FitSugar

STIs Explained: HIV and AIDS

FitSugar — Wed, 27 Jun 2007 02:30:00 -0700

Since today, June 27, is National HIV Testing Day, I thought I could dispel some myths and lay out the facts about HIV and AIDS. It is a serious issue so let's get down to business.

HIV - the human immunodeficiency virus - is a virus that kills your body’s "CD4 cells," (also called T-helper cells), that help your body fight off infection and disease.

HIV can be passed when an infected person's bodily fluids (blood, semen, vaginal fluid, or breast milk) come in contact with an uninfected person's mucous membranes. The HIV virus can be passed during any type of sexual contact - including oral and anal sex. Sharing needles can also transmit HIV from one user to another. HIV-positive mothers can also pass it onto their babies when they are pregnant, when they deliver, or if they breastfeed.

AIDS - the acquired immunodeficiency syndrome - is a disease you get when the HIV virus destroys your body’s immune system. That means that viruses, parasites, fungi and bacteria that usually don't cause any problems can make you very sick since your immune system is damaged.

To prevent HIV and other STIs in the first place abstaining from sexual contact is your best bet, but the likelihood that happening is rare. So always use a latex or polyurethane condom when having sex. Or better yet, have you and your partner get tested before you get intimate.

Fit's Tips: Many people who have HIV do not show symptoms for many years, so the best thing to do is get tested just to make sure.

Want to know more about HIV and AIDS? Then read more

STI	Symptoms	How do you test for it?	Treatment
HIV and AIDS	rapid weight loss dry cough extreme fatigue swollen lymph glands in the armpits, groin, or neck diarrhea that lasts more than a week white spots or unusual blemishes on the tongue, in the mouth, or in the throat red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids memory loss, depression, and other neurological disorders pneumonia	Anonymous HIV testing is available in many places and it's usually free You can have a blood test, or a simple oral test that checks for HIV antibodies. People who have HIV antibodies are called HIV-positive.	There are treatments to help HIV symptoms, but there is no known cure yet

STI

Symptoms

How do you test for it?

Treatment

HIV and AIDS

rapid weight loss
dry cough
extreme fatigue
swollen lymph glands in the armpits, groin, or neck
diarrhea that lasts more than a week
white spots or unusual blemishes on the tongue, in the mouth, or in the throat
red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids
memory loss, depression, and other neurological disorders
pneumonia

Anonymous HIV testing is available in many places and it's usually free

You can have a blood test, or a simple oral test that checks for HIV antibodies.

People who have HIV antibodies are called HIV-positive.

There are treatments to help HIV symptoms, but there is no known cure yet

Source and Source

Sperm Facts Every Woman Should Know

FitSugar — Mon, 22 Jan 2007 03:50:00 -0800

Sperm, as teeny weeny as they are, can affect us in a HUGE way. There are about 200-500 million of those little guys in the average amount of semen produced each time a man ejaculates.

Sperm are produced in the (Ladies, we've got to arm ourselves with knowledge so we can overcome the mighty sperm)
man's testes - it takes 10 weeks for a single soldier to reach maturity.
Mature sperm can wait up to 2 weeks for their big day - they hang out in the epididymis - the coil like structure that runs across the top of each testicle.
If they are not ejaculated, those poor little sperms are broken down and reabsorbed by the body.

What to learn some more facts, like how long sperm can survive in a woman's body? Then read more

Semen only contains about 10% sperm - the rest consists of enzymes, vitamin C, calcium, protein, sodium, zinc, citric acid and fructose sugar.
What men eat can affect the taste of their sperm. Red meat, dairy products, onions, garlic, and coffee may not go down as well as foods containing natural sugars, such as fruits.
Healthy males produce about 70-150 million sperm a day - but when they ejaculate, they lose 3 times that - that's why they seem so wiped out after sex.
When inside a woman's body, a sperm can live up to
5 days.
There are male and female sperm - the females are slower, but stronger, while the males are faster, but weaker.

Semen analysis

admin — Thu, 04 Sep 2008 19:13:16 -0700

Illustrations

Sperm

Semen analysis

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Semen analysis is a test to measure the amount and quality of a man's semen and sperm. Semen is the thick, white, sperm-containing fluid released during ejaculation.

The test is sometimes called a sperm count.

Alternative Names

Male fertility test; Sperm count

How the test is performed

You will need to provide a semen sample. Your health care provider will explain how to collect a sample.

Sample collection may involve masturbation and collecting the sperm into a sterile container. It may also be collected during intercourse by using a special condom supplied by your health care provider.

A laboratory specialist must look at the sample within 2 hours of the collection. The earlier the sample is analyzed, the more reliable the results. The laboratory specialist will look at the sample to determine the following details:

Fluid coagulation (thickening into a solid) and liquefication
Fluid thickness, acidity, and sugar content
Resistance to flow (viscosity)
Sperm movement or motility
Number and structure of the sperm
Volume of semen

How to prepare for the test

Do not have any sexual activity that causes ejaculation for 2 - 3 days before the test.

How the test will feel

If you are uncomfortable about how the sample is to be taken, discuss it with your health care provider.

Why the test is performed

Semen analysis is one of the first tests done to evaluate a man's fertility. It can help determine if a problem in sperm production or quality of the sperm is causing infertility. Approximately half of couples unable to have children have a male infertility problem.

The test may also be used after a vasectomy to make sure there are no sperm in the semen. This can confirm the success of the vasectomy.

The test may also be performed for the following condition:

Klinefelter syndrome

Normal Values

A few of the common normal values are listed below.

The normal volume varies from 1.5 to 5.0 milliliter per ejaculation.
The sperm count varies from 20 to 150 million sperm per milliliter.
At least 60% of the sperm should have a normal shape and show normal forward movement (motility).

However, how to interpret these values and other results from a semen analysis is not completely certain.

Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.

What abnormal results mean

Abnormal results may suggest a male infertility problem. For example, if the sperm count is very low or very high there is a likelihood of being less fertile. The acidity of the semen and the presence of white blood cells (suggesting infection) may influence fertility.

However, there are many unknowns in male infertility. The results from the test may fail to explain the cause. If a low sperm count or abnormal semen is found, further testing may be required.

What the risks are

There are no risks.

Special considerations

The use of the following may affect a man's fertility:

Alcohol
Many recreational and prescription drugs
Tobacco

Review Date: 5/21/2008

Reviewed By: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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

Source Doc: 1_003627

Blood in the semen

admin — Thu, 04 Sep 2008 19:06:33 -0700

Overview

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

Illustrations

Blood in semen

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Blood in the semen, called hematospermia, may be undetectable (microscopic) or visible in the ejaculation fluid.

Alternative Names

Semen - bloody; Blood in ejaculation

Considerations

Associated symptoms may include:

Pain with urination
Pain with ejaculation
Pain with bowel movement
Tenderness in the scrotum
Swelling in scrotum
Swelling or tenderness in groin area
Lower back pain
Fever or chills
Blood in urine

Common Causes

Blood in the semen may be caused by inflammation, infection, blockage, or injury anywhere along the male reproductive tract. It may indicate disease or a problem within the urethra, testicles, epididymis, or prostate.

Blood in the semen is usually the result of inflammation of the seminal vesicles, and will usually go away on its own. Often, the cause cannot be determined. If the blood does not clear and ejaculate is persistently stained with blood, more tests should be done. These tests may include urinalysis and culture, semen analysis and culture, and ultrasound of the seminal vesicles.

Home Care

Minor injuries may be treated with rest, applying ice, and monitoring symptoms. Major injuries may require reconstructive surgery.

Infections can often be treated with antibiotics taken by mouth (or intravenous antibiotics if symptoms are severe).

Blockages are typically treated with surgery. If cancerous tumors are the source of obstruction, radiation or chemotherapy may also be indicated.

Call your health care provider if

Always call your doctor if you notice any blood in semen.

What to expect at your health care provider's office

The doctor will perform a physical examination. The doctor will look for fever, swollen lymph nodes, a swollen or tender scrotum, discharge from the urethra, or an enlarged or tender prostate.

To help diagnose the cause of the problem, your doctor will ask medical history questions, such as:

How much blood was in the semen?
Was microscopic blood ever noticed in the past when the semen was examined for another reason?
When was this first noticed? Is it present all the time?
Is there anything that seems to have caused this symptom?
What other symptoms do you have?

Tests that may be done include:

Urinalysis
Urine culture
Semen analysis
Semen culture
Ultrasound of pelvis and scrotum

Review Date: 7/23/2007

Reviewed By: Marc Greenstein, DO, Urologist, North Jersey Center for Urologic Care, Denville, NJ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003163

Semen analysis

admin — Thu, 04 Sep 2008 19:41:52 -0700

Back

HEALTH GUIDE REFERENCE FROM A.D.A.M

The sperm count test is performed if a man's fertility is in question. It is helpful in determining if there is a problem in sperm production or quality of the sperm as a cause of infertility. The test may also be used after a vasectomy to make sure there are no sperm in the semen.

Review Date: 6/5/2007

Reviewed By: Marc Greenstein, DO, Urologist, North Jersey Center for Urologic Care, Denville, NJ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 2_9875

Blood in semen

admin — Thu, 04 Sep 2008 19:25:13 -0700

Back

HEALTH GUIDE REFERENCE FROM A.D.A.M

The presence of blood in semen (the fluid discharged upon ejaculation) may be caused by inflammation, infection, obstruction or trauma.

Review Date: 7/23/2007

Reviewed By: Marc Greenstein, DO, Urologist, North Jersey Center for Urologic Care, Denville, NJ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 2_17095

Infertility in men

FitSugar — Wed, 08 Oct 2008 17:35:50 -0700

In This Report

Highlights
Introduction
Male Reproductive System...
Sperm Abnormalities
Causes
Diagnosis
Treatment
Assisted Reproductive Techn...
Complications of Assisted R...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test Kit

Fertell, the first at-home fertility test kit, became commercially available in June 2007. The Fertell kit contains tests to screen for both male and female infertility. Men can test their semen for concentrations of motile sperm, while women can test their urine for levels of follicle-stimulating hormone (a marker for egg quality). Results are available in fewer than 90 minutes and, according to the test kit's manufacturer, are 95% accurate. However, Fertell does not screen for all types of infertility problems and should not be used as a replacement for a complete evaluation by a doctor.

Intracytoplasmic Sperm Injection May Be Overused

Use of intracytoplasmic sperm injection (ICSI), in combination with in vitro fertilization (IVF), has increased 5-fold over the past decade, even though the proportion of men treated for male infertility has remained the same. This increase suggests that doctors are now using ICSI to treat problems other than male infertility, according to a 2007 study in the New England Journal of Medicine. Some doctors recommend ICSI for women who have failed IVF cycles or who have few or poor-quality eggs. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI can help couples conceive when male infertility is not a factor.

Infertility and Birth Defects

Although there has been concern that assisted reproductive technologies (ART) may increase the risk for birth defects, infertility itself may be a risk factor, regardless of whether ART is used. Even children born to infertile couples who do not use ART have a slightly increased risk for birth defects, indicates a 2006 study in the British Medical Journal.

Varicocele Embolization

Varicocele embolization, a minimally invasive surgical approach to varicocele repair, can help improve sperm count and motility, according to research presented at the 2006 annual meeting of the Radiological Society of North America. Varicoceles (varicose veins in the testicles) are often linked to male infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond week 20. In many cases, infertility is caused by a combination of problems in both partners that conspire to prevent conception from occurring.

About 8 - 10% of couples of reproductive age experience infertility, and in around 40% of these cases male infertility is the major factor. Another 40% of infertility problems are caused by abnormalities of the woman's reproductive system, and the remaining 20% involve couples who both suffer reproductive difficulties.

Infertility affects one in 25 American men. More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. Whether sperm counts are declining overall in industrialized countries is a controversial issue. However, over the last few years the number of assisted reproductive procedures that target male infertility have increased, while female procedures have declined.

The male reproductive system creates sperm that is manufactured in the seminiferous tubules within each testicle. The head of the sperm contains the DNA, which when combined with the egg's DNA, will create a new individual. The tip of the sperm head is the portion called the acrosome, which enables the sperm to penetrate the egg. The midpiece contains the mitochondria which supplies the energy the tail needs to move. The tail moves with whip-like movements back and forth to propel the sperm towards the egg. The sperm have to reach the uterus and the fallopian tube in order to fertilize a woman's egg.

Male Reproductive System

Male fertility depends on the proper function of a complex system of organs and hormones:

The process begins in the area of the brain called the hypothalamus-pituitary axis, a system of glands, hormones, and chemical messengers called neurotransmitters, all of which are critical for reproduction.
The first step in fertility is the production of gonadotropin-releasing hormone (GnRH) in the hypothalamus, which prompts the pituitary gland to manufacture follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
FSH maintains sperm production, and LH stimulates the production of the male hormone testosterone.
Both sperm and testosterone production occurs in the two testicles, or testes, which are contained in the scrotal sac (the scrotum). (This sac develops on the outside of the body because normal body temperature is too high to allow sperm production.)

The male reproductive structures include the penis, the scrotum, the seminal vesicles, and the prostate.

Sperm are manufactured in several hundred microscopic tubes, known as seminiferous tubules, which make-up most of the testicles.

Surrounding these tubules are clumps of tissue containing so-called Leydig cells. Here, testosterone is manufactured.

Sperm Development. The life cycle of sperm consists of a remarkable journey that depends on hormonal signals combined with a mechanical process. It takes about 74 days:

Sperm begin partially embedded in nurturing amoebae-like cells known as Sertoli cells, which are located in the lower parts of the seminiferous tubules.
As they mature and move along, they are stored in the upper part of the tubules. Young sperm cells are known as spermatids.
When the sperm has completed the development of its head and tail, it is released from the cell into the epididymis. This remarkable C-shaped tube is 1/300 of an inch in diameter and about 20 feet long. It loops back and forth on itself within a space that is only about one and a half inches long. The sperm's journey through the epididymis takes about 3 weeks.
The fluid in which the sperm is transported contains sugar in the form of fructose, which provides energy as the sperm matures. In the early stages of its passage, the sperm cannot swim in a forward direction and can only vibrate its tail weakly. By the time the sperm reaches the end of the epididymis, however, it is mature and looks like a microscopic squirming tadpole.
At maturity, each healthy sperm consists of a head that contains the man's genetic material, his DNA, and a tail that lashes back and forth at great speed to propel the head forward at about four times its own length every second. The ability of a sperm to move forward rapidly and straight is probably the most significant determinant of male fertility.

Ejaculation. When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract, which forces the sperm out through the penis:

In the penis, the sperm first pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles. These are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates, but during orgasm, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally shot out of the penis.

Click the icon to see an image of the vas deferens.

Semen. In addition to providing the fluid that transports the sperm, semen also has other benefits:

It provides a very short-lived alkaline environment to protect sperm from the harsh acidity of the female vagina. (If the sperm do not reach the woman's cervix within several hours, the semen itself becomes toxic to sperm and they die.)
It contains a gelatin-like substance that prevents it from draining from the vagina too quickly.
It contains sugar in the form of fructose to provide instant energy for sperm locomotion.

The Path to the Egg. The sperm's passage to the egg is a perilous journey.

Usually about 100 - 300 million sperm are delivered into the ejaculate at any given time. Even under normal conditions, however only about 15% of these millions of sperm are sound enough to fertilize an egg.
To compound the problem, after the stress of ejaculation, only about 400 sperm survive the orgasm to complete the journey.
Out of this number, a mere 40 or so sperm survive the toxicity of the semen and the hostile environment of the vagina to reach the vicinity of the egg. Normally, the cervical mucus forms an impenetrable barrier to sperm. However, when a woman ovulates (releases her egg, the oocyte), the mucous lining thins to allow sperm penetration.
Sperm that manage to reach the mucous lining in the woman's cervix (the lower part of her uterus) must survive about four more days to reach the woman's fallopian tubes. (Here, the egg is positioned for fertilization for only 12 hours each month.)
The few remaining sperm that penetrate the cervical mucus and are able to reach the fallopian tubes become capacitated.
Capacitation is a one-time explosion of energy that completes the sperm's journey. It boosts the motion of the sperm and triggers the actions of the acrosome, a membrane that covers the head of the sperm and resembles a warhead. The acrosome is dissolved, and enzymes contained within it are released to allow the sperm to drill a hole through the tough outer coating of the egg.
In the end, only one sperm gets through to fertilize the egg.

