner than others in their age group.

Exercise helps kids lower their risk of chronic pain in the future. Research has shown that it helps them prevent back and neck pain. The more flexible men are as teenagers, the lower their risk of neck tension in the future, according to a study published in the February 2006 British Journal of Sports Medicine. The same report found that women who had the greatest endurance strength as teenagers had a lower risk of tension neck than those with lower teenager endurance strength. However, men with the greatest endurance strength had higher rates of knee injuries later on.

Joints are complex structures. They are designed to bear weight and move the body. Above the knee is the femur (thigh bone). Below the knee is the tibia (shin bone) and fibula. The kneecap is also called the patella. It rides on top of the lower portion of the femur and the top portion of the tibia. The muscles and ligaments connect these bones and the space between them is cushioned by fluid-filled capsules (synovia) and cartilage. When you exercise, the muscles pull on the bones, strengthening them. The range of motion of a joint represents how far it can be flexed (bent) and extended (stretched).

Joints require motion to stay healthy. Long periods of inactivity cause the arthritic joint to stiffen and the adjoining tissue to weaken. A moderate exercise program that includes low-impact aerobics, power, and strength training has benefits for osteoarthritic patients, even if exercise does not slow down the disease progression. Many patients who start an exercise program report less disability and pain. They are also better able to perform daily chores, and remain independent longer than their inactive peers. Older patients and those with medical problems should always check with their doctor before starting an exercise program.

Click the icon to see an image of osteoporosis.

The following are useful exercises for osteoarthritis patients:

Strengthening exercises builds muscle strength. Some experts encourage patients to emphasize strengthening leg muscles as a first treatment step, even before using pain relievers. They fear that patients who rely on painkilling drugs may overuse knees, which do not have strong enough muscle tissue to protect the joints from further damage. Strengthening the thigh muscles is certainly protective for those who have not developed osteoarthritis.
Range-of-motion exercises increase the amount of movement in a joint and muscle. The best examples are yoga and tai chi, which focus on flexibility, balance, and proper breathing. In one 2001 study, older adults who practiced the gentle movement, breathing, and meditation exercises of tai chi for 10 weeks reported less pain than their peers who did not learn the technique.
Low-impact aerobic workouts help stabilize and support the joints. Cycling and walking are beneficial, and swimming or exercising in water is highly recommended for people with arthritis. Patients with arthritis should avoid high-impact sports, such as jogging, tennis, and racquetball.
Some researchers are now focusing on "power" training, which involves improving the muscle's ability to move more rapidly against resisting forces, such as gravity. For example, such training helps people stand up or climb stairs more quickly. Muscle power declines more rapidly than muscle strength, and may be particularly important in older people.

Exercise is very important for slowing the progression of osteoporosis, and extremely important for reducing the risk of falling, which causes fractures. Falls are one of the leading causes of death in people over the age of 65. Exercise helps build balance and flexibility, which reduces the risk of falling.

Specific exercises may be especially helpful for reducing the risk of fractures:

Weight-bearing exercise is very beneficial for bones in people of all ages, even older people. This approach applies tension to muscle and bone, and the body responds to this stress by increasing bone density, in young adults by as much as 2 - 8% a year. Careful weight training can also be very beneficial for elderly people, particularly women. In addition to improving bone density, weight-bearing exercise reduces the risk of fractures by improving muscle strength and balance, thus helping to prevent falls.
Regular brisk long walks improve bone density and mobility. In one 2002 study, for example, older women reduced their risk of hip fracture by over 40% by working out just four hours a week.
Exercises specifically targeted to strengthen the back can be beneficial in improving posture, and may even reduce kyphosis (hunchback) in people with osteoporosis.
Low-impact exercises, particularly yoga and tai chi, which improve balance and strength, have been found to decrease the risk of falling. In one study, tai chi reduced this risk by almost half.

Click the icon to see an image of the bone-building exercise.

Note on Female Athlete Triad. Some young female athletes who exercise very intensely, and are subject to intense pressure to remain thin, are at risk for the female athlete triad. This syndrome is a combination of three disorders -- an eating disorder, loss of menstrual periods, and osteoporosis.

People who do not exercise regularly face an increased risk for low back pain, especially during times when they suddenly have to perform stressful, unfamiliar activities. These activities may include shoveling, digging, or moving heavy items. Although no definitive studies have been done to prove the relationship between lack of exercise and low back pain, sedentary living is probably a primary nonmedical cause contributing to this condition.

