FitSugar

DVD Review: Better Sex Through Yoga – Volume 3

FitSugar — Fri, 11 Apr 2008 02:30:00 -0700

I just checked out Volume Three ($14.95), of the Better Sex Through Yoga series. I was excited to try it (no, not in that way), because this DVD is the most advanced video of the three.

The first thing I noticed is that the instructor was scantily clad; I think I actually murmured out loud, "Yeah, like I'd ever practice yoga in a short tank top and my undies." If you can get over the costuming issues, the yoga part is actually pretty good. She gives great instruction, and helpful tips appear on the screen like "spread your fingers wide in Down Dog." Then suddenly, that eerie voiceover lady from the first two DVDs starts piping in with instructions like, "Slowly breathe into your sexual core," and "Stretch your sexual core." To top it all off, the camera zooms in on the instructor's crotch and her little undies while doing a Wide-Legged Forward Bend. So unnecessary. I was also entertained by the fact that the instructor and the two yogis following her were spritzed with oil or glitter or something to make it look like every inch of their skin was glistening.

I was expecting this video to focus more on opening your hips and hamstrings, and to work on increasing flexibility in your entire body, which would then enhance your sex life. This video was borderline like a porno, and the only part about it that touched on sexuality was that the people were wearing next to nothing. There are so many better yoga DVDs out there.

Move It at Home: Better Sex Through Yoga - Volume 2

FitSugar — Fri, 28 Dec 2007 04:00:00 -0800

A while back I reviewed the beginner yoga DVD, Better Sex Through Yoga, Volume 1. Well, I decided it was time to get a little more advanced, or rather intermediate and try Volume 2 ($14.95), the Intermediate edition. This isn't an erotic video with explicit instructions of the Kama Sutra sex positions. It's just like any other yoga video, except this 46 minute workout focuses on opening your hips, hamstrings, and lower back.

Although I really did like the creative sequencing of postures, I must say I found the close up shots of the instructor's shorty shorts, not only unnecessary but unprofessional as well. I thought Volume 2 was a bit more cheesy than the first volume since it included the same annoying music and even more repetitions of the instruction to "Breathe deeply into your sexual core." It also has more of a hint of sexuality, which aggravated me since yoga isn't about sex (for me anyway). I think I might buy this for a yoga friend as a gag gift, or for newlyweds, but aside from that, I'd rather practice along with the many other better yoga videos out there.

Move It at Home: Better Sex Through Yoga - Volume 1

FitSugar — Fri, 26 Oct 2007 09:30:00 -0700

The title of this DVD both intrigued me and made me shake my head with disbelief. Putting the "sex" in a title will certainly grab a shopper's attention. That being said, the connection does make sense since yoga can help in other areas of your life, including sex. Yoga not only benefits the body, but the mind as well. It gives you a stronger sense of self, gets you in touch with your feelings, heightens your awareness of the important things in life, and makes you feel more connected to your world and the people around you. Doing yoga makes you feel good about yourself, which can only enhance your relationships with others.

Better Sex Through Yoga is a 3-part DVD series. I checked out Volume 1 for Beginners. This 35-minute DVD is a lot like taking a regular vinyasa class, except that the poses and movements focus on opening the hips, hip flexors, hamstrings, and chest.

The woman leading the sequence of postures had a sweet and happy energy, and gave great instructions as to what your body should be doing. I liked how she stayed in each pose for a few breaths, but changed it up so it wasn't boring at all. The "class" included many of my favorite poses because hip openers are my fave. She wasn't cheesy at all, but the music sure was; so I was tempted to lower the volume on the DVD and pump up some of my favorite chanting music.

There was one little weird thing about this DVD. Want to know what it was? Then read more

After the woman doing the poses explained what to do, another woman's voice chimed in every once in a while, saying something like "Breathe deeply into your sexual core." It made me laugh because it just seemed so out of place. All in all, I did like this Better Sex Through Yoga Volume 1 DVD ($14.95), and look forward to checking out Volume 2, the Intermediate level.

Another Reason to Exercise: Better Sex Through Yoga

FitSugar — Tue, 06 Jan 2009 09:00:00 -0800

Steering your sex drive in the right direction can easily be derailed by stress, but getting it to a satisfying place could be as simple as incorporating yoga in your fitness regimen. According to a recent article in The Journal of Sexual Medicine, women noticed improved levels of arousal and desire - and even experienced better orgasms - through practicing Eastern techniques of mindfulness and yoga.

Living in the present moment is an important focus of yoga, so it's easy to see how training our minds and bodies to remain present and aware could benefit our time in the bedroom. Venturing to your local studio is one way to get started, but many gyms offer group yoga classes and there's no reason why you couldn't start doing yoga on your own. Check out some yoga DVDs (if you're so inclined, there's the Better Sex Through Yoga series) and maybe get your honey involved by trying partner yoga at home.

Source

Endometriosis

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

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., 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

Uterine fibroids and hysterectomy

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Lifestyle Changes
Medications
Surgery
Other Procedures
Hysterectomy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Uterine Artery Embolization Versus Standard Surgery

Many women with fibroids are considering a procedure called uterine artery embolization (UAE) as an alternative to standard surgery such as hysterectomy or myomectomy. A study published in 2007 in the New England Journal of Medicine compared these treatment approaches. The study suggested that UAE results in shorter hospital stay and faster recovery time, but a small percentage of women may later need repeat embolization or a hysterectomy. There were similar improvements in quality of life regardless of whether a woman had UAE or standard surgery.

Magnetic-Resonance Guided Focused Ultrasound (MRgFUS)

MRgFUS is a new non-surgical approach for treating fibroids. A 2006 study in Obstetrics and Gynecology indicated that taking gonadotropin-releasing hormone (GnRH) agonist drugs before this procedure may help reduce fibroid volume and improve outcomes.

Predictors of Hysterectomy

Combined factors 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

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

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

Introduction

A uterine fibroid (known medically as a leiomyoma or myoma ) is a noncancerous (benign) growth composed of smooth muscle and connective tissue. The size of a fibroid varies from that of a pinhead to larger than a melon. Fibroids have been reported weighing more than 20 pounds.

Fibroids originate from the thick wall of the uterus and are categorized by the direction in which they grow:

Intramural fibroids grow within the middle and thickest layer of the uterus (called the myometrium). They are the most common fibroids.
Subserosal fibroids grow out from the thin outer fibrous layer of the uterus (called the serosa). Subserosal can be either stalk-like (pedunculated) or broad-based (sessile). These are the second most common fibroids.
Submucous fibroids grow from the uterine wall toward and into the inner lining of the uterus (the endometrium). Submucous fibroids can also be stalk-like or broad-based. Only about 5% of fibroids are submucous.

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

The Primary Organs and Structures in the Reproductive System. 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. During pregnancy this inner lining 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.

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.

Click the icon to see an image of the uterus.

Click the icon to see an image of the pituitary gland.

Click the icon to see an image of the hypothalamus.

Causes

Inherited genetic factors may be important in many cases of fibroids. Researchers are investigating unique genetic factors that regulate hormones. Proteins called growth factors may be responsible for some of the abnormalities leading to uterine muscle overgrowth and fibroids. Scientists have identified chromosomes carrying a total of 145 genes that may affect fibroid growth. Some experts report that uterine fibroids are inherited from paternal (the father's) genes.

Uterine fibroids often grow during pregnancy, and they degenerate after menopause. From these observations and certain studies researchers are fairly certain that the female hormones, both estrogen and progesterone, play a role in their growth. Their role, however, is not clear. Some theories about the relationship to fibroids and estrogen include the following:

Estrogen patterns in fibroids are similar to those in pregnancy. That is, like smooth muscle cells in the uterus during pregnancy, fibroid cells exposed to female hormones do not respond normally to signals that would make them self-destruct and return to a nonpregnant state. (This natural self-destruction is a process called apoptosis). Instead, they continue to grow.
Some evidence suggests that estrogen may inhibit a tumor-suppressor gene called p53 in fibroid tissue, therefore triggering cell proliferation leading to fibroid growth. (P53 plays a role in some cancer-cell growth, although in this case the process is not cancerous.)

The formation of fibroids may be attributable to abnormalities in substances called growth factors. These are special proteins, secreted by different cell types, that are responsible for cell-to-cell interaction. Many of these substances regulate a process called angiogenesis, which causes new blood vessels to sprout from pre-existing ones. The production of new blood vessels then feeds any existing growth, such as fibroids.

The growth factors that appear to play an important role in many female reproductive disorders are Basic Fibroblast Growth Factor (BFGF) and Vascular Endothelial Growth Factor (VEGF). BFGFs are involved in the proliferation of cells that form connective tissue, which supports the body's organs and structure. VEGFs are involved with cell growth in smooth muscles that line blood vessels. Some evidence suggests they play a role in uterine fibroids.

Other growth factors being studied specifically for fibroids include Insulin-like Growth Factor (IGF)-I, Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), and Transforming Growth Factor (TGF).

Symptoms

Fewer than 25% of patients with fibroids experience symptoms. When they do, they include:

The most common symptom is prolonged and heavy bleeding during menstruation. This is caused by fibroid growth bordering the uterine cavity. In severe cases, heavy bleeding may last as many as 2 weeks. Fibroids rarely bleed between periods, except in a few cases of very large fibroids.
Large fibroids can also cause pressure and pain in the abdomen or lower back that sometimes feels like menstrual cramps.
As the fibroids grow larger, some women feel them as hard lumps in the lower abdomen.
Very large fibroids may give the abdomen the appearance of pregnancy and cause a feeling of heaviness and pressure. In fact, large fibroids are defined by comparing the size of the uterus to the size it would be at specific months during gestation.
Unusually large fibroids may press against the bladder and urinary tract and cause frequent urination or the urge to urinate, particularly during the night when a woman is lying down.
Abnormal pain during intercourse (called dyspareunia).
If the fibroids press on the ureters (the tubes going from the kidneys to the bladder), obstruction or blockage of urine may result.
Fibroid pressure against the rectum can cause constipation.

Risk Factors

Uterine fibroids are the most common tumor found in female reproductive organs. It is estimated that over 50% of women age 30 - 50 have fibroids, although they cause symptoms in only about 25%. A survey of 1,364 women suggested an even higher prevalence of over 80% in African-American women and almost 70% in white women. A number of possible risk factors have been identified, but very little research exists to confirm them.

Uterine fibroids are particularly common in African-American women, with an estimated prevalence of 50 - 75%. These women are also more likely to have severe pain, anemia, and larger and more numerous fibroids than women in other population groups. Although genetics may play a role, women of African descent who live in other countries do not appear to have as high an incidence of fibroids. This suggests that diet or other environmental factors are at work in the development of fibroids in African-American women.

Fibroids can start to grow soon after puberty, although usually they are detected when a woman reaches young adulthood. Women with fibroids are at risk for accelerated fibroid growth when estrogen levels are high or when lifestyle behaviors keep estrogen levels high.

Some examples of risk factors for fibroids that are also associated with high estrogen exposure include:

Early onset of menstrual period (before age 12)
Being overweight and sedentary
Never being pregnant. The risk for fibroids decreases with more children. (This risk factor, however, may be due to a greater risk for infertility caused by fibroids in the first place.)

Combined Oral Contraceptives. Combined oral contraceptives contain estrogen and progesterone and the evidence on their effects on fibroids have been conflicting. Early reports suggested they might be a risk factor. Most studies conducted more recently, however, have found no association and some even suggest that the newer low-dose OC combinations may be protective.

Hormone Replacement Therapy. Hormone replacement therapies (HRT) contain estrogen alone or estrogen plus progesterone. After menopause, fibroids usually shrink. Researchers are investigating whether the hormones used in HRT could cause existing fibroids to persist or even grow. Some studies, but not all, have found greater fibroid growth with the use of patch-administered hormone drugs. (In one of the studies, taking oral estrogen, however, had no effect.) A 2001 systematic review of studies reported some fibroid growth in women taking HRT, but usually without any significant symptoms.

If HRT has an effect on fibroid growth, it is unlikely to be severe. Any increase in fibroid growth during menopause must be evaluated surgically by a gynecologist since such growth, even if a woman is on hormone replacement therapy, may mean cancer.

High blood pressure (hypertension) may be associated with increased fibroid risk according to a 2005 epidemiologic study. The prospective study tracked women in the Nurses’ Health Study for 10 years and found that for every 10 mm/Hg increase in diastolic blood pressure, the risk for developing fibroids increased by 8 - 10%. (Interestingly, women who used antihypertensive medications had the highest risk.). Researchers reported that women with hypertension were 24% more likely to develop fibroids and that the longer a woman had hypertension, the greater her risk.

Complications

Effect on Fertility. The effect of fibroids on fertility is controversial. A 2002 analysis suggested that they may account for infertility in only 1 - 2.4% of women who have trouble conceiving. Large fibroids may cause infertility by:

Impairing the uterine lining
Blocking the fallopian tubes
Distorting the shape of the uterine cavity
Altering the position of the cervix and preventing sperm from reaching the uterus

Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject.

Effect on Pregnancy.Fibroids can increase pregnancy complications and delivery risks. These include:

Cesarean section delivery
Breech presentation (baby enters the birth canal upside down with feet or buttocks emerging first)
Preterm birth
Placenta previa (placenta covers the cervix)
Excessive bleeding after giving birth (postpartum hemorrhage)

A 2006 study found that pregnant women with at least one fibroid had the following increased risks: cesarean delivery (57%), breech birth (64%), preterm delivery (45%), placenta previa (86%), and postpartum hemorrhage (157%).

Anemia due to iron deficiency can develop if fibroids cause excessive bleeding. Oddly enough, smaller fibroids, usually submucous, are more likely to cause abnormally heavy bleeding than larger ones.

Most cases of anemia are mild. Mild anemia can cause weakness and fatigue. Moderate-to-severe anemia can cause shortness of breath, rapid heart rate, lightheadedness, headaches, ringing in the ears (tinnitus), irritability, pale skin, restless legs syndrome, and mental confusion. Heart problems can occur if prolonged and severe anemia is not treated. Pregnant women who are anemic, particularly in the first trimester, have an increased risk for a poor pregnancy outcome.

Large fibroids that press against the bladder occasionally result in urinary tract infections. Pressure on the ureters may cause urinary obstruction and kidney damage.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Fibroids can cause cramping during a period, which can be quite intense at times.

Pain can also develop if the blood supply is cut off from the fibroid tissue. In such cases, the cells blacken and die (a process called necrosis) from lack of oxygen. This event may occur under the following circumstances:

A very large fibroid outgrows its own blood supply.
A pedunculated fibroid (one that grows on a stem from the uterine wall) becomes twisted, thus cutting off its blood supply.
Pregnancy occurs, in which the risk for fibroid cell degeneration and necrosis increases.

Rarely, a fibroid breaks away from the uterus and develops in other locations. They are typically one of the following:

Benign Metastasizing Leiomyoma or BML (which usually spreads to the lung)
Disseminated Peritoneal Leiomyomatosis (which spreads to the abdominal wall)

Neither is cancerous, although there is some evidence that BML, which often occurs after menopause, may represent a slow-growing variant of leiomyosarcoma.

Fibroids are nearly always noncancerous, even if they have abnormal cell shapes. Cancer of the uterus nearly always develops in the lining of the uterus (endometrial cancer). Only in rare cases (less than 0.1%) does cancer develop from a malignant change in a fibroid (called leiomyosarcoma). Nevertheless, rapidly enlarging fibroids in a premenopausal woman or even slowly enlarging fibroids in a postmenopausal woman require surgical evaluation to rule out cancer.

Click the icon to see an image of uterine cancer.

Diagnosis

A doctor will perform a pelvic examination to check for pregnancy-related conditions and signs of fibroids or other abnormalities, such as ovarian cysts.

The doctor needs to have a complete history of any medical or personal conditions that might be causing heavy bleeding:

Any family history of menstrual problems or bleeding disorders.
The presence or history of any medical conditions that might be causing heavy bleeding. Women who visit their gynecologist with menstrual complaints, particularly heavy bleeding, pelvic pain, or both may actually have an underlying medical disorder, which must be ruled out.
The pattern of the menstrual bleeding. (If it occurs during regular menstruation, nonhormonal treatments are tried first. If bleeding is irregular, occurs between periods, with premenstrual pain, after sex, or is associated with pelvic pain, the doctor should look for specific conditions that may cause these problems.)
Regular use of any medications (including vitamins and over-the-counter drugs).
Diet history, including caffeine and alcohol intake.
Past or present contraceptive use.
Any recent stressful events.
Sexual history. (It is very important that the patient trust the doctor enough to describe any sexual activity that might be risky.)

Almost all women, at some time in their reproductive life, experience heavy bleeding during menstrual periods ( menorrhagia ). Being taller, older, and having a higher number of pregnancies increase the chances for heavier-than-average bleeding. In some cases the cause of heavy bleeding is unknown, but a number of conditions can cause menorrhagia or contribute to the risk:

Miscarriage. An isolated instance of heavy bleeding usually after the period due date may be due to a miscarriage. If the bleeding occurs at the usual time of menstruation, however, miscarriage is less likely to be a cause.
Having late periods or approaching menopause. These events may cause occasional menorrhagia.
Uterine polyps. (These are small benign growths in the uterus.)
Certain contraceptives. (Oral contraceptives or an intrauterine device, an IUD.)

The intrauterine device (IUD) shown uses copper as the active contraceptive; others use progesterone in a plastic device. IUDs are very effective at preventing pregnancy (less than 2% chance per year for the progesterone IUD, less than 1% chance per year for the copper IUD). IUDs come with an increased risk of ectopic pregnancy and perforation of the uterus, and do not protect against sexually transmitted disease. IUDs are prescribed and placed in the uterus by a health care provider.

Bleeding disorders. Bleeding disorders that impair blood clotting can cause heavy menstrual bleeding and, according to different studies, have been associated with between 10 - 17% of menorrhagia cases. Von Willebrand disease, a genetic condition, is the most common of these bleeding disorders. Most, but not all, studies report this problem to be more common in African-American than Caucasian women. Most bleeding disorders have a genetic basis and should be suspected in adolescent girls who experience heavy bleeding.
Uterine cancer.
Pelvic infections.
Endometriosis. (These are small implants of uterine tissue. They are more likely to cause pain than bleeding.)

Click the icon to see an image of endometriosis.

Adenomyosis. This condition occurs when glands from the uterine lining become embedded in the uterine muscle. Its symptoms are nearly identical to fibroids (heavy bleeding and pain), and in one study fibroids were also present in 62% of cases. It is most likely to develop in middle-aged women who have had many children.
A number of medical conditions, including thyroid problems, systemic lupus erythematosus, diabetes, certain cancers and chemotherapies, and some uncommon blood disorder.
Certain drugs, including anticoagulants and anti-inflammatory medications.
In many cases, the cause of heavy bleeding is unknown.

Hysteroscopy is a procedure that may be used to detect the presence of fibroids, polyps, or other causes of bleeding. Although less invasive procedures can also detect causes of abnormal uterine bleeding, hysteroscopy has the added advantage of serving as a surgical procedure for the removal of submucous fibroids. It is also quite useful in ruling out cancer. If cancer is suspected, more invasive procedures, such as dilation and curettage (D&C) or endometrial biopsy, are warranted.

Hysteroscopy is non-invasive; however, 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 during this procedure. Other complications include excessive fluid absorption, infection, and uterine perforation.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and also obstructions in the urinary tract. It uses sound waves to produce an image of the organs and entails no risk and very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. Some experts believe it should be the first-line tool for diagnosing heavy bleeding.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) provides a better image of any fibroids that might be causing bleeding. An MRI can help the doctor decide if a woman is a candidate for minimally invasive uterine artery embolization (UAE). Fibroids with low blood flow (“nonviable tumors”) may not be suitable for UAE. An MRI may also be better than an ultrasound for evaluating uterine size and fibroid location.

When heavy or abnormal bleeding occurs, an endometrial (uterine) biopsy can be performed in the office along with an ultrasound. It is usually used with a procedure called dilation and curettage (D&C), which is particularly important to rule out uterine (endometrial) cancer. A D&C is a somewhat invasive procedure:

A D&C is usually done in an outpatient setting so that the patient can return home the same day, but it sometimes requires a general anesthetic. It may need to be performed in the operating room to rule out serious conditions or treat some minor ones that may be causing the bleeding.
The cervix (the neck of the uterus) is dilated (opened).
The surgeon scrapes the inside lining of the uterus and cervix.

Click the icon to see an image of a D&C.

The procedure is used to take samples of the tissue and to relieve heavy bleeding in some instances. D&C can also be effective in scraping off small endometrial polyps, but it is not very useful for most fibroids, which tend to be larger and more firmly attached.

Lifestyle Changes

Because fibroids are almost never life-threatening, watchful waiting is a reasonable option for many women (even those with large fibroids), particularly if they are approaching menopause.

Any woman who chooses watchful waiting should be sure other causes of heavy bleeding have been ruled out. She should also have regular pelvic examinations and ultrasounds performed to monitor the growth of the fibroid.

Foods for Maintaining Healthy Iron Stores. The following are some suggestions for increasing iron levels in the diet:

The best foods for increasing or maintaining healthy iron levels contain absorbable iron, called heme iron. Such foods include (in order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
About 60% of iron in meat is poorly absorbed; this is a form called non-heme iron. Eggs, dairy products, and vegetables that contain iron only have the non-heme form. Such plants include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.
Increasing intake of vitamin-C rich foods can enhance absorption of non-heme iron during a single meal, although regular intake of vitamin C does not appear to have any significant effect on iron stores. In any case, vitamin-C rich foods are healthy and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or 6 ounces of orange juice can double the amount of iron your body absorbs from plant foods.

Like most vitamins, vitamin C may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Foods containing riboflavin (vitamin B2) may help enhance the response of hemoglobin to iron. Sources include liver, dried fortified cereals, and yogurt.
Cooking in cast iron pans and skillets is known to increase iron content of food. According to one study, however, boiling, steaming, or stir-frying many vegetables in utensils composed of any material significantly increases the release of iron stored in plants so it is available to the body.
Certain nutrients, such as tannin (found in tea) or phytic acid (found in foods such as seeds and bran) interfere with the body's absorption of dietary iron. (It is commonly believed that fiber impedes iron absorption, but researchers report that it most likely has no effect.)

Sources of Vitamins B12 and Folate. Vitamins B12 and folate are important for prevention of anemia related to nutritional deficiencies. Although this anemia is not necessarily related to fibroids, these vitamins are very important for good health in general and for reproductive health in women.

The only natural dietary sources of B12 are animal products such as meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, B12 is added to commercial dried cereals. The recommended daily allowance (RDA) is 2.4 mcg a day. Deficiencies are rare in young people, although the elderly may have trouble absorbing natural vitamin B12 and require synthetic forms from supplements and fortified foods.

Click the icon to see an image of vitamin B12 sources.

Folate is best found in avocado, bananas, orange juice, cold cereal, asparagus, fruits, green, leafy vegetables, dried beans and peas, and yeast. The synthetic form, folic acid, is added to commercial grain products. Vitamins are usually made from folic acid, which is about twice as strong as folate. Many experts recommend that adults have 400 mcg of folic acid daily, which is considerably higher than standard recommendations of 400 mcg of folate. Low levels of folate during pregnancy are common without supplements; deficiencies at that time increase the risk of neural tube defects in newborns. Women who are planning to get pregnant should take 400 mcg of folic acid before conception as well as when they are pregnant or breast feeding.

Click the icon to see an image of folate sources.

Iron Supplements. Iron supplements are best for restoring iron levels, but they should be used only when dietary measures have failed. Women should always discuss such supplements with their doctor.

See In-Depth Report #57: Anemia.]

Many women with menstrual disorders may resort to alternative treatments. There has been little research on whether any such therapies benefit fibroids.

Acupuncture. Some women report relief from pelvic pain and heaviness after acupuncture

Click the icon to see an image of acupuncture.

Yoga. Yoga exercises help some women relieve sensations of heaviness and pressure.

Herbal Remedies. Herbal remedies used for fibroids include ginseng or herbal combinations of rhubarb, cinnamon, and sargassum seaweed. There is no scientific evidence that these herbs are effective. Pycnogenol is a plant extract from the bark of the French maritime tree. Studies suggest it may provide some relief for menstrual pain (dysmenorrhea).

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. Patients should check with their doctor before using any herbal remedies or dietary supplements.

Medications

Because fibroid growth tends to stop and regress after menopause, the important reproductive hormones -- estrogen, progesterone, or both -- most likely play a critical role in their survival. Some drugs that block either of these hormones are used to treat severe fibroids with some success.

Oral contraceptives (OCs) are sometimes used to control the heavy menstrual bleeding (menorrhagia) associated with fibroids, but they do not help prevent fibroid growth. Newer types of continuous-dosing OCs, such as Seasonique, reduce the number of periods a woman has per year. In May 2007, the FDA approved Lybrel, a continuous-dosing OC that completely eliminates periods.

Intrauterine devices (IUDs) that release progestin can be very beneficial for menorrhagia. Specifically, the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena, FibroPlant), has shown excellent results. Many experts now recommend the LNG-IUS as a first-line treatment for menorrhagia, particularly for women who may face hysterectomy (removal of uterus), conservative surgery such as endometrial resection (removal of endometrial lining), or endometrial ablation (destruction of endometrial lining). [See In-Depth Report #100: Menstrual disorders.]

Gonadotropin releasing hormone (GnRH) blocks 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. GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and nafarelin (Synarel), a nasal spray. Such drugs may be used alone or in preparation for procedures used to destroy the uterine lining.

These drugs may be used in the following situations:

As preoperative treatment 3 - 4 months before uterine surgery. In a major analysis, the use of GnRH agonists reduced fibroid size and uterus volume, helped correct any existing anemia due to blood loss, reduced blood loss during surgery, and reduced the duration of hospital stay. (Some experts question, however, whether the benefits outweigh the costs.)
For women with fibroids nearing menopause. (Such women only need them for a short period.)
Possibly helpful in improving subsequent fertility. (However, women should not try to become pregnant while taking these drugs, as they pose a risk for birth defects.)

While GnRH agonists can reduce fibroids by between 30 - 90% of original size, they have certain limitations:

They are not permanent cures, and fibroids regrow after the drugs are discontinued.
They are injected drugs and cannot be taken orally.
They are expensive.
Long-term use of GnRh agonists causes bone density loss, which can lead to osteoporosis.

Before using these drugs, the doctor should be certain that no other complicating conditions are present, particularly leiomyosarcoma (cancer). The use of these drugs can delay treatment of the malignancy and cause severe complications.

Commonly reported side effects, which can be severe in some women, include menopausal-like symptoms. These symptoms include hot flashes, night sweats, 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 should not take these drugs for more than 6 months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density but too low to offset the beneficial effects of the GnRH agonist.
Intermittent leuprolide, which 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 a bone-protective drug may be helpful. The standard ones are bisphosphonates, which 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).

Danazol (Danocrine) resembles a male hormone. It suppresses estrogen and is effective for heavy menstrual bleeding caused by fibroids. In some women it produces male characteristics, such as facial hair and voice change. Other side effects include weight gain, acne, and dandruff. It may increase the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have been reported. There is no available long-term experience using danazol for fibroids.

Gestrinone. Antiprogestins are promising drugs for fibroids. Gestrinone has been shown to reduce uterine volume and stop bleeding. In addition, benefits appear to persist. In one study, 89% of the women maintained smaller uterine volume for at least 18 months after stopping the treatment. In another 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 an anti-progestin that has reduced fibroid size in some studies. In one study, it reduced fibroids as significantly as GnRH agonists, and the fibroids were less likely to recur. However, this medicine can have severe side effects.

Asoprisnil. A promising new antiprogestin called Asoprisnil has been shown to reduce fibroids. The drug is in late-stage clinical trials.