Click the icon to see an image of the uterus.

Sperm Abnormalities

More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. In 30 - 40% of cases of sperm abnormalities, the cause is unknown. It may be the end result of one or more factors that include chronic illness, malnutrition, genetic defects, structural abnormalities, and environmental factors. Partial obstruction anywhere in the long passages through which sperm pass can reduce sperm counts. In one study, obstruction was believed to be a contributing factor in over 60% of low sperm count cases. Obstruction itself can be caused by many factors.

Sperm abnormalities are categorized by whether they affect sperm count, sperm quality, or sperm shape.

In the past, a sperm count of less than 40 million/mL in the ejaculate was believed to cause infertility. Now, however, if the woman is fertile and young, a count as low as 10 million can often accomplish conception over time, even without treatment. In fertilization clinics, men with low sperm counts report fertilization rates of about 30%, while those with average sperm counts have rates between 60 - 80%. Sperm count varies widely over time, and temporary low counts are common. Therefore, a single test that reports a low count may not be a representative result.

Sperm motility is the sperm's ability to move. If movement is slow, not in a straight line, or both, the sperm have difficulty invading the cervical mucous or penetrating the hard outer shell of the egg. If 60% or more of sperm have normal motility, the sperm is at least average in quality. If less than 40% of sperm are able to move in a straight line, the condition is considered abnormal. Sperm that move sluggishly may also have genetic or other defects that render them incapable of fertilizing the egg. An important 2001 study identified a protein in the tail of the sperm called CatSper, which might play a central role in the ability of the sperm to swim and penetrate the egg.

Morphology refers to the shape and structure of an object. Morphology may be even more important than count or motility in determining potential fertility. Abnormally shaped sperm cannot fertilize an egg. About 60% of the sperm should be normal in size and shape for adequate fertility.

The perfect structure is an oval head and long tail. Abnormally shaped sperm may include a number of variations:

A very large round head. (In one study, if 14% or more of sperm had round enlarged heads, the chances for pregnancy fell to about 20%. Such an abnormality indicates early unraveling of genetic material.)
An extremely small pinpoint head
A tapered head
A crooked head
Two heads
A tail with kinks and curls

Sperm carry half the genetic material necessary to make a complete human being. (The egg holds the other half.) Genes are contained in the rod-like structures called chromosomes. The genes themselves are made up of chains of molecules called DNA, which carry the information that defines a human. Genetically fragile sperm are important factors in male infertility. Such sperm have fragmented DNA chains, which make them less capable of fertilization and may also contribute to low quality.

Causes

In one study, the causes of infertility in men seeking to conceive included:

Vasectomy. In the study, 56% of men were seeking a reversal of this procedure. Thirty years ago, this was a factor in only 5% of men seeking help for fertility.
Varicocele (14%). A network of veins carries blood away from the testicles and back up into the body. If these veins become enlarged, twisted, and swollen (similar to varicose veins in the leg), this condition is termed a varicocele. Varicoceles can impair testicular function and fertility.
Unknown infertility (8%).
Absence of sperm (6%). There are many biologic and environmental factors that can lead to low sperm count. For instance, abnormalities in production or obstruction of the tubes that carry sperm can reduce sperm levels. A condition called Sertoli cell-only syndrome is one in which the cells that produce sperm (the Sertoli cells) are absent. This can be a congenital problem that a man is born with or caused by infection, injury, medication, radiation, or genetics. In addition, other conditions may cause infertility in men.

The effect of aging on male fertility is not totally clear. However, growing evidence suggests that it may be a factor (although not to the extent that it is in women). This evidence indicates that age-related sperm changes in men are not abrupt, but are a gradual process. Aging can adversely affect sperm counts and sperm motility (the sperm's ability to swim quickly and move in a straight line). A 2006 study also suggested that the genetic quality of sperm declines as a man ages. The researchers found that poor sperm motility was associated with DNA fragmentation. This led to some older men having an increased risk of passing on gene mutations that cause dwarfism and possibly other genetic diseases.

Nearly any major physical or mental stress can temporarily reduce sperm count. Some common conditions that lower sperm count, temporarily in nearly all cases, include:

Emotional Stress. Stress may interfere with the hormone GnRH and reduce sperm counts.

Sexual Issues. In fewer than 1% of cases, impotence, premature ejaculation, or psychological or relationship problems contribute to male infertility, although these conditions are usually very treatable. Lubricants used with condoms, including spermicides, oils, and Vaseline, can affect fertility. Astroglide, Replens, or mineral oil may not be as harmful to sperm. However, oil-based lubricants can damage latex condoms and should be avoided.

Testicular Overheating. Overheating, such as from high fevers, saunas, and hot tubs, may temporarily lower sperm count. Persistent exposure to high temperatures during work may impair fertility. Several studies have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day.

Substance Abuse. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that may impair the sperm's ability to swim and also inhibit their ability to penetrate the egg. Alcohol does not appear to affect fertility, unless it is so abused that it causes liver damage.

Smoking. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. One study found that men or women who smoke have lower success rates with assisted reproductive technologies. Another study reported that men who smoke also have lower sex drives and less frequent sex.

Malnutrition and Nutrient Deficiencies. Deficiencies in certain nutrients, such as vitamin E, vitamin C, selenium, zinc, and folate, may be particular risk factors for infertility

Obesity. Obesity may be a risk factor for male infertility. A 2006 epidemiological study found that a 20-pound increase in a man's weight increased the chance for infertility by about 10%.

Bicycling. Bicycling has been linked to impotence in men and also may affect fertility. Pressure from the bike seat may damage blood vessels and nerves that are responsible for erections. Mountain biking, which involves riding on off-road terrain, exposes the perineum (the region between the scrotum and the anus) to more extreme shocks and vibrations and increases the risk for injuries to the scrotum. One study found that men who mountain bike are far more likely to have scrotal abnormalities, including calcium deposits, cysts, and twisted veins. Men who cycle can reduce such risks by:

Taking frequent rests while biking
Wearing padded bike shorts
Using a padded or specially contoured bike seat that is raised high enough and sits at the proper angle

Problems in the genes that regulate male fertility and in the genetic material of sperm itself are important contributors to infertility problems in men. In fact, even in men with no known fertility problems, 19% of the sperm are genetically defective. Certain inherited medical conditions also contribute to male infertility. Defective genes themselves can be inherited, produced by environmental assaults (such radiation exposure), or both. Of some concern is the possibility that these mutations will be passed to offspring in men who undergo fertilization techniques that retrieve sperm and directly fertilize the egg. (Under natural conditions, genetically abnormal sperm would be very unlikely to reach and fertilize the egg.)

Defective Genetic Material. Sperm carry half the genetic material necessary to make a human being. Infertile men have been reported to have a relatively high percentage of sperm with broken or damaged DNA (the molecular chain that makes up a gene).

Genetic Factors Specifically Affecting Sperm Production or Quality. Abnormalities in genes that specifically regulate sperm production and quality are major factors in male infertility. Some research suggests that about 10% of cases of male infertility may be due to problems, most likely genetic, in the acrosome. The acrosome is the enzyme-filled membrane cap on the sperm -- its warhead -- that is critical for piercing the egg. In one study, pregnancy was impaired if 7% or more of sperm had abnormalities in the acrosome.

Inherited Disorders that Affect Fertility. Certain inherited disorders can impair fertility. Examples include:

Cystic fibrosis patients often have missing or obstructed vas deferens (the tubes that carry sperm). In fact, men whose infertility is caused by an inborn missing vas deferens have a 60% chance that they carry the gene for cystic fibrosis (even if they don't have the disease itself).
Klinefelter syndrome patients carry two X and one Y chromosomes (the norm is one X and one Y), which leads to the destruction of the lining of the seminiferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
Kartagener syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair-like cells in lungs and sinuses that have a structure similar to the tails of sperm). Sperm motility may also be impaired by this condition.
Polycystic kidney disease, a relatively common genetic disorder that causes large cysts to form on the kidneys and other organs during adulthood, may cause infertility as the first symptom if cysts develop in the reproductive tract.

Exposure to toxins, chemicals, or infections may reduce sperm count by either affecting testicular function or altering hormone systems. The extent of the impact and specific environmental assaults involved, however, are often controversial. Some researchers believe environmental toxins are contributing to a general worldwide decline in male fertility. Data indicate that testosterone levels in American men may have declined over the last several decades. The reasons for this decline have not yet been determined. However, even if testosterone levels are declining, the proportion of men treated for fertility problems has not changed much over the past decade.

Free Radicals (Oxidants). The primary suspects in the link between environmental assaults and infertility are free radicals, also called oxidants. These are unstable molecules, usually containing oxygen, that are released as a by-product of many natural chemical processes in the body. Infections, chemicals, and other environmental assaults can produce high levels of these particles. High levels may even affect the genetic material in cells. Sperm are particularly vulnerable to the damaging effects of this oxidation process. There have been reports that significant levels of oxidants occur in the semen of about 25% of infertile men.

Exposure to Estrogen-Like and Hormone-Disrupting Chemicals. European studies have increasingly reported a worsening in male reproductive health and an increase in testicular and prostate cancers. Many investigators strongly suspect environmental causes, particularly excessive chemicals that disrupt hormones, as a major cause for both these events. Estrogen-like chemicals found in pesticides and other chemicals are of particular concern. Overexposure to estrogen in male animals reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). Some hormone-disrupting chemicals under investigation include:

Treatment of prostate cancer varies depending on the stage of the cancer and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Bisphenol A is a widely used chemical found in plastic food containers and bottles that has provoked concern. It has potent estrogen-like effects in low dose. Use of the chemical in female rats has produced prostate abnormalities in their male offspring.
Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phylates of special concern include dibutyl phthalate (DBP), which is found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phylates have significantly impaired sperm count and abnormalities in their reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring,
Organochlorines are compounds that combine chlorine and organic substances -- usually petrochemicals. Many have estrogen-like effects, including those previously used to make plastics (PCBs) and pesticides (DDT and p,p-DDE). Some, such as dioxins and furans, are byproducts of many chemical processes. Fortunately, most of these chemicals have been banned, but they were heavily used in manufacturing before 1970 and are still widespread in the environment. Studies report that when men had a history of moderate or high on-the-job exposure to pesticides containing organochlorines, their fertility rates were lower than men without such exposures. Studies have found a strong correlation between high levels of polychlorinated biphenyls (PCBs) or p,p-DDE with reduced sperm quality and quantity. In one of the studies, even men with healthy sperm with high organochlorine levels had a lower sperm count than those with lower levels of these compounds.

Most evidence on the hormone of chemical estrogens has occurred in animals and birds. Tests of single chemicals containing estrogen have reported little danger for people. Some studies suggest, however, that exposure to more than one of these chemicals may be very harmful. At this time, there is no strong evidence supporting a serious harmful effect in people who have normal exposure to these chemicals. Major efforts are underway to determine the extent of any possible harm from these chemicals.

Exposure to Heavy Metals. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. Trace amounts of these metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm.

Radiation Treatments. X-rays and other forms of radiation affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to 2 years to resume normal sperm production and, in severe circumstances, may never recover.

Men with fertility problems because of low semen levels when they ejaculate may have a structural abnormality in the tubes transporting the sperm. (A normal amount of semen is 2.5 - 5 mL, or about 1/2 - 1 teaspoon.)

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men, although it is not clear how or even if they affect fertility. They tend to occur more commonly (85%) on the left side. Some theories supporting their possible effect on infertility include:

Click the icon to see an image of a varicocele.

Varicoceles may partially obstruct the passages through which sperm pass.
Varicoceles may elevate temperature in the testes.
Varicoceles may produce higher levels of nitric oxide, a substance that has beneficial effects on blood flow and other functions but which might, in excess, injure sperm.
Varicoceles may block oxygen supply to the sperm.
Varicoceles have been associated with abnormalities in cellular material in the sperm. One study suggested that some men with fertility problems may have genetic defects that cause both varicoceles and impaired sperm.

Some reports indicate that only varicoceles that are large enough to be felt (or palpable) may impact fertility. On the other hand, however, an 8-year study of men with and without varicoceles found no differences in sperm quality or in the ability to conceive. Furthermore, the few well-conducted studies on repair of varicoceles suggest that the procedure does not improve pregnancy rates. Their effect on fertility remains unclear.

Hypogonadism is the general name for a severe deficiency in gonadotropin-releasing hormone (GnRH), the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones. Low levels of testosterone from any cause may result in defective sperm production.

Hypogonadism is uncommon and is most often present at the time of birth, usually the result of rare genetic diseases affecting the pituitary gland that may include selective deficiencies of the hormones FSH and LH, Kallman syndrome, or panhypopituitarism, in which the pituitary gland fails to make almost all hormones. It can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments. Defects in the gene on the X chromosome that regulates receptors that bind to androgens (male hormone) may also prove to be very important causes of male infertility.

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

Autoimmunity is a condition in which antibodies of the immune system attack specific cells in the body, mistaking them for foreign microinvaders. In the case of male infertility, these so-called autoantibodies ("self" antibodies) target the sperm. Antibodies bind to specific parts of the sperm, such as the head or tail and, depending on the site of attachment, cause various problems:

Sperm may stick together (agglutinate)
They may fail to interact with cervical mucous
They may be unable to penetrate the egg

Some experts believe that in most cases the presence of these antibodies will not prevent conception unless a large percentage of sperm are affected.

Vasectomy and Anti-Sperm Antibodies. Vasectomy, the primary sterility procedure in men, is the most common cause of sperm autoantibodies (also called anti-sperm antibodies). Their typical development may be as follows:

Vasectomy works by severing the vas deferens, the tube that carries sperm from the testicles to the urethra (which leads out of the penis).
After vasectomy, sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body.
Here, the immune system may perceive them as foreign invaders and develop antibodies to attack them.

Such antibodies often persist, even if a man restores sperm flow by a successful reversal procedure (vasovasostomy). The persistence of anti-sperm antibodies may result in infertility.

Click the icon to see an illustrated series detailing vasectomy.

Other Causes of Autoantibodies. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all men with fertility problems. They may be linked to genital infections or injury, although the cause is usually not known.

Retrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forward out of the urethra. Sperm quality is often impaired.

Retrograde ejaculation can be the consequence of several conditions:

Surgery to the lower part of the bladder or prostate (the most common cause of retrograde ejaculation)
Diabetes
Multiple sclerosis
Back surgery
Spinal cord injury

Medications such as tranquilizers, certain antipsychotics, or hypertension medications also may cause temporary retrograde ejaculation.

Any structural abnormalities that affect the testes, tubes, or other reproductive structures can have a profound effect on fertility.

Testicular Dysgenesis Syndrome. Testicular dysgenesis syndrome is a recently observed occurrence of three conditions -- impaired sperm production and quality, testicular cancer, and genital tract abnormalities. Environmental factors that increase damage from oxidants are believed to be responsible.

The genital abnormalities identified with this syndrome are undescended testes and hypospadias, each of which is associated with infertility:

Undescended Testes (Cryptorchidism). In some cases, there is a failure of the testes to descend from the abdomen into the scrotum during fetal life. Cryptorchidism is associated with mild to severe impairment of sperm production. In one survey, 38% of men who as youngsters had two undescended testicles and 10% of men with one undescended testicle were infertile, compared with 5% of men who had normal testes. Even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher internal body heat, but this may not totally explain the damage in sperm production that can occur. (Men who suffer from this condition should be aware that even if the testicle is surgically moved to the scrotum, their risk of testicular cancer is significantly increased, warranting careful self-exams and regular follow-up with a doctor.)
Hypospadias. This is a birth defect in which the urinary opening is on the underside of the penis, can prevent sperm from reaching the cervix if not surgically corrected.

Click the icon to see an image of an undescended testicle.

Click the icon to see an image of hypospadias.

Blockage in the Tubes that Transport Sperm. Some men are born with a blockage in the epididymis or ejaculatory ducts or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens.

Anorchia. In the very rare condition known as anorchia, a man is born without any testes.

Syringomyelia. This is a disease of the spinal cord that results in no ejaculate at all (aspermia).