Lack of exercise leads to the following conditions that may threaten the back:

Muscle inflexibility can restrict the back's ability to move, rotate, and bend.
Weak stomach muscles can increase the strain on the back and can cause an abnormal tilt of the pelvis (hip bones).
Weak back muscles may increase the load on the spine and the risk of disk compression.
Obesity puts more weight on the spine and increases pressure on the vertebrae and disks. Studies report only a weak association between obesity and low back pain, however.

Benefits for Chronic Back Pain. People in with sudden and severe back pain should not exercise. Exercise plays a very beneficial role in relieving chronic back pain, however. In one study, patients with back pain lasting for an average of 18 months were assigned eight 1-hour exercise sessions over 4 weeks. They showed greater improvement in nearly every area, including reduced pain, compared to patients who did not exercise.

Exercise should be considered as part of a broader program to return to normal home, work, and social activities. In this way, the positive benefits of exercise not only affect strength and flexibility but they also alter and improve the patients' attitudes toward their disability and pain.

Repetition is the key to increasing flexibility, building endurance, and strengthening the specific muscles needed to support the spine. Some exercise programs used for prevention or treatment of chronic low back pain include the following:

Low-impact Aerobic Exercises: Low-impact aerobic exercises, such as swimming, bicycling, and walking, can strengthen muscles in the abdomen and back without over-straining the back. Programs that use strengthening exercises while swimming may be a particularly beneficial approach for many patients with back pain. In one study, for example, pregnant women who engaged in a water gymnastics program had less back pain, and were able to continue working longer.
Lumbar Extension Strength Training: Exercises called lumbar extension strength training are proving to be effective. Generally, these exercises attempt to strengthen the abdomen, and improve lower back mobility, strength, and endurance. They also enhance flexibility in the hip and hamstring muscles, and in the tendons at the back of the thigh.
Yoga, Tai Chi, and Chi Kung: These exercises combine low-impact physical movements and meditation. They are based on principles of disciplining the mind to achieve a physical and mental balance, and can be very helpful in preventing recurrences of low back pain. In one study of Pilates, an exercise practice that uses yoga principles, the exercises were helpful in a woman with progressive and disabling severe low back pain resulting from early scoliosis. This approach deserves further research.
Flexibility Exercises: Whether flexibility exercises alone offer any significant benefit for chronic back pain is uncertain. One study suggested that any benefits derived from flexibility exercises are lost unless the exercise programs are sustained.
Retraining Deep Muscles: Studies are finding a link between low back pain and poor motor control of deep muscles in the back and trunk. According to these studies, contraction exercises specifically designed to retrain these muscles may be effective for patients with both acute and chronic pain.

It is important for any person who has low back pain to have an exercise program guided by professionals who understand the limitations and special needs of back pain and who can address individual health conditions. One study indicated that patients who planned their own exercise did worse than those in physical therapy or doctor-directed programs.

Hazardous Effects on the Back. Improper or excessive exercise can also cause back pain.

Exercise's Effects on the Lungs

Patients with chronic lung problems have difficulty exercising. Shortness of breath is a major limitation in most patients, but in about a third, muscle fatigue is an even greater problem. Although exercise does not improve lung function, training helps many patients with chronic lung disease by strengthening their limb muscles, thus improving endurance and reducing breathlessness.

In people who already have colds, exercise has no effect on the illness' severity or duration. People should avoid strenuous physical activity when they have fevers, muscle aches, or other symptoms of a widespread viral illnesses.

Long-term exercise may help control asthma and reduce hospitalization. One 2000 study found that aerobic exercise improves breathing capacity and function in patients with mild asthma. People with asthma who enjoy running should probably choose an indoor track, to avoid pollutants. Swimming is particularly excellent for people with asthma. Yoga practice, which uses both stretching, breathing, chest expansion, and meditation techniques may have specific benefits that include stress reduction as well as airway opening. One study reported that two thirds of patients who practiced yoga regularly were able to reduce or eliminate their asthma medications.

Exercise-Induced Asthma. About 40 - 90% of asthma cases are exercise-induced asthma (EIA), in which exercise triggers coughing, wheezing, or shortness of breath. It occurs most often in children and young adults and during intense exercise in cold dry air. EIA is triggered only by exercise. Unlike allergic asthma, there is no long-term increase in airway activity. People who only have EIA do not require long-term maintenance therapy. The warm-up and cool-down periods, which are important for any exercise regimen, may help reduce EIA events. A study of military recruits found that exercise-induced asthma attacks did not hinder their ability to perform or train, suggesting that EIA is not a reason to exclude people from physically demanding occupations.