Although they have not been studied for fibroids, nonsteroidal anti-inflammatory drugs (NSAIDs) taken on a regular schedule reduce heavy menstrual bleeding and pain from unknown causes. These drugs reduce inflammation, in part by their action against prostaglandins, the chemicals that stimulate uterine contractions and cause pain. Aspirin is the most common NSAID, but there are dozens of others, including ibuprofen (Advil, Motrin) and naproxen (Aleve, Anaprox, Naprosyn). Both ibuprofen and naproxen are recommended for menstrual pain. However, long-term use of any NSAID can increase the risk for gastrointestinal bleeding and ulcers. In addition, long-term use of high-dose NSAIDs (with the exception of aspirin) can increase the risk for heart attacks and strokes. To reduce these risks, it is best to take the lowest dose of NSAIDs for the shortest time possible.

A number of other drugs are under investigation for treating fibroids:

Selective estrogen-receptor modulators (SERMs) are drugs that have some of the effects of estrogen but do not produce some of its complications, such as a higher risk for uterine cancer. Raloxifene (Evista) is proving to help prevent bone loss in patients taking GnRH agonists for uterine fibroids, and may also be helpful as a single drug for preventing fibroid growth.
Drugs that block growth factors believed to play a role in fibroids are also under investigation. Pirfenidone is one such drug, which blocks fibroid cell reproduction. Another is interferon alpha, substance that inhibits angiogenesis (the growth of new blood vessels).
Drugs derived from retinoids (vitamin A compounds) may inhibit cell proliferation in fibroid tissue.
Fulvestrant (Faslodex) blocks estrogen and has been studied for uterine fibroids and endometriosis, although progress in these areas has stalled in favor of research for its use in breast cancer.

Surgery

If nonsurgical strategies do not relieve symptoms, surgery may be the best option for treatment. Surgery may be indicated depending on a number of factors:

Intractable Side Effects. Surgery may be warranted if fibroids are causing distressing and intractable symptoms that have not been relieved by nonsurgical or minimally invasive therapies. Assuming, however, that symptoms do not pose serious health or life-threatening conditions, a woman should make her decision based on the factors she deems important (the desire for children, for example).

Ureteral Obstruction. Large fibroids sometimes press down on the ureters (the tubes going from each kidney to the bladder), thereby blocking urine from emptying into the bladder. Because ureteral obstructions can permanently damage kidneys, surgery may be indicated.

Inability to Evaluate Ovaries. The risk for missing a diagnosis of ovarian cancer is higher when fibroids are too large to permit evaluation of the ovaries by pelvic examination or ultrasound. Ovarian cancer is particularly deadly because it is so difficult to catch early enough for curative treatment. The risk for this cancer, however, is very low in women without a family history, especially before menopause. Women with a family history of ovarian cancer and large fibroids may need to consider surgery.

Enlarging Fibroids. Rapidly growing fibroids may signify cancer (leiomyosarcoma), which must be ruled out. In postmenopausal women, even slow growth raises suspicions for cancer. However, many hysterectomies have been inappropriately performed because of large noncancerous fibroids that were only suspected to be cancerous. Women should be sure that diagnostic procedures have been as thorough as possible if they want to avoid an unnecessary hysterectomy.

Severe Anemia from Heavy Bleeding. When iron supplementation, resection (surgical removal) of submucous fibroids by hysteroscopy, or GnRH agonist therapy fails to resolve anemia and bleeding, major surgery (myomectomy or hysterectomy) may be recommended.

Hysterectomy. Until recently, hysterectomy was the only surgical option for uterine fibroids. This procedure involves the surgical removal of the uterus and is often accompanied by oophorectomy (the removal of the ovaries). With this procedure, fertility is not preserved. Other options may be available for many women, even those who have large fibroids. Discuss all possibilities with your physician.
Myomectomy. Myomectomy is the surgical removal of only one or more fibroids. Myomectomy usually involves a laparotomy (a procedure that uses a wide abdominal incision) or less invasive surgical techniques, such as laparoscopy and hysteroscopy. In such cases, unlike with hysterectomy, this technique may preserve fertility.
Uterine Artery Embolization (UAE). UAE, also called uterine fibroid embolization (UFE), is a non-surgical radiology procedure. An interventional radiologist injects small plastic particles through a catheter placed in the uterine artery. The particles block the blood supply to the fibroids and cause them to shrink
Other Procedures. Endometrial ablation (destruction of the lining of the uterus) may be useful in women with small fibroids and heavy bleeding. Myolysis is another procedure best suited for women with specific types of small fibroids. Magnetic resonance-guided focused ultrasound (MRgFUS) is the newest type of fibroid procedure. Myolysis and MRgFUS use heat to cut off the blood supply to fibroids.

Women should discuss each option with their doctor. Deciding on the surgical procedure depends on the location, size, and number of fibroids. Certain procedures affect a women’s fertility and are recommended only for women who are past childbearing age or who do not want to become pregnant. The risk for bleeding increases with the surgeon's inexperience, so patients are urged to investigate the surgeon's track record.

A study published in 2007 in the New England Journal of Medicine compared outcomes for uterine artery embolization (UAE) versus standard surgery (hysterectomy or myomectomy). Researchers found that after 1 year, women experienced similar improvements in quality of life regardless of the procedure. Women who had UAE had shorter hospitalizations and faster recovery than those who had standard surgery. However, around 10% of women who had UAE required a repeat procedure (embolization or hysterectomy) during the first year, and another 10% required additional treatment after the first year.

Other Procedures

In order to operate on the uterus, the surgeon may choose to reach the area through a wide abdominal incision (laparotomy) or use less invasive measures with the use of endoscopy. The decision is usually based on the severity of the case. Women should discuss all options very carefully and be sure that their surgeons have had experience with any procedure they choose.

Laparotomy. Laparotomy is the standard abdominal surgical procedure. It is invasive and usually requires a wide abdominal horizontal incision right above the pubic bone, the so-called bikini incision.

Endoscopy. Endoscopic techniques used for uterine disorders are hysteroscopy and laparoscopy. Endoscopic techniques are used increasingly to replace conventional surgical techniques for many disorders. A common factor in all endoscopic procedures is the use of a fiberoptic scope and tubes, tiny camera lenses, and minuscule surgical instruments. Any incisions made are very small, Band-Aid size.

Operative Hysteroscopy. In this procedure, the cervix is dilated, which requires either a local or general anesthetic. A device called a hysteroscopy is inserted up through the vagina and cervix into the uterine cavity. It contains tiny surgical instruments as well as a mini-camera and light source to view images of the uterus, which are transmitted to a video monitor. This approach is becoming increasingly common. Complication rates include excessive fluid absorption, infection, and uterine perforation.
Laparoscopy. This procedure uses two or more small incisions, one at the navel, and one or more in the lower abdomen. Carbon dioxide gas is injected into the abdomen, distending it and pushing the bowel away. A laparoscope is inserted through the navel incision and a probe is inserted through a second incision above the pubic hairline. The probe allows the doctor to directly view the abdominal cavity, including the outer walls of the uterus, fallopian tubes, and ovaries. The doctor manipulates surgical instruments that are passed through additional small abdominal incisions, using the image of the uterus on the video monitor as the guide.

GnRH agonists, usually depo-Lupron or Synarel, are often used for 2 - 3 months before many uterine surgical procedures.

These drugs may help by:

Reducing the volume of fibroids by 40 - 60%, in some cases to the extent that a less invasive procedure may be performed
Reducing the risk of bleeding
Shortening surgical time
Reducing postoperative symptoms

Treatments may not be useful, however, for small fibroids, which may shrink to the point that they are no longer visible at the time of surgery. Since fibroids regrow after treatment, the problem would recur.

There has also been some question whether these drugs provide any additional advantages for myomectomies that use conventional surgical techniques. Ultrasound may be useful in helping to detect fibroids most likely to benefit from GnRH agonists before such a procedure.

A myomectomy surgically removes only the fibroids and leaves the uterus intact, often preserving fertility. Myomectomy may also help regulate abnormal uterine bleeding caused by fibroids. Not all women are candidates for myomectomy. If the fibroids are numerous or large, myomectomy can become complicated, resulting in increased blood loss. If cancer is found, conversion to a full hysterectomy may be necessary.

To perform a myomectomy, the surgeon may use standard surgical approaches (laparotomy) or less invasive ones (hysteroscopy or laparoscopy).

Laparotomy. Laparotomy uses a wide abdominal incision and conventional surgery. It is used for subserosal or intramural fibroids that are very large (usually more than 4 inches), that are numerous, or when cancer is suspected. Using this approach, the doctor may be able to feel the fibroids, particularly intramural types, which can be missed during laparoscopy or hysteroscopy. (The doctor can only view the uterine cavity or outside surface with these latter procedures.) After the fibroids are removed, careful reconstruction of the uterine wall is critical in both laparotomy and laparoscopy, so that bleeding and infection do not occur. While complete recovery takes less than a week with laparoscopy and hysteroscopy, recovery from a standard abdominal myomectomy takes as many as 6 - 8 weeks. It also poses a higher risk for scarring and blood loss than with the less invasive procedures, which is a concern for women who want to retain fertility.
Hysteroscopy. A hysteroscopic myomectomy may be used for submucous fibroids found in the uterine cavity. With this procedure, fibroids are removed using an instrument called a hysteroscopic resectoscope, which is passed up into the uterine cavity through the vagina and cervical canal. A wire loop carrying electrical current is then used to shave off the fibroid. In one study, nearly 60% of patients conceived after this procedure. However, it is not appropriate for many women.
Laparoscopy. Women whose uterus is no larger than it would be at a 6-week pregnancy and who have a small number of subserous fibroids may be eligible for treatment with laparoscopy. Laparoscopy requires incisions, but they are much smaller than with laparotomy. As with hysteroscopy, a thin scope is employed that contains surgical and viewing instruments. In centers with extensive experience, laparoscopy has fewer complications, and also shorter recovery time and lower costs than laparotomy. On the other hand, compared to the invasive surgery, laparoscopy has a greater chance for fibroid recurrence (over 16% at 5 years in one study), and a greater danger for a weakened uterine wall, which could threaten pregnancies.

Complications and Postoperative Factors. Any procedure for myomectomy is very complex. To reduce the risk for complication, patients should seek a surgeon experienced in myomectomies. Complications that occur during a myomectomy from any procedure include:

Excessive blood loss (occurs more often with laparotomy)
Uterine weakening and rupture during pregnancy (more of a concern with laparoscopy)
Development of scar tissue called adhesions (more common with laparotomy)
Infection
Damage to the bowel or bladder (more common with laparotomy)

Pregnancies After Myomectomy. Studies suggest that pregnancy can be restored in more than half of women after the procedure. In appropriate candidates, there appears to be no differences in fertility rates and pregnancy complications between laparotomy or laparoscopy. The best candidates for retaining fertility include women with pedunculated and superficial serosal fibroids (stalk-like fibroids that grow out from the uterine surface). Women with deep intramural fibroids are at higher risk for infertility after myomectomy.

Although studies indicate that between 40 - 58% of women become pregnant after myomectomy, only about a quarter of the women carry their babies to term. Women who become pregnant face a higher risk for cesarean section or miscarriage. It is unclear whether laparoscopic myomectomy weakens the uterine walls and poses a higher risk for rupture during pregnancy than laparotomy.

Recurrence of Fibroids and Recurrent Surgeries. The recurrence rate for fibroid growth after myomectomy is high. Between 11 - 26% of patients will have recurring fibroids that are severe enough to need additional treatment. One study suggested that women who had uteruses that were less than the equivalent size of a 12-week pregnancy and women who were overweight had a higher risk for needing repeat surgery.

Uterine Artery Embolization (UAE), also called uterine fibroid embolization (UFE), is a relatively new way of treating fibroids. UAE deprives fibroids of their blood supply, causing them to shrink. UAE is a minimally invasive radiology treatment and is technically a nonsurgical therapy. It is much less invasive than hysterectomy and myomectomy, and involves a shorter recovery time than the other procedures. The patient remains conscious, although sedated, during the procedure, which takes around 60 - 90 minutes.

The procedure is typically performed in the following manner:

The patient receives a sedative to cause drowsiness, and a local anesthetic is applied to the skin around the groin.
An interventional radiologist makes a small quarter-inch incision in the skin and inserts a catheter (a thin tube) into the femoral artery. The femoral artery is a large artery that begins in the lower abdomen and extends down to the thigh. The radiologist then threads the catheter into the uterine artery.
Small plastic particles are injected into the artery. These particles block the blood supply to the tiny arteries that feed fibroid cells, and the tissue eventually dies.
Patients usually stay in the hospital overnight after UAE and are given pain medication. Pelvic cramps are common for the first 24 hours after the procedure.
It takes 1 - 2 weeks for the patient to recover from the procedure and return to work. It may take 2 - 3 months for the fibroids to shrink enough so that symptoms improve.

Effect on Fertility. In general, UAE is considered an option for only those who have completed childbearing. Although UAE may protect fertility in many women, the procedure does pose some risk for ovarian failure and infertility. In 2004, the American College of Obstetricians and Gynecologists issued an opinion statement advising women who wish to have children that it is not yet known how this procedure affects their potential for becoming pregnant. A 2005 British study of 671 women who underwent UAE found that the procedure did not interfere with fertility. The study did find a slight increase in caesarean section delivery.

Complications and Postoperative Effects. UAE has a lower rate of complication than hysterectomy and myomectomy and a shorter hospital stay. Compared to other procedures, women who undergo UAE miss fewer days of work. Serious complications occur in less than 0.5% of cases, and no deaths have been associated with the procedure.

Pain. Abdominal cramps and pelvic pain after the procedure are nearly universal and may be intense. Pain usually begins soon after the procedure and typically plateaus by 6 hours. On-demand painkillers may be required. The pain usually improves each day over the next several days. A low-grade fever is also common in the first week after the procedure.
Fibroid slough. Around 2 – 3% of patients pass small fragments of fibroid tissue during the first few days after UAE. This can cause intense labor-like pain and also increase the risk for infection. Some women may require dilation and curettage (D&C) to make sure that infection does not develop.
Early menopause. Most women who have UAE will continue to have normal menstrual periods. Around 1 – 5% of women, however, experience menopause after the procedure. Menopause is more likely to occur in women over age 45 who undergo UAE.

Success Rates. Studies on uterine artery embolization show high patient satisfaction (over 90%) and low complication rates. A 2003 study reported 83% improvement in heavy bleeding, 77% reduction in menstrual cramps, and 85% improvement in urinary symptoms. Results from the first long-term UAE study, presented at the 2005 annual scientific meeting of the Society of Interventional Radiology, reported that 73% of women experienced symptom relief that lasted for 5 years. The success rate for UAE was comparable to that of myomectomy. A 2006 study reported a success rate of 89% for UAE compared to 100% for hysterectomy.

For around 10 - 20% of women, symptom control fails or fibroids reoccur. Some studies suggest that women with large fibroids are not good candidates for UAE.

In either endometrial ablation or endometrial resection, the entire lining of the uterus (the endometrium) is removed or destroyed. These procedures are useful for women with severe heavy menstrual bleeding, including some with fibroids. They are generally not useful for large fibroids. Standard resection uses an electrosurgical wire loop to surgically remove the lining. With ablation, uterine tissue is usually vaporized using a thin powerful laser beam or high electric voltage. Newer ablation procedures include balloon ablation (ThermaChoice) and techniques that use electric wands, freezing, hot saline, lasers, microwaves, and radiofrequency.

Myolysis, or laparoscopic leiomyoma coagulation, uses either lasers or electrosurgery to heat and coagulate and destroy the fibroid tissue. This approach may prove to be beneficial for women with fibroids that measure a diameter of 10 cm (about 4 inches) or less and that respond to hormone treatments with GnRH agonists.

Myolysis uses a needle or a Nd:YAG laser that rapidly punctures a number of holes in the fibroid, heating and destroying the tissue in various locations. This widespread destruction cuts off the blood supply and shrinks the fibroid over ensuing months. The uterus is left intact, but tissue destruction makes childbearing unlikely.

In one study, myolysis performed either alone or with endometrial resection was successful in avoiding the need for major surgery in 97% of women. Advanced techniques that are performed by surgeons who are highly skilled in the procedure may make it possible to destroy even large intramural fibroids, but further study is required.

In most cases, patients return home the same day and can return to normal activities within a week. There are few side effects. However, as the fibroids degenerate over time, many women report considerable pain.

MRgFUS is a non-invasive procedure that uses high-intensity ultrasound waves to heat and destroy (ablate) uterine fibroids. This “thermal ablation” procedure is performed with a device that combines magnetic resonance imaging (MRI) with ultrasound. The FDA approved this device, the ExAblate 2000 System, in 2004.

During the 3-hour procedure, the patient lies inside an MRI machine. The patient receives a mild sedative to help relax but remains conscious throughout the procedure. The radiologist uses the MRI to target the fibroid tissue and direct the ultrasound beam. The MRI also helps the radiologist monitor the temperature generated by the ultrasound.

MRgFUS is appropriate only for women who have completed childbearing or who do not intend to become pregnant. The procedure cannot treat all types of fibroids. Fibroids that are located near the bowel and bladder, or outside of the imaging area, cannot be treated.

Research presented at the 2005 Radiological Society of North America annual meeting reported that MRgFUS helps improve fibroid symptoms and reduce fibroid size. A 2006 study indicated that the procedure provides symptom relief for up to 1 year. Another 2006 study indicated that pre-treatment with GnRH-agonist drugs before the MRgFUS procedure may help improve outcomes. However, because this procedure is new and long-term results are not yet available, some insurance companies do not pay for this treatment.

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 the rise has slowed substantially in recent years. The percentage of hysterectomies performed because of fibroids, however, has risen significantly. Fibroids now account for 38% of these operations, but the rates vary widely by ethnic group. In a major 2002 government report, 68% of fibroid-related hysterectomies were performed in African-American women, 33% in Caucasians, and 45% among women of other ethnic groups.

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

Still, in one study in 70% of cases when doctors recommended hysterectomies, they did not give their patients alternative choices or adequate diagnostic evaluations. Any woman, even one who has reached menopause, uncertain about a recommendation for a hysterectomy for fibroids 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).
Supracervical Hysterectomy (removal of uterus and preservation of the cervix); performed in about 20 - 25% of cases.
Bilateral Salpingo-Oophorectomy (removal of the fallopian tubes and ovaries); used with either total or supracervical hysterectomy.

Total Hysterectomy. In a total hysterectomy the uterus and cervix are removed, which 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) the uterine body is removed, and the cervix is retained. 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.) Bilateral salpingo-oophorectomy is the removal of both fallopian tubes and ovaries. These procedures may be performed with either total or supracervical hysterectomy. When deciding to remove the ovaries, a woman must be aware of various consequences, both positive and negative.

Oophorectomy helps to reduce the risk for ovarian cancer, by elimination of ovaries, and breast cancer, by causing estrogen loss. Ovarian cancer is very rare, in any case, except in women with a family history of the disease. Even in these women, removal is not 100% preventive. Cancer can still develop from cancer cells that may be present in the lining of the pelvis (the peritoneum).
Removal of the ovaries ceases estrogen and testosterone production, which can increase the risk for menopause-related conditions. These include osteoporosis, heart disease, skin wrinkling, and reduced muscle tone. Estrogen replacement, however, can help offset these problems. 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.

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. It is best suited for women with large fibroids, when the ovaries need to be removed, or when cancer or pelvic disease is present. 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 (the 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. This approach is most often performed for small fibroids (although advances in imaging and other techniques may allow it to be used on larger fibroids). At this time, it is used in fewer than 20% of African-American women and slightly under 40% of Caucasians 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. Hospital stays may be longer and costs are greater than with standard vaginal hysterectomy. The use of LAVH has risen significantly and is used in over a quarter of vaginal procedures. LAVH is very costly and time consuming, however, and some experts question whether it adds any significant benefits compared to the standard vaginal procedure.

The 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 speed 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 from abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should discuss with the doctor when exercise programs more intense than walking can be started. 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 while others may recover in only a few weeks.

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.

Infection. Infection occurs in 10 - 15% of patients, the risk being higher with abdominal than with vaginal surgery. Risk factors for infection include 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. Symptoms of infection include:

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

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

Pulmonary embolism (blood clots that travel to the lung).
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 if adhesions (extensive scarring) have formed and obstruct the intestines; may require additional surgery.
Shortening of the vagina is a possible complication specific to vaginal hysterectomy. It can cause pain during intercourse.

Such complications are uncommon.

Two procedures associated with hysterectomy may affect sexuality directly:

Although the clitoris can trigger orgasm even if the cervix is removed, many 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.

Resources

www.asrm.com -- American Society for Reproductive Medicine
www.acog.com -- American College of Obstetricians and Gynecologists
www.sirweb.org -- Society of Interventional Radiology
www.nuff.org -- National Uterine Fibroids Foundation
www.rsna.org -- Radiological Society of North America
www.radiologyinfo.org -- Radiology info from the American College of Radiology and the Radiological Society of North America
www.radiologyinfo.org/content/interventional/ufibroid-embol.htm -- Information on uterine fibroid embolization
www.fibroids.net -- Brigham and Women's Hospital, Center for Uterine Fibroids
www.nichd.nih.gov -- National Institute of Child Health and Human Development

References

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.

Edwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med. 2007 Jan 25;356(4):360-70.

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

Smart OC, Hindley JT, Regan L, Gedroyc WG. Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata. Obstet Gynecol. 2006 Jul;108(1):49-54.

Review Date:
2/28/2008
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, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (6/16/2007).

A.D.A.M. Copyright

adam.com

Chronic fatigue syndrome

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Risk Factors
Causes
Diagnosis
Prognosis
Treatment
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Causes

Four out of five people with chronic fatigue syndrome (CFS) are infected with an enterovirus -- one of the viruses that cause respiratory and gastrointestinal infections -- compared with only one out of five healthy people. The virus might be a trigger for CFS, although research has not yet confirmed a cause-and-effect relationship.

Diagnosis

According to new guidelines, symptoms that suggest a diagnosis of CFS include disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition. Other symptoms may include difficulty concentrating or sleeping, dizziness, headaches, muscle or joint pain, sore throat, and palpitations. Doctors should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children.
Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation.

Treatment

According to one study, people with CFS who used cognitive behavioral therapy (CBT) had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use the therapy.
A 2007 study found that taking two 10 milligram doses of methylphenidate (Ritalin) each day works much better than placebo at relieving fatigue and concentration problems in people with CFS.

Introduction

Chronic fatigue syndrome (CFS), sometimes called immune dysfunction syndrome or myalgic encephalomyelitis (in Europe), is not a new disorder. In the 19th century the term neurasthenia, or nervous exhaustion, was applied to symptoms resembling CFS. In the 1930s through the 1950s, outbreaks of disease marked by prolonged fatigue were reported in the United States and many other countries. Beginning in the early- to mid-1980s, interest in chronic fatigue syndrome was revived by reports in America and other countries of various outbreaks of long-term debilitating fatigue.

Unexplained chronic fatigue describes fatigue that lasts for more than 6 months, impairs normal activities, and has no identifiable medical or psychological problems to account for it. In addition to fatigue, people may complain of other problems, such as difficulty with memory or concentration, headaches, or sore muscles or joints.

The symptoms of CFS may be categorized as follows:

Chronic fatigue syndrome (CFS). A number of criteria must be met in order for a patient's symptoms to be described as CFS. Six million patient visits are made each year because of fatigue, although only a very small percentage of these visits can be attributed to actual chronic fatigue syndrome.
Idiopathic chronic fatigue. If the symptoms do not meet the criteria for CFS, the condition is referred to as idiopathic chronic fatigue, meaning the cause is unknown.

Although the exact causes of CFS are not known, researchers think infection, genetics, hormonal imbalances, and chemical toxins play roles in different patients.

Risk Factors

In studies of large patient groups, 15 - 27% of people complain of long-term fatigue, but the majority of this fatigue can be explained by other medical or psychological problems. According to surveys, chronic fatigue syndrome (CFS) itself affects more than four out of every 1,000 Americans.

CFS occurs in both sexes, at all ages, and in all racial and ethnic groups. The Centers for Disease Control and Prevention estimates 1 million people in the U.S. have the disease, but only 20% of people with CFS may be properly diagnosed. Nevertheless, the true prevalence of CFS is very difficult to determine, since an accurate diagnosis is hard to obtain.

People ages 40 - 50 most often experience chronic fatigue. Studies have found that four out of five people with CFS are women, although a woman's symptoms do not appear to be more severe symptoms than those of men with the disorder.

Children and adolescents are not immune to CFS. Most studies indicate that girls are more likely than boys to develop CFS, although one study found the incidence of the syndrome to be equal in children among the genders.

The link between psychological disorders and chronic fatigue syndrome is problematic because so many of the symptoms overlap. The rates of depression are very high in CFS patients, possibly higher than in patients with other conditions (notably fibromyalgia and multiple chemical sensitivity).

Studies report that most children and adolescents with CFS have psychiatric disorders. Psychological factors during childhood may increase susceptibility for later CFS, although these factors are not consistent. Studies have not found any consistent association between emotional or personality disorders and CFS to explain any causal role. Some psychological factors may, however, serve as a risk factor for CFS.

Depression, in any case, is very common in the general population. It affects up to one-fifth of all Americans at some point in their lives, and most depressed people feel fatigued.

There is some evidence that stress may be a trigger for CFS in people genetically at risk for the disease.

A number of conditions overlap or coexist with chronic fatigue syndrome and have similar symptoms. Patients with CFS may also have a diagnosis of fibromyalgia, multiple chemical sensitivity, or both. It is not clear whether these conditions or others are risk factors for CFS, are direct causes, have common causes, or have no relationship at all with CFS.

Fibromyalgia. Fibromyalgia causes prolonged fatigue and widespread muscle aches. It is the disease most often confused with CFS. The two conditions also commonly appear together. In fact, many experts believe fibromyalgia is simply another variant of chronic fatigue syndrome or different manifestations of the same disease. CFS patients experience severe fatigue, whereas fibromyalgia patients experience more pain. One hypothesis proposes that the connection between the two conditions may be found in central sensitization, which is thought to cause fibromyalgia and may also cause CFS.

A characteristic feature of fibromyalgia is the existence of at least 11 distinct sites of deep muscle tenderness that hurt when touched firmly. The sites often include the following:

The side of the neck
The top of the shoulder blade
The outside of the upper buttock and hip joint
The inside of the knee

Some patients with CFS exhibit similar tender pressure points. Recurrent sore throat, headache, low fever, and depression are also common symptoms of fibromyalgia. Like CFS, fibromyalgia is chronic and not curable.

Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a term now used to describe a condition in which certain chemicals are believed to cause symptoms similar to CFS in some people. It has also been observed in people with CFS. The following proposed criteria can help recognize people with MCS:

The symptoms are reproducible with repeated exposure to a chemical. (These are often common chemicals found in popular products, such as perfumes, fabric softeners, and air fresheners.)
The condition is chronic.
Symptoms can be produced by exposure to the chemical at levels lower than previously or commonly tolerated.
The symptoms improve when the chemical is removed.
Symptoms can be triggered by multiple substances that are chemically unrelated.
Symptoms involve multiple organ systems.

Still, as with CFS and fibromyalgia, there is uncertainty as to whether MCS is an actual medical condition or is psychologically based. In one study, for example, CFS patients who believed their problem was chemically triggered were exposed to either an active chemical or a placebo (an inactive substance). Both groups reported symptoms, including those exposed only to the placebo. It should be noted that everyone is exposed to many chemicals on a daily basis, and it is very difficult to determine whether chemicals are responsible for specific symptoms.

Post-ADD. Young adults who had attention deficit disorder as children can flip from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping at any time or anywhere). These patients respond well to psychostimulant medications.