Birth rates among cancer survivors are only 40 - 85% of normal rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. Cancer treatments such as chemotherapy and radiation can damage sperm quality and quantity, causing infertility. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as 5 years after radiation therapy, many men eventually recover their sperm production ability. Chemotherapy with drugs that harm reproductive function tends to affect fertility more severely in men than in women. New drug regimens are helping to improve fertility rates.

Adolescents and adult men undergoing cancer treatments who may want to father children should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.

There is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. The immune response to some infections may release inflammatory factors and oxidants, chemically unstable particles that can damage sperm. The exact impact of this process on sperm is unclear, however. Infections may alter the liquidity of semen and sperm motility, although these are likely to be temporary effects. Among the infections most implicated in infertility are:

Sexually Transmitted Diseases. Repeated Chlamydia trachomatis or gonorrhea infections are most often associated with male infertility. Such infections can cause scarring and block sperm passage. Human papilloma viruses, the cause of genital warts, may also impair sperm function.

Mycoplasma. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile.

Mumps. When mumps develops after puberty, it damages the testicles in 25% of men afflicted with the disease. (Interferon, an anti-viral drug, may help prevent infertility in adult males with active mumps, but the drug is highly toxic and caution is essential.)

Glandular Infections in the Urinary Tract or Genitals. Glandular infections that may affect fertility include prostatitis (in the prostate gland), orchitis (in the testicle), semino-vesculitis (in the glands that produce semen), or urethritis (in the urethra), perhaps by altering sperm motility. Even after successful antibiotic treatment, infections in the testes may leave scar tissue that blocks the epididymis.

Medical Conditions. Other medical conditions that can affect male fertility include any severe injury or major surgery, diabetes, HIV, thyroid disease, Cushing syndrome, heart attack, liver or kidney failure, and chronic anemia.

The effects of medications on sperm quality and count have not been rigorously studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids (which are often abused by weight lifters and other athletes) deserve special notice because they are known to severely impair sperm production. Among the other drugs that can affect male fertility are cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), thioridazine (Mellaril), and calcium channel blockers.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems as well, including genetic mutations, cancer, or diabetes.

The patients will provide the doctor with a detailed history of any medical or sexual factors that might affect fertility:

Frequency and timing of sexual intercourse
Duration of infertility and any previous fertility events
Childhood illnesses and any problems in development
Any serious illness (diabetes, respiratory infections, cancer, previous surgeries)
Sexual history, including any sexually transmitted diseases
Any exposure to toxins, such as chemicals or radiation
History of any medications and allergies
Any family history of reproductive problems

A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.

Varicoceles large enough to possibly interfere with fertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are greatly reduced when the patient lies down, so the patient should be examined for varicocele while standing.
Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low sperm count, however, suggest possible obstruction. The doctor may also take the temperature of the scrotum with a test called scrotal thermography.
The doctor will also check the prostate gland for abnormalities.
The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).

A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.

The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:

A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. To ensure an accurate sample, most doctors recommend abstaining from ejaculation for at least 2 days, but not more than 5 days, prior to semen collection.
A man collects a sample of his semen in a collection jar during masturbation either at home or at the doctor's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms are also available that enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
The sample should be kept at body temperature and delivered promptly. If the sperm are not analyzed within 2 hours or kept reasonably warm, a large proportion may die or lose motility.
A semen analysis should be repeated at least three times over several months.

The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.

In June 2007, the first at-home fertility test kit became commercially available. Fertell includes both male and female tests that allow couples to test sperm motility (for men) and follicle-stimulating hormone (for women). Results are available in less than 90 minutes, and are 95% accurate. The test is available on-line and at some pharmacies. It does not require a prescription. However, Fertell does not screen for all types of fertility problems and should not be used as a substitute for a professional evaluation by a doctor.

Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Although in a large analysis sperm counts below 13.5 million were considered a strong indication of infertility, pregnancy was possible so long as any motile sperm were present. If there are no sperm cells at all in the semen, the doctor checks for obstruction in the tubes or for Sertoli cell-only syndrome, in which there are no sperm-producing cells in the testes. An at-home test (FertilMARQ) is now available to help gauge sperm quantity.

Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.

Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
Grade 3 sperm move in a straight line at a reasonable speed and can home in on an egg accurately.
Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed.

More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is particularly valuable for predicting the success of artificial insemination and which men might be candidates for the intracytoplasmic sperm injection (ICSI) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.

Sperm Morphology. Morphology is the shape and structure of the sperm and, of the three main sperm values, may be the best predictor of fertility. Older reports indicated that about 60% of the sperm should be normal in size and shape for adequate fertility. However, one major analysis used a much broader range of criteria for sperm morphology and concluded that values over 12% were good predictors of fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Seminal Fluid. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.

The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) or cubic centimeters (cc) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of trouble:

Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse.
A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities.
No ejaculate at all may signal retrograde ejaculation.
High amounts of ejaculate may, in some cases, also contribute to infertility.

The semen will be tested for how liquid it is. (Normal semen is liquefied within 20 minutes after adding certain enzymes.) Abnormal results suggest the following:

Overly sticky fluid suggests problems in the prostate gland (which adds fluid to sperm)
Overly watery fluid suggests lack of sperm

The amount of sugar (fructose) in sperm will be measured:

Since fructose is added to the semen in the epididymis, an absence of fructose indicates that an obstruction has occurred either in the vas deferens or the epididymis.
Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production.

Other factors may also be measured:

White blood cell counts are taken to detect infection.
Low levels of a substance called inhibin B, which appears to be produced only in the testes, may indicate blockage or other defects in the seminiferous tubules.
Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.

Blood tests are used for measuring several factors that might affect fertility:

Hormonal Levels. Tests for certain hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.

Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
If testosterone levels are low, then luteinizing hormone (LH) are measured.

Low levels of FSH, LH, and testosterone indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.

Infections. Blood tests can also determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.

The postcoital test, also known as the cervical mucus penetration test, is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus should then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.

If a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti-sperm antibodies will be conducted. Anti-sperm antibodies may also develop after genital infection or injury to the testes. The primary negative effect of these antibodies is to bind the sperm to the woman's cervical mucus, preventing the sperm from swimming further up.

Occasionally, a testicle biopsy may be performed, particularly for the following:

If Sertoli cell-only syndrome is suspected, in which sperm-producing cells in the testes are absent. It should be noted that specific cellular patterns can determine whether this condition is congenital (inborn) or caused by some later injury. This distinction is important in predicting the potential success of later sperm retrieval procedures.
For detecting obstruction in the transport system when sperm production looks normal but the count is low.

The standard biopsy procedure requires incisions (called an open approach) under anesthesia. It can be painful afterward. More than one biopsy may be needed in the case of suspected Sertoli cell-only syndrome, since one area may not have cell-producing cells, but other regions may contain normal sperm. Biopsies of both testes are more accurate than one. (Doctors must be careful to avoid the epididymis during a biopsy, since it is a continuous tiny tube and would be destroyed.) Patients may consider freezing any sperm retrieved during biopsy for later use.

Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It also can detect testicular cancer, which some experts believe make it worthwhile as a routine procedure for any male infertility work-up.

Click the icon to see an image of testicular ultrasound.

Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. One study of men attending a fertility clinic showed that a third had genetic defects. If genetic abnormalities are suspected in either partner, counseling is recommended. Researchers are testing techniques such as preimplantation genetic diagnosis (PGD) that can examine all the chromosomes in a human embryo and detect defective genes, such as those for cystic fibrosis, at the very earliest stages. If it proves useful, it may help identify numerous abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring. In fact, a 2003 study suggested that performing an initial genetic analysis to determine DNA fragmentation in sperm may be a better way of predicting whether conception will succeed than analyzing semen.

In men who wish to undergo fertility treatments, certain tests will help determine the right strategies.

The Hamster Test. The hamster test, or micro-penetration assay test, uses the sperm sample to fertilize hamster eggs that have had their covering removed to allow penetration. If fewer than 5 - 20% of the eggs are fertilized, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.

The Human Zona Penetration Test. The human zona penetration test uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Results may provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.

Acrosome Reaction Test. Tests that induce the ability of the sperm's enzyme-rich covering (acrosome) to dissolve can be very useful.

Other Tests. Additional advanced laboratory tests to measure sperm function, such as computer-aided sperm motility analysis, may also be performed. Some of these tests assess such factors as level of cell-damaging oxidants.

Treatment

Many men diagnosed with infertility in the past would be considered treatable now, even some men with spinal cord injuries. Unless a man produces no sperm at all, recent developments in treatment have made fertility possible for many men willing to undergo treatment and bear the expense. Before undergoing more advanced procedures, most couples trying to conceive should attempt some simple lifestyle changes.

Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. In one study of men, their sexual activity was highest in October, when conception rates were also high.

Fertility and Seasonal Changes. Different studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.

Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Hormone Monitoring Systems for Women. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine are also available. They are less costly than the saliva test but are messier. Monitoring hormone levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some experts say that having sex more than 2 days a week adds no benefits. And, in fact, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Fish is also a good choice, and fish oils may have benefits for men with infertility. Certain specific nutrients, vitamins and minerals may also improve fertility.

Higher antioxidant intakes of vitamin C, vitamin E, and beta-carotene may help improve sperm numbers and motility, according to a 2005 study. The study included both food and supplement sources.
Vitamins C and E may also help repair DNA damage to sperm. According to a 2005 study, men who took 1 gram per day of these vitamins significantly reduced their percentage of DNA sperm fragmentation within 2 months.
The dietary supplements L-carnitine and L-acetylcarnitine may help improve sperm motility, according to several recent clinical trials.

A man who wants to increase his sperm count should also pursue a healthy lifestyle.

Avoid cigarettes and any drugs that may affect sperm count or reduce sexual function.
Overweight men should try to reduce their weight.
Get sufficient rest, and exercise moderately but regularly. (Those who exercise excessively might cut back, but not stop altogether.)
Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility, but they may help couples endure the difficult processes involved in fertility treatments.
Although studies now indicate that tight underwear and pants pose no threat to male fertility, there is no harm in wearing looser clothing.
To prevent overheating of the testes, men should avoid hot baths, showers, and steam rooms.

The fertility process is a roller coaster of emotions that are present throughout both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other seemingly fertile couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions in both men and women can be viewed as important as medical treatment. The process of fertility evaluation can be very difficult for many men. In a 2003 study, over 10% of men who required a second semen sample were unable to collect a semen sample using masturbation. Such men had had no problems with a first collection, but after being asked for additional samples they suffered severe anxiety during both masturbation in the fertility clinic and during regular sexual activity at home. Numerous studies reported a significant association between psychologic factors, particularly anxiety, and fertility treatment failure in women.

Managing the Emotional Effects of the Outcome. After enduring the process of fertility evaluation, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. Needless to say, the emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple's own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% from 1996 - 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Choosing a good fertility clinic is important. The government does not always regulate centers offering assisted reproductive techniques, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure. The clinics offering them are often significantly more expensive than those that don't.

Artificial insemination it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. Artificial insemination either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard artificial insemination procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive.
When donor sperm are required.
If the man's sperm count is very low (although it is preferable if at least 5 million per milliliter are motile).
When unexplained infertility exists in both partners.

Those in whom artificial insemination fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although in vitro fertilization procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The artificial insemination procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation. One study suggested that women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main factor. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days and then is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While other studies have shown a higher number of birth defects in children conceived with ICSI, the results may have more to do with the genetic background of the parents than ICSI itself. A 2006 study of 8-year-old children conceived with ICSI, meanwhile, found no important differences between these children and children who were conceived naturally.

A 2007 study in the New England Journal of Medicine indicated that ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. In 1995, 11% of IVF cycles used ICSI. By 2004, 57.5% of IVF cycles used ICSI.

While ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technology success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer) and the lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In one study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over age 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. About 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures are currently conducted outside the United States.

Before fertilization using intrauterine insemination (IUI) or advanced assisted reproductive technologies (ART) can take place, the sperm must be collected and prepared for optimal chances for success.

Retrieval Procedures

When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques.

Surgical Biopsy. In men without obstruction, sperm can be retrieved using a surgical testicular biopsy.

Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risks of complications, such as bleeding or infection.

Percutaneous Epididymal Sperm Aspiration. Percutaneious epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often, it can cause permanent alterations in testicular function that may even reduce male hormone levels.

Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results.

Sperm Washing

A sperm's energy output is 20 times greater once it is removed from the seminal fluid. Methods for washing sperm can have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves:

The sperm is mixed with a nutrient-rich fluid (or culture media) in a test tube.
They are then centrifuged (spun very rapidly) for about 5 minutes.
The sperm, which are heavy, settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off.
This procedure may be repeated.

This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria, which may impair fertility. Scientists are developing new techniques, such as adding a substance called platelet-activating factor during the sperm washing process, which may enhance pregnancy rates.

Swim-Up Technique

The swim-up technique is not only a useful diagnostic procedure for testing the ability of sperm to escape from the semen into the cervical mucus, but it also achieves the goal of removing sperm from semen.

A specially prepared semen sample is placed in a tube.
A culture media (a nutrient-rich substance in which cells thrive) is placed on top of the sample.
The medium is a hospitable environment for sperm, and those that are healthy will swim up to it.
After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen.

The result gives a fair estimation of the number of sperm potentially capable of fertilization. It is superior to sperm washing because the live sperm will swim up to the culture media, leaving behind most of the debris, although some may float up into the medium. There is also some evidence that such sperm may have fewer genetic abnormalities than those retrieved through sperm washing. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about half a million very active sperm.

Freezing Sperm

Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provide excellent results and can be used confidently for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.

Complications of Assisted Reproductive Technology

Since assisted reproductive technology (ART) procedures have become more widespread since 1980, multiple births have significantly increased. About 35% of all ART births are multiple ones, with 4.3% being triplets or more. Multiple births increase the risk of complications, for both the mother and the child.

Assisted reproductive technology (ART), and multiple births, increase the risks for pregnancy complications. According to a 2005 study, the type of complications may depend on the infertility treatment:

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (placental abruption), third trimester miscarriage, and gestational diabetes.
IVF. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (placenta previa), dangerously high blood pressure during pregnancy (pre-eclampsia), and Caesarean sections.

Multiple births can also increase the risk of pregnancy death. A 2006 study indicated that women who carry multiple fetuses have a 3.6 times greater risk of dying from pregnancy complications than women with singleton pregnancies. The leading causes of death were blood clot (embolism), high blood pressure complications, excessive bleeding (hemorrhage), and infections.

The main risks for children conceived with assisted reproductive technology (ART) are complications associated with pregnancy problems and multiple births. Children conceived with ART are more likely to be born premature and to have extremely low birth weight. These conditions increase the risk for heart and lung problems, as well as learning and developmental disabilities. Premature delivery is also associated with cerebral palsy, a brain injury condition that affects muscle coordination. A 2006 study indicated that children born after in vitro fertilization have an increased risk for cerebral palsy.

However, unlike earlier research, recent studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with fertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

Preimplantation genetic diagnosis (PGD) is now available in a few fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Experts are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly and it too reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Other Treatments

Hormone therapy has been effective for women with infertility problems, but has been disappointing in men except in a few specific cases:

Gonadotropin-releasing hormone (GnRH) is often very helpful in restoring fertility in men with gonadotropin deficiency and hypogonadism.
GnRH may be useful for restoring sperm production after chemotherapy treatments.
Sperm production occasionally responds to low doses of estrogen and testosterone or testosterone alone, menotropins (Pergonal, Repronal), clomiphene citrate (Clomid), human chorionic gonadotropin (hCG), or human follicle-stimulating hormone (r-hFSH, Gonal-F).
Prolonged treatment with follicle-stimulating hormone (FSH) prior to intracytoplasmic sperm injection (ICSI) may improve implantation rates.
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole. (Femara). They may be helpful for specific men whose infertility is associated with abnormal testosterone-to-estrogen ratios.

Bromocriptine. Bromocriptine (Parlodel) is used in men whose infertility is related to excess prolactin manufactured by the pituitary.

Antibiotics. Infections interfering with fertility may be successfully treated with antibiotics.