Exercise-induced asthma is distinct from allergic asthma in that it does not produce long-term increase in airway activity. People who only experience asthma when they exercise may be able to control their symptoms with preventive measures such as warm-up and cool-down exercises.

Walking is the best exercise for people with emphysema. Patients should try to walk three to four times daily for 5 - 15 minutes each time. Devices that assist ventilation may reduce breathlessness that occurs during exercise.

Inspiratory muscle training involves exercises and devices that make inhaling (breathing in) more difficult, in order to strengthen breathing muscles. In a 2001 study, patients who took part in an inspiratory muscle training group improved their breathing, walking capacity, and quality of life. Yoga or martial arts exercises, such as tai chi, which emphasize breathing techniques and balanced movements, may be particularly beneficial for patients with emphysema.

Exercise's Effects on Weight

Exercising helps people reduce their weight, maintain weight loss, and fight obesity. Research has shown that women who regularly exercise but do not change their diet can lose significantly more weight than less active women.

Thirty minutes of moderate-intensity exercise may be adequate to maintain cardiovascular health, but it might not prevent weight gain. Recommendations published in 2003 and 2004 suggest that 45 - 60 minutes of exercise per day is necessary to promote weight loss. Children may need more activity.

Losing significant weight requires both exercise and calorie restriction. In addition, if a person exercises without dieting, any actual weight loss may be minimal because dense and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant.

Exercising without dieting still adds health benefits. One study found that overweight but fit people have half the death rate of overweight, unfit people. Research suggests that people who have trained for a long time develop more efficient mechanisms for burning fat and are able to stay leaner.

Lifting weights builds muscle, which burns calories more efficiently than other body tissues.

The following are some suggestions and observations on exercise and weight loss:

The treadmill burns the most calories of standard aerobic machines. It may be particularly effective when used in short multiple bouts during the day. Exercise sessions as short as 10 minutes, which are done frequently (about four times a day), may be the most successful program for obese people.
The more strenuous the exercise, the longer the body continues to burn calories before returning to its resting level. This state of fast calorie burning can last for as little as a few minutes after light exercise, to as long as several hours after prolonged or heavy exercise.
Resistance (strength) training is excellent for replacing fat with muscles. It should be performed two or three times a week.
Fidgeting may be very helpful in keeping pounds off. Regular exercise is certainly the best course, but for people who must sit for hours at work, frequently shifting positions while sitting may have some benefit.
It is important to realize that as people slim down, they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this trend and keep adding to their daily exercise routine.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. A study of women who practiced aerobic and strength training showed the training resulted in fat loss in the women's arms and trunk. However, they did not gain muscle tissue in those areas.

Because obesity is one of the risk factors for heart disease, anyone who is overweight must discuss their exercise program with a physician before starting.

Exercise's Effects on Other Conditions

Physical activity makes you healthier. It lowers your risk for cardiovascular disease and reduces bone loss. Physical activity also helps the body use calories more efficiently, which helps you eliminate body fat and lose weight. It also helps you maintain weight loss by increasing your metabolism and reducing your appetite.

A number of studies have indicated that regular exercise may reduce the risk of breast, colon, and possibly prostate cancers.

Studies confirm that exercise significantly reduces the risk of both colon cancer (by up to 50%) and breast cancer (by up to 30%).

A 2006 study found that, though protection from breast cancer may vary among the types of tumor, exercise offered the most marked protection from the more aggressive tumors. A second study, also done in 2006, supported this finding. Several studies also suggested that more intense exercise is more protective against breast cancer. Exercising consistently throughout life gives the best protection. Exercise not only lowers a woman's chance of getting breast cancer, it can help those who have received chemotherapy for the disease fight off fatigue.

While endurance athletes may suffer from stomach problems, low intensity exercise has a marked protective effect against colon cancer, according to studies, including the Nurses Health Study and the American Cancer Society's Cancer Prevention Study II. Furthermore, a 2006 study found that people with colon cancer who exercise reduce their risk of a recurrence.

Exercise also has a beneficial effect on people receiving treatment for prostate cancer. A new study found that aerobic and resistance training significantly reduced fatigue in men undergoing radiation treatments for prostate cancer. Fatigue is a common side effect of such treatments. In this study, 122 patients received supervised aerobic training, resistance training, or neither. At the end of 24 weeks, participants in both exercise groups noted significant improvement in their fatigue symptoms, compared to the control group. Participants in the resistance training group also lost a significant percentage of their body fat.