Eating Disorders. Eating disorders, notably bulimia and anorexia, have been observed in patients with CFS. The conditions often have overlapping risk factors, although it is unclear whether there is a causal relationship.

Other Conditions that Commonly Coexist With CFS. A number of other conditions also often coexist with CFS and, in fact, occur at higher-than-average rates among CFS patients:

Chronic headaches
Cognitive problems such as difficulty concentrating, impaired memory, and symptoms of attention deficit disorder
Interstitial cystitis
Irritable bowel syndrome
Sleep problems
Temporomandibular disorder (TMD)

Causes

Theories abound about the causes of chronic fatigue syndrome. Indeed, no primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition.

Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:

Genetic factors
Brain abnormalities
A hyper-reactive immune system
Viral or other infectious agents
Psychiatric or emotional conditions

For example, the majority of patients report some preceding moderate-to-serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression). Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger the event.

Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific brain or nervous system problem that experts can point to with assurance. Research indicates that CFS is more common among identical twins (who share the same genes) than fraternal twins (who share only some genes). Inheritance, then, may play a role in roughly 30 - 50% of cases, similar to the influence thought to occur in depression or alcoholism, although specific genes have not yet been identified.

New evidence suggests genes involved in the body's response to stress may play key roles in CFS. A series of 14 articles published in 2006 linked CFS with genes involved in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. The researchers were able to locate a common variation of DNA sequences that predicted CFS with 76% accuracy. The genes control response to trauma, injury, and other stressful events. Nevertheless, the researchers were unable to find genetic markers of CFS or to determine how the genetic variations influenced symptoms.

In 2005, English researchers found that people with CFS are more likely than people without CFS to have human leukocyte antigen (HLA) class II alleles, variations that produce antibodies to certain immune factors. Another British study of people with CFS found alterations in 16 specific genes involved with immune function, communication between cells, and transfer of energy to cells.

Abnormal levels of certain chemicals regulated in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, response to stress, and depression. Of particular interest to researchers are the following chemicals and other factors controlled by the HPA axis:

Changes in Important Neurotransmitters. Research has reported that some patients with CFS have abnormally high levels of serotonin, a neurotransmitter (chemical messenger in the brain). Such elevated levels in the brain are associated with fatigue. Studies also suggest that deficiencies of dopamine, an important neurotransmitter associated with feelings of reward, may play a role in CFS. Imbalances between norepinephrine and dopamine have been identified in certain CFS patients in several studies. Unfortunately, routine clinical testing for such chemical imbalances is cost-prohibitive.
Stress Hormone Deficiencies. A number of studies on CFS patients have observed lower levels of cortisol, a stress hormone produced in the adrenal glands. Cortisol is a precursor of dehydroepiandrosterone (DHEA), a weak male hormone that may also be important in CFS. Deficiencies may be the reason why CFS patients have an impaired and weaker response to psychological or physical stresses, such as infection or exercise. (Administering replacement cortisol improves symptoms only in some patients, indicating other factors are involved.)
Disturbed Circadian Rhythms. Evidence suggests that, in certain patients, CFS is a disorder of the sleep-wake cycle, which is regulated by the so-called circadian clock, a nerve cluster in the hypothalamus-pituitary-adrenal (HPA) axis. Some mentally or physically stressful event, such as a viral infection, may disrupt natural circadian rhythms, and an inability to reset these rhythms results in a perpetual cycle of sleep disturbances. Medications that improve sleep can be very helpful for certain patients with CFS.

However, it is still not clear whether any of these changes are causes of chronic fatigue syndrome, or merely findings in some patients.

Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases.

Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, subtypes of viral-related and non-viral CFS may both exist.

Viruses. The theory that CFS has a viral cause is not based on hard evidence, but on various observations that suggest an association, such as the following:

CFS patients typically have elevated levels of antibodies to many organisms that cause fatigue and other CFS symptoms. Such organisms include those that cause Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLV), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus. Many of these infectious agents are very common, however, and none has emerged as a significant cause of CFS.
In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition.
In the U.S., there have been reports of cluster outbreaks of CFS occurring within the same household, workplace, and community (but most have not been confirmed by the Centers for Disease Control and Prevention).
One study found that four out of five people with CFS are infected with an enterovirus -- one of the viruses that causes respiratory and gastrointestinal infections -- compared to only one out of five healthy people. The virus could be a trigger for CFS, although research has not confirmed a cause-and-effect relationship.

Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS.

Evidence suggesting that some CFS cases may not be due to a virus includes the following:

Most cases of CFS occur sporadically. They occur in individuals and do not appear to be contagious.
There is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact.
No single virus has been implicated in chronic fatigue syndrome. Well-designed studies of patients who met strict criteria for chronic fatigue syndrome and of patients with chronic fatigue without any known cause have not found an increased incidence of any specific infections.

CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system. Some components appear to be over-reactive, while others appear to be under-reactive, but no consistent picture has emerged to explain CFS as a disease of the immune system.

Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities leading to CFS. (Most allergic people do not have CFS.)

Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases. Studies are inconsistent, however, in reporting the presence of autoantibodies (antibodies that attack the body's own tissues) in CFS, and the disease is unlikely to be due to autoimmunity.

Studies have observed that some patients who fit the strict criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as short a time as 10 minutes. Its immediate effects can be lightheadedness, nausea, and fainting.

However, not all CFS patients experience NMH, and studies have reported no higher incidence of NMH in chronic fatigue patients.

Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS to explain a causal role. Psychological factors, then, are unlikely to be a primary cause of CFS. They may play a role in increasing susceptibility to the disorder. Certainly, in many cases, CFS promotes psychological and social dysfunction.

Overall, doctors are increasingly adopting the view that CFS is probably a disease category that includes a range of subtypes, in the same way that cancer is a broad term within which numerous specific forms occur. Mounting evidence suggests that different subtypes of CFS have different causes and manifestations, and that these various types require different treatment approaches.

Research on subgroups of CFS is underway, but it is still in the very early stages. To date, however, clinical experience and limited data suggest that subgroups of CFS may include the following:

Post-ADD CFS: Young adults who had attention deficit disorder as children, who have flipped from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping any time or anywhere). Such patients respond well to psychostimulant medications.
Neurological CFS: These patients have more severe cognitive symptoms than do patients in the other groups. They may have trouble thinking, remembering, and paying attention. Although cognitive difficulties affect the vast majority of patients with CFS, this group experiences significantly more severe symptoms. Visual-spatial problems are common, as are sensitivities to light and noise. Other symptoms in this group include seizure-like episodes and other abnormalities that suggest temporal lobe seizures. Patients in this group tend to have severe sleep problems in which they never achieve stages 3 or 4 of the sleep cycle, awaken unrefreshed, and respond well to sleep-improving drugs.
Post-viral CFS versus gradual-onset CFS: According to some experts, an estimated 70% of patients are healthy until a particular illness strikes. In gradual-onset patients, however, symptoms develop gradually, and patients are unable to recall any specific viral or infectious illness that initiated the process.
Patients with immune abnormalities versus those without such abnormalities: Immune dysfunction (such as CD4, CD8, RNase, and TH1-TH2 imbalances) can leave some CFS patients unable to fight viruses effectively and cause their bodies to launch wrongful attacks against healthy tissues. Other CFS patients, however, do not have these immune abnormalities, or have only borderline shifts in immune factors.
CFS with Orthostatic Intolerance or Neurally Mediated Hypotension (NMH). These conditions cause dizziness (or unconsciousness) when a person stands up, due to a drop in blood pressure.
CFS with neuroendocrine abnormalities: Such problems may include dysregulation of cortisol or ACTH levels.
Activity level: There may be a difference between low-active versus high-active patients.
Patients with CFS alone: This subgroup may be different than CFS in patients with other conditions, such as fibromyalgia or multiple chemical sensitivity.

Observations that different treatments work for select patients appear to support the idea that subtypes of CFS require distinct approaches. The existence of subgroups may also explain why CFS researchers are frequently unable to replicate their results in subsequent studies; patient selection in studies to date has not reflected such careful discrimination. Researchers are now, however, working to define the subgroups of CFS and identify which treatments are most effective for each.

It should be noted that while the subgroup theory is interesting, in some cases the differences among patient populations may also reflect stages of disease. For instance, in the initial stages of the disease, many patients are symptomatic and have particular psychological symptoms, including alarm, denial, and anger. In contrast, patients in later phases of the disease typically have learned to cope better with their symptoms and have a degree of acceptance. Patients' mental and emotional status may have biological consequences that bear on their physical symptoms. Such a relationship is not yet documented in CFS patients, however, and remains subject to research.

Sudden- and Gradual-Onset CFS. One interesting theory is that CFS can be categorized as either sudden- or gradual onset, with each subgroup having different causes. In over half of patients, the onset is sudden, while the remaining patients have a slow onset. Some experts believe that sudden-onset CFS may be triggered by a virus or neurologic abnormality, while gradual-onset CFS might have a psychological or other cause. Supporting this theory was a study that looked at MRI scans of the brains of CFS patients who didn't have an accompanying psychiatric problem, and showed small injuries suggesting either a viral infection or neurologic problem. Still other experts believe that in some cases, gradual-onset CFS may be traced to cognitive disorders that were present during childhood, but went unrecognized until symptoms advanced into adulthood.

Diagnosis

It is very difficult to diagnose chronic fatigue syndrome. Even experts do not have a clear definition of what chronic fatigue actually is or what mechanisms in the brain or nervous system are responsible for it. The best diagnostic approach is to determine if the patient matches the criteria for CFS and to rule out other possible causes of symptoms.

In May 2006, the Centers for Disease Control and Prevention (CDC) released a revised definition for Chronic Fatigue Syndrome based on a consensus of many of the leading CFS researchers and doctors (including input from patient group representatives). In the revised definition, chronic fatigue syndrome is considered a subset of chronic fatigue, a broader category defined as unexplained fatigue that lasts for 6 months or longer. Chronic fatigue is considered a subset of prolonged fatigue, which is defined as fatigue that lasts for 1 month or more.

Unexplained chronic fatigue can be classified as CFS if the patient meets the following criteria:

Unexplained persistent or relapsing chronic fatigue that is either new or that started at a definite period of time; is not the result of ongoing exertion; is not substantially relieved by rest; and significantly reduces activities such as work, education, and social life.
Also, four or more of the following symptoms, which must have continued or recurred during 6 or more consecutive months of illness and must not have started before the fatigue:
- Significant impairment in short-term memory or concentration
- Sore throat
- Tender lymph nodes
- Muscle pain
- Joint pain without swelling or redness
- Headaches of a new type, pattern, or severity
- Unrefreshing sleep
- Malaise that lasts more than 24 hours after exertion

Any active medical condition that may explain the presence of chronic fatigue, such as:
- Untreated hypothyroidism
- Sleep apnea and narcolepsy
- Side effects of medication
An illness (such as cancer or hepatitis B or C virus infection) that relapsed or did not completely get better during treatment, that could explain the presence of chronic fatigue.
A past or current major depressive disorder, such as:
- Bipolar affective disorder
- Schizophrenia
- Delusional disorder
- Dementia
- Anorexia nervosa or bulimia nervosa
Alcohol or other substance abuse that occurs within 2 years of the onset of chronic fatigue and any time afterward.
Severe obesity as defined by a body mass index (BMI) equal to or greater than 45. (Note: Body mass index values vary considerably among different age groups and populations. No "normal" or "average" range of values can be suggested. The range of 45 BMI or higher was selected because it falls within the range of severe obesity.)

Any other abnormality found during an exam or other tests that could explain CFS symptoms must be resolved before further attempting to classify the condition.

In 2007, the National Institute for Health and Clinical Excellence (NICE) released new guidelines for the diagnosis and management of CFS in adults and children. According to these guidelines, CFS may be diagnosed if the person has disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition.

People with CFS also can have the following symptoms:

Difficulty thinking, concentrating, remembering, finding the right words, planning, and organizing
Difficulty sleeping
Dizziness or nausea
General malaise or flu-like symptoms
Headaches
Muscle or joint pain in many areas of the body without inflammation
Painful lymph nodes without disease
Fast heartbeat (palpitations) without heart problems
Sore throat
Worsening of symptoms with physical exertion

After ruling out other possible causes, the doctor should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children. Children should be diagnosed by a pediatrician.

A doctor should first take a careful personal and family medical history, which may include a psychological profile, as well as perform a thorough physical examination. Patients should be prepared to answer questions such as:

When did the fatigue first begin?
Does anything make it worse or better?
Is it better at certain times of the day?
Does physical activity make it worse?
Are there any other symptoms?
Has anyone else in the family ever complained of fatigue?
Is your personal and professional life stressful?

The doctor may also ask about any changes in weight or request a patient to monitor morning and afternoon body temperatures. Patients should report any drugs they are taking, including vitamins and over-the-counter or herbal medications.

Standard tests are typically recommended to rule out specific conditions that can cause persistent fatigue. These tests include:

Blood count
Blood tests for gluten sensitivity
C-reactive protein
Creatine kinase
Erythrocyte sedimentation rate or plasma viscosity
Liver function
Random blood sugar (glucose)
Serum calcium
Serum creatinine
Serum ferritin levels (only in children)
Thyroid function
Urea and electrolytes
Urine test for protein, blood, and glucose

No blood, urine, or other laboratory test can specifically diagnose CFS. If any test is abnormal, it is not useful for diagnosing CFS specifically, and the doctor should look for other causes of these abnormalities.

That being said, research published in 2005 found that certain components in urine were unique in people with CFS, and may someday be considered biomarkers of the disease. Additionally, antibodies to Epstein-Barr virus and increased levels of isoprostanes -- markers of oxidative stress -- have been found in the blood of people with CFS.

Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:

Depression
Infections
Pregnancy
Extreme exercise
Excessive stress

In most of these cases, fatigue can be relieved with adequate rest. It is important to note that longstanding fatigue can be the harbinger of a serious medical or psychological problem. A number of more serious conditions may cause persistent fatigue and other symptoms of CFS and should be ruled out. Patients and doctors should not overlook these diseases, even if the conditions have been previously treated, because they may not have completely resolved or they may cause residual fatigue. Doctors can usually distinguish these diseases from CFS after a clinical evaluation and laboratory testing.

Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis is marked by fatigue and swollen glands. It primarily affects adolescents and young adults. Some patients may have lingering fatigue that lasts for many months and blood tests that indicate a persistence of the Epstein-Barr virus (EBV), which causes mononucleosis.

Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, are caused by autoimmunity, a condition in which the person's immune system attacks the body's own tissues. The early symptoms of these conditions may mimic some of those that appear in CFS, such as muscle and joint pain and fatigue. These diseases, like CFS, also occur more often in women than in men. Most of these conditions can be confirmed with laboratory or x-ray/radiologic findings. However, some autoimmune diseases may evolve slowly, and even if a diagnosis of chronic fatigue syndrome is considered, doctors should keep track of any changes in symptoms over time in order to rule out these serious illnesses.

Post-Lyme Disease Syndrome. Rarely, patients treated for a diagnosis of Lyme disease continue to have nonspecific symptoms, which can last for years after antibiotic treatment and that resemble symptoms of chronic fatigue syndrome.

Psychosis and Severe Mental Disorders. The Centers for Disease Control (CDC), which set up the definitions in the U.S. for research in chronic fatigue syndrome, recognizes depression as one of the symptoms of CFS. However, according to the CDC, anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia, does not meet the criteria for chronic fatigue syndrome.

Symptoms of major depression include the following:

A depressed mood every day
Significant weight gain or loss (10% or more of an individual's typical body weight)
Insomnia or excessive sleeping
Restlessness or a sense of being slowed down
Low energy every day
Worthless or inappropriately guilty feelings
An inability to concentrate or to make decisions
Suicidal thoughts

Major depression is likely to be responsible if a person has several of these symptoms and no physical symptoms (such as sore throat, aches and pains, or fever). The longer fatigue has continued without such physical symptoms, the more likely that the diagnosis is depression.

Of note, a persistent form of minor depression called dysthymia may be more difficult to differentiate from CFS and may actually account for a subset of CFS cases. Dysthymia is characterized by many of the same symptoms that occur in major depression, but they are less intense and last much longer, at least two years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities.

Patients with depression and those with CFS generally perceive their illnesses differently:

Patients with depression have significantly lower self-esteem, more thought distortions (for instance, focusing on the negative or personalizing their situations), and believe their conditions stemmed from psychological factors.
CFS patients, even those with concurrent depression or dysthymia, tend to identify medical causes as the source of their problems and to focus on physical symptoms.

Many previously healthy patients with CFS become depressed and anxious because they feel so exhausted all the time. CFS may also lead to highly stressful socioeconomic situations, such as social isolation and poverty, that can contribute to and even cause emotional disorders in susceptible individuals, which in turn can worsen CFS.

Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and can be confused with CFS:

Sleep apnea is a common disorder that can cause daytime fatigue without the patient being aware of the problem. Apnea is actually a breathing disorder often marked by loud snoring and thrashing in bed. A person may not realize the problem exists unless it is brought to his or her attention by a sleeping partner or observer.
Narcolepsy is a peculiar and rare disorder in which a person suddenly falls asleep without any previous signs of fatigue.
Other sleep disorders that cause daytime fatigue include insomnia and restless legs syndrome.

Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation. Non-restorative sleep and nighttime restlessness are the most common complaints of people with CFS.

Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more of CFS symptoms, including arthritic symptoms, fever, and fatigue.

Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by the weight. People who are obese are also at particular risk for sleep apnea, which can confuse the diagnosis.

Other Medical Conditions that Usually Rule Out CFS. Many diseases, both benign and serious, can fully explain prolonged or chronic fatigue, including:

Hepatitis
Anemia
Hemochromatosis (a hereditary disease caused by iron overload) infections
Various forms of cancer
Neuromuscular diseases (such as myasthenia gravis)
Hypothyroidism
Diabetes

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependency on or abuse of alcohol or illicit drugs may manifest as chronic fatigue. Medications should be considered as a possible cause of fatigue if an individual has recently started, stopped, or changed medicines. Withdrawal from caffeine can produce depression, fatigue, and headache.

Prognosis

The physical severity of chronic fatigue syndrome varies. Most commonly, patients with CFS report that they have trouble fulfilling both home and work responsibilities.

CFS sufferers typically work part-time. In extreme cases, patients are severely disabled and even bedridden. Such patients can do virtually nothing, including even light housework.

Patients with CFS are more likely to lose their jobs, possessions, and support from friends and family than are people who have other conditions that cause fatigue.

Most patients say that while fatigue is the most incapacitating symptom, mental impairment, such as an inability to concentrate or remember, is the most distressing symptom. The effects of CFS on mental functioning are complex, however. Some experts believe that the impaired mental functioning is due to depression, which is common in CFS patients.

Some studies indicate that, although general intelligence is not impaired, CFS patients test lower in certain mental functions, particularly speed and efficiency in processing complex information, and that 40 - 60% have memory impairments. In such studies, this impaired mental function occurs regardless of the presence or absence of depression or other psychiatric disorders.

Because the illness remains elusive and poorly defined, and there are few objective measures for recovery, experts have found it difficult to determine the long-term course of the disease. Many patients are not covered by insurance or have difficulty finding good care, so available statistics may be incorrect. Bearing these factors in mind, some studies have reported that more than half of patients who complain of chronic fatigue are still fatigued at 2 years. Although a variety of studies have attempted to identify factors that predict a more chronic or severe course, no clear conclusions can be made. Even if patients get progressively worse, however, the disorder is not fatal.

Although children with symptoms of chronic fatigue have not been as rigorously studied as adults, limited evidence suggests that CFS can be significantly disabling in young people. Studies report that adolescents who meet the criteria for CFS also have greater anxiety, depression, and school absenteeism than their peers. Still, some studies indicate that children have a better prognosis than adults and that most will recover after 1 - 4 years. Several studies have indicated that cognitive-behavioral therapy is an effective treatment for adolescents with CFS.

Treatment

There is no proven or reliable cure for CFS, and no drug has been developed specifically for this disorder. Because CFS remains poorly understood, many patients have problems finding good care. Overall, the recommended strategy for treatment includes a combination of the following:

A healthy diet
Antidepressant drugs in some cases, usually low-dose tricyclics
Cognitive-behavioral therapy (CBT) and graded exercise for certain patients
Medication
Sleep management techniques

Patients with the best chance for improvement are those who remain as active as possible and who seek to have some control over the course of the disorder. Patients should choose physicians who are willing to consider the problem as a medical condition with psychiatric components. They should be very wary, however, if the physician recommends excessive and expensive treatments that may have serious adverse effects and that have no proven benefits. For patients with severe CFS that cannot be managed with lifestyle changes and standard medications, asking the physician about enrolling in any available clinical trials may be helpful.

Cognitive-Behavioral Therapy

CBT is designed to help CFS patients regain a sense of control, and is proving to have substantial benefits for some patients. Some experts believe that patients who are diagnosed with CFS should be referred to therapists trained in cognitive-behavioral therapy. (Psychoanalysis and other interpersonal psychological therapies, which are concerned with subconscious thoughts and early childhood memories, are not generally helpful for the CFS patient.)

The Goals of Cognitive-Behavioral Therapy. The primary goals of cognitive-behavioral therapy (referred to below as just cognitive therapy) are to change any distorted perceptions that individuals have of the world and of themselves, and to change their behavior accordingly. For CFS patients, this means learning to think differently about their fatigue and to improve their ability to deal with stressful situations and manage their disorder. It can also help manage their sleep problems and find the appropriate activity levels for them. Cognitive therapy is particularly helpful in defining and setting limits, behaviors that are extremely important for these patients.

The Procedure. CBT is usually performed over 6 - 20 sessions, each lasting about an hour. Patients are also given homework, which usually includes keeping a diary and attempting tasks that they have avoided because of negative attitudes.

A typical cognitive therapy program may involve the following measures:

Keep a Diary. The patient is almost always asked to keep an energy diary, which can be a key component of CFS cognitive therapy. The diary serves as a general guide for setting limits and planning activities. The patient uses the diary to track any factors, such as a job or a relationship that may be making the fatigue worse or better. It is also used to track the times of day when energy levels are at their highest and lowest peaks.
Adjust Schedule. The patient adjusts schedules to conform to energy peaks and valleys recorded in the diary. For instance, the patient may plan to take a nap during low-energy times and plan important activities during high-energy times. Developing fairly rigid daily routines around probable energy spurts or drops may help establish a more predictable pattern.
Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs (such as "I'm not good enough to control this disease, so I'm a total failure."), and to use coping statements ("Where is the evidence that I can control this disease?")
Be Flexible. Energy levels will most likely never be entirely predictable. Patients must be prepared to adapt to energy variations. Instead of taking a long nap, for instance, patients may need 5- to 10-minute rest periods every hour or more, possibly involving relaxation or meditation.
Set Limits. Limits are designed to keep both mental and physical stress within a manageable framework so that patients do not get discouraged by forcing themselves into situations in which they are likely to fail. For example, tasks are broken down into incremental steps and patients focus on one step at a time.
Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.
Manage Impaired Concentration. Patients seek out activities that are appealing, focus attention, and help increase alertness. They learn to request instructions given as concise, simple statements. External distractions, such as music or talking, are kept to a minimum.
Accept Relapses. Over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of treatment- or self-failure.

Using both self-observation and specific tasks, patients gradually shift their fixed ideas that they are helpless against the fatigue that dominates their lives. They move to the perception that fatigue is only one negative and, to a degree, a manageable experience among many positive ones.

Success Rates. One review of CFS trials reported that, of all therapies available to CFS patients, only cognitive behavioral therapy (CBT) and graded exercise showed conclusive benefits. Although CBT doesn't appear to bring patients completely back to normal, research has found that people who used the therapy had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use CBT. A 2005 study found that cognitive therapy is an effective treatment for adolescents with CFS. Patients who received CBT reported improvements in fatigue, functional status, and school attendance.

Not all studies support the benefits of cognitive therapy for CFS. It is important to note that different therapists may have different fundamental assumptions about CBT and may use different techniques. For instance, some therapists believe that CFS is purely a psychological problem and that patients must reject the notion of physical causes, abandon all reliance on assistive devices, and participate in challenging exercise programs. In contrast, other therapists do not attempt to change patients' underlying beliefs at all, but instead focus on helping patients conserve energy and better cope with the limitations of their illness. When considering CBT, patients and their families must be aware of such important differences.

Regardless of whether specific organic causes of CFS are identified, the power of the mind to improve or oppose health problems is significant, and treatments that promote a positive outlook are beneficial for any disease.

A number of studies have suggested that a graded exercise program, in which patients perform increasingly more intense levels of exercise tailored to their individual abilities, has benefits for many patients with CFS. Exercise is best performed in combination with cognitive behavioral therapy.

Reports have found that 75% of CFS patients who were able to engage in exercise, particularly aerobic exercise, reported less fatigue and better daily functioning and fitness after a year. A 2004 review of clinical trials found that exercise therapy is beneficial for CFS, particularly when combined with patient education.

Some patient groups and experts contend that such studies use only patients with less severe conditions and do not apply to many CFS patients. Many patients have severe conditions, and some are very incapacitated (such as being wheelchair bound). These patients are unlikely to undergo even graded exercise. All CFS patients, in fact, have a lower exercise capacity than healthy individuals, and over-exercising can intensify symptoms. Some patients experience profound fatigue following even modest exercise. It is the primary factor in perpetuating the low-activity levels observed in these patients.

The following tips may be helpful for CFS patients when embarking on an exercise program:

Work with your health care provider to determine a good starting level of activity for you. Start slowly and incrementally, beginning with as few as 3 - 5 minutes of moderate exercise a day. The goal is to increase activity by about 20% every 2 - 3 weeks, until you can handle about 30 minutes a day. Once you reach 30 minutes a day, start to increase the aerobic intensity of your workouts. (Capacity varies greatly among CFS sufferers, however, and some may not be able to achieve this.)
Establish limits and keep within them in order to avoid overexertion and relapse.
Experiment with different forms of physical activity that suit your available energy levels. Some patients report great benefits from yoga or Tai Chi, which combine exercise with meditation.
Setbacks will occur, but do not become discouraged.

Work with your health care provider to find a level of activity you can handle. Then gradually increase your activity level. Activity management should involve:

Balancing your time between activity, rest, and sleep
Spreading out more challenging tasks throughout the week
Breaking big tasks into smaller, more manageable ones
Avoiding doing too much on days when you feel tired

Although there is no evidence to support any specific dietary factors in CFS, patients should be sure to maintain a healthy diet that includes:

Plenty of fresh dark-colored fruits and vegetables, which are rich in antioxidants
Fiber-rich foods
Limited saturated fats (found in animal products)
Omega-3 essential fatty acids, found in certain fish and oils
Increased salt (only for those with demonstrated low blood pressure)
Starchy foods, particularly for nausea

Stress Reduction Techniques. One panel of experts concluded that relaxation and stress-reduction techniques were helpful in managing chronic pain. These techniques also can help relieve the stress associated with the disease. They are not useful, however, as the primary treatment for CFS. A number of relaxation techniques are available:

Biofeedback
Deep breathing exercises
Hypnosis
Massage therapy
Meditation
Muscle relaxation techniques
Yoga

Light Therapy. Patients with seasonal affective disorder (SAD) experience more depression during the winter, when the hours of sunlight decrease. With light therapy (phototherapy), the patient sits for about 30 minutes each day a few feet away from a box-like device that emits very bright fluorescent light (4,000 lux). Light therapy is best performed immediately after awakening in the morning.

Some CFS patients don't have much improvement from light therapy. However, the treatment may still help some patients with CFS whose symptoms are similar to those of patients with seasonal affective disorder (SAD).