Mast Cell Blocking Antihistamines. Studies report that certain antihistamines that block mast cells may be beneficial for some men with low sperm counts. Mast cells are inflammatory immune factors that may play a role in lower sperm quality. Studies have reported that two such drugs used overseas, ebastine and tranilast, improved pregnancy rates. Similar antihistamines in the U.S. are fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec).

Repair of a varicocele (varicocelectomy) in men with infertility problems is a common surgical practice. Nevertheless, although many urologists favor varicocele repair, the few well-conducted studies on this procedure suggest that it does not improve the chances for a successful pregnancy. Some experts argue that such studies were not using the most advanced techniques, which may be more effective. Some studies report that repair may improve the success rate of assisted reproductive technologies, such as intrauterine insemination (IUI). Still, the overall benefits remain uncertain, and additional rigorous trials are needed. In any case, the procedure does not appear to be beneficial for improving fertility in men whose varicoceles are very small.

Varicocele repair for fertility is sometimes considered when the following conditions are met:

When the varicocele can be felt during a physical examination.
Surgical treatment of varicoceles may be important in boys and adolescents to prevent later testicular damage.
When the male partner with varicoceles has abnormal semen quality or abnormal sperm function test results.
When the couple has known infertility, and the man has varicoceles but the woman is either fertile or can be treated for her infertility.

Varicocelectomy. Varicocelectomy, the standard repair procedure, involves tying off the swollen and twisted veins. Recovery takes 6 days, and most men cannot resume full activity for about 3 weeks. This technique eliminates 90% of varicoceles.

Recent surgical techniques use laparoscopy, which only requires tiny incisions (less than an inch). This approach allows for quicker recovery, although the procedure itself takes longer. It also has a higher rate of complications than the standard approach.

Varicocele Embolization. A nonsurgical technique called varicocele embolization may eventually prove to be an effective and less painful treatment for varicoceles, including those in young boys. It involves inserting a narrow tube (catheter) through a small incision in the neck or leg. Tiny steel plugs are passed through the catheter to block off the affected veins. The procedure takes 15 - 45 minutes to perform and uses local anesthetic. Some studies suggest that recurrence occurs in more than 10% of men, often requiring conventional surgery. This procedure is not yet widely available, and it may not be appropriate for some men.

Men with retrograde ejaculation and failure of emission caused by surgery, severe disease, or spinal cord injury are treated with various methods.

Drugs known as alpha-adrenergic agonists, including pseudoephedrine (Sudafed, Actifed), stimulate muscle contraction and help ejaculation. The tricyclic antidepressant imipramine (Tofranil) has similar effects, and in one analysis of 35 studies was more effective than pseudoephedrine. Promising investigational drugs include amezinium, which increases blood pressure.
If drugs are not effective, a technique called electrovibration (or electrical stimulation) is often beneficial. (Drugs in any case are not helpful for men with complete failure of emission.)

With any of these methods, the sperm can be collected for intrauterine insemination or assisted reproductive techniques. Spontaneous conception is possible, but not common, even with these treatments.

To prepare sperm for in vitro fertilization (IVF), men with retrograde ejaculation typically use sodium bicarbonate four times a day to reduce the acidity of the urine. After ejaculation, the man urinates or has a catheter (a tube) inserted to withdraw urine, which is then submitted for washing techniques to separate out the sperm.

Procedures that assist ejaculation are helping men with spinal cord injury conceive children. Vibratory or electronic stimulation is proving to be very beneficial for many of these men. The sperm retrieved using these methods are inserted into the women using self-insemination, intrauterine insemination, in vitro fertilizaiton, or intracytoplasmic sperm injection. Nearly a third of couples achieve pregnancy, a success rate that approaches natural conception.

Vasovasostomy. For men who wish to conceive after vasectomy, reversal surgery (vasovasostomy) may restore fertility. In vasovasostomy the severed ends of the vas deferens (which were cut during vasectomy) are reconnected to reestablish the flow of sperm. The reversal procedure is difficult. It involves sewing together the two ends of both tubes, each with pinhead sized openings. [See In-Depth Report #37: Vasectomy and vasovasostomy.]

Pregnancy Rates After Vasovasostomy. An Australian study reported that pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after a vasovasostomy. One study indicated that when successful conception occurs, it does at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long
The original procedure was performed on straight sections of the vas deferens
The pieces joined during the vasovasostomy are of equal size

The closer in time the vasovasostomy is to the original vasectomy, the better. In one large study, the pregnancy rates were 76% for those who had vasectomy less than 3 years before reversal surgery, but decreased to 30% for those men who had a vasectomy more than 15 years earlier. The decrease in rates as time goes by is probably due to an increase in the chance for obstruction of the epididymis and the development of anti-sperm antibodies. Success rates, according to some studies, are slightly better if the male partner does not change female partners after the procedure. Other studies suggest that it makes no difference if the man has a new female partner. The age of the woman is an important factor, and the chances of achieving pregnancy are best for women younger than age 35. Some research suggests that men who have a vasectomy reversal may have a greater rate of sperm chromosomal abnormalities than normal fertile men.

Reversal Versus Assisted Reproductive Technologies. Even though newer techniques such as ICSI are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was 25 - 30% (ICSI is the ART treatment of choice for men who have had vasectomy). Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

ART may, however, be a better approach than reversal for men with evidence of anti-sperm autoantibodies due to vasectomy. ICSI may also be more effective than reversal surgeries in men whose vasectomy was conducted at least 15 years or more beforehand.

Surgical Treatment of Obstructions. Obstructions in the area of the ejaculatory ducts have been successfully treated by excising or scraping the area where the prostate gland surrounds the urethra and by reconstructing the ducts.

Correcting Undescended Testicles. Undescended testicles of young boys may be repositioned surgically to prevent later infertility. It is important to perform the operation before 15 - 18 months of age to prevent the destruction of most of the sperm-producing cells, which occurs if the testicles remain in the abdomen.

Stem Cells. Researchers are investigating using sperm stem cells to treat male infertility. The research is still in its earliest stages. In 2004, researchers announced that they had successfully grown sperm progenitor cells in the laboratory. These types of cells could potentially develop into sperm cells capable of fertilizing an egg. This discovery was an important first step for developing stem cell infertility treatments.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.urologyhealth.org -- American Urological Association
www.afafamilymatters.com -- American Fertility Association
www.ssmr.org -- Society for the Study of Male Reproduction
www.sart.org -- Society for Assisted Reproductive Technology
www.cdc.gov/ART/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Report

References

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007 Jan;92(1):196-202. Epub 2006 Oct 24.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Vasectomy and vasovasostomy

FitSugar — Wed, 08 Oct 2008 17:35:49 -0700

In This Report

Highlights
Introduction
Considerations
Male Contraception
Surgery
Complications
Unexpected Pregnancy
Long-Term Complications
Reversal Surgery
Assisted Reproductive Techn...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Search Continues for the "Male Pill"

Research is progressing on a male contraceptive, but there have also been setbacks. The drug miglustat (Zavesca), which is used to treat a rare condition called Gaucher's disease, had shown success in animal studies but failed to work in a clinical trial, according to results published in 2007 in Human Reproduction. Researchers are now investigating an experimental drug, Adjudin (AF-2364), which disrupts sperm production.

Reversible Inhibition of Sperm Under Guidance

Reversible inhibition of sperm under guidance (RISUG) is one of the investigational male contraceptives furthest along in clinical trials. It is currently in phase III trials in India, but it is not yet known when or if clinical trials will be conducted in the United States. RISUG is a non-hormonal contraceptive method that uses an injectable polymer gel to stop sperm flow within the vas deferens.

No-Scalpel Vasectomy

The no-scalpel vasectomy is gaining in popularity as an alternative to standard vasectomy, but it requires a well-trained doctor to perform it. Performed correctly by an experienced doctor, no-scalpel vasectomy can result in shorter surgical time and less bleeding, infection, pain, and postoperative complications, according to a 2007 review published in the Cochrane Database. If you are considering a no-scalpel vasectomy, make sure that your doctor has performed at least 15 - 20 of these procedures.

Vasectomy Reversal

Vasectomy reversal may work better than assisted reproductive technologies (such as sperm retrieval) for men who have had a vasectomy but later decide to have children, according to research presented at the 2007 annual meeting of the American Urological Association.

Introduction

In the United States, vasectomy emerged as a popular method of permanent contraception during the 1960s. Within a decade, 750,000 men were undergoing vasectomies each year. Vasectomy rates markedly declined in the 1990s and have now plateaued at about 500,000 a year. Worldwide, an estimated 42 million couples use vasectomy as a method of birth control.

The procedure works by surgically interrupting the route that the sperm take from the testicles (where they are produced) to the penis. After vasectomy, the testicles still continue to generate sperm, but their movement is blocked at the site of the vasectomy. Eventually the sperm die, and the patient's body absorbs them. During sex, semen is produced in the same amount as before vasectomy, but this fluid does not contain sperm.

The testes are where sperm are manufactured in the scrotum. The epididymis is a tortuously coiled structure topping the testis, and it receives immature sperm from the testis and stores it several days. When ejaculation occurs, sperm is forcefully expelled from the tail of the epididymis into the deferent duct. Sperm then travels through the deferent duct through up the spermatic cord into the pelvic cavity, over the ureter to the prostate behind the bladder. Here, the vas deferens joins with the seminal vesicle to form the ejaculatory duct, which passes through the prostate and empties into the urethra. When ejaculation occurs, rhythmic muscle movements propel the sperm forward.

Click the icon to see an animation about vasectomy.

Vasectomy should not be confused with castration. It has no noticeable impact on a man's ability to perform sexually, or on his sensation of orgasm and pleasure. It does not affect the balance of male hormones, male sex characteristics, or sex drive. Testosterone continues to be produced in the testes and delivered into the bloodstream. Sperm form a very small portion of semen, so patients notice no difference in the amount of semen produced during orgasm.

The male reproductive tract performs three functions:

It enables a man to produce offspring.
It provides him with a supply of male hormones.
It enables him to experience sexual pleasure.

The Traveling Sperm. The sperm's journey through the male body -- from the testes (the testicles) to the final stage (the orgasm) -- is long and complex:

Sperm are produced in the testes at a rate of 50,000 an hour within tiny ducts called seminiferous tubules.
Sperm do not mature in the testes. They must first pass into the epididymis, a C-shaped storage chamber adjoining the testes composed of a 20-foot coiled tube. The sperms' journey through the epididymis takes about 2 - 3 weeks. They are held here until sexual activity forces them to move on.
When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract. This forces the sperm to pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens. It is the vas deferens that is cut during vasectomy.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles, which are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates. During orgasm, however, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally thrown out of the penis.

Click the icon to see an image of sperm.

Considerations

Having a vasectomy is a serious decision. The surgery is intended to be permanent. The great majority of men who seek a vasectomy have been married for 10 years or more. Not all are good candidates, however. It is important that both the woman and the man completely agree that they no longer want to have children. They should also agree that permanent birth control is the right decision for them. Ideally, the couple should view the operation as a mutual commitment to an already successful marriage or relationship. Vasectomy generally is not a good idea if the couple's relationship is under great stress. It is not a cure for emotional or sexual problems between a man and woman.

After deciding that permanent birth control is the best solution, a couple still has the option of either vasectomy for the male or tubal ligation for the female.

Studies indicate that 5 -11% of men who have vasectomies regret the decision. In one study, 56% of men seeking treatment for fertility were hoping to reverse their vasectomies. Thirty years ago, this percentage was only 5%.

A reversal procedure called vasovasostomy is available, but it is a major operation that provides no guarantee of restored fertility. In a study of procedures performed between 1980 - 1996, vasectomy rates had leveled off but vasovasostomy rates had increased in men by nearly 70% in the most recent 5-year period compared to the earliest 5-year period.

Vasectomies may be right for:

Men in relationships in which both partners agree they have all the children they want and both do not want to use or are unable to use other methods of contraception
Men in relationships whose partners have health problems that make pregnancy unsafe
Men in relationships in which one or both have genetic disorders that they do not want to transmit

Vasectomies may not be right for:

Men in relationships in which one partner is unsure about his or her desire to have children in the future. (Couples in which the woman is working when they make the decision are at particular risk for regretting the decision later on.)
Men whose current relationships are unstable, going through a stressful phase, or are marked by substantial conflict
Men who are considering the operation just to please their partners
Men who are counting on having children later by storing sperm or by surgical reversal of the vasectomy
Young men, who still have many life changes ahead
Men who are single (including those divorced or separated) at the time of vasectomy
Men who are having the operation primarily for the sake of their partners and not wholly for their own reasons
Men or couples whose only motive is freedom from distraction imposed by other contraceptive methods during sexual activity

Vasectomy should not be undertaken in response to temporary stressful situations that might block the desire for children. Such conditions may include illness, temporary financial crisis, death in the family, or birth of a child. Couples should wait through such short-term stresses or seek counseling or psychotherapy to be sure that they are not making a decision they will later regret.

All Future Scenarios. Before deciding on a vasectomy, the couple should consider all future scenarios for their life together, such as the following examples:

If a couple already has children, how would they feel about a vasectomy if one of their children died?
If financial stress is triggering the decision for a vasectomy, would improved affluence increase their desire for children?
How would the man consider the vasectomy if his current relationship ended, either by divorce or the woman's death?

The word "sterilization" has a deep emotional connotation for many people. Even though a couple may rationally accept the idea of a vasectomy, it is extremely important for each partner to be as open as possible about any negative feelings they might associate with the procedure. Such feelings on the part of either partner can have devastating consequences on a relationship if they surface only after the procedure has been performed. Openness with each other is essential in order to make a decision that is clear of any hidden apprehensions. Neither partner should be too embarrassed to request counseling if the emotional aspects involved in making the decision are too difficult to solve between themselves.

What the man may be feeling:

A man may have a poor self image, including concerns for his own physical health or sexual ability. Such men are likely to have a difficult time adjusting psychologically to vasectomy.
A man may not actually really want the procedure but may not want to confront a partner he loves who wants him to have it.

What the woman may be feeling:

A woman might believe, incorrectly, that a vasectomy is emasculating, but she might not want to express this idea to her partner.
On the other hand, some women fear that vasectomy may make their partner more attractive and encourage outside affairs. (Research from the 1970s indicates that married men who have a vasectomy are no more likely to indulge in extramarital sex than fertile men.)

Storing frozen sperm in a sperm bank before vasectomy might enable men to have children later. Before the vasectomy, the man collects sperm, which are frozen and stored until he wants to have a child. In one study, 1.5% of men who had stored sperm later used it for conception and most were successful. Other studies have shown a lower success rate, however, and it is a very expensive process. Experts believe that a man who wants to bank sperm should probably reconsider his decision to have a vasectomy because such a concern may indicate doubts about giving up his ability to father a child.

Male Contraception

As many as 40% of couples seeking vasectomy have experienced a failure with their previous method of nonpermanent birth control. Such failures can occur from misplacement of a diaphragm, an incorrectly implanted intrauterine device (IUD), or noncompliance with an oral contraception regimen. Couples who are unsure about permanent sterility should still consider carefully all birth control options.

Withdrawal before ejaculation is a form of natural contraception, but it is extremely risky and most people find it unsatisfactory. If used on a regular basis, the average risk for pregnancy is 24%.

The only other form of male contraception currently available is the condom. However, the average rate of pregnancy for couples that rely only on condoms for protection is still 12%. In adolescents, the risk with condoms is even higher, 18%. Even for those who use a good-quality condom correctly, the annual risk for pregnancy is 3%.

The condom should be put on before intercourse when the penis is erect, long before ejaculation, since the male can discharge sufficient semen to cause pregnancy before ejaculation occurs. (Even after a vasectomy, men who are not in a monogamous relationship with an HIV-negative partner should always wear a condom during sex for protection against sexually transmitted diseases. Vasectomy is not protective.)

Click the icon to see an illustrated series detailing how to apply a condom.

Condom Materials.