Endurance athletes often report stomach problems, such as bloating, diarrhea, and gas, even at rest. Experts suggest that moderate regular exercise might reduce the risk for some intestinal disorders. These disorders include ulcers, irritable bowel syndrome, indigestion, and diverticulosis. Older people who exercise moderately may have a lower risk for severe gastrointestinal bleeding.

Patients with end-stage kidney disease who exercise four to five times per week have better survival rates than those who are less active, according to researchers involved in the Dialysis Morbidity and Mortality Wave 2 study. However, the majority of study participants said that severe physical limitations prevented them from exercising so often.

Studies have shown that regular exercise, particularly walking, helps reduce one's risk for memory loss. A 2005 study found that older men who walked less than a mile daily had a 71% higher risk of dementia than those who walked more than two miles a day. A 2006 study found that people older than 65 who exercise regularly had lower risk of developing dementia, particularly Alzheimer's disease. An earlier study found that walking regularly protects women from mental decline. To date, there are no clear explanations for this apparent benefit. A preliminary study in mice suggests that physical activity changes the way brain-damaging proteins are processed in the brain, thus slowing the development of Alzheimer's disease. Aerobic exercise has been linked with improved reaction time, perception, and math skills in people of all ages.

Doctors found that exercise improves the physical and emotional well-being of patients who already have Alzheimer's disease. The patients exercised moderately for as little as 60 minutes each week. Doctors noted patients who exercised were less depressed, wandered away less, suffered fewer falls, and were placed in nursing homes later, compared to patients who did not exercise.

People with existing neurological diseases, such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease, should be encouraged to exercise. Specialized exercise programs that improve mobility are particularly valuable for patients with Parkinson's disease. Patients with neurological disorders who exercise experience less stiffness, as well as reduction in, and even reversal of, muscle wasting. In addition, the psychological benefits of exercise are extremely important in managing these disorders. Exercise machines, aquatic exercises, and walking are particularly useful.

Some research has suggested that exercise may have antidepressant effects. Although there is little strong evidence that exercise can help manage depression, a number of studies have suggested benefits. Research findings include:

Just 30 minutes of brisk exercise three times a week was as effective as medication in relieving symptoms, and reducing relapse, in many patients with mild-to-moderate depression.
Over half of older women with depression that did not respond to medication improved with 10 weeks of exercise. (About a third of women who did not exercise also improved during that time.)
Studies on elderly, depressed patients report modest benefits from exercise, even in those who do not response to antidepressants. Simply participating in a group activity may help improve mood.
Teenagers who are active in sports have a greater sense of well-being than their sedentary peers. The more vigorously they exercise, the better their emotional health.
Physical inactivity is strongly linked to depression in children 8 - 12 years of age.

Specific exercises may be particularly beneficial:

Aerobics. Either brief periods of intense training or prolonged aerobic workouts can raise levels of certain chemicals in the brain. These chemicals -- which include endorphins, adrenaline, serotonin, and dopamine -- produce the so-called runner's high. Weight loss and increased muscle tone can boost self-esteem.

Yoga. Yoga practice, which involves rhythmic stretching movements and breathing, has been found to positively affect mood. It may have clinical potential as a technique for improving and stabilizing mood. A study comparing yoga to aerobic exercise found that men have significantly lower levels of tension, fatigue, and anger after yoga, compared with levels after swimming. Yoga and swimming tended to produce equal benefits in women.

Click the icon to see an image of the benefits of yoga.

Moderate exercise in healthy pregnant women does not increase the risk for miscarriage, preterm labor, or rupture of the membrane. Not exercising increases the risk for complications, including low-birth weight babies. Exercising increases the fetal heart rate, which in turn protects the baby.

Healthy women with normal pregnancies should exercise at least three times a week, being careful to warm up, cool down, and drink plenty of liquids. Many prenatal calisthenics programs are available.

The following are specific exercises that may benefit the pregnant woman:

Swimming and water aerobics may be the best option for most pregnant women. Swimming has special benefits for those with fluid buildup. Water exercises involve no impact, overheating is unlikely, and swimming face down promotes optimum blood flow to the uterus.
Performing yoga exercises under the guidance of informed instructors can be very helpful.
Walking is also beneficial.

To strengthen pelvic muscles, women should perform Kegel exercises at least six times a day. This involves contracting the muscles around the vagina and urethra for three seconds 12 - 15 times in a row.