Supportive Family and Groups. Having strong, supportive relationships with family and friends can help CFS patients get better. However, CFS patients should try not to impose unreasonable expectations on loved ones that cannot be met. Ongoing support groups with fellow patients may be very helpful. In one study, sharing experiences in a group therapy setting proved to be the most valuable component in treatment, and one that improved patients' coping abilities.

Medications

No medications are specifically approved for the treatment of CFS. However, some may be useful for pain or other specific symptoms, or in cases where CFS may have a specific cause. Doctors generally use combinations of drugs to accomplish specific goals, such as medication at night to improve sleep and medication in the morning to improve cognition and energy. Treatment is very individualized.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Patients with CFS may find relief using NSAIDs -- common pain relievers that reduce pain and swelling. Types of NSAIDs include aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox).

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Due to its proven cardiovascular benefits, aspirin was excluded from these labeling revisions.

NSAIDs can also increase blood pressure, particularly among people already being treated for hypertension. (About 12 - 15% of elderly people take both an NSAID and an antihypertensive drug.) Piroxicam, naproxen, and indomethacin appear to pose the greatest risk of high blood pressure. Sulindac has the smallest effect.

Other side effects of NSAIDs include:

Dizziness
Ringing in the ears
Headaches
Skin rashes
Possibly depression

NSAIDs can cause kidney damage. (The damage gets better once the patient stops using the drug.) People with high blood pressure, severe circulation disorders, or kidney or liver problems, as well as people taking diuretics or oral hypoglycemics, must be closely monitored if they need to use NSAIDs on a long-term basis. Because NSAIDs reduce blood clotting, NSAID users scheduled for surgery should stop taking those drugs a week before the operation.

COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of cardiovascular events, skin rashes, and other adverse effects prompted the FDA to re-evaluate the risks and benefits of the COX-2 drugs. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. Celecoxib (Celebrex) was still available at the time of this report, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Because of the association between depression and CFS, antidepressants are often tried, with varying degrees of success. Common side effects of many antidepressants include:

Dry mouth
Restlessness
Reduced sexual drive
Slightly increased heart rate
Constipation

Virtually all antidepressants have complicated interactions with other drugs, and some are very serious.

Tricyclic Antidepressants. Antidepressants known as tricyclics may be particularly helpful for CFS patients. For example, the tricyclic amitriptyline (Elavil) is known to relieve many of the symptoms of CFS, including sleeplessness and low energy levels. These drugs may provide benefits by promoting deep sleep and inhibiting pain pathways in the nervous system. Improvement in symptoms can take 3 - 4 weeks. Other tricyclics include doxepin (Sinequan), desipramine (Norpramin), nortriptyline (Pamelor), clomipramine (Anafranil), and imipramine (Tofranil, Janimine). Patients with CFS normally respond to much lower doses than those used to treat people with depression. In fact, many CFS patients cannot tolerate the higher doses commonly used to treat the psychiatric disorder. Like all medications, tricyclics must be taken as directed. Overdose can be life-threatening. Tricyclics should not be taken together with SSRIs, because of the possibility of dangerous side effects.

Other Antidepressants. Newer, so-called designer SSRIs, including bupropion (Wellbutrin), nefazodone (Serzone), or mirtazapine (Remeron), affect combinations of different neurotransmitters, and some may have moderate benefits for CFS patients. For example, in one study, nefazodone improved mood, fatigue, and sleep disturbances.

SSRIs. The popular antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) may be helpful for the subgroup of CFS patients who experience significant depression. They include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Cymbalta (duloxetine) is a new antidepressant that is classified as a selective serotonin and norepinephrine reuptake inhibitor (SSNRI).

In a 2006 UK study of 275 CFS patients, those treated with antidepressants recovered faster than those who did not receive the medication. SSRIs were found to be more effective than tricyclic antidepressants, producing improvements, including a reduction in fatigue, that were maintained at the 3-year follow-up.

Psychostimulants. Psychostimulants may be helpful for a subgroup of patients with CFS who have cognitive problems, such as difficulty concentrating, memory problems, and other attention deficit disorder (ADD)-like characteristics. Psychostimulants include Dexamphetamine, Adderal, methylphenidate (Ritalin) and Ritalin-like drugs such as Focalin, Concerta, Ritalin LA, and Metadate, as well as Strattera and Provigil. The NICE guidelines for CFS do not advise taking Dexamphetamine or Ritalin. However, a 2007 study found that taking two 10 mg doses of Ritalin each day works much better than placebo at relieving fatigue and concentration problems. More research is needed to study the long-term effects of Ritalin on CFS patients.

Because of the difficulties in treating chronic fatigue syndrome, many patients seek alternative therapies. Some, such as acupuncture, yoga, and relaxation techniques, may be helpful and are not dangerous. No scientific evidence exists that vitamin and mineral supplements will relieve CFS, but some people do report that they find supplements helpful.

Herbal and Supplements. Popular herbal and dietary supplement remedies for CFS include coenzyme Q10, vitamin B12, vitamin C, magnesium, multivitamins, DHEA, ginseng, and acetylcarnitine. None have been rigorously tested. Some herbs, such as St. John’s wort, ginkgo, and comfrey, may cause serious side effects and drug interactions.

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 can affect 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 lethal side effects from herbal products.

Some so-called natural remedies have been found to contain standard prescription medication. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China have been laced with potent pharmaceuticals, such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia. One study reported that a significant percentage of such remedies contain toxic metals.

CFS patients should be wary of any company that promises a cure or urges the purchase of expensive but useless and sometimes potentially dangerous treatments, such as the following:

St. John's wort. This herbal remedy is being investigated for mild depression. In one study, St. John's wort lessened fatigue in CFS patients, even in those who did not consider themselves to be depressed. However, the substance may have some serious side effects; for example, it can interact with blood thinning medication. In a brand comparison, only three St. John's wort products out of eight contained within 10% of the active ingredient amounts claimed on the labels.
Melatonin. Some patients use melatonin, based on the association between CFS and possible sleep abnormalities. However, the small amount of research available has not shown melatonin to be helpful.
Gingko. Although the risks for gingko appear to be low, there is an increased risk of bleeding at high doses. In addition, gingko can interact with high doses of vitamin E and anti-clotting medications. Commercial gingko preparations have also been reported to contain colchicine, an agent that can be harmful in pregnant women and people with kidney or liver problems. Some brands of gingko have no effect at all.
Comfrey. Comfrey is an herbal remedy used for a number of inflammatory problems. Recently, evidence has emerged that comfrey can be toxic to the liver, and animal studies have reported a possible cancer risk. Comfrey is banned in Canada and other countries, but is widely available in the U.S.

Of particular note for CFS patients are products containing the ingredient Ma Huang, which contains the stimulants ephedrine and kola nut, a caffeine source. Serious adverse reactions, including seizures, psychosis, and several deaths, have been reported in people taking this supplement for increased energy or weight loss. Products that have only one of these ingredients do not appear to have the same effect, but people should take so-called energy boosting supplements only with the knowledge and recommendation of their doctor.

Other alternative remedies with no proven benefit and possible toxic and dangerous side effects include the following:

Hydrogen peroxide injection (can cause blood clots or strokes)
Megadoses of vitamins (can be toxic and have shown no benefits)
High colonic enemas
Bee pollen (can cause an allergic reaction)
Injections of liver extract
Superoxide dismutase (SOD)

Resources

www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/cfs - Centers for Disease Control and Prevention, Chronic Fatigue Syndrome information
www.cfids.org -- The Chronic Fatigue and Immune Dysfunction Syndrome Association of America
www.ncfsfa.org -- National Chronic Fatigue Syndrome and Fibromyalgia Association
www.aacfs.org -- American Association for Chronic Fatigue Syndrome
www.theacpa.org -- American Chronic Pain Association
www.ampainsoc.org -- American Pain Society
www.iasp-pain.org -- International Association for the Study of Pain
www.medicalacupuncture.org -- American Association of Medical Acupuncture
www.aabt.org -- Association for Advancement of Behavior Therapy

References

Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome. Sleep. 2007;30:657-662.

Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006;119:e23-30.

Chia J, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008;61:43-48.

Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier, 2007.

Hampton T. Researchers find genetic clues to chronic fatigue syndrome. JAMA. 2006;295(21):2466-2467.

Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes preciptated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575. Epub Sept 1.

Jones JF. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. 2005;118:1415.

Kato K, Sullvan PF, Evengard B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006;63(11):1267-1272.

Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2006. Nov 18 (Epub ahead of print).

National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. August 2007.

O'Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A. Cognitive behavioural therapy in chronic fatigue syndrome: a randomized controlled trial of an outpatient group programme. Health Technol Assess. 2006;10:iii-iv, ix-x, 1-121.

Thomas MA, Smith AP. An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome. Hum Psychopharmacol. 2006;21(:503-509.

Vermeulen RC, Scholte HR. Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data. J Transl Med. 2006;4:34.

Review Date:
1/4/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Smoking

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

In This Report

Highlights
Introduction
Nicotine Addiction
Health Risks
Secondhand Smoke
Smoking Bans
Quitting Smoking
Symptoms of Withdrawal
Failure to Quit
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Your Health

Smoking may worsen knee osteoarthritis in men. A study published in the Annals of Rheumatic Disease found that male smokers have more pain and cartilage loss than men who do not smoke. Previous studies have not found such a link.
Smoking greatly increases the risk of age-related macular degeneration. An Australian study reports that smokers are four times more likely to develop the eye condition than those who have never smoked. Smokers also developed the condition at an earlier age.
Analysis of several studies suggests that smoking cigarettes and, in some cases, cigars or pipes, may reduce the risk of Parkinson's disease. However, smoking causes many other serious health conditions and should not be considered a means for preventing Parkinson's.
A small study suggests that infants who are breastfed just after their mother smokes sleep less than those whose mothers did not smoke.

Smoking Cessation

Certain genes may make it easier for you to quit smoking. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Smoke Free Zones

More and more households in the United States are banning smoking. The U.S. Centers for Disease Control and Prevention (CDC) reports that 75% of households now forbid smoking at any time or place in the home.

Smoking in the Movies

Teens who see actors smoke on screen are more likely to become established smokers, according to an updated study in the Archives of Pediatric Adolescent Medicine. Study authors say the likelihood of smoking increases with exposure to movies that depict such behavior.

Introduction

More than 20% of adults in the United States smoke, according to a 2006 report by the U.S. Centers for Disease Control and Prevention (CDC). More than 80% of them smoke every day. Although smoking had steadily declined among adults in recent years, the trend now appears to have stalled. Between 2004 and 2005, the CDC says there was no observable change in smoking rates among U.S. adults.

The addictive effects of tobacco have been well documented. Tobacco is considered to be a mood and behavior altering substance that is psychoactive and abusable. Tobacco is believed to be as potentially addictive as alcohol, cocaine, and morphine. Tobacco and its various components increase the risk of cancer (especially in the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, and cervix), heart attacks, strokes, and chronic lung disease.

The younger children start smoking, the more likely they will smoke as an adult. Smoking is often immediately addictive. According to the American Cancer Society, the earlier you start smoking, the more likely you are to develop long-term nicotine addiction.

In the past, advertising was responsible for encouraging some teens to smoke. New regulations have made it much more difficult for advertisers to promote smoking to young people. However, scenes that show people smoking are still common in movies and television shows, often in a positive light. This may be a major influence on the attitude toward smoking in children and adolescents. An updated study in the Archives of Pediatric Adolescent Medicine found that adolescents that watch movies that portray smoking are more likely to become established smokers.

To prevent children from smoking, parents should not smoke, and they should tell their child that they disapprove of smoking. Schoolchildren who believed that both their parents strongly disapproved of smoking were less than half as likely to smoke as those kids whose parents did not show as much disapproval towards smoking. Other research has supported these findings.

Children whose parents closely monitor their television and music-listening habits are less likely to drink, use drugs, and smoke cigarettes.

Neglected children, or children with absentee parents, were four times as likely to abuse drugs, drink, and smoke as children living with parents who were regularly present and who offered a structured lifestyle.

In a 2002 study, children who regularly attended religious services were also less likely to smoke.

Doctors can have a major effect on young people. However, in one survey, less than half of teenagers had ever been asked by their doctors if they smoked or were counseled not to smoke, even though most teen smokers said they would admit to it if asked.

More American men smoke than women. The following chart details the rate of current smoking in the United States among adults aged 18 years and over, grouped by age and sex:

Age	Total	Men	Women
18 - 44 years	24.1%	27.1%	21.2%
45 - 64 years	21.9%	25.2%	18.8%
65 years and older	8.6%	8.9%	8.3%

Source: CDC/National Health Interview Survey 2005

While the number of adults over 65 who smoke is lower than those in other age groups, older adults usually have smoked for a long time (about 40 years) and tend to be heavier smokers, according to the American Lung Association. Because of this, older smokers are more likely to have smoking-related illnesses.

Caucasian students (under age 18) are more likely to smoke than Hispanics and African-Americans. In 2005, the rate of smoking was highest among American Indians and Alaskan natives. Hispanics and Asians had the lowest rates.

In general, the rate of smoking is highest in the Midwest and South and lowest in the Northeast and West. Utah has the lowest rate of smoking in the United States.

A major U.S. government study reported that people who have not graduated from high school or received their General Education Development (GED) certificate tend to have higher smoking rates than those who attended college.

Higher rates of cigarette smoking have been reported among adults who have earned a GED and those with a 9 – 11 grade education. The lowest rates are seen among those with advanced college degrees.

People with low self-esteem and adolescents with behavioral problems have a higher risk for smoking. Men and women with mental disorders are 50% more likely to smoke than those without such illness.

For example, depression and schizophrenia are known risk factors for smoking. Both may actually have biologic effects that are responsible for this higher risk.

Smoking is much more common among persons with disabilities than those without emotional, mental, or physical limitations. A 2007 Centers for Disease Control study found that the rate of smoking is nearly 50% higher among persons with disabilities. The CDC survey included those with mental illness and drug and alcohol addictions in the disabled group.

Evidence now strongly supports the idea that genes play a role in a person's dependence on nicotine. Researchers are now targeting specific genes that may be responsible for nicotine dependence. So far, research has been shown that there is a common genetic vulnerability to both nicotine and alcohol dependence.

Some studies suggest that the cheaper it is to buy cigarettes and smoke, the more widespread smoking will be. For example, states that have low taxes on cigarettes have a high proportion of smokers. Making it more expensive to smoke may reduce the number of smokers.

Nicotine Addiction

Nicotine is the chemical in cigarettes that makes them addictive. Higher levels of nicotine in a cigarette can make it harder to quit smoking. A report by the Massachusetts Department of Health found that the amount of nicotine in cigarettes has steadily increased over the last 6 years. Higher nicotine levels were found in all cigarette categories, including “light" brands. Massachusetts is one of several states that require tobacco manufacturers to submit yearly reports regarding cigarettes.

Some researchers feel nicotine is as addictive as heroin. In fact, nicotine has actions similar to heroin and cocaine, and the chemical affects the same area of the brain.

Depending on the amount taken in, nicotine can act as either a stimulant or a sedative. Cigarette smoking has definite immediate positive effects. For example, it can:

Boost mood and relieve minor depression
Suppress little fits of anger
Enhance concentration and short-term memory
Produce a modest sense of well-being

Most smokers have a special fondness for the first cigarette of the day because of the way brain cells respond to the day's first nicotine rush. Nicotine, particularly taken in the first few cigarettes of the day, increases the activity of dopamine, a chemical in the brain that elicits pleasurable sensations, a feeling similar to achieving a reward.

Over the course of a day, however, the nerve cells become desensitized to nicotine. Smoking becomes less pleasurable, and smokers may be likely to increase their intake to get their "reward." A smoker develops tolerance to these effects very quickly and requires increasingly higher levels of nicotine.

A smoker may "forget" their craving for nicotine if a part of the brain called the insula becomes damaged. A 2007 study published in the journal Science found that smokers with brain damage to this area were 136 times more likely to forget their addiction to nicotine. The findings may one day lead to new drugs that better help a person quit.

Smokeless tobacco, also called spit tobacco, includes chewing tobacco (dip and chew), tobacco powder (snuff), as well as flavored tobacco lozenges. These products also contain nicotine. There are two forms of spit tobacco.

These products allow tobacco to be absorbed by the digestive system or through mucous membranes. Smokeless tobacco contains at least 28 cancer-causing substances. Smokeless tobacco is not a safe substitute for smoking cigarettes or cigars. According to the National Institutes of Health, chewing on an average-size piece of chewing tobacco for 30 minutes can deliver as much nicotine as smoking three cigarettes.

Although research is inconsistent, some evidence suggests that smokeless tobacco produces a 50-fold increase in the risk of oral cancer, gingivitis, and tooth loss.

Health Risks

Smoking -- even just a few cigarettes a day -- has been linked to many serious health risks. Some are listed below.

According to the American Lung Association, smoking is directly responsible for about 90% of the deaths due to lung cancer. Smoking is also responsible for the majority of deaths due to chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis.

A study in the July 2006 American Journal of Respiratory and Critical Care Medicine showed that smokers with asthma who give up smoking can improve their lung function in as little as 1 week. The small study involved 21 smokers with asthma. Ten of them quit smoking for 10 weeks, while the others continued to smoke. After just a week, lung function test scores in those who stopped smoking improved considerably. In less than 2 months, lung function scores among those who stopped smoking improved by more than 15%.

Study authors say their findings show that there is a “reversible component to the harmful effects of smoking on the airways in asthma.”

All forms of tobacco raise heart attack risk. Smoking, chewing tobacco, and being exposed to secondhand smoke greatly increase the risk of a heart attack. In some cases, the risk of heart problems in people who smoke or are exposed to smoke may be three times greater, according to a study published in the journal Lancet. However, the study also found that the risk of a heart attack among those who stopped smoking slowly decreased over time.

Smoking has a negative affect on a man's sexuality and fertility. Heavy smoking is frequently cited as a contributory factor in impotence because it decreases the amount of blood flowing into the penis. One study noted that among men with high blood pressure, smoking caused a 26-fold increase in impotence.

Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that can affect a man's offspring. One 2002 trial found that men or women who smoke have lower success rates with fertility treatments. An earlier study reported that men who smoke also have lower sex drives and less frequent sex.

Studies have linked cigarette smoking to many reproductive problems. Continuing to smoke during pregnancy may also cause health problems in the baby.

Negative effects of smoking on female fertility include:

Greater risk for infertility. Women at greatest risk for fertility problems are those who smoke one or more packs a day and who started smoking before age 18.
Earlier menopause. Women who smoke tend to start menopause at an earlier age than nonsmokers, perhaps because toxins in cigarette smoke damage eggs.
Pregnancy complications. Women who smoke have a greater risk for ectopic pregnancy and miscarriage.

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

Effects on Unborn Child. Smoking during pregnancy increases the risk for stillbirth, prematurity, and low birth weight in their babies. Women who smoke during pregnancy have lower levels of folate, a B vitamin that is important for preventing birth defects.

Children of mothers who smoke during pregnancy may also be at increased risk for obesity and diabetes.

Some women have particular genes that may make them especially likely to deliver low birth weight infants if they smoke, although newborns of all female smokers have a greater risk for low weight. The good news is that women who quit before becoming pregnant or even during the first trimester reduce the risk for a low birth weight baby to that of women who never smoked.

Women who want to become pregnant should make every attempt to quit and should use smoking cessation aids before they try to conceive. After birth, if new mothers cannot quit, they should at least be sure not to smoke in the same room as their infant.

Smoking and Breastfeeding. Smoking right before breastfeeding may interrupt the child's sleep patterns. A small study found that such infants sleep less than other infants, and that their sleep time dropped significantly as levels of nicotine in breast milk increased.

Smoking has many harmful effects on bones and joints:

Smoking can keep new bone from forming. Women who smoke are at high risk for loss of bone density and osteoporosis.

Click the icon to see an image of osteoporosis.

Postmenopausal women who smoke have a significantly greater risk for hip fracture than those who do not.
Men who smoke may have more severe symptoms of knee arthritis, according to a study published in the Annals of Rheumatic Disease.
Smokers are more apt to develop degenerative disorders and injuries in the spine.
Smokers have more trouble recovering from surgeries, including knee or hip replacements. A 2006 study published in the Journal of Bone & Joint Surgery suggests that smoking delays tendon-bone healing, which may lead to a slower recovery after rotator cuff repair surgery.
Smokers whose jobs involve lifting heavy objects are more likely to develop low back pain than nonsmokers.
Smoking may increase the risk of rheumatoid arthritis in some older women. A 2006 study in Annals of the Rheumatic Diseases showed that smoking nearly doubled the risk of rheumatoid arthritis in postmenopausal women who did not have the most established genetic risk factor for the disease, a genotype called HLA-DRB1 SE.

Click the icon to see an image of rheumatoid arthritis.

Smoking may increase the risk of developing diabetes. Researchers involved in the Insulin Resistance Atherosclerosis Study (IRAS) looked at the relationship between smoking and diabetes and found that 25% of smokers who started the trial with normal blood sugar had diabetes 5 years later compared to 14% of nonsmokers. The results were published in Diabetes Care.

A study released in 2006 supports earlier beliefs that smokers have a higher risk of developing glucose intolerance, a condition that precedes diabetes. The study, published in the British Medical Journal, involved 4,572 people. The findings suggest that chemicals in smoke could affect the pancreas. The pancreas is the organ that produces insulin, which helps control blood sugar (glucose) levels.

Smoking increases acid production in the stomach. It also reduces blood flow and production of compounds that protect the stomach lining.

Diverticulitis. One study suggested that smoking was a major risk factor in diverticulitis, a condition in which small bumps develop in the wall of the colon. In addition, smokers were at risk for complications from diverticulitis, including bleeding and abscess. Diverticulitis mostly affects people over age 50.

Inflammatory Bowel Disease. Smoking has mixed effects on inflammatory bowel disease. Inflammatory bowel disease is the collective term for ulcerative colitis and Crohn's disease. Smokers have been shown to have lower than average rates of ulcerative colitis, but higher than average rates of Crohn's disease. Smokers with Crohn's disease who quit are said to have less severe symptoms.

Click the icon to see an image of inflammatory bowel disease.

Peptic Ulcers. Results of studies on the effect of smoking on ulcers are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of smokers relapsed after a year, and that all heavy smokers relapsed after 3 months. Other studies, however, have found no increased risk for ulcers in smokers. Smoking does not appear to increase susceptibility to Helicobacter pylori (H. pylori), the bacteria that causes many peptic ulcers.

Click the icon to see an image of peptic ulcers.

Hepatitis and Cirrhosis. Smoking is linked to increased liver scarring (cirrhosis) caused by either excessive drinking or chronic hepatitis B or C viruses.

Cyanide, a chemical found in tobacco smoke, interferes with thyroid hormone production. Smoking triples the risk for developing thyroid disease, particularly hyperthyroidism and hypothyroidism. Women smokers with subclinical hypothyroidism (a symptom-free condition in which the thyroid gland is mildly underactive) have a higher risk for developing full-blown hypothyroidism than their nonsmoking peers. Smoking has also been linked to goiter, a swelling of the thyroid that occurs in people who do not get enough iodine.

Click the icon to see an image of the thyroid.

Smokers are at increased risk for heart and circulatory problems and delayed wound healing after surgery. In one study, patients who were able to cut down or quit smoking 6 - 8 weeks prior to knee or hip replacement surgery were much less likely to suffer complications.

The following age-related conditions occur at higher rates in smokers than nonsmokers:

Cataracts. Quitting smoking reduces your chances of needing cataract surgery in the future, although not to the level seen with nonsmokers.

Click the icon to see an image of a cataract.

Age-related macular degeneration (AMD). AMD is a leading cause of blindness in older people. An Australian study, published in 2007 found that the condition is four times more likely in persons who smoke than those who have never done so. Symptoms of macular degeneration include a loss of central vision, which makes it difficult to read.
Gum disease and tooth loss. A government study found that more than half of the cases of severe gum disease in adults in the United States may be due to cigarette smoking.
Wrinkles. Studies confirm that smokers are nearly five times more likely to develop more and deeper wrinkles as they age compared to nonsmokers.
Baldness and premature gray hair. Certain chemicals in smoke break down in hair cells, which leads to hair damage.
Hearing loss, particularly high-frequency hearing loss. Some experts believe that losing the ability to hear high pitched sound in smokers may be due to a decrease in blood flow to the cochlea, the part of the ear that carries sound to the brain.
Incontinence. One study of 600 women indicated that smokers and former smokers are twice as likely to develop incontinence as women who never smoked.

Secondhand Smoke

Secondhand smoke is produced by a burning cigarette or other tobacco product. An estimated 4 million children a year get sick from being around secondhand smoke. Parental smoking has been shown to affect the lungs of infants as early as the first 2 - 10 weeks of life, and such abnormal lung function could persist throughout life.

Exposure to secondhand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children who have existing asthma.

Parental smoking is believed to increase the risk for lower respiratory tract infections (such as bronchitis or pneumonia) by 50%. Environmental exposure to smoke is thought to be responsible for 150,000 - 300,000 such cases every year.

Smoking Bans

Smoking bans have spread across the country. By October 2007, at least 22 states and the District of Columbia have passed some type of law banning smoking in almost all public places and workplaces, including restaurants and bars. The date an individual state's ban takes effect varies greatly; some do not take effect until 2008 or 2009.

As of January 1, 2006, nine states were considered "smoke-free" -- California, Connecticut, Delaware, Massachusetts, Maine, New York, Rhode Island, Vermont, and Washington.

Quitting Smoking

It's never too late to quit smoking. According to the American Cancer Society, about half of all smokers who keep smoking will die from a smoking-related disease. Quitting has immediate health benefits.


Time after last cigarette	Physical Response
20 minutes	Blood pressure and pulse rates return to normal.
8 hours	Levels of carbon monoxide and oxygen in the blood return to normal.
24 hours	Chance of heart attack begins to decreases.
48 hours	Nerve endings start to regrow. Your ability to taste and smell increases.
72 hours	Bronchial tubes relax and the lungs can fill with more air.
2 weeks to 3 months	Improved circulation; lung function increases up to 30%.
1 to 9 months	Decreased rates of coughing, sinus infection, fatigue, and shortness of breath; regrowth of cilia in the airways, increasing the ability to clear mucus and clean the lungs and reducing the chance of infection; overall energy level increases.
Long-Term Effects	After a year, the risk of dying from heart attack and stroke is reduced by up to 50%.

According to the National Institutes of Health, about 40% of smokers who want to quit make a serious attempt to do so each year, but fewer than 5% actually succeed. A June 2006 report published by the NIH says that the available smoking cessation products and therapies are greatly underused. If more smokers asked for or were offered such help, the agency says quit rates could double or triple.

Some people have certain genes that make quitting easier. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Methods of quitting smoking include counseling and support groups, nicotine patches, gums, lozenges, and sprays, smoking cessation pills, and slowly cutting back on the number of cigarettes smoked (incremental reduction).

About 4% of smokers who quit without any outside help succeed. Nevertheless, most people try to quit alone, and many have reported activities that can help the process of withdrawal. The primary obstacle in trying to quit alone is making the behavioral changes necessary to eliminate the habits associated with smoking. Excellent books, tapes, and manuals are available and are strongly recommended to help people who want to quit without other assistance.

Nicotine replacement therapy involves the use of products that provide low doses of nicotine that do not contain the contaminant found in smoke. The goal of therapy is to relieve cravings for nicotine and ease the symptoms of withdrawal.

In general, nicotine replacement therapy benefits moderate-to-heavy smokers the most. However, it does appear somewhat helpful for light smokers (people who smoke fewer than 15 cigarettes a day).

Nicotine Patches. Nicotine patches deliver nicotine through the skin. This is called transdermal nicotine delivery. It is effective in reducing symptoms during withdrawal. Nicotine patches are available over the counter.