Latex. Condoms made of latex rubber are the most common types. When they are contoured for better fit and contain a spermicide, they can provide fairly effective protection. Some people are allergic to latex, however, and in some cases the reaction can be very dangerous. The latex smell may also be unpleasant for some people.
Polyurethane. Polyurethane condoms (Avanti, eZ-on) are also available. At this point, they have good acceptance by couples but have a higher breakage rate (6 - 7.2%) compared to the latex condom (1.1 - 2%). Other synthetic materials are under investigation.
Animal Membranes. Condoms made from animal membrane can prevent pregnancy, but sexually transmitted infections can permeate them.
Lubricants. Lubricants can be used to prevent tearing. Petroleum-based products (such as Vaseline and baby oil) and vegetable oils should not be used because they can corrode the condom.

Spermicides. Some condoms come prelubricated with sperm-killing substances called spermicides. The standard active ingredient in spermicides in the U.S. is nonoxynol-9, which attacks the surface of the sperm cell. These spermicidal-coated condoms, however, are no longer recommended for a number of reasons. Side effects include irritation of the vagina or penis, particularly if used often or in large amounts. It can also promote yeast and urinary tract infections in women. Evidence now strongly suggests that nonoxynol-9 does not provide any additional protection against sexually-transmitted diseases. In fact, research indicates that it actually increases the risk for HIV in women, possibly by causing injury in the vaginal area. Spermicides are no longer recommended for use with male condoms.

Researchers are developing male hormonal contraceptives that reduce levels of sperm. Animal studies and clinical trials are progressing, and a "male pill" may become a reality in the not-so-distant future. Current trials are focusing on male hormonal contraceptives that combine testosterone (the primary male sex hormone) with progestin, a synthetic form of progesterone (one of the primary female sex hormones).

Testosterone suppresses levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH and FSH are hormones that stimulate ovulation in women and production of testosterone in men. Low levels of these hormones interfere with sperm production, but they do not completely stop it. For this reason, researchers are investigating combining testosterone with progestin. The addition of progestin further decreases LH and FSH levels, along with sperm counts. Researchers are also investigating combining testosterone with gonadotropin-releasing hormone (GnRH), another type of hormone that interferes with LH and FSH secretion.

Most of the male contraceptives currently in late-stage clinical trials deliver hormones through implant, injection, or both. The implant is surgically placed under the skin where it releases a steady stream of the hormone. The injection is given once every several months. Some of the investigational male hormonal contraceptives use a testosterone implant with progestin injections, while others use a progestin implant with testosterone injections. Forms taken by mouth are also being investigated. It generally takes around 3 - 4 months for the treatment to take effect, and for sperm production to be reduced. Research indicates that the male hormonal contraceptives are easily reversible. A 2006 study in the Lancet reported men regained their full fertility within 3 - 4 months after stopping hormonal treatment.

Side effects of male hormonal contraceptives include weight gain, acne, and changes in mood. These side effects are typical of hormone-based therapies.

Because of hormonal side effects, researchers are also investigating non-hormonal male contraceptives. Several initially promising drugs (such as miglustat) have performed well in animal studies, but have failed in human studies. Some non-hormonal research is now focusing on an experimental drug called Adjudin, which appears to work by disrupting sperm maturation in the testes. A 2006 animal study showed positive results, but it is still unknown if this drug will work in humans.

Researchers are investigating procedures that block sperm flow in the vas deferens using various drugs or materials that are reversible. One promising method is called Reversible Inhibition of Sperm Under Guidance (RISUG). RISUG is a non-hormonal contraceptive that uses a polymer gel. The gel is injected into the vas deferens, where it coats the vas deferens' inner walls and kills sperm. The gel can be injected through the skin through a needle or by using the no-scalpel vasectomy technique of making a tiny hole in the skin. The procedure takes around 10 - 15 minutes to perform, and men can resume sexual activity within a week.

The effects of RISUG are long-lasting. Studies indicate that a single injection can provide contraceptive effect for 10 years or more. It is also easily reversible. When a man wishes to discontinue the contraceptive, the gel is removed by flushing the vas deferens with a solvent. The major side effect so far has been a temporary swelling of the scrotum following the injection.

RISUG is mostly being investigated in human trials in India. American researchers are also interested in investigating RISUG, but animal studies need to be conducted first. It will be several years before any human trials are started in the U.S.

The intra vas device (IVD) is an investigational non-hormonal contraceptive that uses tiny silicone plugs to block sperm from traveling through the vas deferens. The plugs are surgically inserted into the vas using the no-scalpel vasectomy procedure. In 2006, the Food and Drug Administration granted approval to expand human trials of the IVD in several U.S. cities.

Unlike hormonal contraceptives, the IVD does not cause side effects like weight gain and acne. But researchers are still figuring out how to make this contraceptive method reversible.

Gossypol, a yellow pigment extracted from the roots, seeds, and stems of the cotton plant, has been used in China, Africa, and Brazil as a male contraceptive. Cotton root was also used as folk medicine in the American South to treat menstrual pain and to induce abortions. The chemical destroys the lining of tubules in the testicles where sperm are produced, thereby inhibiting their formation.

Gossypol does not appear to reduce sexual desire or frequency of intercourse. In about 20% of men, sperm production does not come back, so it should be considered as potentially permanent birth control. It also may not be effective in some men, since small numbers of sperm may survive. Researchers are investigating gossypol-derived compounds that may have less toxicity. No one should take any so-called natural gossypol product without consulting their doctors.

Surgery

Vasectomy is a minor operation that takes about 30 minutes and is usually performed in a doctor's office or a family planning clinic. If the operation is performed under local anesthesia, the cost ranges from about $500 - $1,000. Most insurance policies will cover vasectomies performed as a minor outpatient procedure, but will not cover vasectomies performed as major surgery in an operating room. If a Vasclip procedure is performed, there may be an additional cost of $400 - $500 for this device.

The Procedure.

To prevent increased risk of bleeding, patients should avoid taking aspirin or NSAIDs (Advil, Motrin) for 10 days prior to the procedure.
Before the operation, the patient's scrotum is shaved and cleaned.
A local anesthetic is injected into the scrotum. Patients should ask their doctor about applying an anesthetic cream (EMLA) before the injection to reduce its pain.
The surgeon makes a tiny incision on one side of the scrotum and locates one vas deferens. The vas deferens is isolated, drawn through the incision, and clamped at two sites close to each other.
The segment between the clamps (which should be more than 15 mm, or a little over 1/2 inch) is then removed.
The surgeon then seals off (ligates) the tube with surgical clips, sutures, or cauterization with an electric needle. Fascial interposition is an additional technique that may be used in combination with these methods to improve closure. With fascial interposition, the surgeon pulls the fibrous layer covering the vas (the fascia) over the cut end of the vas and sews it closed. This increases the barrier and further reduces residual sperm. Recent research suggests that fascial interposition combined with cauterization or ligation/excision is the best method for sealing off the vas.
The surgeon may choose to close off either one end of the vas (called an open-ended procedure) or both ends (closed-ended technique). In the open-ended procedure, the vas section connected to the testis is left open, and the one leading to the prostate is sealed. In the closed-ended approach, both are sealed. Many surgeons now prefer the open-ended version because it has lower complication and failure rates than the closed-ended method, and it results in fewer cases of chronic pain.
After closing off the tube, the vas deferens is gently placed back into the scrotum.
The procedure is then repeated on the other side.
After a short rest, usually about half an hour, the patient can leave the doctor's office or clinic. Arrangements should be made ahead of time for someone else to drive the patient home.

Click the icon to see an illustrated series detailing a vasectomy.

A method of vasectomy called no-scalpel vasectomy (NSV) that does not require the use of a scalpel was developed in China in 1974. NSV is now used in at least one-third of vasectomies.

The technique takes about 10 minutes and is performed in a doctor's office or a family planning clinic. The no-scalpel vasectomy differs from a conventional vasectomy in the method of accessing the vasa deferentia:

In NSV, the doctor feels for the vas deferens under the skin and holds them in place with a small ring clamp.
Instead of making two incisions, the doctor employs a sharp hemostat, a special instrument that makes one tiny puncture and then is used to gently stretch the opening until the vas deferens can be pulled through it. (The surgeon must rotate his wrist to pull the vas out -- called a supination maneuver -- which may be difficult to perform.)
The vas is then sealed off using the same methods (clips, sutures, cauterization using an electric needle, or some combination) as conventional vasectomy. As with standard vasectomy, the closures can be open- or closed-ended.
There is very little bleeding with the no-scalpel vasectomy. No stitches are needed to close the tiny opening, which heals quickly and leaves no scar.

When performed correctly, NSV works just as well as conventional vasectomy, takes less time, and (according to a 2007 review) causes less bleeding, infection, and pain. Current research indicates that NSV is the safest type of vasectomy procedure. NSV is difficult to perform, however, and most surgeons must do about 15 - 20 procedures in order to be proficient. NSV is becoming a popular alternative to standard vasectomy, but it is important to select a doctor who is experienced with this procedure.

A simpler method of NSV, called percutaneous vasectomy, is now being used. Recent research suggests that it works as well as standard NSV and is easier to perform. Percutaneous vasectomy uses the same instruments as no-scalpel vasectomy, but with a different surgical technique. The hemostat is used to first puncture the skin (instead of spearing the vas and lifting it out). The ringed clamp is then passed through the incision and used to enclose the section of the vas that is then pulled out for closure. This avoids the need for the difficult wrist maneuver in NSV.

Vasclip. The Vasclip is a recent alternative to standard vasectomy. This very small rice-sized plastic clip locks around the vas deferens and stops the flow of sperm. Some studies have reported fewer post-surgical complications than with standard vasectomy, including infection and swelling. It may be more easily reversible than a standard vasectomy.

Complications

Vasectomy is a low-risk procedure, and the complications, which occur in about 10% of patients, are usually easy to control. One study of no-scalpel vasectomy, for example, reported only 7 complications out of 4,255 procedures and they were mostly minor. Pain or soreness typically lingers for a few days after the procedure, but this is normal and usually does not require a return visit to the doctor. No deaths resulting from vasectomy have been reported in the United States.

Nearly all men recover completely in a few days. The following are some guidelines after the operation to help recovery:

The local anesthetic wears off about 1 - 2 hours after the procedure, and most patients then experience a dull ache in the testicles and groin. The doctor may prescribe a painkiller for the first few days, continuing with mild over-the-counter pain relievers if discomfort persists. Acetaminophen (Tylenol) with or without codeine is the primary choice for postoperative pain. Aspirin, ibuprofen (Advil, Medipren, Motrin, Nuprin), naproxen (Aleve), or other non-steroidal anti-inflammatory drugs (NSAIDs) can cause bleeding and should be avoided.
The patient should stay in bed on his back for at least one day and apply ice packs for 8 hours. The doctor may suggest that the patient wear an athletic supporter.
Some oozing of blood onto the gauze pads is normal during the first 2 days after the operation.
The patient should not perform any heavy physical labor for at least 2 days. Sports and heavy lifting may be resumed 2 - 3 weeks after surgery.
A semen analysis is done about 6 - 12 weeks after surgery to ensure that no live sperm remain in the semen. Many urologists recommend delaying a semen analysis until 2 months after a vasectomy or 12 ejaculations (whichever comes first). The semen is usually collected at home in a small jar and delivered to the doctor's office, where it is examined under a microscope. A second semen analysis is sometimes performed again about 4 months after the vasectomy, although many experts now believe that a second sample is unnecessary unless sperm found the first time were motile (still able to move). According to a 2006 study, 25% of men never bother to return for follow-up sperm testing. Without a follow-up test, men do not know whether the vasectomy was successful. Until test results verify that there are no sperm in the semen, men are at risk of fathering unwanted pregnancies.

All men experience some pain in the scrotum (the sac that contains the testes) after the operation. This pain generally disappears within two days, although the patient may feel sore for a few more days. In rare cases, pain can be persistent, which is known as post-vasectomy pain syndrome. The cause of this is unclear.

A few men may have an allergic reaction to the local anesthesia and develop itching and hives.

Frequently, blood may seep under the skin, so that the scrotum and penis appear to be bruised. If there is no dangerous swelling, this painless problem usually disappears without treatment within 1 - 2 weeks. If the patient bleeds excessively in the days after the operation and requires more than two or three gauze changes per day, he should call his doctor.

In 2 - 5% of cases, bleeding inside the scrotum can cause a painful swelling known as a hematoma. In these cases, the scrotum swells up shortly after vasectomy. The doctor should be called immediately.

Infections occur in 4 - 9% of men after vasectomy. The incision site may become infected, causing redness and swelling around the incision. Antibiotics, antimicrobial creams or ointments, or both, along with hot baths several times a day will usually clear the infection in a few days. There have been a few cases of infections in the lining of the heart (endocarditis) and severe gangrene of the scrotum, but they are extremely rare.

Unexpected Pregnancy

Pregnancy rates after a vasectomy are estimated to be very low, about 1 in 1,000. There are two main reasons for an unexpected pregnancy:

Residual sperm were still alive when the partners had unprotected sex. This is the most common reason for an unexpected pregnancy after a vasectomy. Men should make sure they have follow-up sperm analysis testing. They should also continue to use birth control until their doctor notifies them that the test results confirm sterility.
Failure of the procedure and recanalization. Failure in some cases is due to a technical error, but most often it is due to recanalization -- when the cut ends of the vas spontaneously reconnect. Success rates are best when an experienced surgeon performs the vasectomy.

Once the patient feels comfortable, he can resume sexual activity, usually in about a week. During ejaculation, the patient may experience some discomfort in the groin and testicles at first due to the contraction of the vas deferens. This almost always diminishes as the tissues heal.

However, after the operation there are always some active sperm left in the semen for several months so the risk for pregnancy persists. It is essential that the patient and his partner continue to use other methods of birth control until his sperm count is zero. The patient is considered sterile only when there are no live or moving (motile) sperm in his semen. It takes, on average, around 3 months or 20 ejaculations to clear the viable sperm from the reproductive system, but it may take some men as long as 6 months to become sterile.

About a third of men experience a recurrence or persistence of sperm that have no ability to move (immotile) 12 weeks after surgery and, in one study, about 7% had persistently immotile sperm. Immotile sperm, however, cannot swim up the vaginal canal and pose no danger for fertility. In rare cases, vasectomies have to be repeated because live sperm persisted in the semen. The risk for sperm surviving indefinitely is, however, very low.

The primary reason for vasectomy failure itself is recanalization-- when the cut ends of the vas deferens spontaneously reconnect. Recanalization in some cases may be due to sperm granulomas. These are tiny balls of debris that form from sperm, scar tissue, and white blood cells at the incision site. Cells lining the inside of the vas deferens grow through the scar tissue and form a new channel through which the sperm can now move. In general, surgeons can reduce the risk for recanalization by leaving a gap between the two cut ends.

This natural vasectomy reversal can occur after any vasectomy surgical procedure, but it is uncommon, with most studies reporting it occurring in less than 1% of cases. When recanalization does occur, sperm counts are almost always very low and pregnancies are still rare. Most cases of recanalization develop within several months after the operation. In very rare cases (about 0.6%), sperm have reappeared a year or even longer after vasectomy.

Long-Term Complications

Sperm Granulomas. After vasectomy, sperm often leak from the vasectomy site or from a rupture in the epididymis, the tightly coiled, thin tube that connects the testicle to the vas deferens. Sperm elicit a very strong response from the immune system, which views them as foreign substances and attacks them. Sperm leakage therefore provokes an inflammatory reaction. The body forms pockets to trap the sperm in scar tissue and inflammatory cells. Firm balls of tissue about 1/2 inch in diameter then form; these are known as sperm granulomas. They occur in about 60% of vasectomy patients.

Although they rarely cause serious problems, one study reported that sperm granulomas were troublesome in 15% of patients. In about 3 - 5% of cases, sperm granulomas obstruct the already blocked ends of the vas deferens and generate pressure build-up in the epididymis. This can cause a rupture from the pressure of the fluid. In such cases, the testicles may become enlarged and painful. A damaged epididymis can be repaired, but if the patient later wishes a reversal of the vasectomy, disruption of this tiny tube makes success much less likely.

Epididymitis. Epididymitis occurs when an inflammation at the site of the vasectomy causes swelling of the epididymis. This condition may occur within the first year and can be treated with heat and anti-inflammatory medications. It usually clears up within a week.

The male reproductive structures include the penis, the scrotum, the seminal vesicles and the prostate.