Experts generally recommend the following precautions for pregnant women who exercise:

Fit women who have exercised regularly before pregnancy may work out intensely as long as the doctor approves and no discomfort occurs.
As a rule for previously sedentary, low-risk expectant mothers, the pulse rate should not exceed 70 - 75% of the maximum heart rate, or more than 150 beats per minute. Any sedentary expectant mother should check with her doctor before starting an exercise program.
According to one study, vigorous exercise may improve the chances for a timely delivery. All pregnant women, however, should avoid high-impact, jerky, and jarring exercises, such as aerobic dancing, which can weaken the pelvic floor muscles that support the uterus.
During exercise, women should monitor their temperature to avoid overheating, a side effect that can damage the fetus. (Pregnant women should also not use hot tubs or steam baths, which can cause fetal damage and miscarriage.)

Note: Strenuous exercise may affect the flavor of breast milk for a short time afterward. Nursing mothers who engage in such activity might want to wait about an hour after exercising before they feed their infant.

Complications

Exercise may lead to injury if not done properly. Always exercise with care.

Competitive running or high-impact aerobics pose a high risk of a number of injuries to the bones and muscle. The effect of high-impact exercise on the back is not entirely clear. Some research suggests that over time, high-impact exercise may increase the risk for degenerative disk disease. A survey of people who played tennis, however, found no increased risk for low back pain or sciatica.

High-impact exercise can also cause dizziness, ringing in the ear, motion sickness, or loss of high-frequency hearing.

Some research further suggests that in people unused to exercise, intense activity increases production of harmful particles in the body called free radicals. These unstable oxygen particles injure muscle tissue. Muscle pain in this case does not occur until 24 - 48 hours after exercise.

Some people have a higher than average risk for injury:

About half of people at any age who participate in competitive running or high-impact aerobics experience minor injuries at least once a year. Young, intensely competitive athletes may be at risk for permanent injury. Studies are mixed over whether intensive high-impact sports in younger people cause long-term degenerative joint disease.
As the number of older people who start exercising increases, there has also been an increase in injuries for this age group. Between 1990 and 1996, injuries from active sports increased by 54% in people age 65 and older.
Women are far more likely than men to suffer knee injuries.
Urinary incontinence affects many female athletes who engage in high-impact exercise.
Tennis players are at high risk for injuries from repetitive force on the shoulder joint.

Preventing High-Impact Injuries. The following may be helpful for preventing injury:

Wear shock-absorbing footwear with weight-dampening inserts.
Combine weight lifting with jumping exercises. This may prevent injury by strengthening hamstrings and improving coordination.
Vary training and alternate easy and harder workouts.
Be careful to warm up, cool down, and stretch. Flexibility is the key to preventing many muscle strains.
Take days off now and then. The risk of injury increases when athletes train more than five times a week.

Because of the association between high-impact exercises and oxidation, some experts suggest eating foods rich in antioxidants, such as vitamins A, C, and E. Such foods, which may protect against damage from free radicals, include many fresh fruits and vegetables.

Treating Minor Injuries. Most mild or moderate injuries respond well to a simple, four-step treatment: rest, ice, compression, and elevation (RICE). This combination works well for both spot injuries and chronic problems. Ice packs, which reduce inflammation and pain, can help new injuries, and can be useful for the first few hours after a chronically injured area is exercised. How much or how long to compress the injury is unclear.

Evidence suggests that early movement is helpful, although taping or bracing in people with a recurrent ankle sprain is known to be protective. It may not be helpful in those without a previous ankle injury.

Minor injuries like sprains may be treated at home if broken bones are not suspected. The acronym RICE can help you remember how to treat minor injuries: "R" stands for rest, "I" is for ice, "C" is for compression, and "E" is for elevation. Pain and swelling should decrease within 48 hours. Gentle movement may help, but pressure should not be put on a sprained joint until pain is completely gone. This can take up to a few weeks.

Heat, ultrasound, whirlpool, and massage may speed healing if applied a day or two after the initial injury or for warm-up before another workout session.

Some young female athletes who exercise very intensely, and are subject to intense pressure to remain thin, are at risk for a syndrome known as the female athlete triad. This combination of symptoms includes loss of menstruation, eating disorders, and osteoporosis. Eating disorders among young female athletes are estimated at 15 - 62%. Women at higher risk include ballet dancers, gymnasts, and divers. Continued intense exercise causes a stress response in which estrogen (the primary female hormone) is lost. Estrogen loss can lead to infertility and osteoporosis. Iron loss and anemia may also be a problem in women who exercise frequently, even at moderate intensity. A doctor should be consulted for any of these concerns.