Patches may work in different ways:

Step-Down Approach. Patches that use this method include NicoDerm CQ. The patches come in three strengths (21, 14, and 7 mg). You use the strongest dose first and reduce it gradually over a period of 8 - 10 weeks. A 21 mg patch is about equal to 15 cigarettes. A heavy smoker may need to wear two patches at first.
Single-Step Approach. The single-step patch (Nicotrol) can be taken off after 16 hours and replaced 8 hours later. It can be used for only 6 weeks.

Patches are applied and used in similar ways:

A single patch is worn each day and replaced after 24 hours.
To avoid skin irritation it is applied to different hairless locations above the waist and below the neck each day.
People can wear the patches for 24 hours, but some have reported odd dreams and have disliked the sensation of the patch during the night. People who wear the patch all the time, however, have fewer withdrawal symptoms and slightly better abstinence rates than those who take it off at night.
Patches should be stored and discarded safely, particularly in homes with small children. Small children have been poisoned and gotten sick from wearing, chewing, or sucking on nicotine patches. There have been no reports of death from children who have been poisoned.
The FDA recommends using the patches for 3 - 5 months, although some studies suggest that using them for 8 weeks achieves the maximum benefits.

Children should not come in contact with the patches, even while the smoker is wearing them. If the child has worn the patch, the affected skin should be washed right away. Urgent medical care may be required if the child has eaten nicotine or worn a patch for a prolonged time.

Nicotine Gum. Nicotine gum (Nicorette) is available over the counter and has helped many people quit. Some prefer it to the patch because they can control the nicotine dosage, and chewing satisfies the oral urge associated with smoking.

Tips for using the gum:

If you are just starting to quit, chew 1 - 2 pieces each hour. A smoker should not chew more than 20 pieces a day.
The goal is to stop using the gum by 6 months, but about 3% of people continue to use it long after they have quit smoking.
The gum must be chewed slowly until it develops a peppery taste. It is then tucked between the gum and cheek where it is stored so that the nicotine can be absorbed.
Coffee, tea, soft drinks, and acidic beverages may interfere with nicotine absorption, so people should wait at least 15 minutes after drinking before chewing a piece of gum.

Some people prefer other methods or cannot use the gum for the following reasons:

They find the gum unpleasant tasting.
Side effects specific to the gum may include upset stomach, mouth ulcers, hiccups, and throat irritation.
They are embarrassed by chewing gum.
They wear dentures.

Long-term dependence may be a problem with the gum. Although such dependence is probably safer than smoking, research is needed to confirm this, and experts recommend people chew gum for no more than 6 months.

The Nicotine Inhaler. The nicotine inhaler resembles a plastic cigarette holder. It comes with a number of nicotine cartridges, which are inserted into the inhaler and "puffed" for about 20 minutes, up to 16 times a day. The dose is gradually decreased. It requires a prescription in the United States. Several studies have reported that the inhaler triples abstinence rates (between 17 - 28%) compared with placebo (6 - 9%) after 6 months. It has some specific advantages over other nicotine replacement products:

The inhaler provides varying doses of nicotine on demand (as opposed to continuously with the patch or the gum) and is relatively fast-acting. Blood nicotine levels peak about 20 minutes after using the inhaler, comparable to the gum and faster than the 2 - 4 hours seen with the patch.
It satisfies oral urges.
Most of the nicotine vapor is delivered in the mouth, not into the lung airways (although some people experience mouth or throat irritation and cough).

Using a combination of the inhaler and the patch may be particularly effective. In one study, the combination led to an abstinence rate of over 60% after 6 weeks. While this percentage dropped off over time, it was still a large improvement over the use of the inhaler and a placebo patch.

The Nicotine Nasal Spray. The nasal spray satisfies immediate cravings by providing doses of nicotine rapidly and thus may play a useful role in conjunction with slower-acting nicotine replacement therapies. (Nicotine levels peak within 5 - 10 minutes after administering the spray). The spray can irritate the nose, eyes, and throat, so it may not be suitable for those with allergies or sinus infections. Most people, however, can tolerate the side effects, which usually go away within the first few days.

Nicotine Lozenge. A nicotine lozenge (Commit) is available over the counter. It is made from pressed tobacco and comes in two strengths for heavier or lighter smokers. In a large 2002 study, 15 - 18% of smokers who used it remained smoke free, compared to 6 - 10% who were given a dummy lozenge. Side effects included heartburn, hiccups, nausea, headaches, and cough. The Commit lozenge also contains phenylalanine, a chemical that certain people may need to avoid.

Facts about Nicotine Replacement Therapy:

Not cheating on the very first day of nicotine-replacement use increases the chance of quitting permanently by tenfold.
The more cigarettes a patient smokes, the higher the dose of nicotine replacement may be required at the start.
Adding a counseling program may boost the effect of any nicotine replacement program.
Do not smoke while using nicotine replacement. It can cause nicotine to build up to toxic levels.
Nicotine replacement helps prevent weight gain while it is being used, but people are still at higher risk for gaining weight when they stop all nicotine.

Side Effects. Side effects of any nicotine replacement product may include headaches, nausea, and other gastrointestinal problems. People often experience sleeplessness in the first few days, particularly with the patch, but the insomnia usually passes. Patients using very high doses are more likely to have symptoms. Reducing the dose can prevent them.

Special Concerns for Specific Individuals. There has been some concern that the patch might be harmful for people with heart or circulatory disease, but studies are finding that it poses no danger for these individuals. In fact, it may help reduce angina attacks brought on by exercise. However, unhealthy cholesterol levels (lower HDL levels) caused by smoking remain abnormal with use of the nicotine patch. HDL levels improve when all nicotine is stopped.

Nicotine replacement may not be completely safe in pregnant women, although it has been used successfully in this group without ill effect. There is an increase in heart rates in unborn children of women who use the patch as compared with those who smoke.

Keep all nicotine products away from children. Nicotine is a poison. All nicotine products should be kept safely away from small children. A parent should call a physician or a poison control center immediately if a child has been exposed to a nicotine replacement product, even for a short duration. Parents should also call the doctor if a small child has been exposed to a nicotine product and has any symptoms, including stomach upset, irritability, headaches, a rash, or fatigue.

Warnings Against Long-Term Use. No one should use nicotine replacement therapies as a long-term substitute for smoking. Any nicotine replacement therapy should be temporary. In one study, use of nicotine gum for more than a year was associated with insulin resistance, an abnormality that occurs in diabetes. Some studies have now suggested that nicotine itself may have properties that increase the risk for cancer, independent of carcinogenic chemicals in smoke. More studies are needed.

Bupropion (Zyban, Wellbutrin) is a type of antidepressant that is also an FDA-approved product for smoking cessation. It differs from most other antidepressants because it increases the effects of dopamine, the brain chemical that appears to play a strong role in nicotine addiction. Using Zyban along with nicotine replacement therapy may help you better control cigarette smoking cravings. Zyban does not contain nicotine. In most cases, Zyban is taken a week or two before quitting, and must be taken for 7 - 12 weeks. The usual maintenance dose is 150 mg tablet twice a day. No single dose should be higher than 150 mg.

Side effects of bupropion include gastrointestinal problems, headaches, insomnia, dry mouth, and irritation. In very rare cases, seizures have occurred, although usually in people who exceeded the recommended dose or who already had risk factors for seizures.

A newer drug called varenicline (Chantrix) may significantly reduce cigarette cravings and work better than Zyban. A study in the Archives of Internal Medicine found that almost 50% of those who took varenicline successfully quit. Varenicline mimics some effects of nicotine on the brain, but blocks others. Previous studies published in the Journal of the American Medical Association showed that Chantrix works twice as well as Zyban and quadruples one’s chances of successfully quitting. The FDA approved Chantrix as a smoking cessation aid in May 2006. It is for use in cigarette smokers age 18 and older. It should not be combined with nicotine replacement therapy.

The tricyclic antidepressant nortriptyline (Pamelor, Aventyl) may help reduce nicotine action. Quit rates with either of these medicines are as high as 30%. Long-term abstinent rates are more than twice those of placebo. Most other antidepressants, including fluoxetine (Prozac), have no additional benefits for smokers.

Nortriptyline has been specifically studied for helping smokers. It is best to start taking the medication 10 - 28 days before your intended quit date. Studies have reported quit rates of 14 - 24%. Side effects of nortriptyline include dry mouth and changes in taste. It should be noted that in rare cases, tricyclics can have serious side effects, and overdose can be deadly. Tricyclics may pose a danger for some patients with certain types of heart disease.

Smokers who use outside help have the best record for quitting, with success rates of 25 - 35%. Those who are counseled in addition to using nicotine replacement and Zyban have the best chance. Brochures, audio tapes, and other self-help materials are often ineffective when used alone, but may be helpful in conjunction with a counseling program.

Types of behavioral approaches:

Problem Solving or Coping Strategies. Smokers more likely to quit smoking when they learn thinking (cognitive) and behavioral techniques for breaking the link between certain cues and smoking, stress management techniques, and ways to handle the symptoms of withdrawal and the urge to relapse. The more intense the counseling program, the better. Smokers should look for programs that offer the following:

Session lengths of 20 - 30 minutes
Four to seven sessions
A 2-week program
Additional 2 weeks or more of follow-up contact

Scheduled Reduction. Scheduled reduction is a gradual way to stop smoking.

Divide the number of minutes per day that you are awake by the number of daily cigarettes you smoke. The number you get is how long you wait between smokes.
Week 1: Set up a schedule with time intervals based on this result and using a timer, smoke only at those intervals. If the "cigarette appointment" is missed by more than 5 minutes, you must skip that cigarette.
Week 2: Reduce the number of cigarettes you smoke by one-third and recalculate your time between smokes based on the lower number.
Week 3: Reduce the count again.
Week 4: Quit smoking

Those who are unable to smoke during working hours could try calculating the intervals based on the usual smoking times of the day.

The Staged Approach. The intent of the staged approach is to plan quitting interventions customized for each individual rather than imposing some general method for quitting. The approach takes the smoker through six stages with behavioral interventions at each point:

Pre-contemplation
Contemplation
Preparation
Action
Maintenance
Termination

Although some studies report this approach is significantly more effective than non-staged methods, an analysis of 23 trials did not find the staged approach to be any more effective than other methods. Most studies, however, were weak, and better research is needed on this approach.

People who follow this approach 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 quitting in the past and didn't stick with it, don't consider yourself a failure. Just try again.

Stage 1: Pre-Contemplation.

People at this stage have no plans or desire to stop smoking. They aren't even considering quitting. People at this stage are generally unaware of the specific benefits that quitting can bring. Or, they may simply have "failed" in the past and have given up. There's no point in talking about how to start a cessation program at this stage. Instead, it is important to think about how quitting will help you feel better, have more confidence, or live longer. The benefits must be identified before a person will consider quitting. If you are at this stage, a good activity is to ask several friends or family members why they quit.

Stage 2: Contemplation.

A person at this stage is thinking, "I think I should probably quit, but I need help getting started." People at this stage know that quitting 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. It's important for people at this stage to consider some of the truths and falsehoods of quitting. If you are at this stage, write down (brainstorm) all your potential roadblocks -- the things that you believe make quitting difficult -- and 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 identify the roadblocks and ways to overcome these hurdles, and make a commitment to quitting.

Stage 3: Preparation.

Smokers at this stage are ready to quit. The goal of this stage is to create a specific action plan that takes all factors into account, so that quitting is successful. People at this stage need to know what methods work and what support exists to help them. If you are at this stage, you should consider some backup plans -- what to do when the urge to smoke hits you.

Stage 4: Action!

People at this stage have just quit. This stage is where the most behavioral change occurs. It 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. Having a fellow smoker quit with you can be a huge support as you both get through this stage.

Stage 5: Maintenance.

People at this stage have been smoke-free at least 6 months. The goal now is to prevent relapse. If you are at this stage, continue to be wary of roadblocks and keep reminding yourself of the benefits you have gained. Think about what you have found most enjoyable about being smoke-free.

Hypnosis. Although rigorous studies are lacking, some people report successful cessation from smoking when hypnosis is given in individual sessions. The process is effective only if you trust the therapist and can feel completely at ease in the vulnerable and passive state necessary for hypnotic suggestion.

During a typical session, the hypnotherapist will use various techniques (such as imagery, silent counting) to put you in a relaxed state.

When you are very relaxed, but not asleep, the hypnotherapist quietly suggests motivations for not smoking. The hypnotherapist should also reinforce a positive self-image while you are in deep relaxation. This helps many people avoid the depression that accompanies withdrawal.

The sessions usually takes about 1 hour.

You should be taught methods of self-hypnosis to use at home, and follow-up once to reinforce what you've learned.

Acupuncture and Acupressure. The acupuncture technique for quitting smoking usually uses very tiny curved staples inserted into three different points around the edge of the ear. The procedure is painless. You will be told to press each staple in a certain order for a few seconds whenever the craving for a cigarette occurs. The acupuncturist may also use acupuncture points elsewhere on the body. There are no side effects except for some soreness if the acupuncture staple is pressed too hard.

A related technique called acupressure involves simply pressing select points on the body when a craving hits. Some studies have reported good quit rates with acupuncture, but few rigorous studies have been conducted using this approach.

Aim to Quit Completely

Everyone who quits should aim to quit completely. Most people who return to smoking "cheat" in the first few weeks. Quitting completely is essential to regain good health and reverse bad effects caused by smoking. Reducing smoking, even by half, does not eliminate the risk for cancer and other health problems. Although smokers take in less smoke and nicotine, the body is still unable to heal itself from the ongoing intake of toxins. It should also be noted that changing to low-tar cigarettes is not a solution. In fact, smokers of these cigarettes tend to inhale deeper, perhaps even increasing health risks.

Create a List

Write down 10 reasons to quit. In addition to health reasons, the list might include having better smelling hair, clothes, and breath; having fewer wrinkles; enjoying the taste of food; and saving money. Read the list often during the quitting process to help stay motivated.

Decide on a Specific Quit Date

Some people find it helpful to choose a particular date to quit when little or no stress is anticipated for at least the first 3 days. Women affected by PMS should avoid quitting right before their menstrual cycle. It may help to write out a quit contract, putting the date on paper, and getting a friend to sign it. Discard all smoking paraphernalia on the eve before the quit date, and make plans to stay busy on the day itself, and especially at night, when the urge to smoke will be high.

Make an Oath

Take an extreme oath. For example, "If I smoke one more cigarette my dog will die." Although this seems absurd, some people, even well-educated individuals, who have failed all other methods have reported that they quit completely and successfully after taking such an oath.

Let the Body and Mind Heal During Withdrawal

Retreat from the world when cravings become overwhelming. Take naps, warm baths or showers, meditate, or read novels.
Help your body get rid of nicotine. Drink plenty of water, eat fresh fruits, vegetables, whole grains, and fiber-rich foods. Carrots, apples, and celery are good munching foods.
When cravings occur, hold your breath as long as possible or take a few deep rhythmic breaths.
Use meditation or relaxation and deep breathing exercises. In fact, taking deep breaths when the urge to smoke occurs is a good stopgap measure.

Get Family and Friends Involved

Tell all your friends and family that you've already quit, so you'll be embarrassed if they catch you smoking.
Pay a family member or friend if they catch you smoking. The amount should be large enough ($5 - 20) to be a deterrent, but not so large as to be ridiculous.
If your partner or friend smokes, try persuading them to quit or, at the very least, not to smoke around you and others.

Exercise

Studies continue to show that smokers who exercise can greatly increase their ability to quit smoking while reducing their risk for weight gain. Move the muscles when cravings occur. Dance, run, walk, jump up and down, stretch, do push-ups. Yoga is an excellent exercise program for quitting. Older people and anyone with health problems should consult their health care provider before starting such a program.

Maintain a Healthy Diet

Eat plenty of fresh, crunchy fruits and vegetables. This is also a useful way of satisfying oral cravings without adding many calories.
Drink plenty of water and healthy beverages.
Moderate intake of coffee or tea may be helpful. A small study suggested that drinking caffeinated beverages (such as coffee or tea) while on nicotine replacement may enhance energy expenditure and may help prevent weight gain. Moderate coffee intake may also have antidepressant properties. Avoid caffeine in the evening, however, since sleep disturbances can be a problem during withdrawal.

Change Daily Habits

Change your daily schedule, particularly eating times, as much as possible. Eat at different times or eat many small meals instead of three large ones. Sit in a different chair or even a different room.
If you smoke after eating, find other ways to end a meal. Play a tape or CD, eat a piece of fruit, get up and make a phone call, or take a walk (a good distraction that burns calories as well). For example, if you normally have a cigarette with coffee, drink tea instead or use a different cup.
Substitute oral habits by eating celery, chewing sugarless gum, sucking on a cinnamon stick, or carrying worry beads.
Go to public places and restaurants where smoking is prohibited or restricted.
Set short-term quitting goals and reward yourself when they are met.
Every day put the money normally spent on cigarettes in a jar and buy something pleasurable at the end of a predetermined period of time.
Find activities that focus the hands and mind but are not taxing or fattening: Computer games, solitaire, knitting, sewing, whittling, and crossword puzzles.

Denormalization is the idea that smoking is no longer normal. This concept of denormalization is best instituted by laws and local regulations making smoking inaccessible in public places, raising prices, and putting stricter limitations on cigarette advertising.

Increasing taxes on cigarettes may be one of the most important methods for reducing smoking in the population, particularly in younger people.

Evidence is suggesting that banning smoking in work and public places may be leading to a higher quit rate than in places where smoking is permitted.

Denormalization can also work on a personal level. A British study showed that when one spouse makes healthy changes, including quitting smoking, the other one follows. In couples where smoking continues, it usually continues in both.

Symptoms of Withdrawal

After you quit smoking, you with have some withdrawal symptoms. Such symptoms generally peak in intensity 3 -5 days after you quit, and usually disappear after 2 weeks, although some may persist for several months.

The symptoms of withdrawal include both physical and mental difficulties.

Physical Symptoms.

Tingling in the hands and feet
Sweating
Intestinal disorders (cramps, nausea)
Headaches
Sore throat, coughing, and signs of a cold

Withdrawal symptoms should be treated accordingly, just as you would with physical symptoms due to an illness or disease.

Mental and Emotional Symptoms. Tension and craving build up during periods of withdrawal, sometimes to a nearly intolerable point. Nearly every moderate-to-heavy smoker experiences more than one of the following strong emotional and mental responses to withdrawal:

Temper tantrums, intense needs, feelings of dependency, and a state of near paralysis
Insomnia
Mental confusion, vagueness, or difficulty concentrating
Irritability, restlessness, impatience, or anger
Anxiety
Depression

The first signs of nicotine withdrawal seem to appear within 30 minutes of a smoker’s last cigarette. The findings, published in Psychopharmacology, are believed to be the first to show just how early nicotine withdrawal occurs. The study involved 50 people who smoked a pack of cigarettes daily. Half refrained from smoking for 4 hours, while the others smoked as usual. After 30 minutes, those who did not have a cigarette craved one and did more poorly on tasks requiring attention than those in the smoking group. Within 3 hours, the non-smoking group showed increases in anxiety, sadness, and difficulty concentrating.

Depression is common during withdrawal and over the long term. In the short term, it may mimic the feelings of grief felt when a loved one is lost. A smoker should plan on a period of actual mourning in order to get through the early withdrawal depression.

There is a significant association between cigarette smoking and a susceptibility to depression. People who are prone to depression face a 25% chance of becoming depressed when they quit smoking, and this increased risk persists for at least 6 months. What's more, depressed smokers have a very low level of success. Only about 6% remain smoke-free after a year. There are strong reasons for this:

Smoking may be masking depression, which can become severe even after the early stages of withdrawal have passed.
For some smokers, the future physical damage incurred by smoking is an abstraction, which fails to motivate quitting when measured up against the very real emotional pain triggered by nicotine withdrawal.
Not only does the smoker suffer, but the negative emotions often harm relationships with friends and family, who might even urge the ex-smoker to take up cigarettes again.

People who suffer from depression while quitting might do better using a combination of emotionally supportive therapy (as opposed to behavioral therapy), nicotine replacements, and antidepressants, such as bupropion (Zyban). If severe depression lasts beyond the withdrawal period, professional help should be sought as soon as possible.

Quitting smoking does increase the risk for weight gain. But, kicking the habit of smoking may cause more weight gain than previously thought. A study in Health Services Research found that the average weight gain among former smokers was about 21 pounds, rather than the 5 - 15 pounds commonly cited. But, fear of weight gain shouldn’t stop a person from quitting smoking. Instead, the study authors encourage weight-control measures after quitting. To come up with a new average, the scientists re-analyzed data from the 1998 Lung Health Study of 5,887 American smokers. That study found that those who quit smoking gained about 12 pounds.

Smoking uses up calories -- about 200 a day according to one study. Burning calories helps you lose weight. After quitting, the body's metabolism slows down, and food is digested better. Insulin levels increase, enabling the body to process more sugar for energy. When you quit smoking, you may snack more frequently.

How to Keep the Weight Off After Smoking. Exercise is very helpful in controlling weight. To burn the same amount of calories as you did while smoking, you need only take an extra 15-minute daily walk and eliminate 100 calories a day from meals. Just a moderate increase in physical activity can help keep weight gain to a minimum.

Nicotine replacement therapy can help protect against weight gain. See the section on "Quitting Smoking" in this report.

Failure to Quit

Biologic, psychological, behavioral, and cultural factors all play a role in nicotine addiction, making smoking one of the hardest addictions to beat. About half of people who quit return to smoking. Even after years of not smoking, some ex-smokers still have occasional cravings for cigarettes.

Some experts suggest that, in addition to depression, there are three major areas responsible for the inability to quit:

Mental performance. Nicotine improves concentration and thinking. Quitting smoking temporarily impairs one's mental performance.
Stress. Although smoking many not reduce stress, stopping certainly increases it.
Weight gain. Quitting smoking can cause you to gain weight. Studies are mixed on whether weight gain is permanent in most smokers or not. Certainly, it is a major factor in relapse. [See "Weight Gain" section in this report.]

How well a person does in the first 2 weeks is critical to their success. Smokers should not be shy about seeking all the help they can during this period. Although withdrawal symptoms can be intense, treatments are available to reduce them.

Attempts to quit are never a waste of time, since the amount of smoking is reduced during these periods. People who keep trying still have a 50 - 50 chance of finally quitting.

Researchers have been trying to discover individual risk factors or sets of behaviors that can help predict why specific people fail to quit. Some factors include:

Being female
Being a heavy smoker
Inhaling deeply
Being a long-term smoker
Having severe withdrawal symptoms

Among many studies, however, only one found a single consistent factor for failure to quit:

Cheating during the first 2 weeks of withdrawal, even with the patch, nearly guarantees that a person will smoke again in 6 months.

Studies show that women have a harder time trying to quit smoking and have less success with abstinence programs than men. There are many proposed reasons for this:

Nicotine has different effects on mood in women compared to men. Women who quit may have greater anxiety and stress than men who quit.
Women are not as physically dependent on nicotine as men, but they are more addicted to the actual behavior of smoking, which is the more powerful deterrent to quitting. This may be the reason why nicotine replacement, which only reduces cravings, tends not to be as effective in women.
Women may fear weight gain after quitting more than men.
Certain phases in the menstrual cycle may reduce the response to drugs that are used to help women quit smoking.
Men may be less supportive than women in helping their partners to quit.
Women trying to quit may miss the feeling of control associated with smoking more than men.

On the positive side, evidence suggests that when women quit, their lung function seems to improve more rapidly than in men who quit.

Lifestyle Changes

Smokers and former smokers should immediately begin to implement a healthier lifestyle and change any other behaviors that might be damaging their health.

Everyone should also maintain a healthy diet, with foods rich in whole grains and fruits and vegetables (particularly dark colored ones). Avoid saturated fats and instead choose monounsaturated fats, which are found in olive oil or fats from oily fish. Two studies have indicated that eating fish more than twice a week might help limit the tobacco damage in people who do not smoke more than a pack and a half a day.

Even with a healthful diet, however, smoking reduces the levels of a number of vitamins, importantly vitamin C. Some research suggests that supplementation of folic acid, a B vitamin, and the antioxidants vitamins E and C and selenium may improve lung function or reduce the damage done by cigarette smoke. Studies have shown that daily vitamin E supplements are associated with reduced risk for prostate cancer among smokers and that higher levels of vitamin E are linked to a lower risk for lung cancer. The best way of achieving healthy levels of important nutrients is from healthy foods.

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

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

Women who are pregnant and continue to smoke must be sure to take appropriate vitamins, particularly folic acid. In this way, they might reduce the increased risk of fetal injury and death, although they do not eliminate that risk.

Regular exercise reduces a smoker's risk of heart disease (although still not to the level of a nonsmoker). Exercise does not lower a smoker's risk for lung cancer or emphysema.

If you smoke, you should be screened for any smoking-related disorders. Have your cholesterol and blood pressure checked regularly. Women should have annual Pap smears to detect cervical cancer. All older adults should be screened for colon cancer. Computed tomography (CT) screening programs, which are becoming increasingly available, may detect lung cancer at an early stage. Ask your health care provider if you should have this test, and if your insurance will cover it.

Resources

www.cancer.org -- American Cancer Society
www.lungusa.org -- The American Lung Association

References

Alati R, Al Mamun A, O'Callaghan M, Najman JM, Williams GM. In utero and postnatal maternal smoking and asthma in adolescence. Epidemiology. 2006 Mar;17(2):138-44.

Amin S, Niu J, Guermazi A, et al. Cigarette smoking and the risk for cartilage loss and knee pain in men with knee osteoarthritis. Ann Rheum Dis. 2007 Jan;66(1):18-22. Epub 2006 Dec 7.

Breslau N., Novak SP, Kessler RC. Psychiatric disorders and stages of smoking. Biological Psychiatry. 55(1):69-76, 2004.

Centers for Disease Control and Prevention (CDC). Tobacco use among adults -- United States, 2005. MMWR. 2006 Oct 27;55(42):1145-8.

Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and productivity losses -- United States, 1997-2001. MMWR. 2005;54:625-628.

Centers for Disease Control and Prevention (CDC). State-specific prevalence of smoke-free home rules -- United States, 1992-2003. MMWR. 2007 May 25;56(20):501-4.

Chaudhuri R, Livingston E, McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006 Jul 15;174(2):127-33.

Dobson R. Smoking may increase abdominal obesity. BMJ. 2005 Sep 17;331(7517):596.

Eisenberg D, Quinn BC. Estimating the effect of smoking cessation on weight gain: an instrumental variable approach. Health Services Research. 2006 July 6; (early online version).

Galatz LM, Silva MJ, Rothermich SY, Zaegel MA, Havlioglu N, Thomopoulos S. Nicotine delays tendon-to-bone healing in a rat shoulder model. J Bone Joint Surg Am. 2006 Sep;88(9):2027-34.

Health, United States, 2005, with Chartbook on Trends in the Health of Americans. Hyattsville, Md. National Center for Health Statistics; 2005.

Hendricks P, Ditre J, Drobes D, Brandon T. The early time course of smoking withdrawal effects. Psychopharmacology. 2006;187(3): 385-396.

Houston TK, Person SD, Pletcher MJ, Liu K, Iribarren C, Kiefe CI. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ. 2006 May 6;332(7549):1064-9.

Linn-Rasker SP, van der Helm-van Mil AHM, van Gaalen FA, et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis. 2006;65:366-371.

Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41.

Mennella JA, Yourshaw LM, Morgan LK. Breastfeeding and smoking: short-term effects on infant feeding and sleep. Pediatrics. 2007 Sep;120(3):497-502.

Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007 Jan 26;315(5811):531-4.

Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8.

Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, Anziano R, Reeves K. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006 Aug 14-28;166(15):1571-7.

Ritz B, Ascherio A, Checkoway H, et al. Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol. 2007 Jul;64(7):990-7.