Positive Effects. Surveys indicate that about 90% of men are satisfied with vasectomy and that the feeling persists. One study reported even higher satisfaction in the partners, with more than 95% of wives reporting satisfaction with the procedure. Younger and older couples, with or without children, were all equally likely to have favorable reactions to vasectomies. Most men who have vasectomies feel relieved that the worry about pregnancy is over, and most couples respond well to their new-found contraceptive freedom.

Negative Effects. Some men go through a brief period of self-consciousness, wondering whether others notice some difference in their masculinity. About half of vasectomy patients keep their operations a secret. They may believe that vasectomy is tainted by the stigma of emasculation and that knowledge of it would degrade them in the eyes of their friends and family. For most men, this tentativeness passes quickly.

In a few men, however, problems of poor self-image persist and require counseling. Some may experience depressed and angry emotions. They may actually require a mourning period over the loss of their reproductive ability (similar to what some women go through during menopause). These negative feelings usually resolve over time as the patient moves on to the next stage of his life.

A small percentage of couples experience serious difficulties with the adjustment. Their emotional distress most often manifests itself in sexual dysfunction, such as impotence, premature ejaculation, or painful intercourse. In such cases, however, the vasectomy is probably the catalyst but not the cause of such extreme reactions. Studies have indicated that men who experience erectile dysfunction after vasectomy are more likely to have female partners who are unable to accept the operation.

Research indicates that up to a third of men have some pain in or around the testes that lasts longer than 3 months. In a study of 700,000 patients with vasectomies, up to 10% reported long-term chronic pain around the testicles. In one survey, 19% of subjects reported chronic pain that was simply a nuisance, and 12% reported more severe pain. Another study that followed men for an average of 19 months reported that 27% had some pain in the testicles, although, in the great majority, the pain was brief.

Causes of Chronic Pain. In many cases the source of the pain after vasectomy is not known, although some of the following conditions may be a source of pain:

Scarring from the surgery
Obstruction of part of the epididymis that causes swelling in another section
Pinched nerves
In about 1% of all vasectomies, the epididymis becomes so congested with dead sperm and fluid that the patient feels a dull ache in his testicles. This condition, called chronic orchialgia, usually disappears within 6 months.
Some doctors believe that granulomas may cause more chronic pain than generally believed. Others point out, however, that open-ended procedures, which increase the risk for granuloma production, result in less pain than closed-ended techniques that produce fewer granulomas.

Treatments for Chronic Pain. Surgery may be required if time or more conservative measures fail to relieve pain. Procedures may include:

Removal of the epididymis and surrounding tissue tends to be effective if the pain is in the scrotum (the sac that contains the testes) and if abnormalities in the epididymis can be observed using ultrasound.
A surgical procedure that blocks nerves in the sperm cord can bring relief in severe cases.
Surgery to reverse vasectomy (vasovasostomy) may relieve chronic pain. In one study, nearly 70% of men became pain free, although researchers were unable to discover any biologic differences after the procedure that might explain such relief.

Prostate Cancer. Prostate cancer is the second most common cause of cancer death among American men. About 30% of all American men will develop at least localized prostate cancer at some time in their lives. Long-term high-normal levels of testosterone may be associated with an increased risk for prostate cancer. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have been concerned that such men have a greater chance for developing the cancer.

Click the icon to see an image of prostate cancer.

A 2002 review indicated a 10% increase in risk for every 10 years after the procedure. The authors of the study reported, however, that such increased risk may not be caused by vasectomy since the association was small and could be due to bias. Most recent studies report no higher danger. A rigorous 2002 study from New Zealand, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation. Another 2002 study, in fact, reported a lower risk for prostate cancer in men who had had vasectomies.

It is possible that the higher rates reported in the early studies may simply be due to earlier prostate screening in men who have had vasectomies. One study reported that about 25% of doctors screened men with vasectomies earlier for prostate cancer than those without the operation.

An expert panel has recommended that vasectomy reversal is not warranted to prevent prostate cancer and that screening criteria for prostate cancer should be the same for men with and without vasectomies. Men with a family history of prostate cancer can discuss the risks and benefits of vasectomy with their doctors, although the weight of evidence to date indicates there is no link between vasectomy and prostate cancer.

Testicular Cancer. There have also been some concerns that vasectomy could increase the risk of testicular cancer. However, studies show there is no association between the two.

Vasectomy is known to provoke immune system changes.

Anti-sperm Antibodies. Sperm continue to be produced after vasectomy but are disposed of in the body. In some men the immune system mistakes these sperm as foreign proteins (antigens) and produces anti-sperm antibodies that are designed to target and interfere with sperm's motility (ability to move). Up to two thirds of vasectomized men develop such anti-sperm antibodies. Infections in the genital tract, such as orchitis or sexually transmitted diseases, increase the risk for anti-sperm antibodies. The anti-sperm response itself appears to be a problem only if a man wishes to reverse the vasectomy.

Heart Disease and Other Changes. Some researchers are concerned that changes in the immune system might cause damage in other parts of the body, including contributing to heart disease. However, a large 2002 follow-up study of men who had vasectomies found no increase in risk for heart disease, stroke, or peripheral artery disease, even after more than 20 years. Nor did researchers find any evidence of greater risk for hardening of the arteries (atherosclerosis) or inflammation, which play a role in cardiovascular disease.

Click the icon to see an image of atherosclerosis.

Some experts have voiced concern that vasectomy may increase the risk for the bone-thinning condition known as osteoporosis. However, evidence to date does not support an association.

Studies suggest that men younger than their mid-40s who have vasectomies have twice the risk for kidney stones as their peers who have not had vasectomies. The increased risk persists for up to 14 years after the operation. Kidney stones are not life threatening, but they can be extremely painful. Drinking plenty of fluids is the best way to prevent kidney stones.

Click the icon to see an image of kidney stones.

Reversal Surgery

Although men should consider vasectomy a permanent decision, vasovasostomy is a reversal procedure that may restore fertility in men who change their minds. Vasovasostomies are also effective in relieving chronic pain from vasectomies in the rare case that this occurs.

One Australian study suggested that although the rate of vasectomies has not changed over the past few decades, the desire for reversal surgery increased by over 70% in the late 1990s compared to the early 1980s. Men who had vasectomies in their 20s are more likely to seek reversal later on than older men. The main reasons for requesting a reversal are remarriage, the death of a child, or an improvement in finances. Reversal may also be performed to relieve post-vasectomy pain, which occurs in a small percentage of men. However, fewer than 10% of patients who request reversals do so because of physical or psychological problems following vasectomy.

Standard Procedure. Vasovasostomy reconnects the severed ends of the vas deferens to reestablish the flow of sperm. The procedure is difficult:

It involves sewing together the two tiny ends of both tubes, each with pinhead-sized openings.
If the vas deferens is blocked, the surgeon may try to connect the epididymis to an area in the vas deferens that bypasses the blockage.

Vasovasostomy can usually be done on an outpatient basis, and patients can usually return to work within 1 - 2 weeks. It is far more difficult and expensive than vasectomy itself, however, and is even costlier if the procedure involves connecting the vas to the epididymis, which takes about 3 hours. It should be noted that reversal surgery is usually not reimbursed by insurance companies, and that the results may not be known for some time.

Microscopic versus Magnification Techniques. The surgeon may view the surgical site using either magnification instruments (called macroscopic vasovasostomy) or microscopic techniques. Advanced microscopic techniques are proving to increase the chances of a reversal's success. Although macroscopic vasovasostomy has a slightly lower success rate, pregnancy rates can still be over 50%, and it is less expensive and has a shorter operating time than microscopic procedures. Still, a 2003 study suggested the microscopic approach is preferable for repeat vasovasostomies when the initial procedure failed.

Laser Techniques. Laser surgery is being investigated and may prove to require less surgical expertise, reduce operating time, and result in fewer complications. At this time, however, results vary widely.

An Australian study reported that the pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after vasovasostomy. One study indicated that when successful conception occurs, it does so at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long.
The original procedure was performed on straight sections of the vas deferens.
The pieces joined during the vasovasostomy are of equal size.

Even though tubes are re-opened and sperm is restored in as many as 85% of men who undergo vasovasostomy, pregnancy is not guaranteed. Several factors may play a role in the failure of reversal surgery.

Epididymis Obstruction. If the sperm count does not recover within a reasonable period after vasovasostomy, it is often due to blockage from scarring that has occurred in the epididymis. This sometimes can be corrected with a second procedure. The doctor may be able to detect obstruction before the vasovasostomy by pressing and manipulating (palpating) the epididymis. If any part seems swollen or larger than other parts, an obstruction is very likely to be present and the patient is likely to need a vasoepididymostomy, which creates a bypass around the obstruction.

Antisperm Antibodies. In many cases in which vasovasostomy fails, the reversal procedure reopens the tubes but fertility is impaired because of a process called autoimmunity. With this condition, important immune factors called antibodies attack the body's own cells, mistaking them for antigens (any foreign microinvader that the immune system perceives as a threat).

In the case of vasectomy, the autoantibodies attack the sperm, and so are called antisperm antibodies. Such antibodies develop when sperm continue to be produced after vasectomy, but, instead of being confined to the reproductive passages, they leak out into the body. Once out of their natural habitat, the immune system perceives them as foreign invaders and develops antibodies to attack them.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy substances containing antigens.

The antisperm antibodies bind to specific parts of the sperm (the head or tail) and cause problems depending on the site of attachment. Sperm may stick together (agglutinate), fail to interact with the woman's cervix, or fail to penetrate the egg. Even after vasovasostomy, such antibodies often persist.

Oxidation. The immune factors that trigger the autoimmune process may have other harmful effects as well. In a process called oxidation, they can trigger the release of particles called free radicals, highly reactive oxygen molecules that, in excess, can do considerable damage to cells and genetic material. When high levels of free radicals persist after a vasectomy, they may, in theory at least, injure sperm DNA, contributing to infertility.

Repeat Vasovasostomy. If pregnancy fails, in some cases a repeat vasovasostomy may be effective. Success rates depend on several factors:

The doctor's skill
Complications from the original operation
Effects of anti-sperm antibodies
Time elapsed since vasectomy (the shorter the better)
History of previous children. In one study, conception rates after reoperations were highest (80%) in couples who had had previous children. The pregnancy rate was only 17% when men had remarried.

A 2003 study indicated that the microscopic approach may be preferable for many repeat vasovasostomies.

Vasoepididymostomy. Vasoepididymostomy is a microsurgical technique that is useful when a vasovasostomy has failed because of damage to the epididymis. This procedure creates a bypass around the obstruction. It may be done on one or both sides of the testes.

To appreciate the difficulty of this operation, one should realize that the epididymis is 1/300th of an inch wide with a wall thickness of 1/1000th of an inch. Microscopic techniques are critical for the success of this procedure and require a surgeon who specializes in them. Refinements in vasoepididymostomy techniques are showing promising results, opening tubes in 77 - 85% of cases.

Success rates are higher for repairing obstructions closer to the testicles, because the epididymis is wider in this area. In general, pregnancy rates are around 25%, but higher rates have been reported. In one study of men who had vasectomy reversal more than 15 years after the original procedure, 62% required vasoepididymostomy, and the overall pregnancy rate was 43%. Pregnancy rates ranged from 49% in those who had had their vasectomy 15 - 19 years earlier to 25% in those who had the surgery 25 or more years before, with the highest rates occurring, not surprisingly, in those with the youngest wives.

Damage in other ducts and small tubes are a major reason for vasoepididymostomy failure. Ultrasound before the operation may be valuable to determine if these abnormalities exist, which would make it unlikely that the procedure would be successful.

If an initial vasoepididymostomy fails but conditions are favorable, a repeat procedure may still succeed.

If the patient did not contribute sperm for freezing and banking before vasectomy, some doctors suggest freezing sperm obtained during vasovasostomy as insurance against failure. Such sperm can be used in assisted reproductive methods later on if natural intercourse fails to achieve pregnancy.

There is some controversy, however, surrounding routine use of frozen sperm before a vasovasostomy. One study reported that so many sperm were non-motile at the time of the reversal surgery that freezing sperm obtained during the procedure provided little benefit. Nevertheless, new fertilization techniques are using even non-motile sperm with some success. Studies report successful pregnancies with frozen sperm. Some experts recommend routine sperm retrieval only for men undergoing bilateral vasovasostomy (those performed on both sides) and possibly for men who are having vasovasostomy with vasoepididymostomy. Men should discuss these options with their doctor.

Even though newer techniques such as intracytoplasmic sperm injection (ICSI) are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was between 25 - 30%. (ICSI is the ART treatment of choice for men who have had vasectomy.) Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are available for men who want to conceive children after a vasectomy. The shorter the period since the vasectomy the better the chances of success. In one study, success rates after ART were highest (34%) when it was performed within 10 years of the vasectomy and lowest (8%) when ART occurred more than 20 years after vasectomy. Of course, the couples would be older as the duration between procedures increased, so pregnancy rates would be lower in any case. However, time elapsed after vasectomy appears to have an effect independent of a couple's age. Debate is ongoing about its advantages versus reversal surgeries for men who have had vasectomies and want children. Research presented at the 2007 American Urological Association annual meeting suggested that vasectomy reversal may work better than sperm retrieval or other ART.

The best assisted reproductive technology procedure for men who have had vasectomies or failed reversal surgery is intracytoplasmic sperm injection (ICSI). In this procedure, sperm are taken from the epididymis or testes using needles or microsurgical techniques.

The procedure itself injects a single sperm into an egg with the aid of powerful microscopic and robotic instruments. The fertilized egg is then implanted in the woman. [See In-Depth Report #67: Infertility in men.]

If a reversal surgery is not successful, a doctor may be able to retrieve sperm from the testes or the epididymis for use in assisted reproductive technologies (ART). Various techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques. Rigorous trials on the best technique are lacking, although all can be successful. The choice will depend on the experience of the clinic and any underlying problems.

Testicular Fine Needle Aspiration. Testicular fine needle aspiration (TFNA) employs a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Percutaneous Epididymal Sperm Aspiration. Percutaneous epididymal sperm aspiration (PESA( uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often it can cause permanent alterations in testicular function that may reduce male hormone levels.

Resources

www.engenderhealth.org -- EngenderHealth
www.nichd.nih.gov -- National Institute of Child Health and Human Development
www.plannedparenthood.org -- Planned Parenthood
www.fhi.org -- Family Health International
www.auanet.org -- American Urological Association
www.urologyhealth.org -- Urology Health
www.newmalecontraception.org -- Male Contraception Information Center
www.imccoalition.org -- International Male Contraception Information Coalition
www.vasectomy.com -- Information on vasectomy

References

Amory JK, Muller CH, Page ST, Leifke E, Pagel ER, Bhandari A, et al. Miglustat has no apparent effect on spermatogenesis in normal men. Hum Reprod. 2007 Mar;22(3):702-7. Epub 2006 Oct 25.

Cook LA, Pun A, van Vliet H, Gallo MF, Lopez LM. Scalpel versus no-scalpel incision for vasectomy. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004112.

Mruk DD, Wong CH, Silvestrini B, Cheng CY. A male contraceptive targeting germ cell adhesion. Nat Med. 2006 Nov;12(11):1323-8. Epub 2006 Oct 29.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Prostate cancer

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Prognosis
Risk Factors
Symptoms
Conditions with Similar Sym...
Screening and Diagnosis
Tests to Determine Severity...
Treatment
Treatment Options by Stagin...
Treatment for Localized Pro...
Surgery
Radiation Treatments
Options if Treatments Fail...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Localized Prostate Cancer

In 2007, the American Urological Association (AUA) released updated guidelines for treatment of localized prostate cancer. The guidelines recommend that:

Patients should be classified as low, intermediate, or high risk, depending on their PSA levels, cancer stage, and tumor aggressiveness.
Doctors need to consider patients’ personal preferences and quality of life concerns as well as their clinical status.
Standard treatment options include active surveillance (watchful waiting), surgery, or radiation therapy. Initial androgen deprivation therapy (hormone therapy) is seldom recommended for localized prostate cancer.

New Guidelines for Androgen Deprivation Therapy

The American Society of Clinical Oncology (ASCO) 2007 guidelines recommend that doctors delay androgen deprivation therapy for advanced prostate cancer until patients develop symptoms. When treatment is started, ASCO recommends either removal of both testicles (orchiectomy) or luteinizing hormone releasing hormone (LHRH) drug treatment.
Androgen deprivation therapy can increase the risks for heart disease death and diabetes, according to a 2006 Journal of Clinical Oncology study.