Incorrect movements can literally cause mechanical problems in the muscles. These problems are usually the result of improper exercise instruction, and lack of attention. A single jerky golf swing, or the incorrect use of exercise equipment (especially free weights, nautilus, and rowing machines), can cause serious back injuries.

Between 30 - 70% of cyclists experience low back pain. Pain may be improved by adjusting the angle of the bicycle seat.

Everyone should drink lots of fluid during intense exercise. Thirst is often a poor indicator of dehydration in people who exercise, particularly older people. During a tough workout in a hot environment, the body can lose two liters of fluid per hour through sweat.

Anyone who exercises intensely should take the following precautions:

Drink 6 - 8 ounces of fluid about 15 minutes before a workout, and then pause regularly during exercise to drink more.
Water is the best choice for replenishing body fluids. Glucose-sodium-potassium solutions, the so-called "sports drinks," which promise instant energy, appear to be no better than water at improving endurance during prolonged intense running.
Caffeinated beverages like coffee and soft drinks give short bursts of energy, but can actually cause fluid loss. Caffeine before a workout has been shown to temporarily raise blood pressure, and reduces blood flow to inactive limbs.

Contrary to popular belief, drinking fluids will not cause cramps. Drinking enough, in fact, helps prevent the painful involuntary muscle spasms that sometimes occur during exercise.

Overheating, or hyperthermia, can be a problem with hard exercise, or when working out in hot weather. Overheating can cause mild to life-threatening conditions. Heat exhaustion, a moderate form of hyperthermia, is characterized by the following symptoms:

Lightheadedness, nausea, headache, hyperventilation, fatigue, and loss of concentration
A high temperature (above 103° F), possibly accompanied by complaints of chills and clammy skin

Individuals should rest in a cool, dry place, drink plenty of fluids, and bring down their body temperature with ice packs pressed against the skin.

Heatstroke. Heatstroke is the most dangerous complication of hyperthermia. The victim may suddenly stop sweating, after which symptoms such as altered consciousness, seizures, and even coma may quickly follow. Heat stroke is a medical emergency and requires immediate cooling of the victim in an ice-water bath or with ice packs. One study suggests that risk for serious complications from exercising in high temperatures may persist as late as the following day, even if the weather has cooled down.

Click the icon to see an image of the dangers of heatstroke.

Precautions are also necessary in cold weather. When exercising in winter dress in layers, including gloves and socks, which create insulated air pockets that trap heat. In cold weather, wear shoes with less ventilation than those worn in the summer. Fingers, toes, ears, and nose are most susceptible to frostbite. Frostbite progresses from stinging or aching to numbness. Fingers and toes may become white. Soaking the hands and feet in warm water can help, but only once there is no risk of refreezing, since a second bout of frostbite after thawing can quicken tissue damage.

Hypothermia can be life-threatening and can occur even after long exposure to temperatures that are above freezing. The condition is characterized by extreme fatigue, mental confusion, apathy, and a lack of coordination. The victim should be warmed as soon as possible with blankets, body heat, and warm fluids.

Motivation

Motivation, or a lack thereof, is one reason many people stop exercising. Here are some tips for avoiding burnout:

Think of exercise as a menu rather than a diet. Choose a number of different physical activities that are personally enjoyable such as sports, dancing, or biking. Although experts say you should get 30 minutes of aerobic exercises at least five times a week, those times can be divided into shorter periods -- such as 10 minute sessions. In addition, people can achieve health benefits from other exercise programs, including weight training, yoga, or tai chi.
Stick to a prepared schedule and record progress.
Develop an interest or hobby that requires physical activity.
Adopt simple routines such as climbing the stairs instead of taking the elevator, walking instead of driving to the local newsstand, or canoeing instead of zooming along in a powerboat.
Try cross training (regularly switching from one type of exercise to another). Studies suggest it is more beneficial than focusing only on one form of exercise.
Exercise with friends.
Join a gym or take classes. Many affordable programs are available.
For those who can afford them, personal trainers can be very helpful and are available in many gyms and exercise clubs. Personal trainers without any connection to a well-reputed gym or fitness club should be certified by a major fitness organization, such as the Aerobics and Fitness Association of America (AFAA) or the American Council on Exercise.
Exercise videos may also be helpful, but people should be sure they are suited to their individual age and health needs, and bear the seal of the AFAA.
Consider getting a dog. A study in the February 2006 American Journal of Preventive Medicine found that dog owners in Canada walk almost twice as much as those who don’t own a dog. Regular walking is a good way to improve health.