Sargent JD, Stoolmiller M, Worth KA, et al. Exposure to smoking depictions in movies: its association with established adolescent smoking. Arch Pediatr Adolesc Med. 2007 Sep;161(9):849-56.

Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006 Aug 19;368(9536):647-58.

The Health Consequences Of Smoking: A Report Of The Surgeon General. Atlanta, GA: US Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, US Dept of Health and Human Services; 2004.

Tonnesen P, Mikkelsen K, Bremann L. Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support. Chest. 2006 Aug;130(2):334-42.

Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE. Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genet. 2007 Apr 3;8:10.

Wagena EJ, Knipschild P, Zeegers MP. Should nortriptyline be used as a first-line aid to help smokers quit? Results from a systematic review and meta-analysis. Addiction. 2005;100:317-326.

Review Date:
10/8/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

Herpes simplex virus

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Herpes simplex virus (HSV) infections are very common worldwide. HSV-1 (usually known as a cold sore) is transmitted through kissing or sharing drinking utensils, and HSV-2 (usually known as genital herpes) through sexual contact. You may be infected and not show symptoms for a long time. Often symptoms are triggered by exposure to the sun, fever, menstruation, emotional stress, a weakened immune system, or an illness.

There is not cure for herpes, and once you have it, it is likely to recur; however, some people may have one outbreak and then never have another one. In between herpes outbreaks, the virus lies dormant (as if it is hibernating or sleeping) in nerve cells.

While exposure to HSV-1 is extremely common – as many as 90% of American adults have been exposed to the virus – and there is no stigma to having a cold sore, HSV-2 or genital herpes can cause embarrassment. Although there is no cure for genital herpes, an infected person can take steps to preventing spreading the disease and can continue to have a sex life.

While most herpes infections do not cause serious complications, infections in infants and in people with weakened immune systems or herpes infections that affect the eyes can be life-threatening.

Signs and Symptoms

HSV-1

Small, painful blisters filled with fluid around the lips or edge of the mouth
Tingling or burning around the mouth or nose (often a few days before blisters appear)
Fever
Sore throat
Swollen lymph nodes in neck

HSV-2

Small red blisters or open sores on genitals or inner thighs; in women, often occur inside the vagina
May be painful or not
In women, vaginal discharge
Fever, muscle aches
Headache Painful urination
Swollen lymph glands in the groin

Causes

HSV-1 is transmitted through saliva. Kissing, using the same eating utensils, sharing personal items (such as a razor), and receiving oral sex from someone who has HSV-1 can cause you to contract the virus.

HSV-2 is a sexually transmitted disease.

Both herpes viruses can be contagious even if the infected person does not have active symptoms or visible blisters.

Also, a mother can pass the infection to her baby during vaginal birth, especially if there are active blisters around the vagina at the time of delivery.

Risk Factors

Oral herpes (cold sores)

Everyone is at risk for oral herpes from HSV-1. In fact, studies suggest that by adolescence 62% of Americans are infected with HSV-1 and by the time people are in their 40s, 90% have been infected.

Genital herpes

All sexually active people are at risk for genital herpes. Having multiple sexual partners puts you at even greater risk. Women have a greater risk of being infected after sex with an unprotected partner than men do. Estimates of how many Americans are infected range from 20% to 30%.

Other factors

People with weakened immune systems, such as people with HIV/AIDS or those who take immunosuppressant drugs to treat an autoimmune disease or because of organ transplant, are at increased risk for severe cases of herpes.

Diagnosis

In many instances, your doctor is able to make the diagnosis of herpes from examining you and no tests are required. If your doctor is not 100% certain, however, then he or she make take a sample from the blisters to test for the virus. Finally, there is a blood test that may be helpful for making a diagnosis, especially if your doctor suspects herpes but you don't have an active infection.

Preventive Care

HSV-1

Avoiding kissing people with visible core sores
Don't share personal items
Wash your hands frequently
If you have HSV-1, be careful touching your eyes and genitals; don't perform oral sex on your partner
Use sunscreen
Reduce stress

HSV-2

Avoid having sex if you or your partner has an outbreak (active infection) of herpes. Herpes outbreaks are not always obvious and your partner may be contagious without you knowing it. Anyone involved in an ongoing sexual relationship with a partner infected with HSV-2 should get counseling from a healthcare practitioner on how to best keep yourself safe.
Avoid touching the sores
Use or have your partner use a latex condom (even when sores are not visible)
Limit the number of sex partners

Treatment Approach

Herpes cannot be cured, so the goals of treatment are to reduce the number of outbreaks and to lessen symptoms when you do have an outbreak.

Cold sores usually go away by themselves in no more than 1 to 2 weeks. Using medications may shorten the outbreak and decrease discomfort.

Antiviral medications for genital herpes can reduce outbreaks and help speed recovery when an outbreak does occur. They can also lessen the chances of spreading the virus.

Coping with the emotional and social aspects of having genital herpes is part of treatment. Relaxation techniques and support groups can help.

Lifestyle

For cold sores, applying either heat or cold to blisters may help relieve pain. Try ice or warm compresses.

For genital herpes, wear cotton underwear and avoid tight fitting clothes as they can restrict air circulation and slow the healing of lesions.

Be sure to tell your partner or potential partner that you have herpes.

Medications

Antiviral medicines - may help shorten the duration of a herpes outbreak and suppress recurring outbreaks. For genital herpes, there are two types of therapy: episodic and suppressive. With episodic therapy, you take medication at the first sign of an outbreak and for several days to shorten the duration or prevent a full outbreak. With suppressive therapy, you may take medication daily to keep outbreaks from occurring. Antiviral medications include:

Acyclovir (Zovirax)
Famciclovir (Famvir)
Valacyclovir (Valtrex)

Topical medications (for oral herpes) - include the antiviral cream Penciclovir (Denavir) and an over-the-counter cream, docosanol (Abreva).

Nutrition and Dietary Supplements

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider.

Lysine (1 to 3 g per day) - Although not all studies agree, several studies suggest that lysine may help reduce the number of recurring outbreaks of cold sores and possibly genital herpes. Most of the studies have involved people with cold sores or with both cold sores and genital herpes. A few studies also suggest that lysine may help shorten the duration of an outbreak. The evidence is somewhat stronger for cold sores: the research to date is not entirely conclusive, lysine supplements have been used to help treat or prevent mouth and genital lesions caused by herpes. Taking lysine supplements or increasing lysine in your diet (from foods like fish, chicken, eggs, and potatoes) may speed recovery time and reduce the chance of recurrent breakouts of the herpes infection. If you have high cholesterol, heart disease, or high triglycerides (type of fatty material in the blood, generally measured when you have your cholesterol checked), it is best, at this point, not to use lysine because animal studies suggest that this supplement may raise cholesterol and triglyceride levels.
Propolis - A resin made by bees, propolis is loaded with flavonoids (antioxidants that help fight infection and boost immune function). Test tube studies show it can stop HSV-1 and HSV-2 from reproducing. One small study of people with genital herpes compared an ointment made from propolis to Zovirax ointment. People using propolis saw the lesions heal faster than those using topical Zovirax. More studies are needed to say for sure whether propolis works.
Zinc - In test tubes, zinc is effective against HSV-1 and HSV-2. In one small study in people, those who applied zinc oxide cream to cold sores saw them heal faster than those who applied a placebo cream.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a healthcare practitioner.

Lemon balm (Melissa officinalis) - Several studies suggest that topical ointments containing lemon balm may help heal cold sores. In one study, for example, those who applied lemon balm cream to their lip sores saw a reduction in redness and swelling after two days.
Aloe (Aloe vera) - Preliminary evidence suggests that aloe gel used topically may improve the symptoms of genital herpes in men. In two studies, men who used the aloe vera cream (0.5% aloe) saw lesions heal faster than those who used a placebo cream. It isn't know whether aloe vera would also help heal cold sores.
Rhubarb cream (Rheum palmatum) - In one Swiss study, a cream made from sage (Salvia officinalis) and rhubarb was as effective as Zovirax in healing cold sores. Sage by itself was not beneficial. More research is needed.
Eleutherococcus or Siberian ginseng (Eleutherococcus senticosus/Acanthopanax senticosus) -Although not all studies agree, one 6-month study of 93 people with genital herpes found that Siberian ginseng reduced the frequency, severity, and duration of outbreaks. This herb should not be taken if you have high blood pressure, obstructive sleep apnea (repeated, prolonged periods when breathing stops while sleeping), narcolepsy (frequent day time sleeping), are pregnant or breastfeeding.
Peppermint oil (Mentha x piperita ) - In test tubes, peppermint oil has stopped a number of viruses from reproducing, including herpes. However, it isn't known whether peppermint oil would have any effect on the herpes virus in humans.

Homeopathy

Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the remedies described below for the treatment of herpes based on their knowledge and experience. One study of 53 people with genital herpes did show that the majority had improvement in their symptoms and were less likely to have recurrent outbreaks when treated with homeopathy. Participants in this study were followed for up to 4 years.

Before prescribing a remedy, homeopaths take into account a person's constitutional type. A constitutional type is defined as a person's physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for each individual.

For cold sores:

Natrum muriaticum - for eruptions at the corners of the mouth that occur during periods of emotional stress and tend to worsen in the daytime
Rhus toxicodendron - for eruptions consisting of many small blisters that itch intensely at night
Mercurius - for children who drool and may have a fever
Sepia - for outbreaks that do not improve with other homeopathic remedies; this remedy is most appropriate for individuals who tend to have a lack of energy and don't tolerate cold weather

For genital lesions:

Graphites - for large, itchy lesions in individuals who are overweight
Natrum muriaticum - for eruptions that occur during periods of emotional stress and symptoms that tend to worsen in the daytime
Petroleum - for lesions that spread to anus and thighs; symptoms tend to worsen in winter and improve in summer
Sepia - for outbreaks that do not improve with other homeopathic remedies; this remedy is most appropriate for individuals who tend to have a lack of energy and don't tolerate cold weather

Mind/Body Medicine

Support groups - Having genital herpes can impact your social and emotional life. In fact, if you have herpes, it is quite common to feel depressed, angry, and even guilty. Worrying about possible rejection by someone with whom you are hoping to become intimate is also typical. Joining a support group where members share experiences and problems can help relieve the stresses associated with having genital herpes. If you are in a committed relationship, seeing a couples' therapist with your partner may also be helpful.
Relaxation techniques - Using relaxation techniques, such as yoga, guided imagery, and meditation, on a daily basis may help you feel better overall and cope with stresses related to having herpes.
Self-hypnosis - Self-hypnosis using guided imagery may also help relieve stress. In one 6-week training program, participants with frequently recurring genital herpes were able to reduce outbreaks by nearly 50% and improve their mood, including reducing feelings of depression and anxiety.
Other - Individual therapy with a psychiatrist, psychologist, or social worker; and techniques such as biofeedback can help reduce emotional symptoms associated with herpes.

Other Considerations

Pregnancy

Herpes viruses can be transmitted to a newborn during vaginal delivery, especially if the mother has active lesions in the vagina at the time of delivery. Herpes infections in newborns can be life-threatening or cause disability. Delivery by cesarean section (C-section) will be recommended to avoid infecting the baby.

Special Populations

Newborns – herpes infections contracted during delivery from the mother can lead to meningitis, herpes infection in the blood, chronic skin infection, and may even be fatal.

You are more likely to have severe, frequent outbreaks and to experience complications from herpes if your immune system is suppressed from:

HIV or AIDS
Chemotherapy for cancer
Long-term use of high doses of corticosteroids
Medications that intentionally suppress the immune system

Warnings and Precautions

If you are diagnosed with genital herpes, you should be tested for other sexually transmitted diseases such as chlamydia and gonorrhea.

Prognosis and Complications

Herpes is a chronic, recurrent infection. The initial symptoms usually appear within 1 to 3 weeks of exposure to the virus and last 7 to 10 days (for cold sores) or 7 to 14 days (for genital lesions). Usually the number of outbreaks is greatest in the first year and higher for HSV-2 genital lesions than HSV-1 cold sores. Each year after that, the number of outbreaks usually goes down and they become less severe. But you can never completely get rid of the virus.

Complications of herpes include:

Herpetic keratitis – herpes infection of the eye leading to scaring within the cornea and possible blindness
Persistent herpes infection, without lesion-free periods
Herpes infection in the esophagus
Herpes infection of the liver which can lead to cirrhosis (liver failure)
Encephalitis and/or meningitis (serious brain infections)
Lung infection
Eczema herpetiform – widespread herpes across the skin

Supporting Research

Allen P. Tea tree oil: the science behind the antimicrobial hype. Lancet. 2001;358(9289):1245.

Ames M. Herpes: Comprehensive treatment strategy. Int J Integra Med. 2000;2(5):6-9.

Beauman JG. Genital herpes: a review. Am Fam Physician. 2005 Oct 15;72(:1527-34. Review.

Binns SE, Hudson J, Merali S, Arnason JT. Antiviral activity of chacterized extracts from Echinacea spp. (Heliantheae: Asteraceae) against herpes simplex virus (HSV-I). Planta Med. 2002;68(9):780-783.

Brennan P. Homeopathic remedies in prenatal care. J Nurse Midwifery. 1999;44(3):291-299.

Carson CF, Ashton L, Dry L, Smith DW, Riley TV. Melaleuca alternifolia (tea tree) oil gel (6%) for the treatment of recurrent herpes labialis. J Antimicrob Chemother. 2001;48(3):450-451.

Cummings S, Ullman D. Everybody's Guide to Homeopathic Medicines. 3rd ed. New York, NY: Penguin Putnam; 1997: 259-260.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1080-1086.

Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J. Antiviral effects of Glycyrrhiza species. Phytother Res. 2007 Sep 20; [Epub ahead of print]

Fox PA, Henderson DC, Barton SE, et al. Immunological markers of frequently recurrent genital herpes simplex virus and their response to hypnotherapy: a pilot study. Int J STD AIDS. 1999;10(11);730-734.

Fried RG. Nonpharmacologic treatments in psychodermatology. Dermatol Clinics. 2002;20910;177-185.

Gaby AR. Natural remedies for Herpes simplex. Altern Med Rev. 2006 Jun;11(2):93-101. Review.

Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med. 2001;7(3):49-56.

Griffith RS, Walsh DE, Myrmel KH, Thmpson RW, Behforooz A. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175(4):183-190.

Gruzelier JH. A review of the impact of hypnosis, relaxation, guided imagery and individual differences on aspects of immunity and health. Stress. 2002;5(2):147-163.

Hijikata Y, Tsukamoto Y. Effect of herbal therapy on herpes labialis and herpes genitalis. Biotherapy. 1998;11(4):235-240.

Huleihel M, Isanu V. Anti-herpes simplex virus effect of an aqueous extract of propolis. Isr Med Assoc J. 2002;4(11 Suppl):923-927.

Jenaer M, Henry MF, Garcia A, Marichal B. Evaluation of 2LHERP in preventing recurrences of genital herpes. Institut International 3IDI. Br Homeopath J. 2000;89(4):174-177.

Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996: 234.

Koch C, Reichling J, Schneele J, Schnitzler P. Inhibitory effect of essential oils against herpes simplex virus type 2. Phytomedicine. 2007 Oct 30; [Epub ahead of print]

Koytchev R, Alken RG, Dundarov S. Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis. Phytomedicine. 1999;6(4):225-230.

L-lysine. Monograph. Altern Med Rev. 2007 Jun;12(2):169-72.

Marcason W. Will taking the amino acid supplement lysine prevent or treat the herpes simplex virus? J Am Diet Assoc. 2003;103(3):351.

McCaleb R. Melissa relief for herpes sufferers. HerbalGram. 1995;34.

Milman N, Scheibel J, Jessen O, et al. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol. 1980;60:85-87.

Robbers JE, Tyler VE. Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York, NY: The Haworth Herbal Press; 1999:67-68, 246-247.

Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia, PA: Hanley & Belfus, Inc; 2002:249-251.

Saller R, Buechi S, Meyrat R, Schmidhauser C. Combined herbal preparation for topical treatment of Herpes labialis. Forsch Komplementarmed Klass Naturheilkd. 2001;8(6):373-382.

Schnitzler P, Nolkemper S, Stintzing FC, Reichling J. Comparative in vitro study on the anti-herpetic effect of phytochemically characterized aqueous and ethanolic extracts of Salvia officinalis grown at two different locations. Phytomedicine. 2007 Dec 7; [Epub ahead of print]

Schnitzler P, Schon K, Reichling J. Antiviral activity of Australian tea tree oil and eucalyptus oil against herpes simplex virus in cell culture. Pharmazie. 2001;56(4):343-347.

Shenefelt PD. Hypnosis in dermatology. Arch Dermatol. 2000;136(3):393-399.

Tomblin FA Jr, Lucas KH. Lysine for management of herpes labialis. Am J Health Syst Pharm. 2001;58(4):298-300, 304.

Ullman D. Homeopathic Medicine for Children and Infants. New York, NY: Penguin Putnam; 1992: 60.

Ullman D. The Consumer's Guide to Homeopathy. New York, NY: Penguin Putnam; 1995: 277-278.

Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical effectiveness. Br J GenPract. 1999;49:823-828.

Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomized clinical trials. Eur J Clin Pharmacol. 1999;55(:567-575.

Vynograd N, Vynograd I, Sosnowski Z. A comparative multi-centre study of the efficacy of propolis, acyclovir, and placebo in the treatment of genital herpes (HSV). Phytomedicine. 2000;7(1):1-6.

Review Date:
12/23/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Multiple sclerosis

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
The Autoimmune Disease Proc...
Symptoms
Causes
Risk Factors
Complications
Diagnosis
Treatment
Drug Treatment
Other Treatments
Treating the Complications...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Gender and Multiple Sclerosis (MS)

MS is increasingly affecting women, according to research presented at the 2007 annual conference of the American Academy of Neurology. Researchers found that in the 1940s, women were twice as likely as men to be diagnosed with MS. By 2000, women were about four times more likely than men to develop MS. Experts are uncertain why this ratio is growing.

Family History

If MS runs in your family, there’s a chance you may develop the disease at the same age that other family members did, suggests a 2007 Neurology study. However, family history does not predict disease course or severity.

Vitamin D

Higher blood levels of vitamin D may reduce the risk for MS, at least among Caucasians, indicates a 2007 study in the Journal of the American Medical Association. (The researchers found no protective effect for African-Americans or Hispanics.) However, until further research is conducted, doctors do not recommend taking vitamin D supplements for MS prevention.

Infections and Symptom Relapse

Both viral and bacterial systemic infections can trigger relapses, according to a study in Neurology. Researchers found that relapses and new brain lesions appeared within 2 weeks after an infection.

Drug Research

Natalizumab (Tysabri) may help reduce vision loss in patients with relapse-remitting MS, indicates a 2007 Neurology study. In 2006, the FDA enforced safety restrictions on the use of this drug due to cases of progressive multifocal leukoencephalopathy (PML), a rare brain disorder. Since the restrictions were put in place, no new cases of PML have been reported.
Glatiramer acetate (Copaxone) shows little benefit for primary progressive MS, according to a 2007 study in Annals of Neurology.
Testosterone gel may help men with relapse-remitting MS, suggests a small study published in 2007 in the Archives of Neurology.

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS), the nerves that comprise the brain and spinal cord. It has two major features:

Destruction of myelin, a fatty insulation covering the nerve fibers, is the main characteristic of MS. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. (Multiple sclerosis is well named. Sclerosis comes from the Greek word skleros, which means hard.)
Destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is also a major factor in the permanent disability that occurs with MS.

Myelin is the layer that forms around nerves. Its purpose is to speed the transmission of impulses along nerve cells.

The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination. Experts generally group multiple sclerosis into two major symptom categories:

Relapsing-remitting
Chronic-progressive

Chronic-progressive MS is often subcategorized as primary-progressive, secondary-progressive, and progressive-relapsing.

Recent evidence suggests that the disease process starts long before symptoms begin. By the time symptoms appear, there are often already signs of brain and spinal cord atrophy. The cause of MS is unknown, and it cannot be prevented or cured. It is not fatal, however, and great progress is being made in treating it and identifying underlying mechanisms that trigger this disease.

Relapsing-remitting multiple sclerosis generally occurs in younger people and is the most common form of MS. It generally follows this course:

Most patients first experience a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis.
The characteristic feature of relapsing-remitting MS is the attack (also referred to as relapse, flare-up, or exacerbation), which is a bout of specifically MS symptoms (facial pain, Lhermitte’s sign, or bladder instability) that lasts at least 24 hours and typically several days. Such attacks are fairly mild in about half of patients with this form of MS.
The disease then goes into remission (when symptoms improve or disappear), usually for about 4 - 8 weeks. To be considered in remission, attacks need to be separated by at least 30 days. Remission periods may be spontaneous or induced by immunosuppressive drugs. A person with multiple sclerosis in remission may have subtle attacks and not realize it. For example, hands may be a little numb for a few days, or there may be slight awkwardness in gait or coordination.
Remissions are almost always followed by relapses, in which symptoms flare-up or the patient experiences a period of deteriorating ability.

About 20% of patients with relapsing-remitting MS experience little or no progression after a first attack for long periods of time, although by 25 years most patients have converted to a progressive phase.

The term chronic-progressive multiple sclerosis is used to describe cases in which symptoms continue to worsen slowly without remission. About 20% of multiple sclerosis patients (usually those whose first symptoms occur after age 45) have the chronic-progressive form without first developing relapsing-remitting MS. Chronic-progressive MS generally follows a downhill course, but its severity varies widely. Three variants are commonly used to define this patient group:

Secondary-Progressive MS (SPMS). SPMS is the natural evolution of relapsing-remitting MS and develops in about half of patients during the first 10 years and nearly all of them within 25 years. It follows a progressive course of nerve and muscle deterioration with occasional acute flare-ups, remissions, and plateaus.
Primary-Progressive MS (PPMS). PPMS progresses continuously and gradually from the first onset of symptoms and has no remissions. It occasionally levels off, and minor improvement is even possible. This occurs in about 10% of patients, who tend to be older than average at the time of diagnosis.
Progressive-Relapsing MS (PRMS). PRMS is progressive from the start with acute symptom flare-ups, but may have some relapses with continued deterioration between them. It occurs in less than 5% of patients.

Because the natural courses of primary-progressive and progressive-relapsing MS are similar, some experts believe this distinction is unnecessary.

Click the icon to see an image depicting multiple sclerosis.

The Autoimmune Disease Process

Multiple sclerosis is referred to as an autoimmune disease. The general theory for the development of MS is that a genetically damaged immune system is unable to distinguish between virus proteins and the body’s own myelin and so produces antibodies that attack. In other words, the body becomes allergic to itself, a condition known as autoimmunity.

Autoimmunity may develop when the body's immune system is damaged by genetic or environmental factors or both, causing it to attack its own tissues. In the case of MS, the immune system attacks the tissues that make up myelin:

Myelin is made from layers of cell membranes that are produced in the brain and spinal cord by specialized cells called oligodendrocytes. The destruction of this myelin sheath during the disease process is the hallmark for multiple sclerosis.
The myelin coat is distributed in segments along the axons, the long filaments that carry electric impulses away from a nerve cell.
The segments are separated from each other by tiny clusters called nodes of Ranvier, which house channels for sodium ions. These sodium ions are important for boosting the electrical charge required to pass signals from one nerve to another.
As the myelin insulation is destroyed, signals transmitted from nerve cell to nerve cell throughout the central nervous system are disrupted.
Experts once believed that axons themselves were spared during the disease process. Research, however, has shown that many are severed in MS and, in fact, axon destruction appears to start at an early stage in the disease and may be a major cause of its irreversibility.

The body often makes corrective actions to offset the effects of the nerve cell destruction:

For example, researchers have observed an increase in the density of the sodium channels, which carry electric charges. By increasing their numbers, the nerve cells can continue to communicate, in spite of the loss of myelin.
The nerves also retain some capacity to remyelinate (to restore the insulating myelin).

Such processes are probably responsible for the remissions that most patients experience. Unfortunately, the disease process nearly always eventually outpaces these corrective actions.

The Normal Immune Response.

The most important critical immune factors in the disease process are white blood cells called lymphocytes, which consist of T cells and B cells. These cells are the warriors in the immune defense system.
Receptors on T cells acquire the ability to recognize specific molecules called antigens. Antigens are typically proteins from infecting organisms, such as bacteria or viruses, and perceived as a threat to the body.
Once the antigen is identified, specific T cells, called helper T cells, trigger the B cells to release antibodies. These molecules are designed to attach to and destroy the targeted antigen.

Autoimmunity.

Multiple sclerosis, and probably all autoimmune diseases, involves an error in the education of T cells, which makes them unable to distinguish self from non-self.
In multiple sclerosis, the miseducated T cells mistake molecules in the body's own myelin as a foreign antigen. Such targets are referred to as self-antigens.
In response to detection of these self-antigens, the T cells set off the usual cascading immune events, including the release of B lymphocytes, to rid the body of the perceived threat.
The B lymphocytes fire off antibodies as usual, but in this case they are referred to as autoantibodies, because they are attacking antigens that belong to the body's own self.
In MS, the immune system is tricked into targeting self-antigens that are myelin proteins, the fatty insulation covering the nerve fibers. Another autoantibody target may be the oligodendrocytes themselves -- the specialized cells that make up myelin.
To make matters worse, the process perpetuates through a cascading series of events in which the B cells and T cells continue to interact, creating numerous different self-antigens. The attacks continue and, in the process, the original self-antigen is unrecognizable.

Cytokines and the Inflammatory Response. The inflammatory response is the product of an overactive immune system and is a major destructive force in an autoimmune disease.

Once the lymphocytes have launched a response to an antigen, they also release masses of other white blood cells to gather at the injured or infected site.
The major players in this response are white blood cells called leukocytes. Researchers are particularly interested in leukocytes called cytokines. These are small powerful proteins that, in tiny amounts, are indispensable for healing. When they are overproduced, however, which occurs in MS, they play a major role in the destructive process.
Their intensive convergence on the affected area causes it to become inflamed and injurious to the very cells they are designed to protect. Under normal conditions, this inflammatory process is controlled and self-limiting, but in people with autoimmune diseases such as multiple sclerosis, the process persists and damage occurs in the surrounding tissues.

Important cytokines in MS appear to be tumor necrosis factors, interleukin-12, and interferon-gamma. Other cytokines, including interleukin-10 and transforming growth factor beta, may play a protective role and help block inflammatory activity.

The inflammatory response may trigger the disease, but afterward a progressive course takes over that does not appear to be related to inflammation. Experts have found that destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is a major feature of multiple sclerosis. In fact, it may be the major cause of permanent disability that occurs with this disease. Microscopic studies reveal that axons are injured early on as "bystanders" while myelin is being peeled off. As the disease progresses, these weakened and exposed axons degenerate further. Most of the damage occurs early in the disease process and decreases over time, although some destruction can still be observed years and decades afterward. Such evidence is having significant effect on approaches to treatment and research.

Symptoms

Most patients first experience multiple sclerosis as a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis. Much less commonly, the disease is progressive from the start and symptoms are more or less continuous.

Early symptoms may include the following:

Optic neuritis and other problems in the eye. Optic neuritis, which is inflammation of the nerves in the eye, affects over 50% of patients and is the first symptom in about 16% of patients. Symptoms include unclear or doubled vision, usually in one eye. Some people see a shimmering effect. Patients may also experience pain or involuntary jerking or movement of the eye (called nystagmus). In 20% of people with this condition, MS develops within 2 years after the onset. In 45 - 80%, MS develops within 15 years. About 17% of people eventually experience impaired eye movement.
Fatigue. Fatigue is typically worse in the afternoon and may be accompanied by an increase in body temperature. At the onset, this occurs in about 20% of patients, but as the disease progresses, this is a significant symptom in nearly all patients.
Changes in sensations in the arms and legs. Patients can experience heaviness, weakness, or clumsiness in the limbs. Tingling or loss of sensations can also occur, most commonly in the legs. The first symptoms for patients with primary progressive MS often develop slowly in the upper legs.
Muscle weakness in the legs and poor coordination.
Lhermitte’s sign. This is an electrical sensation that runs down the back and into the legs, which is produced by bending the neck forward.
Spasticity. Spasticity is the inability to control muscle tone and leads to spasms and stiffness. It is very common in MS.
Disturbances in the bladder.