Diagnosis

Experts do not recommend prostate specific antigen (PSA) tests for men over age 70, yet many of these men continue to receive unnecessary tests, indicates a 2006 Journal of the American Medical Association study.
A new investigational test for early prostate cancer antigen-2 (EPCA-2) may be more accurate than the PSA test and may eventually replace it, suggests a 2007 study in Urology.

Genetic Research

Researchers have identified a set of genetic variations that may account for about 68% of prostate cancer cases in African-American men. Scientists hope that further investigation of this chromosomal region may help in developing genetic tests for prostate cancer.

Introduction

Prostate cancer is a malignant tumor that arises in the prostate gland. As with any cancer, if it is advanced or left untreated in early stages, it can eventually spread through the blood and lymph fluid to other organs. Fortunately, prostate cancer tends to be slow growing compared to other cancers. As many as 90% of all prostate cancers remain dormant and clinically unimportant for decades. This high incidence of latent or incidental malignancy is unique to the prostate gland. Most older men eventually develop at least microscopic evidence of prostate cancer, but it often grows so slowly that, as one specialist has written, many men with prostate cancer "die with it, rather than from it."

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid which mixes with sperm to make semen.

Male hormones (androgens) play major roles in the development of prostate cancer. Some research, for example, reports a higher risk with increasing testosterone and a lower risk with increasing estrogen levels. Dihydrotestosterone (DHT) is the principal male hormone in the prostate gland. It affects the size of the prostate gland itself and may play a role in prostate cancer. Nevertheless, researchers have not yet fully clarified the specific mechanisms that may be important in the development of this disease. Most likely, genetic mutations affecting androgens trigger the process. Certain growth hormones, such as insulin-like growth factor-I, are unrelated to testosterone and may increase the risk for prostate cancer.

Description of the Prostate Gland

The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen
Glandular cells, which produce a milky fluid that liquefies semen
Stromal cells (which form the structure of the prostate)

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland

The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate gland also contains an enzyme, called 5 alpha-reductase, that converts testosterone to dihydrotestosterone, another male hormone that has a major impact on the prostate.

Changes During the Lifespan

The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly, attaining normal adult size and shape, about that of a walnut, when a man reaches his early 20s. The gland generally remains stable until about the mid-forties, when, in most men, the prostate begins to enlarge again through a process of cell multiplication.

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

Prognosis

Prostate cancer is the most common male cancer in the U.S. Only lung cancer causes more cancer deaths in American men. The lifetime probability of developing prostate cancer is about 16%. Each year, approximately 218,890 men in the United States will be diagnosed with prostate cancer, and about 27,050 will die from the disease. According to the American Cancer Society, 5-year survival rates for all stages of prostate cancer have increased during the past 20 years from 67% to nearly 100%.

A survival rate indicates the percentage of patients who live a specific number of years after the cancer is diagnosed. For prostate cancer, the 10-year survival rate is 93% and the 15-year survival rate is 77%. After 15 years, survival rates stabilize. A 2006 study in the Journal of the American Medical Association found that men who are diagnosed with low-grade prostate cancers have a minimal risk of dying from prostate cancer up to 20 years after diagnosis. However, men diagnosed with more severe forms of prostate cancer have a higher risk of dying within 10 years.

Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Because so many prostate tumors are low-grade and slow growing, survival rates are excellent when prostate cancer is detected in its early stages. Cure rates can be as high as 98% in some cases.

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

Locally Advanced. If the disease is at the locally-advanced stage, in which it has spread beyond the prostate but only to nearby regions, it is more difficult to cure, but survival rates can be prolonged for years in many men. (When cancer has metastasized to the pelvic lymph nodes, the outlook is worse than if it has spread to other areas.)

Metastasized Cancer. If prostate cancer has spread to distant organs (metastasized), average survival time is 1 - 3 years, but some of these patients may live longer or die of other causes.

If cancer recurs after initial treatment for early-stage tumors, it is still potentially curable if it is contained within the prostate, although in most cases the cancer has spread. Hormone treatments for such recurring cancers can often prolong survival for years, although the cancer almost always returns again.

Risk Factors

The major risk factors for prostate cancer include genetic, dietary, and environmental factors that affect male hormones (androgens) and make a man more susceptible to this cancer.

Prostate cancer occurs almost exclusively in men over age 40 and most often after age 50. It is estimated that by age 70, about 65% of men have at least microscopic evidence of prostate cancers. Fortunately, the cancer is often very slow growing and older men with the cancer nearly always die of something else.

Heredity plays a role in some types of prostate cancers. Men with a family history of the disease have a higher risk of developing prostate cancer. Having one family member with prostate cancer doubles a man's own risk, and having three family members increases risk by 11-fold.

In 1998, scientists discovered a gene, located on chromosome 1, which may be involved in 1 in 500 cases of prostate cancer. They named this gene HPC1. (HPC stands for “hereditary prostate cancer.”) In 2005, scientists announced another major breakthrough in understanding the genetic components of prostate cancer. Research published in Science suggested that, in some cases, prostate cancer occurs when a specific set of genes merge. The genes are part of the ETS gene family and include ETV1, ETV4, and ERG.

In 2007, three separate studies published in Nature Genetics focused on DNA variations located on chromosome 8 in the 8q24 region. The research suggested that men who carry these genetic variations have a substantially increased risk of developing prostate cancer. The DNA variations may be associated with as many as 32% of prostate cancers in Caucasian men and 68% of prostate cancer cases in African-American men.

Doctors hope that future research will help develop genetic tests to identify men most at risk and, eventually, targeted drug therapy for prostate cancer.

A gene is a short segment of DNA which is interpreted by the body as a plan or template for building a specific protein. Genes reside within long strands of DNA which in turn make up the chromosomes.

African-American men have the world's highest risk for prostate cancer, more than 50% higher than the risk for Caucasian males. The disease is also more lethal among African-Americans. Men who live in Asia have lower risks for prostate cancer, but their risk increases if they move to North America. This indicates that there are unknown environmental or dietary factors that can alter a man's underlying genetic risk of developing this disease.

Socioeconomic Issues. The higher mortality rates in African-American men may be partly due to socioeconomic factors, such as lack of insurance, irregular screening and a late diagnosis, and unequal access to health care.

Dietary Factors. Dietary factors may play some small role in the higher risk in African-American men. This is suggested by the fact that prostate cancer is rare in many parts of Africa.

Biologic Factors. Evidence suggests that African-American and Asian men have certain genetic factors that may affect male hormones differently and may help account in part for the higher risk in the first group and the lower risk in the second.

Higher PSA Levels. African-American men also tend to have higher PSA levels than Caucasians. They are overdiagnosed with prostate cancer by 37% compared to 15% in Caucasians using PSA screening tests.

Chemicals. The relationship between prostate cancer and chemical exposure is controversial. Men whose work involves heavy labor and those exposed to certain metals and chemicals, including cadmium, dimethylformamide, and acrylonitrile, may be at higher risk for prostate cancer. Some studies have indicated that farmers might be at higher risk.

A 2001 study concluded that certain leisure activities may expose men to the same chemicals as those that pose a possible danger in the industrial setting. These chemicals included:

Home or furniture maintenance
Painting, stripping, or varnishing furniture
Activities that involved exposure to lubricating oils or greases, metal dust, or pesticides or garden sprays

Scientists think that specific genes that affect the body's response to viruses may be associated with certain types of prostate cancer. Some theories suggest that there may be a relationship between prostate cancer and infections, such as herpes virus, human papillomavirus, and cytomegalovirus. In 2006, scientists identified a new virus, XMRV, which is 30 times more common in men with prostate cancer who have a genetic mutation with the HPC1 gene. Scientists know that men who have the HPC1 genetic mutation are more likely to get prostate cancer. This new research suggests that the genetic mutation may make them more vulnerable to a virus that causes the cancer. Researchers will continue to investigate XMRV and other possible infectious causes of prostate cancer.

Obesity. Obesity may increase the risk for prostate cancer, particularly more aggressive forms of the disease. Obesity may also make prostate cancer more difficult to diagnose. A 2005 study found that overweight and obese men were more likely to be diagnosed with advanced prostate cancer and to die of the disease than normal-weight men.

Nonmelanoma Skin Cancers and Sunlight. Some studies report that patients with prostate cancer and a history of nonmelanoma skin may have a higher risk for a poorer outlook. Such skin cancers are highly associated with exposure to sunlight. However, sunlight triggers production of vitamin D in the body, which research indicates may help protect against prostate cancer. Prostate cancer rates are, in fact, lower in southern, sunny regions.

Vasectomy. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have theorized that such men have a greater chance for developing the cancer. While some studies have suggested a higher risk with vasectomy, other studies have reported no higher danger. A rigorous 2002 study from New Zealand, for example, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation. A 2002 study in California, in fact, reported a lower risk for prostate cancer in men who had had vasectomies. It is possible that the higher rates reported in earlier studies may have been due to earlier prostate screening in men who have had vasectomies. Indeed, one study reported that about 25% of doctors screened men with vasectomies earlier for prostate cancer than those without the operation. [See In-Depth Report #37: Vasectomy.]

Click the icon to see an illustrated series detailing a vasectomy.

Click the icon to see an animation on vasectomy.

A Western lifestyle is associated with prostate cancer, so obesity, high-meat intake, and dietary fats have been intensively studied. Results have been inconsistent, however. Certain factors, such as cancer-causing compounds in well-cooked meat or high-calorie intake, may help explain the associations between such dietary factors and cancer risk.

Click the icon to see an image on different types of weight gain.

Fats. Some studies have found an association between high fat-intake and prostate cancer. This association may be explained by other suspected dietary factors for prostate cancer, such as high-calorie diet, high meat intake, and calcium (found in dairy products), all of which are associated with fat intake. The effects of specific fatty acids (compounds that make up fats) may also help clarify the role of fats in prostate cancer. The omega-3 fatty acids in fish (EPA and DHA) and the omega-3 fatty acids found in certain vegetables (ALA) can all protect the heart, but they may have different effects on the prostate.

Marine Omega-3 Fatty Acids. Research indicates that docosahexanoic acid (DHA) and eicosapentaneoic acid (EPA), the omega-3 fatty acids found in fish, may be protective against prostate cancer. Some studies have reported a lower risk for prostate cancer in men who ate fish frequently (two or more times a week).
Alpha-Linolenic Acid. On the other hand, some research has indicated that alpha-linolenic acid (ALA), the omega-3 fatty acid found in certain plants and nuts (flaxseed, canola, walnuts), may increase the risk of prostate cancer. However, some studies suggest that flaxseed, a plant food that is also rich in omega-3 fatty acids, may help slow the growth of prostate tumors.

Meat and High-Temperature Cooking. Some evidence suggests that a high intake of red meat raises the risk for prostate cancer. Because red meat is high in saturated fat, such findings may explain the inconsistencies found in studies that simply look at fat content as a risk for prostate cancer. High-temperature cooking (grilling, broiling, or pan-frying) of meat or poultry has been specifically associated with increased risk for cancer in some studies. Over-cooking meat increases the amount of compounds called heterocyclic amines, which has been associated with cancerous changes in general and prostate cancer in particular, at least in some studies. Cooking meats in liquid does not appear to increase these compounds. As with all dietary studies, some have observed no association between high intake of well-cooked meat and prostate cancer.

Vegetarian Diet. Small studies suggest that a vegetarian diet may be protective. Specific foods may be especially helpful in reducing the risk of prostate cancer:

Whole grain cereals, seeds, and nuts have been associated with a lower risk for prostate cancer. Part of this protection may be due to their high fiber content. Fiber binds to sex steroids and is excreted, carrying the hormones with it. Whole grains also contain selenium, a trace mineral that may have some protective properties.
Many studies have reported a significantly lower risk for prostate cancer with high intake of cooked tomatoes, which are high in a beneficial plant chemical called lycopene. (However, other studies have not reported such protection.)
Soy may also be protective, which may partially explain the low rate of prostate cancer observed in Japanese men and vegetarians (who typically use soy as a protein replacement). Theoretically soy, which is a rich source of an estrogen-like plant compound, may inhibit hormones that promote prostate cancer. Laboratory studies are mixed on such effects, however.
Cruciferous vegetables (cauliflower and broccoli) may have cancer-fighting chemicals.
Boron-rich foods (nuts, red grapes, avocados, and dried fruits) may also be protective.
Green tea. Scientists have speculated that the antioxidants contained in green tea may help to inhibit prostate cancer growth. Investigators are researching the effects of both green tea and green tea extract supplements, but results to date have been inconclusive.

Dairy Products, Calcium, and Vitamin D. Studies have reported an association between consuming large amounts of dairy products and a modestly increased risk for prostate cancer. (Moderate intake has not been associated with a higher risk.) There is some evidence that calcium (contained in dairy products) may increase the risk for prostate cancer by reducing levels of the most active form of vitamin D (1,25 dihydroxyvitamin D). Many studies indicate that vitamin D may help protect against prostate cancer. Men should make sure they are getting enough vitamin D through sunlight exposure, food, or vitamin supplements.

Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has lactose intolerance or another reason, such as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also affects the heart and circulatory system, as well as the secretion of essential hormones. There are many ways to supplement calcium, including a growing number of fortified foods.

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

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

There is some evidence that certain vitamin and mineral supplements (such as vitamin E and selenium) can protect against prostate cancer, and also some evidence that excessive use of supplements may increase risk. In a 2007 National Institutes of Health study, men who took multivitamin supplements more than seven times a week increased their risks for developing advanced prostate cancer and for dying from the disease. The risks were highest for men who had a family history of prostate cancer and for those who took individual supplements of selenium, beta-carotene, or zinc. However, using multivitamin supplements occasionally or once a day does not appear to increase prostate cancer risk.

The National Cancer Institute is conducting a large-scale clinical trial of more than 35,000 men to investigate whether selenium, vitamin E, or a combination of these two dietary supplements can help to prevent prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is the largest prostate cancer prevention trial ever initiated.

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.

In general, a healthy diet with nutritious fruits and vegetables is the best way to meet your daily requirement of vitamins and minerals.

Alcohol consumption does not appear to be associated with increased prostate cancer risk. A recent study, however, suggested a linear trend between red wine consumption and reduced risk of prostate cancer. In a study of over 1,400 newly diagnosed middle-aged patients with prostate cancer, researchers found that each additional glass of red wine consumed per week reduced the relative risk of prostate cancer by 6%. Researchers theorize that the flavonoids contained in red wine may inhibit tumor cell growth. More research is needed to confirm these results.

Regular physical activity may help reduce the risk of prostate cancer and slow the progression of the disease. The beneficial effects of exercise may be particularly important for older men. A 2006 study found that men ages 65 and older who exercised vigorously for at least 3 hours weekly had a 70% lower risk of being diagnosed with advanced prostate cancer.

Finasteride (Proscar) is a drug used to shrink the prostate in men with benign prostatic hyperplasia (BPH). It blocks an enzyme that converts testosterone to dehydroepiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. Researchers are investigating whether finasteride may help prevent prostate cancer. In the 2003 Prostate Cancer Prevention Trial (PCPT), more than 18,000 men were randomly assigned to receive either finasteride or placebo. The men took the pills daily for 7 years. Results, published in 2003 in the New England Journal of Medicine, indicated that men who took finasteride were 25% less likely to develop prostate cancer than men who took placebo. However, although the finasteride group had fewer prostate cancers overall, those that did develop were higher-grade and more aggressive. Men who took finasteride had more sexual problems, including episodes of erectile dysfunction, but were less likely to have urinary problems, such as incontinence. It is still unclear if finasteride is an appropriate preventive approach.

Frequent ejaculations from masturbation or sexual activity have been associated with a lower risk for prostate cancer. Some experts speculate that certain carcinogens may be concentrated in prostate fluid, so that frequent ejaculation helps eliminate them. Of note, risky sexual activity, such as with multiple partners, increases the risk for sexually transmitted disease, which in turn may increase the risk for prostate cancer.