Differences in Motivation Between Men and Women. Motivation factors may differ by gender, and women appear to have a harder time. In one study, weight loss was the greatest motivator to exercise for women, and muscle tone was the primary motivator for men. Unfortunately, effects on appearances may take a long time to show, discouraging people from continuing an exercise program even though their health is improving.

Overweight among children and adolescents has now become an epidemic in the United States. Experts say that children should be vigorously active for at least 20 - 60 minutes 3 - 5 days a week. Parents and schools must be imaginative and rigorous in encouraging children to exercise.

Role of Parents. Parents must make conscious efforts to limit sedentary activities, and to encourage physical ones for their children. This includes monitoring the time children spend on the computer, in front of the TV, or playing video games. Parents should suggest different forms of entertainment. Even children who aren't interested in joining a Little League team may enjoy a round of catch with their parents, walking in the park, or swimming in a local lake.

Role of Schools. Early school physical education programs can make a significant difference and the earlier these routines are learned, the more likely they will be carried forth into a healthy adulthood. Schools should emphasize team cooperation or individual improvement and self-mastery. Studies have shown that people tend to give up more quickly and feel less competent if their perceptions of success are based only on comparison to their peers.

People mature at different rates, and there seems to be a genetic component to coordination, strength, speed, and one's response to resistance exercise. Nonetheless, everyone should strive to be as fit as they possibly can, given their strengths and limitations.

The decision to adopt a healthier behavior -- whether it's more exercise, weight loss, or quitting smoking -- is not as simple as just deciding to do it. Behavior change expert James Prochaska and his colleagues outlined a theory, which has been supported by numerous studies, showing that people cycle through a variety of stages before a new behavior is successfully adopted over the long term. It may help you to understand how this works. As you read the description of each stage -- specifically as it relates to exercise -- you may find yourself nodding and saying to yourself, "Yes, that's me!"

Stage 1: Pre-Contemplation. People at this stage have no plans or desire to exercise. They aren't even considering exercising. They are generally unaware of the specific benefits that exercise can bring -- exercise may seem more like a hassle than something worth doing. Or, they may simply have "failed" in the past and have given up.

There's no point in talking about how to start an exercise program if you are at this stage. Instead, it is important to think about how exercise might be good for you personally -- by helping you to lose weight, feel better, have more confidence, live longer, sleep better, or reduce your stress levels. The benefits must be identified before a person will consider exercise.

If you are at this stage, a good activity is to ask four friends or family members why they exercise. Their answers may show you some real-life benefits, and inspire enough interest to compel you to take the next step.

Stage 2: Contemplation. A person at this stage is thinking, "I think I should probably exercise, but I need help getting started." People at this stage know that exercise is good for them, but it seems like a daunting task or they don't think they can pull it off. Some may have tried and "failed" in the past, but they are still receptive to another go-round.

It's important for people at this stage to consider some of the truths and falsehoods of exercise. For example, it is helpful to know that there are many forms of physical activity to select from, and that you can do your exercising in small chunks. It is not true that exercise has to be painful, or that you either succeed or fail. There is no such thing as "failure" -- people become more or less active at different stages of their lives, and it is never too late to get moving again. And people at this stage should find assurance that an exercise plan can be very simple.

If you are at this stage, a good activity is to write down all the things that you believe make exercise difficult -- and to learn strategies for overcoming or side-stepping those hurdles. People at this stage might benefit from making a pledge, contract, or other commitment that they are going to get more active in the near future. The goal is to get un-stuck by identifying the roadblocks and the ways to overcome these roadblocks. The final goal at this stage is to make a commitment.

Stage 3: Preparation. These folks are primed and motivated. They are ready to give exercise a try. The goal of this stage is to create a specific action plan that takes all factors into account, so that the "launch" is successful. People at this stage need to know how much they should be exercising, their target heart rate, and the types of exercises. They should explore the different kinds of exercises and decide which ones to try.

At this stage, people will evaluate exercise machines and health plans, if that interests them, pick the proper clothing or accessories, and consult a doctor if necessary. They also need to think about how they are going to fit their exercise plans into their daily and weekly schedule.