In addition to the persistence of early symptoms, some patients experience the following symptoms as the disease progresses:

Imbalance and dizziness.
Tremors.
Facial pain.
Spasm-related symptoms. They include burning, itching, aching, quivering sensations. They usually occur in the extremities and last seconds to minutes.
Speech difficulties.
Difficulty swallowing.
Symptoms in the gastrointestinal, urinary, and genital tracts. Possible sexual dysfunction and loss of bowel and bladder control in severe cases.
Emotional mood swings. Depression is very common. About 10% of patients suffer from psychosis (manic depression and paranoia). About 5% of patients with severe MS experience uncontrolled and extreme mood swings called the laughing/weeping syndrome.
Problems in concentration and memory.
Hearing loss.

Infections. Viral infections have long been known to worsen MS symptoms. An important 2006 study indicated that bacterial infections can also trigger MS relapses. In the study, relapses appeared within 2 weeks of a viral or bacterial infection.

Heat. Heat, whether generated by ambient temperature, infection, or physical activity, worsens MS symptoms in about 60% of patients.

Stress. There is a strong correlation between severe stress and exacerbation of MS symptoms. For example, in one study, 85% of instances of MS exacerbations were associated with stressful events that occurred within an average of 14 days before the episode. Stress is not a cause of MS, however.

Trauma. Some experts believe that injury (trauma) to the head, neck, or upper back may trigger new or recurrent symptoms by disrupting the blood-brain barrier and allowing immunological attacks on the brain. This is a highly controversial theory, however, with very little supporting evidence.

Causes

The cause, or causes, of multiple sclerosis remains a mystery. Genetic factors certainly play a role in MS. No single gene, however, is likely to be responsible for causing MS. Rather, the current theory is that the disease occurs in people with a genetic susceptibility who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack (a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Some research suggests that all autoimmune diseases are basically due to the same genetic error. A 2001 study found, for example, that the T cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders. Nor, why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

Genetic factors probably play some role in making a person susceptible to the disease process leading to multiple sclerosis. In particular, abnormalities in the human leukocyte antigen (HLA) region located on chromosome 6 appear to be more prevalent among people with MS. Researchers theorize, however, that a combination of genes (not a single gene) is implicated in the development of MS, and the risk for someone inheriting all of these genetic factors is less than 5%. Advanced techniques called microarray technologies are now making it possible to scan hundreds of genes and identify those most likely to be contributors to MS. Genetic research may also pave the way for the development of new drugs to treat this disease. For example, researchers have recently identified the Olig1 gene as a key regulator in repairing damaged myelin-producing cells.

Infectious organisms, most likely viruses, are the top suspects for triggering the autoimmune response in people genetically susceptible to MS. There are a number of reasons for this belief:

The geographical distribution of the disease. The number of MS cases increases the further one gets from the equator in either direction.
Multiple sclerosis clusters. Four separate clusters of multiple sclerosis outbreaks occurred between 1943 - 1989 in the Faroe Islands, located between Iceland and Scandinavia. During World War II, this region was occupied by British troops. The incidence of MS increased each year for 20 years after the war, leading some researchers to think that the troops might have brought with them some disease-causing organism. In fact, one theory suggests that these findings offer evidence that MS is a sexually transmitted infection that occurs during adolescence. For example, the disease clusters observed in the Faroe Islands could be related to high sexual activity between the troops and local young women. A high incidence of MS is found in countries with a high degree of sexual permissiveness. MS is very rare in traditional cultures, but increases in people from these regions when they immigrate to industrialized Western nations.
Viral similarity to myelin. Some viruses are strikingly similar to the myelin protein and may therefore cause confusion in the immune system, causing the T cells to continue to attack their own protein rather than the viral antigen. More than one antigen may be involved; some may trigger the disease, and others may keep the process going.

Infectious Organisms Under Suspicion. Although many infectious microorganisms have been investigated, no one organism has emerged as a proven trigger. It is possible that different patients may be affected by different organisms, and that infections cause some, but not all, cases of MS. Organisms that are at the top of the suspect list are those that can affect the central nervous system. The following are three primary suspects:

HHV-6. Herpesvirus 6 (a form of herpesvirus that causes roseola, a benign disease in children) is also known to cause encephalitis (brain inflammation) in patients with impaired immune systems. A number of studies have reported higher than normal rates of HHV-6 infection in patients, and some experts believe that may be important in MS. Other experts argue, however, that nearly everyone harbors this virus and there is still no evidence of a causal relationship. Other herpes viruses can also infect brain cells. They include herpes simplex 1 and 2 (the causes of oral and genital herpes), varicella-zoster virus (the cause of chicken pox and shingles), and cytomegalovirus.
Epstein-Barr virus (EBV). Evidence suggests an association between EBV, the cause of mononucleosis, and MS. EBV is an extremely common virus and another member of the herpes virus family. Nearly all people have been exposed to EBV. However, researchers have discovered that people who are especially sensitive to the virus and have unusually high levels of EBV antibodies may have a greater risk of developing MS. Scientists are still uncertain if EBV is a cause of MS. EBV has also been linked to other autoimmune diseases such as lupus.
Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation. A few studies have reported significantly higher rates of previous Chlamydia infection in patients with MS than in individuals without MS. An important group of 2000 studies reported no connection at all between Chlamydia and MS, and any experts now believe there is no strong evidence linking the microbe to MS. It is still possible, however, that the infection, which can cause widespread inflammation, plays a role early in the course of the disease in some individuals.

Other viruses that have been investigated include measles virus, adenovirus, and the retroviruses (HIV, HTLV-I, and HTLV-II), but none have emerged as having any importance.

Note on Vaccinations: Concerns about a link between the hepatitis B vaccine and MS led France to halt a major vaccination program in 1998. Subsequent research investigating whether the hepatitis B vaccine is indeed associated with an increased risk of MS has yielded mixed results. It appears that the vaccine would be, at most, a contributing -- but not the sole -- factor in MS development. At present, the evidence has not warranted any change in American immunization policies. Research has ruled out a link between any other vaccinations, such as or influenza or tetanus, and relapses of MS.

Risk Factors

An estimated 400,000 Americans and 2.5 million people worldwide suffer from MS.

Age. Onset occurs between the ages of 20 - 40 years in 70% of patients with the average age being 30 and the peak incidence occurring in the mid-twenties. The disease can still occur in both younger and older individuals. It rarely develops before age 15 or after age 60, however.

Gender. MS is more common among women than men. The gender gap is strongest among people who develop MS at a younger age. According to research presented at the 2007 American Academy of Neurology annual conference, the ratio between women to men has been growing. Researchers found that in the 1940s, the ratio of women to men with MS was 2 to 1. By 2000, the ratio had grown to 4 to 1. However, some research indicates that men may be more disabled by the disease than women.

Ethnicity. Multiple sclerosis occurs worldwide but is most common in Caucasian people of northern European origin, especially those of Scottish descent. It is extremely rare among Asians, Africans, and Native Americans. Specific groups (gypsies, Eskimos, Bantus) have never reported a case. While the risk of MS for African-Americans is around half of that for Caucasians, a recent study suggested that African-Americans are more likely to develop a more aggressive form of the disease and to suffer impaired mobility.

Geography. The risk for MS is higher in different regions of the world. In general, MS is more prevalent in temperate regions than in the tropics. Specifically, prevalence is highest in northern and central Europe (except northern Scandinavia), Italy, southern Australia, and northern regions of North America. Middle-risk areas include southern Europe (except Italy), southern US, northern Australia, and northern Scandinavia. Low-risk areas include parts of Africa and Asia, the Caribbean, Mexico, and possibly northern South America. It is unclear whether this pattern is attributable to environmental factors, genetics, or both.

Family History. A family history of the disease also puts people at risk for MS, although the risk for someone inheriting all the genetic factors contributing to MS is only about 2 - 4%. A 2007 study indicated that family members who have MS tend to develop the disease at around the same age. However, family history does not predict whether one family member will experience the same disease severity as another family member.

Cow's Milk During Early Infancy. Breast milk contains factors that may help regulate the immune response, and there is some evidence that infants fed only on cow's milk may have a higher risk for either diabetes type 1 (another type of autoimmune disease) or multiple sclerosis later in life. Studies on national differences in diabetes suggest that the risk may vary with different milk proteins, suggesting that not all cow's milk is the same and that some proteins carry higher risks than others.

The Hygiene Theory: Early Infections as Protection Against Allergies and Autoimmune Diseases. Over the past decades, there has been a dramatic increase in asthma, allergies, and autoimmune diseases, such as multiple sclerosis, Crohn's disease, and type 1 diabetes. One theory blames this rise on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. Studies supporting this have observed a higher incidence of allergies and autoimmune diseases, including MS, among populations with good hygiene and in animals that have been raised in a germ-free environment. The basic theory rests on the idea that early infections stimulate production of specific immune factors that protect against allergies and autoimmune diseases. The exact mechanisms of these effects are as yet unknown.

Vitamin D. Higher blood levels of vitamin D have been associated with a lower risk for MS, at least among Caucasians. (Studies have not shown that vitamin D has a protective effect for other racial groups.) However, there is not yet enough evidence to indicate that taking vitamin D supplements can help prevent MS.

Exposure to Sunlight. In a 2003 study, higher exposure to sunlight during childhood and early adolescence was associated with a lower risk for MS, perhaps because UV radiation produces higher levels of vitamin D, which has been associated with protection against MS. The effect of sunlight during winter seemed to be more protective than summer light. Unfortunately, higher exposure to sunlight also coincides with a higher risk for skin cancer, which is far more common than MS.

Estrogen and Oral Contraceptives. Higher estrogen levels may temporarily lower the risk of developing multiple sclerosis. Studies indicate that oral contraceptives (which contain estrogen) and pregnancy delay the onset of multiple sclerosis. The risk for a first clinical attack increases, however, in the 6 months after a woman gives birth.

Complications

Multiple sclerosis is not a fatal disease. Some data suggest that it shortens the average life span by only about 6 or 7 years. Still, in about half of MS cases, patients die of complications of the disease, and the disease has significant negative emotional and physical consequences. Suicide rates among patients with MS are higher than average.

The severity of the disease varies widely from patient to patient and is unpredictable. About 20% of patients remain asymptomatic or become only mildly symptomatic after an initial clinical event. Another 20% experience a rapidly progressive condition. Most patients, however, will experience some degree of progression.

Women tend to have a better outlook than men. Factors the determine a higher risk for a severe condition include:

Age over 40 years at the time of onset of symptoms
Initial symptoms that affect motor control, mental functioning, or urinary control, or initial symptoms affect multiple regions
Attacks in the first years that are frequent or interval between the first two attacks is short
Incomplete remissions
Rapid progression to disability
MS that is progressive from the beginning or becomes progressive shortly after the onset

Doctors and researchers often use a scale called the Kurtzke Disability Status Scale to assess and predict future disability. The system uses a score of 1 to 10 to rate the degree of walking disability. Experts have used the scale to attempt to predict average times for progression from one stage to the next depending on whether patients have relapsing-remitting or chronic progressive MS.


Score	Disability Description	Relapsing-Remitting MS: Average time until onset of symptoms*	Chronic Progressive MS: Average time until onset of symptoms*
1	No disability and minimal neurologic symptoms.	11.4 years from Score 1 to Score 4	0 years from Score 1 to Score 4
2	Minimal disability in one or two functional areas. Slight weakness or stiffness, mild walking impairment or visual disturbances
3	Moderate disability in one functional area, such as vision or the urinary tract, and possibly more than one minimal disability in several others. Either a part of one of the limbs or a whole side can be partially paralyzed. May stagger at times.
4	Disability is relatively severe but there is full ability to walk without aid. Patients are self-sufficient and can be active 12 hours a day and carry on normal activities. Can walk without aid or rest for 300 to 500 meters.
5	Disability is severe enough to impair or even preclude a full day's activities. Able to walk unaided and without rest for 100 to 200 meters.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
6	Can walk unaided for about 100 meters only with assistance or devices, such as two canes, crutches, or braces.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
7	Mostly restricted to wheelchair, although can manage the wheelchair and leave it unassisted. Can walk with aids no further than about five meters.	33.1 years from Score 1 to Score 7	13.4 years form Score 1 to Score 7
8	Mostly restricted to wheelchair or even bed, but still has effective use of arms remains and able to perform many self-care functions.	(Data not available)	(Data not available)
9	Bedridden. Patient can communicate or eat.
10	Fatality occurs from complications.
* Data taken from Relapses and Progression of Disability in Multiple Sclerosis, The New England Journal of Medicine, November 16, 2000, Vol. 343, No. 20

Because the effects of nerve injury are widespread, complications can be very severe and affect all parts of the body. Although not all patients experience all of the following problems, any of them can negatively impair quality of life.

Fatigue. Fatigue is one of the most common and debilitating MS symptoms and affects at least two-thirds of patients with MS. Fatigue specifically attributed to MS and not to other causes is defined as abnormal fatigue that lasts at least half of the time or more than 6 weeks. It causes a general lack of energy that significantly limits daily functioning regardless of any neurologic symptoms or specific muscle weaknesses. Up to 40% of patients describe fatigue as the most disabling MS symptom, which is higher than weakness, spasticity, motor control, or bowel or urinary problems. Many conditions that are common in MS (sleep disorders, depression, hypersensitivity to sensation, hypothyroidism, medications, heat) may contribute to fatigue. None fully explain the consistent presence or severity of this problem in MS. Researchers using imaging techniques have identified possible changes in part of the brain in MS that may play a role in the fatigue of MS.

Loss of Mobility and Spasticity. Nearly every patient loses some mobility, which may take the form of less or impaired motor control, muscle weakness, impaired balance, and, importantly, spasticity. Spasticity is one of the primary symptoms of MS. It is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso. (Ironically, mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking.) Mobility can be affected by many non-physical factors, including mental well-being, social networks, fatigue, and even the weather.

Pain. About two-thirds of patients experience pain at some point during the course of the disease, and 40% are never pain free. MS causes many pain syndromes; some are acute while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis (pain in the eye), pressure pain, stiffened joints, and a variety of sensations, including feelings of itching, burning, and shooting pain.

Bowel Dysfunction. Bowel dysfunction, which can include constipation or fecal incontinence, is a serious problem for many patients. Constipation may be caused by the disorder itself or by medications used to treat spasms or other symptoms.

Sexual Dysfunction. Sexual dysfunction is a common problem, occurring in over 70% of patients. Men are likely to have impotence and women, problems with vaginal lubrication. It appears to be highly associated with urinary dysfunction.

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal function. When there is CNS damage, the function of these organs and tissues may be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems and sexual dysfunction.

Urinary Dysfunction. Urinary problems from bladder dysfunction occur in two-thirds of patients. Some patients have difficulties in urinating at will, called urinary retention. Often it takes the form of urge incontinence (also called hyperactive or irritable bladder). People with urge incontinence need to urinate frequently or are unable to reach the bathroom before leakage. In such cases, the bladder is overactive. Complications in the urinary tract also produce a high rate of urinary tract infections.

Difficulty Swallowing. A third to a half of patients experience difficulty in chewing or swallowing, problems that may be caused or made worse by many MS medications.

Speech and Hearing Problems. Problems in speech may occur because of difficulty in controlling the quality of the voice and articulating words. (Problems with language itself, however, are very rare in MS.) Hearing problems also occur in MS and may affect speech.

Problems in the Lungs. As the muscles that control breathing weaken, the ability to cough is impaired and the patient is at higher risk for pneumonia and other complications in the lungs.

Osteoporosis. Osteoporosis (loss of bone density) and subsequent fractures are common and under-recognized problems among patients. Osteoporosis is caused and worsened by immobility and by some MS medications. Fractures caused by falls can be far more serious in patients than in the normal population, leading to problems, including deconditioning or even inability to walk, obstruction of the intestines (from pain-relieving medications), and respiratory complications.

Cognitive problems, such as having trouble concentrating and solving problems, affect about half of patients. More people with MS leave work because of such cognitive difficulties than because of physical problems, according to a 2000 study. In about 10% of cases, mental dysfunction may be severe and resemble dementia. The severity of such mental changes appears to be associated with the degree of loss of brain tissue. This offers another argument for early treatment as interferon medications may improve these symptoms.

Between 40 - 60% of patients suffer from depression at some point over the course of the illness, and studies have reported risks for suicide ranging from 3 - 15%. Some evidence suggests that depression in multiple sclerosis is not only due to the social and psychologic impact of MS but also to the disease process itself. Depression may have biologic effects, such as increasing production of inflammatory cytokines, that could exacerbate the disease itself. Doctors should assess patients for depression, even if there are no obvious signs of it. The risk for suicide may be present even in patients who are not obviously depressed. People at highest risk for suicide are those who live alone, those with a history of an emotional disorder (depression, anxiety, alcohol abuse), a family history of mental illness, and people with high social stress.

Diagnosis

Multiple sclerosis is characterized by recurring neurologic episodes that are due to multiple lesions (injured areas) in different locations in the central nervous system. The diagnostic challenges in multiple sclerosis are two-fold:

Making an initial diagnosis as early as possible in order to slow down the disease progression. Most patients first seek medical help after an initial inflammatory event (known as a clinically isolated syndrome) originating from demyelination in the eye, the spinal cord, or the brain. About 30% of these individuals will develop progressive MS within the year. At this time, however, experts cannot predict who among these patients are at highest risk for rapid progression.
Predicting the severity of the disease. Once MS has been diagnosed, the pattern of the disease is uncertain. It can be very benign to rapidly progressive and severe. Magnetic resonance imaging (MRI) is able to detect lesions in the brain indicating MS. But, the severity of the disease does not appear related to the number of lesions, the rate of their appearance, or their location. Researchers are hoping to identify some biologic marker, possibly certain antibodies, that will enable doctors to accurately determine the onset and severity of the problem once a diagnosis has been made.

The McDonald Criteria. There is no single test that can accurately diagnose MS, and a number of other conditions may mimic its symptoms. Some doctors use a set of factors, called the McDonald criteria, for diagnosing multiple sclerosis in early stages. The criteria include the presence of specific symptoms, spinal fluid evaluation, and magnetic resonance imaging techniques for detecting lesions within the central nervous system and tracking them over time. The criteria show high reliability in identifying MS in patients with a variety of disease stages or states, including having only one episode, a typical relapsing-remitting course, or a slow insidious progression without clear attacks or remissions. Depending on the MRI and other findings, the patient is then categorized as having MS, possible MS, or no MS.

The symptoms of MS are similar to a number of other diseases, which must be ruled out. These include stroke, alcoholism, emotional disorders, Lyme disease, chronic fatigue syndrome, fibromyalgia, AIDS, and certain other autoimmune disorders (hypothyroidism, scleroderma, Sjögren syndrome, and systemic lupus erythematosus).

Doctors and investigators generally use a test called the Expanded Disability Status Scale (EDSS) to rate the severity of symptoms. It is also used after a diagnosis to gauge the status of the disease, and score the effectiveness of treatments. The scale ranges from 0 to 10 with higher scores indicating more severe symptoms. These are subjective ratings that require doctor observation skills.

Objections to the use of the EDSS are that it assesses only limp and walking problems and does not assess other important complications, including fatigue, sexual function, and mental function.

No reliable single laboratory procedure or test can establish the diagnosis of multiple sclerosis. Several are necessary before a diagnosis can be made.

Analysis of Cerebrospinal Fluid (CFS). Obtaining a sample of spinal fluid requires a lumbar puncture, or spinal tap. Testing spinal fluid is becoming increasingly important for detecting abnormal proteins, tiny fragments of myelin, or specific white blood cells that can help in making a diagnosis. For example, high levels of the immunoglobulin IgG is useful for making a diagnosis and may be a marker for disease progression. (Immunoglobulins are protein chains that are part of the immune system.)

A lumbar puncture, or spinal tap, is a procedure to collect cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine. Once the needle is properly positioned in the subarachnoid space (the space between the spinal cord and its covering, the meninges), pressures can be measured and fluid can be collected for testing.

Evoked Potential (EP) Test. This is a simple and painless electrical test of nerve function that assesses how long it takes nerve impulses from the eye, ear, or skin to reach the brain.

Magnetic resonance imaging (MRI) scans are important diagnostic tools in MS and are used for diagnosing multiple sclerosis, tracking changes over time, and helping to determine treatment effectiveness.

Click the icon to see an image of a brain MRI.

Making a Diagnosis and Tracking the Disease. Magnetic resonance imaging (MRI) scans can detect bright patches that indicate injured tissue (lesions) caused by MS. Such lesions may also indicate other conditions, such as infections, migraines, or clots. Importantly, a very sensitive MRI technique using enhancement by a contrast material called gadolinium can indicate recent activity by showing if the blood-brain barrier has been broken down (the first step in the development of MS lesions). Detecting lesions and treating MS early in the disease process may help reduce progression. Many experts therefore now advocate performing a brain MRI as soon as symptoms appear.

Once diagnosed, periodic follow-up MRIs can be used to track the disease and effectiveness of treatments in two ways:

By distinguishing new lesions from old ones
Revealing increasing or decreasing numbers of lesions within the central nervous system over time

Unfortunately, neither the rate nor the number of new or growing lesions necessarily predicts whether symptoms will worsen or if the patient will develop secondary progressive MS.

Measuring Atrophy in Brain and Spinal Cord. As myelin, axons, oligodendrocytes, and neurons are destroyed, the brain begins to shrink. Processing MRI images to determine brain volume may be a useful way to monitor progression and treatment effects. MRI can also detect shrinkage in the spinal cord, which is proving to be a very strong marker of disease progression. A variation of MRI, magnetic resonance spectroscopy (MRS), provides information on the biochemistry of the brain, and may be particularly helpful in detecting this destructive aspect of MS.

Detecting Black Holes.Severe disease progression can be gauged by the presence of so-called "black holes.” These are lesions in the brain that emit very low signals on an MRI scan. Some evidence suggests that they may represent iron deposits in the brain.

Researchers are continuously searching for biologic markers that might help make an accurate diagnosis, predict outcome, or both. Promising markers are antibodies that target two key protein components of myelin: Myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). If future studies confirm the predictive value of these antibodies, scientists may be able to develop a blood test for MOG and MBP.

Treatment

Patients diagnosed with multiple sclerosis face great uncertainty, since the course of the illness varies so widely among patients. Experts recommend a multidisciplinary approach to the disease, which might involve a neurologist, a nurse or social worker expert in MS, and possibly a specialist in mental health (since depression is so common and the suicide rate is higher than average).

Evidence now strongly suggests that the most destructive changes from multiple sclerosis in the brain occur very early on in the disease process -- and may cause considerable damage even before symptoms begin.

Many experts are now urging treatment after a first episode of relapsing MS (a clinically isolated syndrome) using medication called disease-modifying drugs. They include three interferons -- IFN1b (Betaseron) and IFN1a (Avonex, Rebif) -- and glatiramer (Copaxone). These drugs are all effective and may help slow down or even prevent progression in some patients. Definitive studies comparing them are ongoing.

The best current approach is to use specific findings from advanced MRI techniques to help determine which patients are at highest risk for progression and would be likely candidates for early treatment with disease modifying drugs.

Interferons and other disease-modifying drugs can have significant side effects and are expensive. Furthermore, a significant number of patients have a mild course that can be managed with less toxic drugs. Nevertheless, strong evidence suggests that delaying treatment in most patients increases the risk for severe disability.

Corticosteroids are the standard drugs for treating an acute relapse and hastening recovery. Typically, intravenous methylprednisolone (IVMP) is given once a day for 3 days. Sometimes this is followed by oral prednisolone for a few days.

Disease Modifying Drugs. Since the introduction of disease modifying drugs -- interferons beta (Betaseron) and alpha (Avonex, Rebif) and glatiramer (Copaxone) -- relapsing-remitting multiple sclerosis is now considered a treatable disease. In patients with very active MS, some experts start with Betaseron or Rebif. For patients with possible or probable MS, they begin with Avonex. This drug is slightly less effective than Rebif and Betaseron but has fewer side effects. Copaxone is also a reasonable choice for early mild MS. It appears to have the fewest side effects, longer relapse-free rates than interferons, and its benefits persist for years.

The newest drug, the monoclonal antibody natalizumab (Tysabri), was approved in November 2004 for treatment of relapsing forms of MS. The FDA withdrew it from the market, however, in February 2005 following reports of serious neurological events. In June 2006, the FDA allowed natalizumab back on the market but with special restrictions (see Drug Treatment section).

Other Approaches. Some research has reported benefits from the use of pulsed administration of intravenous methylprednisolone (IVMP) or intravenous immunoglobulin, although there is not enough evidence for either approach to recommend them as first-line choices. Other drugs showing promise include azathioprine (an immunosuppressant) and laquinimod (an oral immune-modulating drug).

Treating Secondary Progressive Multiple Sclerosis (SPMS). Interferons and other standard treatments for relapsing-remitting MS may be helpful for patients with SPMS who are still experiencing relapses. It is not clear if they help those whose condition has become continuously progressive.

Mitoxantrone (Novantrone) was the first drug approved for SPMS. The drug is an immunosuppressant and is proving to delay relapse and progression. Side effects, however, can be serious in some cases. Some experts recommend using mitoxantrone when evidence suggests progression to SPMS, and continuing the interferons Betaseron or Rebif for maintenance.

Other immunosuppressants, such as cyclophosphamide, methotrexate, and cladribine, may help some patients with SPMS. They can have very toxic side effects, however, and there must be clear treatment indications for patients who take these drugs.

Treating Primary Progressive Multiple Sclerosis. No treatments have been proven yet to slow progressive multiple sclerosis. Studies using interferons and glatiramer are under way.

A number of treatments are available for managing symptoms and complications.

Drug Treatment

Corticosteroids (commonly called steroids) are mainstay treatments for acute relapses patients with relapse-remitting MS. High-dose methylprednisolone given intravenously (IVMP) is typically administered for major relapse, often followed by oral prednisone for a few days. Steroids reduce inflammation in the central nervous system and may help suppress the immune system's attack on myelin and even improve electrical conduction.

Steroids, in general, do not improve the long-term course of the disease and can lose effectiveness if overused. They are not generally used for maintenance therapy. Some research, however, is reporting benefits from the use of pulsed administration of intravenous methylprednisolone. Such an approach typically administers the steroid daily for 5 days every 4 months for 3 years, then every 6 months for 2 years. Some research suggests that this approach might reduce destruction in central nervous system, although more evidence is needed before it can be recommended. They can also have considerable adverse effects when used over time.

Side Effects. Side effects of long-term use of steroids include weight gain and facial fullness, hypertension, diabetes, osteoporosis, cataracts, intestinal bleeding, and increased susceptibility to infections. In addition, side effects of steroids on the central nervous system (sleeplessness, memory loss, anxiety, and depression) can be particular problems for patients. It is extremely important to taper withdrawal very carefully after continuously taking steroids for a prolonged period of time. This gives the body time to recover its own ability to produce natural steroids. A serious condition known as adrenal insufficiency can otherwise develop.

Interferons (so-called because they “interfere” with viral replication) both suppress important inflammatory factors in the immune system and have anti-viral properties. Interferons specifically block immune factors known as class II MHC molecules, which are associated with the attack on myelin and the breach in the blood-brain barrier that allows the destructive T cells to pass through.