If you are at this stage, you should also consider some backup plans -- what to do if it rains, or if you don't feel like exercising. That way you are prepared to overcome that hurdle when you encounter it. You should be aware of what to expect realistically at the beginning -- for example, be aware that weight loss takes time, but health benefits begin immediately.

Stage 4: Action! People at this stage have just started exercising. This stage is where the biggest behavior change occurs -- these people have started to exercise but it is not yet a long-term, ingrained habit. This stage requires significant commitment and energy.

If you are at this stage, keep talking to friends and family for inspiration. Review your backup plans. Reward yourself for small achievements. Give yourself notes and reminders to exercise. Having a friend to exercise with can be very helpful as you get through this stage. You want to build and maintain momentum, because exercising gets easier once it is a habit!

Stage 5: Maintenance. The people at this stage have been exercising for at least 6 months. At this point, exercising has started to become a habit. The goal here is to prevent relapse. If you are at this stage, identify ways that you can fine-tune your program. Continue to identify roadblocks and improve your backup plans. Think about what you have found most enjoyable about exercising.

What benefits have you gained? Keep reminding yourself of these perks. If giving yourself a challenge was part of your initial motivation, set new goals and find new challenges. If you risk getting bored with your routine, find ways to vary it. Or maybe you have found a comfortable routine that you enjoy -- if it's working, great! There is no need to change it. You might want to read or learn more about your method of exercising, and develop a deeper level of understanding about it. Soon you'll be a pro!

One point about this theory is that people do not proceed from one stage to another in a simple, step-by-step fashion. They actually cycle or spiral back and forth, so that they may move from stage 1 to 2 to 3, and then back to 2 again. They may stay in maintenance mode for years and then fall back to stage 2. Remember that this is normal -- if you tried exercising in the past and didn't stick with it, don't consider yourself a failure. Just know that it's time to try again!

Resources

http://fitness.gov -- The President's Council on Physical Fitness and Sports
www.ncppa.org --National Coalition for Promoting Physical Activity
www.acefitness.org --American Council on Exercise
www.arthritis.org --The Arthritis Foundation offers tips on exercising with arthritis
www.justmove.org -- Just Move (American Heart Association)

References

Taylor, A.H., Ussher, M., & Faulkner, G. The acute effects of exercise on cigarette cravings, withdrawal symptoms, affect and smoking behaviour: a systematic review. Addiction. 2007;102:534-543.

Kruk J. Lifetime physical activity and the risk of breast cancer: a case-control study. Cancer Detect Prev. 2007;31(1):18- 28.

Tehard B, Friedenreich CM, Oppert JM, et al. Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):57-64.

Adams SA, Matthews CE, Hebert JR, et al. Association of physical activity with hormone receptor status: the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1170-8.

Larson EB, Wang L, Bowen JD et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006 Jan 17;144(2):73-81.

Meyerhardt JA, Heseltine D, Niedzwiecki D, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol. 2006 Aug 1;24(22):3535-41.

Slattery ML. Physical activity and colorectal cancer. Sports Med. 2004;34(4):239-52.

Peters HP, De Vries WR, Vanberge-Henegouwen GP et al. Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract. Gut. 2001 Mar;48(3):435-9.

Abbott, RD, White, LR, G. Ross, W, et al. Walking and Dementia in Physically Capable Elderly Men. JAMA. 2004;292:1447-1453

Calton BA, Lacey JV Jr, Schatzkin A, Schairer C, Colbert LH, Albanes D, Leitzmann MF. Physical activity and the risk of colon cancer among women: A prospective cohort study (United States). Int J Cancer. 2006 Feb 17; [Epub ahead of print]

Di Loreto C, Fanelli C, Lucidi P, et al. Make your diabetic patients walk: long-term impact of different amounts of physical activity on type 2 diabetes. Diabetes Care. 2005 Jun;28(6):1295-302.

Mikkelsson LO, Nupponen H, Kaprio J, Kautiainen H, Mikkelsson M, Kujala UM. Adolescent flexibility, endurance strength, and physical activity as predictors of adult tension neck, low back pain, and knee injury: A 25 year follow up study. Br J Sports Med. 2006 Feb;40(2):107-13.

Brown SG, Rhodes RE. Relationships among dog ownership and leisure-time walking in Western Canadian adults. Am J Prev Med. 2006 Feb;30(2):131-6.

Simons R, Andel R. The effects of resistance training and walking on functional fitness in advanced old age. J Aging Health. 2006 Feb;18(1):91-105.

Review Date:
4/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com