Specific Interferons Used for MS. Interferon drugs used for MS are IFN1b (Betaseron) and IFN1a (Avonex, Rebif). They are now the treatments of choice for relapsing-remitting MS. Expert organizations urge that they be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects.

Successes and Drawbacks. Interferons can reduce flare-ups overall by 30% and have an even greater effect on reducing major relapses. Disease activity, as measured by MRI scanning, is reduced by over 80%. They appear to be about equal in reducing disability. To date, only Avonex has demonstrated slowing progression of mental impairment. It also appears to be better tolerated than other interferons. Studies on their effects on quality of life are limited. None of the interferons are a cure, in any case, and when the drug is discontinued, disease activity may increase. All of these drugs need to be injected. (Oral forms are under investigation.)

Side Effects and Complications. Side effects include:

Pain at the injection site. Many patients taking Betaseron complain of severe pain at the injection site caused by damaged tissue. Experts recommend taking acetaminophen (Tylenol) before the injection and then every 6 hours after each injection for 24 hours during the first 6 months of treatment.
Skin injury at the injection site. Black dead tissue may form around the site, and many patients taking Betaseron have reported severe skin eruptions. These skin injuries heal after the drug is withdrawn, but scarring can occur. This side effect is least severe with Avonex, followed by Rebif.
Other physical side effects. Both drugs cause flu-like symptoms, nausea, vomiting, headaches, and dizziness. Such side effects usually fade after 2 - 3 months.
Depression. Early studies associated taking interferon with a higher risk for depression during the first 2 - 6 months following initial therapy. More recent studies, however, have reported no greater risk for depression in patients taking any of these drugs. MS itself, in any case, is highly associated with depression.
Thyroid abnormalities. Interferon has been associated with autoimmune thyroiditis, a cause of hypothyroidism. Some experts recommend monitoring for thyroid function, particularly in the first year and in those with a history of thyroid problems. If there is no evidence of the condition during that period, the risk for its occurrence appears to be very low.
Liver damage. Interferon may cause liver damage and, in rare cases, liver failure. Patients should avoid alcohol and have regular liver function tests while taking this drug

Neutralizing Antibodies That Reduce Effectiveness. Over time, people taking interferons develop antibodies to the drugs, some of which can neutralize their effects. The risk for neutralizing antibodies (NAbs) increases with higher doses and greater frequency of use. Interferons injected under the skin (Betaseron, Rebif) are more likely to produce neutralizing antibodies than Avonex, which is injected into a muscle. Patients who experience this, however, often can be effectively treated with an alternative interferon or with glatiramer, which has an extremely low risk, for NAbs. In many cases, after switching drugs, NAb levels decline, and the patient may be able to return to the original interferon.

Glatiramer acetate (Copaxone) is a synthetic molecule that resembles a basic protein found in myelin. It is used as a decoy to trick white blood cells into attacking it instead of myelin. It is approved to help reduce the frequency of relapses in patients with relapse-remitting MS. The best results are in patients in early stages, but the longer patients remain on the drug, the greater the improvement. Benefits have persisted for years. Glatiramer acetate can also help reduce the number of new brain lesions.

Glatiramer acetate is also being studied for its effects in patients with primary progressive MS. A 2007 study indicated that while the drug had little benefit for most patients with this type of MS, it may help slow disease progression and delay disability in men with primary progressive MS.

Side Effects. Side effects occur in about 15% of patients, usually right after the injection. They include pain at the injection site, chest pain, rapid heartbeat, flushing, anxiety, and shortness of breath.

Monoclonal antibodies (MAbs) are drugs that target specific antibodies involved with the immune response. In 2004, natalizumab (Tysabri) became the only MAb approved for treatment of MS. Shortly afterwards, reports emerged of progressive multifocal leukoencephalopathy (PML) occurring among patients who took natalizumab for more than 2 years. PML is a rare neurological disease that can affect people with compromised immune systems. Based on these reports, the FDA suspended marketing of natalizumab in February 2005 and recommended that patients discontinue its use.

In June 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. Doctors can prescribe the drug only to patients who have failed to respond to or who cannot tolerate other MS treatments. Natalizumab can only be taken alone, not in combination with other immune-modifying drugs. Patients who take natalizumab must enroll in a special program called TOUCH, which is run by the drug’s manufacturer. Patients need to get magnetic resonance imaging (MRI) brain scans before they begin taking the drug, and they are evaluated regularly during drug treatment to make sure they are not at risk of developing PML. In the year after these restrictions were implemented, no new cases of PML were reported.

Clinical trials indicate that natalizumab’s benefits may outweigh its risks. Several studies published in 2006 in the New England Journal of Medicine showed that natalizumab, alone or in combination with IFN1a (Avonex) can help prevent disability in patients with multiple sclerosis. Another study suggested that the risk of PML is very low if patients use natalizumab for less than 18 months.

Natalizumab is also being studied for treating complications associated with MS. In a 2007 study, natalizumab helped reduce vision loss in patients with relapsing MS. Vision loss is one of the most common symptoms associated with MS.

Other MAbs under investigation for MS include daclizumab (Zenapax), alemtuzumab (Campath), and rituximab (Rituxan). Results from a 2005 phase II trial for alemtuzumab indicated that the drug helped prevent relapse but also caused serious side effects. Patients who took the drug had a high risk for developing a serious bleeding disorder caused by a low blood platelet count. Daclizumab is currently in phase II trials as is rituximab. Unlike other MAbs, which affect T cells, rituximab targets and depletes B cells. In several studies presented at the 2007 meeting of the American Academy of Neurology, rituximab showed promising results in reducing relapse frequency and number of brain lesions in patients with relapse-remitting MS.

Intravenous immunoglobulin treatments are monthly infusions of natural antibodies. They appear to have some modest benefits for relapsing-remitting MS. Studies suggests that intravenous immunoglobulin reduces relapse rates and occurrences of new lesions and slows disease progression in relapsing-remitting MS. It does not appear to reduce disability. It is extremely expensive and does not appear to have any benefits for patients with secondary progressive MS.

Many drugs being investigated for chronic progressive multiple sclerosis are immunosuppressants, which block certain factors in the immune system that contribute to the inflammatory process. Each of these drugs can produce serious side effects, including susceptibility to infection. Evidence on benefits is uncertain, mainly because of high toxicity or study limitations. Still, some immunosuppressants may help certain patients with severe MS. Among immunosuppressant drugs or procedures that have been investigated with little or no obvious benefits or unacceptably high side effects are total lymphoid irradiation, sulfasalazine, cyclosporine, acyclovir, and oral bovine myelin.

Mitoxantrone. Mitoxantrone (Novantrone) was the first drug approved specifically for secondary progressive MS. Studies suggest that it may help reduce progression and relapse rates. Cumulative doses can have toxic effects on the heart, however, so the drug is only used for a limited period. Mitoxantrone is also being studied in combination with glatiramer acetate. In one preliminary study, initial treatment with mitoxantrone, followed by maintenance treatment with glatirimer acetate, helped reduce relapses for up to 5 years.

Methotrexate. In some patients, low doses of the immunosuppressant methotrexate may slow the course of chronic-progressive MS, particularly in those with secondary progressive MS. To date, studies have found beneficial effects only on the upper body, however. Although this drug, like all immunosuppressants, can have toxic side effects, it may be taken in low doses for MS and so side effects are generally minimal.

Cyclophosphamide. Cyclophosphamide (Cytoxan) blocks cell growth and also suppresses the immune system. Some studies, but not all, have reported benefits for patients with chronic progressive MS. Small studies suggest that monthly intravenous administration or a combination with interferon-beta may help some patients with rapidly deteriorating MS. Cyclophosphamide has many side effects, including hair loss, nausea, vomiting, infertility, lung scarring, and blood abnormalities, and should be used for patients who do not respond to methotrexate.

Azathioprine. Azathioprine (Imuran) is designed to suppress the immune system and reduce the number of cells attacking the CNS myelin. It is used with or without steroids and is sometimes used as an alternative to patients with relapsing-remitting MS who do not respond to either interferon beta or glatiramer acetate. One study reported that 40% of patients had not experienced a relapse after taking the drug for 3 years, although others report only modest benefits. The drug has no effect on progression of disability.

Cladribine. Cladribine (Leustatin) may be effective in delaying progression in patients with chronic progressive MS. It has no significant effect on relapsing-remitting MS.

A number of treatments are under investigation that may prove to be helpful for multiple sclerosis. Those discussed below are only some of them.

Immune-Modulating Drugs. Most MS drugs are injected, but researchers are developing several new drugs that can be taken by mouth. Four of the most promising candidates are cladibrine (Mylinax), fingolimod (FTY720), teriflunomide, and fumarate (BG00012). In late-stage clinical trials, these drugs have shown positive results in the treatment of relapse-remitting MS.

Sex Hormones. Women with MS have a reduced risk of experiencing relapses during pregnancy, probably because of their high levels of the female sex hormones estrogen and progesterone. Because of this association, researchers have investigated whether oral estrogen therapy (estriol) can help prevent relapses. Some small studies have indicated that estriol treatment may help reduce lesions and disease activity, but the overall evidence is still inconclusive. The male sex hormone testosterone is also being studied as a treatment for men with relapse-remitting MS. A small 2007 pilot study suggested that treatment with testosterone gel is safe and may help improve cognitive function, slow brain degeneration, and increase muscle mass.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis), which may have properties that protect nerve cells. Cannabis has been found to improve pain, mobility, tremor, mood, appetite, fatigue, vision, sexual and urinary function, and memory. In a 2003 study, patients reported less pain and improved mobility (although spasticity itself did not improve). Not all patients respond. The drug may also worsen balance and posture in patients with spasticity. Synthetic versions are being investigated that allow rapid delivery without the unwanted side effects of natural cannabis.

Potassium Channel Blockers. Aminopyridines are potassium-blocking compounds that appear to improve nerve conduction through demyelinated areas. In small, preliminary trials, 4–aminopyridine (also called AP) was associated with mild-to-marked improvement in vision, strength, and coordination and was well tolerated. Beneficial effects, however, lasted only a few hours. A related compound, 3,4–diaminopyridine, or DAP, is being studied for relieving fatigue associated with MS.

Statins. Statins are currently the most important drugs for lowering cholesterol. They are also showing additional possible benefits, including anti-inflammatory and nerve protecting properties, which may help patients with neurologic conditions, including multiple sclerosis.

Plasmapheresis. Plasmapheresis with plasma exchange is a procedure in which blood is removed from the body. Blood cells are separated from plasma (the liquid portion of blood) and mixed with replacement plasma, which is then returned to the body. The replacement plasma is thought to dilute antibodies and other immunologically active substances that may trigger MS. Small studies suggest this procedure may have significant benefits for some patients with severe MS, particularly if they are younger and have an early response to this treatment. Side effects include risk of infection and blood clotting problems.

Stem Cell Transplantation. Investigators are studying the benefits of stem-cell transplantation procedures. Stem cells are produced in the bone marrow and are the early forms for all blood cells in the body (including red, white, and immune cells). Early studies indicate that stem cell transplantation may slow progression, although at this point it is not a cure.

Oligodendrocyte Implants. A newly developed, minimally invasive method to transplant modified oligodendrocyte cells directly into the brain is under investigation. Such cells stimulate nerve and axon growth. If feasible, this approach might be helpful in patients whose MS is not caused by an autoimmune response (where the new cells would be attacked, just as the patient's own cells were).

Other Treatments

Nearly 60% of patients try some form of nontraditional remedies. Research on any benefits is slim, and there may be some danger with many remedies commonly used by patients. The following are a few alternative remedies sometimes used for MS.

Relaxation and Meditation Techniques. Generally harmless, and possibly helpful, nontraditional therapies for MS are relaxation and meditation techniques and Eastern martial art exercises. Such techniques include biofeedback, music therapy, yoga, tai chi, and massage therapy.

Acupuncture. Some patients report benefit from acupuncture, which does carry a very small risk, usually for infection.

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.

Electromagnetic Stimulation. A few centers have studied pulses of weak electromagnetic fields applied to the brain. Very small studies have reported improvement in fatigue, tremors, depression, and other symptoms in patients who were severely affected by MS. In one controlled study, this approach relieved symptoms more effectively than placebo. The effect was small however and more research is needed.

Linoleic Acid. Linoleic acid, commonly known as evening primrose oil, is a polyunsaturated fatty acid believed by some people to be helpful because myelin is composed of fatty acids. No study has proven that it is beneficial, but supplements sold in health food stores do not appear to be harmful.

Oral Enzymes. Oral drugs containing various natural enzymes, including bromelain, trypsin, papain, and rutin, have been used overseas to treat arthritic pain. They appear to reduce inflammation and are also being studied in patients with MS. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). In one small study, Phlogenzym was associated with a decline in complications and longer remission. They are not painkillers; any benefits derived from them may take several weeks. As with any natural remedy, there are few clinical studies on these products and no U.S. regulation of quality, safety, or effectiveness.

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. Patients should check with their doctor before using any herbal remedies or dietary supplements

The following warnings are of particular importance for people with multiple sclerosis:

Antioxidants. Some patients use antioxidant vitamins or supplements (A, E, C, Q10, pycnogenol, OPC, grape seed extract), since the destruction in the MS disease process may be partly due to oxidation (chemical damage from particles called oxygen-free radicals). Theoretically, however, antioxidants can trigger T cells and macrophages (inflammatory components of the immune system) and, therefore, may pose some danger to patients. Small studies to date have not found any worsening of the disease from taking vitamin supplements, but patients should be cautious. No vitamins studied for MS, including carotenoids, vitamin C, vitamin E, B12 injections or vitamin D, have been proven to be beneficial.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses. Ginkgo can also interact with high doses of vitamin E, anti-clotting medications, aspirin, and NSAIDs. Large doses have also been known to cause convulsion. Commercial gingko preparations may contain colchicine, a drug that can be harmful in pregnant women and people with kidney or liver problems.

Bee Venom. For years, anecdotal reports have claimed that bee stings relieve some MS symptoms, although a study on mice indicated that it may worsen MS. Bee venom contains many chemicals, some of which can cause severe and sometimes deadly allergic reactions in some people.

Other Remedies. Herbal or natural remedies that supposedly boost the immune system (echinacea, ginseng, garlic, zinc) may worsen MS. Melatonin has been associated with worsening of some autoimmune diseases. Toxic effects have also been reported with herbal remedies such as borage seed oil, chaparral, and comfrey.

Treating the Complications

Fatigue affects at least two-thirds of patients. It is among the most disabling problems in MS and is difficult to treat. Treating any problem (depression, hypothyroidism) that may be causing fatigue is important. Aerobic exercise programs scheduled early in the day have been helpful for patients who can participate. Preventing overheating can improve fatigue.

Modafinil (Provigil, Alertec) is a promising drug that promotes long-lasting wakefulness and is currently used in narcolepsy. Small studies report that it is effective in reducing fatigue and sleepiness, with lower doses (200 mg) being more effective than higher ones. Studies also suggest that the antiviral drug amantadine (Symmetrel) may be helpful.

Managing pain and spasticity in the lower limbs can be difficult. Although many drugs are used to reduce spasticity and lower-limb pain, most studies investigating these drugs have been poorly designed and no treatment has emerged as a front-runner.

Exercise. Mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking. This benefit can be lost with drug treatment. Mild spasticity, then, should be treated with exercises several times a day that improve range of motion.

Drugs Used for Spasticity.

Baclofen (Lioresal) has long been the drug of choice to alleviate more severe spasticity. It is available both orally and infused through an implanted pump. Distressing side effects include confusion, drowsiness, and a rubbery-like sensation in the legs that makes it hard to stand.
Antiseizure medications, such as gabapentin (Neurontin) or levetiracetam (Keppra), may help reduce spasticity without increasing fatigue or impairing concentration. Studies on gabapentin also suggest that it also have other specific benefits for patients, including reducing facial pain and improving vision.
Tizanidine (Zanaflex) is an oral drug that works after one week. In one study, 75% of patients taking tizanidine reported improvement without the leg-muscle weakness experienced using baclofen. The drug does not appear to be any more effective than baclofen, however. Side effects include dizziness, drowsiness, dry mouth, and fatigue. Liver function must be monitored.
Diazepam (Valium) is also used for spasticity and may be particularly useful for patients who also experience anxiety. Drug dependence is the primary problem with diazepam, as well as dizziness, drowsiness, and confusion. The medication should not be used by people who are seriously depressed.
Botulinum toxin (Dysport) injections are being investigated for spasticity in specific regions such as the hip.
Dantrolene (Dantrium) may be an effective alternative for patients who cannot tolerate diazepam or baclofen. Because dantrolene causes muscle weakness, however, it is best suited for either patients who are wheelchair bound but still suffer from spasticity, or for those whose muscles are still strong so that the drug-induced weakness isn't unduly debilitating. It also causes nausea, vomiting, and anorexia, and with high dosages it can cause dangerous liver damage.

Surgery. In very severe cases where medication and exercise are not helpful, surgery may be considered. In such cases, the surgeon cuts the tendons that are involved with spasticity.

Spinal Injections. In very severe cases, administering phenol using spinal injections in the lower back may reduce pain and spasms for some patients with severe conditions. Most patients are not appropriate candidates for this approach.

Other Treatments. Researchers are also investigating non-drug treatments for spasticity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that uses a magnet placed on the scalp to generate a magnetic field that stimulates the cortex of the brain. In a small 2007 study, rTMS showed promise in improving lower-limb spasticity in patients with relapse-remitting MS.

Urge Incontinence. Urge incontinence (the need to urinary frequently) is common in patients. To help reduce social difficulties, patients should not drink fluids before going to places where restrooms are not easily available. When possible, they should urinate every 3 - 4 hours. A number of medications are available for urge incontinence, including anticholinergic drugs, such as propantheline bromine (Pro-Banthine), tolterodine (Detrol), or oxybutynin (Ditropan). Sacral nerve stimulation (InterStim) sends electrical pulses to help retrain nerves in the pelvic area, and is also proving to be helpful. Botulinum toxin injection into the urinary tract muscles is being investigated and may be helpful for incontinence caused by spasticity. [See In-Depth Report #50: Urinary incontinence.]

Urinary Retention. Urinary retention occurs in some patients. Sometimes urination can be stimulated simply by pressing the bladder area with the fist or hand, by tapping against it, or by straining. Drugs being tried with some success for this problem are desmopressin (DDAVP), ordinarily used for bed wetting in children, and maprotiline (Ludiomill), an antidepressant. If medication is ineffective, a catheter may be needed, either one used intermittently by the patient or placed in the urinary tract. Various new surgical procedures that reconstruct the bladder or divert urine flow may be effective in severe cases of bladder dysfunction. Because urinary symptoms usually remain intermittent for years, treatment approaches for bladder dysfunction should be limited to medications and other reversible therapies, for as long as possible.

Urinary Tract Infections. Urinary tract infection is common in patients, and a urinalysis should be performed with any symptom flare-ups, fever, or change in bladder symptoms. Treatment uses appropriate antibiotic regimens. Some evidence suggests that cranberry juice may help prevent infections. [See In-Depth Report #36: Urinary tract infection.]

In addition to maintaining a high-fiber diet and drinking plenty of fluids, bulk fiber such as psyllium (Metamucil), with or without a stool softener, may be needed. Going to the bathroom the same time every day, particularly after a meal and waiting there for a movement, reduces the risk of losing control later in the day. Exercise helps patients avoid becoming dependent on laxatives, enemas, or colonic irrigation, which can eventually slow down the bowel and cause imbalances in electrolytes. Biofeedback techniques may be helpful in some patients with limited multiple sclerosis.

Major tremors can be very distressing and are particularly hard to treat. Carbamazepine and glutethimide have some possible benefits, but in general drug therapy has been disappointing. Weight applied to the affected limb has been beneficial in about 20% of cases. Surgery is very controversial.

Trigeminal neuralgia is facial pain, usually on one side, that can be very severe and may be triggered by an event as mild as a breeze or teeth brushing. If nonprescription painkillers fail to alleviate facial pain, it can be treated with anticonvulsive medications. Carbamazepine (Tegretol) is currently the drug of choice. Carbamazepine is also effective on other types of MS pain and spasm-related symptoms, including itching and aching. Another antiseizure drug, gabapentin (Neurontin), however, may be particularly effective for MS. This drug also appears to improve blurred vision associated with MS and may help spasticity in general.

Other drugs used for this symptom include phenytoin (Dilantin), diazepam (Valium), or pimozide (Orap), and the antidepressant amitriptyline (Elavil). If severe pain persists and interferes with function, some patients elect to have a section of a nerve surgically removed or blocked. This relieves pain but causes numbness. Before patients commit to such a procedure, they should ask the doctor to temporarily block the nerve with an anesthetic in order to experience the effect of numbness before undergoing irreversible surgery.

A small percentage of patients suffer from pseudobulbar affect (uncontrollable laughing or crying). Neurodex is an investigative drug that is showing promise in controlling these symptoms. The drug combines dextromethorphan (an ingredient contained in many cough suppressants) and the enzyme inhibitor quinidine.

Sildenafil (Viagra) may help improve sexual dysfunction in some patients. Corticosteroids, which are sometimes used for other MS symptoms, also improve sexual function. Other treatments are available that might be very beneficial. Patients should not be shy about discussing sexuality with their doctor. [See In-Depth Report # 15: Erectile dysfunction.]

Techniques for helping patients with swallowing problems include using specific head and tongue positions to assist swallowing, and preparing pureed food. Patients may need to work with otolaryngologists (doctors specializing in ear, nose, and throat disorders) to address swallowing problems. Left untreated, swallowing problems can increase a patient's risk of aspiration pneumonia, malnutrition, dehydration, and other problems.

MS is a strong risk factor for osteoporosis. In addition to calcium and vitamin D supplements, a number of drugs are now available to help prevent bone loss and reduce the risk of fractures due to osteoporosis. [See In-Depth Report #18: Osteoporosis.]

Treating Depression. Treating depression may not only improve mood but may also have direct benefits for patients.

Antidepressants known as tricyclics may have specific benefits for MS in addition to managing severe depression. Amitriptyline (Elavil), for example, may be effective in alleviating the extreme mood swings that frequently occur in patients. This “emotional incontinence,” the inability to control emotions, can distress some patients more than physical symptoms. Other tricyclics include desipramine (Norpramin, Pertofrane) and imipramine (Tofranil), which have additional effects that improve bladder symptoms in some patients. These drugs, however, can have severe side effects.
Newer antidepressant drugs, known as SSRIs (serotonin-reuptake inhibitors), which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), may be better tolerated. A study on sertraline suggested that it may also reduce the immune system's inflammatory response.

Stress Reduction and Supportive Measures. Stress can worsen symptoms, and may worsen the disease itself. Reducing stress is an important part of general health maintenance. Studies on methods for reducing stress report improved well-being in patients. A sense of control and connection appears to be extremely important for patients. Relaxation or meditation exercises can be beneficial, although cognitive-behavioral methods may be more effective in these patients. [See In-DepthReport # 31: Stress.]

Support for Caregivers. Many patients require long-term physical, financial, and psychological support from family and friends. The physical and mental health of the caregiver are critical. In one study, caregivers reported that among the most distressing aspects were the psychological impact of MS on the patient and the incurability of the disease. Most caregivers identified the best form of support to be practical help, cooking, cleaning, and better availability of medical and financial advice. Therapeutic help for family members may also be helpful.

Interferon, used to treat MS, may improve mental function. Other medications and therapies may also be helpful. For example, drugs called cholinesterase inhibitors, such as donepezil (Aricept), which are used for Alzheimer's disease, may help improve mental functioning. Vocational programs for the patient may also be helpful. Therapeutic programs for both patients and their families can help them better understand and cope with cognitive weaknesses such as concentration and problem solving.

Lifestyle Changes

People with multiple sclerosis should make every effort to preserve their general health. A healthy diet, sufficient rest, establishing priorities to conserve energy, and developing emotional support networks can all be very helpful.

Some dietary suggestions for patients with MS include:

Drink two quarts of water a day and avoid caffeine-containing beverages, which are actually dehydrating. This helps avoid constipation (although may cause difficulties in patients who also have urge incontinence).
Eat a diet rich in fiber, particularly from whole grains (especially bran, oats, or flax), fruits (particularly prunes), and vegetables.
Low-fat diets have not proven to have much effect on MS but are, in any case, generally healthy.
Fish and fish oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation and some reduction in symptoms in people with various autoimmune conditions. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however. Some experts recommend that people with MS eat three fish meals a week.

Special diets, such as those that are gluten- or yeast-free, have not shown to have any direct effect on the symptoms or course of MS.

Exercise is an important component in managing MS. An active patient with MS is less likely to develop certain complications, such as bladder and bowel dysfunction, osteoporosis, permanent muscle contractions, ulcerations of the skin, or abnormal blood clotting. MS symptoms can temporarily worsen during physical activity, however, so any program must be planned carefully. A health professional should be consulted to determine the best form of physical activity. One study reported that physical rehabilitation for 3 weeks in a hospital setting was significantly more effective in achieving functional independence than home exercise. It is not known if the same benefits can be achieved with a similar program outside the hospital.

Some suggestions include:

Exercise programs must be designed to stimulate working muscles, but at the same time avoid overload and overheating, which can block nerve conduction.
Stretching and range-of-motion exercises are important because they can relieve muscle spasticity.
Pool exercises are particularly helpful. Water supports the body, and cool water dissipates heat.
Specific exercises that strengthen and increase the endurance of muscles that control breathing functions may be helpful. However, it is unclear if such exercises reduce lung complications over the long-term.
Gradually, patients may be able to build up to more complex exercise programs.

Body overheating causes demyelinated nerves to function less efficiently than usual. Although this effect is resolved within a few hours of regaining normal body temperature, active cooling can help reduce fatigue and improve stability. As a result, researchers are studying the effectiveness of cooling suits.

The following measures may be helpful:

Use air conditioners in the summer.
Keep the home slightly cool in winter.
Avoid swimming in heated pools.
A portable helmet that uses cold liquid to cool the head and neck and therefore lower core body temperatures may help MS symptoms during daily activities.

MS symptoms worsen during a cold or the flu, probably because of increased immune system activity. Experts recommend that patients with MS receive a flu shot in the fall. However, experts warn that patients should not take the nasal spray version of the flu vaccine (FluMist Intranasal). Unlike the flu injection vaccine, which uses an inactivated virus, FluMist contains a live virus. Live virus vaccinations may be harmful for people with MS, especially those who take immune-suppressing drugs.

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.msaa.com -- Multiple Sclerosis Association of America
www.nmss.org -- National Multiple Sclerosis Society
www.msfacts.org -- Multiple Sclerosis Foundation
www.www.fda.gov/cder/drug/infopage/natalizumab -- FDA information on natalizumab (Tysabri)
www.myelin.org -- The Myelin Project
www.abledata.com -- National database of assistive devices and rehabilitation equipment

References

Balcer LJ, Galetta SL, Calabresi PA, Confavreux C, Giovannoni G, Havrdova E, et al. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology. 2007 Apr 17;68(16):1299-304.

Boggild M. .Rationale and experience with combination therapies in multiple sclerosis. J Neurol. 2006 Nov;253 Suppl 6:vi45-vi51.

Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045-50.

Correale J, Fiol M, Gilmore W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006 Aug 22;67(4):652-9. Epub 2006 Jul 26.

Hensiek AE, Seaman SR, Barcellos LF, Oturai A, Eraksoi M, Cocco E, et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007 Jan 30;68(5):376-83.

Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.

Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64:683-688.

Wolinsky JS, Narayana PA, O'Connor P, Coyle PK, Ford C, Johnson K, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007 Jan;61(1):14-24.

Review Date:
5/26/2007
Reviewed By:
Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

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