There is some evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) offer some protection against prostate cancer. NSAIDs suppress chemicals in the body called COX-2, a protein that may cause prostate cancer cells to spread. Standard NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve). However, NSAIDs taken on a long-term basis can increase the risk for heart and gastrointestinal problems.

Symptoms

Prostate cancer usually causes no symptoms in the early stages. As the malignancy spreads, it may constrict the urethra and cause urinary problems.

Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

Later-stage urinary symptoms typically include:

Weak urinary stream
Inability to urinate
Blood in the urine
Interruption of urinary stream (stopping and starting)
Frequent urination (especially at night)
Pain or burning during urination

Significant pain in one or more bones may indicate the occurrence of metastases (spread of disease). This chronic pain occurs most often in the spine and sometimes flares in the pelvis, the lower back, the hips, or the bones of the upper legs. It may be accompanied by significant weight loss.

Conditions with Similar Symptoms

In up to half of men in their 40s, the prostate begins to enlarge through a process of cell multiplication called benign prostatic hyperplasia (BPH). The symptoms of BPH can mirror late-stage prostate cancer because the enlarging inner portion of the prostate puts pressure on the urethra, which can potentially cause urinary problems. About 80% of men eventually develop enlarged prostates, but only some experience significant symptoms. BPH is a normal condition and is not life-threatening. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Benign prostatic hypertrophy (BPH) is a non-cancerous enlargement of the prostate gland, commonly found in men over the age of 50.

Relationship to Prostate Cancer. Because the prostate enlargement in BPH is affected by testosterone, many men are concerned that it may be related to prostate cancer. Fortunately, current evidence indicates that it has no effect one way or the other. The two conditions develop in different parts of the prostate. BPH occurs in the inner zone of the prostate, while cancer tends to develop in the outer area. A 10-year study found no higher risk for prostate cancer in men with BPH.

Click the icon to see an animation about benign prostatic hypertrophy.

Prostatitis is an inflammation of the prostate, often caused by bacterial infections. Symptoms include urgency, frequency, and pain in urination, sometimes accompanied by fever or blood in the urine.

Screening and Diagnosis

The prostate specific antigen (PSA) blood test is widely used for screening men for prostate cancer. However, there is great uncertainty over whether regular screening has major benefits for most men. The most recent guidelines from the U.S. Preventive Services Task Force report that there is no conclusive evidence that routine prostate screening saves lives. Indeed, it may lead to invasive testing, and to treatments for many men who, considering the slow growth of the cancer, might derive no benefits from them. It is a difficult subject, and men must discuss all aspects carefully with their doctor.

A 2006 study in the Archives of Internal Medicine also suggested that screening tests for prostate cancer may not reduce men’s risk of death. The small study of 1,000 men found no differences in survival between men who had prostate specific antigen tests or digital rectal exams, and men who were not screened. Doctors should inform men of the uncertainty of prostate cancer tests so that patients understand the relative risks and benefits of screening

Standard Screening Tests for Early Detection. Two standard tests are used for early detection of prostate cancer:

Digital rectal examination (DRE). With the DRE, a doctor palpates the prostate in order to feel lumps or masses.
PSA test. The PSA blood test measures the level of a protein called prostate-specific antigen. It is able to detect early prostate cancer, although it has limitations.

If the digital rectal examination indicates the possible presence of cancer, regardless of the PSA results, a doctor may also obtain a visual image of the prostate through an ultrasound procedure called transrectal ultrasonography (TRUS). Only a biopsy, however, in which a tiny sample of prostate tissue is surgically removed, can actually confirm a diagnosis of prostate cancer.

Candidates for Annual Screening. Until major studies report on the survival benefits of prostate screening, expert groups recommend the following:

Men ages 50 - 70 should be offered annual screening. (Some experts believe that men whose PSA levels are under 1.0 and possibly under 2.0 may safely be screened only every 2 years thereafter.)
Men with a family history of prostate cancer and all African-American men should consider annual screening at about age 45.
Experts agree that PSA testing is inappropriate for men over age 70. PSA testing in this age group can cause more harm than good by leading to overly aggressive treatment. Despite this fact, many elderly men continue to receive unnecessary PSA tests.

The best age to start annual screening is under debate. Some experts advocate performing a first PSA test in all men aged 40 and then monitoring anyone whose PSA levels are over 0.60 ng/mL. They argue that such men are at high risk for developing prostate cancer within 25 years. A study presented at the 2007 meeting of the American Urological Association suggested that even a small increase in PSA in men age 44 - 50 may predict whether advanced prostate cancer will develop later in life.

Researchers are working on developing more accurate tests that, hopefully, will one day replace the PSA test. A promising test in development measures a protein called early prostate cancer antigen-2 (EPCA-2). A 2007 study suggested that the EPCA-2 test is highly accurate. It can distinguish between benign prostatic hyperplasia (BPH) and prostate cancer and can evaluate whether or not a man has prostate cancer, regardless of what his PSA levels indicate. Researchers hope that this test may eventually provide better diagnoses of prostate cancer, and help prevent men from receiving unnecessary biopsies.


	DRE alone	PSA alone and in Combination with DRE
Chance of Cancer	Only 20% of men with abnormal DREs have cancer. Unfortunately, 70% of prostate cancers detected with DRE alone have already spread beyond the prostate gland.	The odds of cancer with PSA readings are: 3 ng/mL or below indicates 2% or less chance of cancer. 3 - 10 ng/mL indicates about a 25% chance of cancer. 10 ng/mL and over indicates a very strong chance. Men with abnormal results from both DRE plus PSA tests have a 60% chance for cancer.
Risk of Missed Cancers with Normal Results	About 60% of men who have prostate cancer have normal DRE results.	Some evidence suggests that only performing biopsies at levels above 4.0 would miss over 80% of cancers present below that level in men under 60 years and 65% in older men. As a result, some experts recommend biopsies with PSA levels at 3.0 or below in young men. Still, cancer at low PSA levels is very uncommon, particularly in younger men.

About 90% of all prostate cancers arise in the outer part of the prostate where they may be detected by a digital rectal exam (DRE), which is the simplest and most widely-performed screening procedure. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate for bumps or other abnormalities. The exam is quick and painless but some men find it embarrassing. It is not very accurate in detecting early cancers, but studies indicate that regular DREs still save lives.

Prostate Cancer is the most common cancer in men in the United States. Prostate cancer forms in the prostate gland, and can sometimes be felt on digital rectal examination. This is one of the purposes of the digital rectal exam.

Prostate specific antigen (PSA) is a protein produced in the prostate gland that keeps semen in liquid form. Prostate cancer cells appear to produce this protein in elevated quantities. Measuring PSA levels increases the chance for detecting the presence of cancer when it is microscopic. There are many unresolved questions surrounding PSA testing. The test is not accurate enough to either completely rule out or confirm the presence of cancer. Relying too much on the test may lead to unnecessary biopsies. Not relying on it enough may miss cancers. It is still unclear if PSA testing is actually saving lives.

Click the icon to see an image of a PSA blood test.

Indications for Biopsy. A biopsy is usually performed to confirm or rule out cancer after screening tests that report:

PSA level of 4.0 ng/mL or higher. Some evidence indicates that men with an initial test showing PSA levels above 4.0 should take a second PSA test several weeks afterward before having a biopsy, since many non-malignant factors can increase PSA levels. (Some experts urge biopsies even if PSA levels fall below 4.0 mg, particularly in men under 60, since lower levels do not necessarily rule out cancer.)
Abnormal digital rectal examination (DRE).

Men with abnormal results from both tests have a 60% chance of prostate cancer. The chances for cancer if only one test is abnormal are considerably lower. To further complicate matters, biopsies themselves may miss very small cancers detected by PSA levels alone.

Factors Affecting PSA Levels. A number of factors and noncancerous conditions can influence PSA levels:

Ethnicity. Normal levels in Caucasian males may be different from those for African-American or Asian men. For example, using PSA screening, one study suggested that 15% of Caucasians and 37% of African-Americans are overdiagnosed with prostate cancer based upon PSA results. Some experts believe that there should be different scales for determining risk among these groups, but there is still not enough information to determine a specific range for various ethnic groups.
Age. PSA levels tend to rise naturally with age, so an elevated level in a man who is 70 may be less serious than the same level in a younger man. Some experts believe that men older than 65 who have low PSA levels are at such low risk for prostate cancer that they may be able to forgo further testing.
Benign Prostatic Hyperplasia (BPH) and Its Treatments. Between 25 - 56% of patients with BPH have elevated PSA levels. Certain treatments for this condition can also elevate PSA.
Prostatitis. About half of men with elevated PSA levels but no signs of cancer on biopsy have signs of prostatitis as indicated by urine and prostate secretion tests. (Prostatitis simply means inflammation in the prostate. Inflammation is usually due to bacterial infection, but it can also be caused by nonbacterial factors.) In one study, screening for prostatitis increased the accuracy of the PSA test significantly and reduced the number of unnecessary biopsies.
Other Noncancerous Conditions. Other noncancerous conditions that can increase PSA levels include surgical procedures or drug treatments for BPH, acute urinary retention, digital rectal examinations, and prostate biopsies themselves.
Ejaculation. Ejaculation within 48 hours before testing can raise PSA levels.

Even with its limitation, the PSA test has increased the number of detectable early-stage and therefore treatable cancers. Because of the slow-growing nature of prostate cancer, however, it is not known whether all of these very early cancers will result in significant or life-threatening disease. It is possible that PSA screening could result in the detection of some possible cancers that would never have bothered the patient and would never have posed a threat to his life.

To improve the accuracy of the PSA tests, particularly when PSA levels have risen to an intermediate range of between 4 - 10 ng/mL, researchers are developing methods for measuring other factors. To date, no test has emerged as clearly superior to the PSA test.

Free PSA Test. A small amount of prostate specific antigen leaks out of the prostate into the bloodstream. There, PSA can circulate without binding to other proteins and is referred to as free PSA. It can also form chemical combinations with other proteins. If cancer is present, PSA is more likely to be bound, and so there is less free PSA in circulation. The free PSA blood test, then, is a ratio of free PSA to the total PSA (free PSA plus chemically bound PSA).

The following results are used to determine if an elevated PSA level could mean cancer:

A free-to-total PSA ratio of 20% or lower, plus total PSA levels of 4 - 10 ng/mL, are suggestive of prostate cancer. (Some experts use 25% as a cut-off, but studies suggest that using this cut-off would miss cancers in many African-American and older men.)
A free-to-total PSA level of more than 20% plus normal or even moderately elevated total PSA tend to indicate the presence of other, benign conditions, such as benign prostatic hyperplasia (but it still does not rule out cancer).

Some studies have reported that adding a test for free PSA may improve prostate cancer detection by roughly 40% and may also reduce the need for unnecessary biopsies. In addition, any cancers that the test misses would not develop into significant disease for many years, providing ample opportunity to identify them before they became serious. Not all studies support its advantages, however, compared to measuring total PSA alone, and to date there is no consensus among doctors for how it can be used.

Complexed PSA Test. Complexed PSA (cPSA) is a form of circulating PSA that is bound to a molecule called alpha1-antichymotrypsin. It represents about 90% of the total PSA in men and is significantly higher in men with prostate cancer than in those with BPH. To date, studies have reported conflicting results on its benefits for diagnosing prostate cancer.

Transition Zone PSA Test. Some tests have been developed to measure the density of the PSA in the transition zone of the prostate gland. (The transition zone is the central area of the prostate that wraps around the urethra.) A major comparison study in 2002 reported more accurate results than with complexed PSA.

An ultrasound procedure called transrectal ultrasonography (TRUS) provides a visual image of the prostate and is used if the DRE indicates the presence of cancer. Ultrasound is not effective as a diagnostic tool by itself because it cannot differentiate very well between benign inflammations and cancer, but the procedure may help to confirm an uncertain preliminary diagnosis and is useful as a guide for needle biopsies. Ultrasound enhancements, such as Doppler imaging or computer modeling techniques called artificial neural networks (ANN), may increase the accuracy of TRUS.

Initial Biopsies. If preliminary tests raise the suspicion of cancer, doctors will perform a biopsy. Biopsy is used to diagnose prostate cancer, and is a very accurate method for predicting the severity of an existing cancer. However, biopsies can still miss cancers if they are very small.

Core Biopsy. The standard method is called a core biopsy, which uses a spring-loaded biopsy device inserted into the rectum. The device propels a needle into the prostate, obtaining a core of tissue, which is examined by pathologists.
Fine Needle Aspiration. A more recent procedure, called fine needle aspiration, is less painful and may be as accurate as a core biopsy if the sample obtained is sufficient for analysis and if it is analyzed by a skilled pathologist.

More than half of the men who have a biopsy experience discomfort and anxiety, with men under 60 reporting higher levels of discomfort than older men. Taking a sedative 1 - 2 hours before the procedure can help reduce distress. Complications of biopsy are low, but urinary tract infection, fever, or bleeding occurs in 0.1 - 4% of men.

Repeat Biopsies. Because a biopsy can miss very small cancer cells, sometimes three or even more biopsies are recommended if cancer is still suspected after negative results, such as when:

PSA levels are high. Two or more biopsies may be taken if a man has very high PSA levels and still has normal results on a biopsy. Even men with mildly elevated PSA (between 4 - 10 ng/mL) who test negative may be given a repeat biopsy. Cancer will be detected in about 10% of this group. Whether a third biopsy is useful in these men if they still test negative after a second biopsy is uncertain.
DRE results are abnormal.
Ultrasound results are abnormal.
The initial biopsy yields microscopic findings that are suspicious.
The initial biopsy detects precancerous cells known as high-grade prostatic intraepithelial neoplasia (PIN). No treatment is necessary with this finding, but these patients should be rechecked every 3 - 6 months for the next 2 years, and then annually.

Doctors may also perform a lymph node biopsy to see if the cancer has spread.

Tests to Determine Severity of Cancer

Once cancer is diagnosed, PSA levels may help to determine its extent. If PSA levels are less than 20 ng/mL, it is possible that the cancer has not spread to distant sites. PSA levels over 40 ng/mL are a strong indicator that cancer has metastasized (spread throughout the body). PSA levels are also monitored after treatments begin. Changes in the level can show if a treatment is working or if the cancer has come back.

Doctors also monitor how quickly PSA levels rise over time. This rate is called PSA velocity (PSAV). The PSAV is very helpful in determining when treatment should begin and which treatment should be used. A high rate of PSAV is considered to be 2 ng/mL a year. Recent research suggests that men with early-stage prostate cancer who have a slow PSAV are more likely to live longer than men with rapidly rising PSA levels.

A number of biological factors are being used or investigated as markers for cancer or its severity:

Chromosomal Sets. The number of chromosomal sets in the nucleus of the tumor's DNA, known as its ploidy, is an important marker for patients in late stages of prostate cancer. Tumors with the normal two sets of chromosomes, called diploid tumors, usually have a more favorable outcome than tumors that have four sets of chromosomes (tetraploid tumors) or have an abnormal number of individual chromosomes (aneuploid tumors).

Blood Vessel Density. The density of blood vessels in the tumor is an important indicator of outcome. The greater the density, the more likely the tumor is to be aggressive.

Serum Acid Phosphatase. High levels of this enzyme indicate a more aggressive disease and the need for intensive treatments.

Testosterone Levels. Higher total testosterone levels may increase the risk for metastasis. A 2000 study found an association with low free testosterone and more extensive prostate cancer, suggesting free testosterone could be a marker for aggressive disease. (Free testosterone, as with free PSA, is not chemically bound.)

Genetic Markers. Researchers have identified a genetic marker (EZH2), which may prove to be an important marker for aggressive prostate cancer. It may, in fact, prove to be a better predictor of outcome than the tumor grade, stage, or surgical margins. Other genes being studied are those that regulate tumor growth (p53, p27, bcl-2).

Other Markers. Other markers being investigated for predicting cancer progression include prostate-specific membrane antigen, prostatic acid phosphatase, and growth factors.

The ProstaScint is a scanning technique that uses tiny amounts of radioactive material with a monoclonal antibody that can attach specifically to prostate cancer cells. A special camera then can detect tumor cells that cannot be detected with other diagnostic tools. It may help doctors make better treatment decisions. The role of this test in the routine management of prostate cancer is still being defined.

If the biopsy indicates cancer, the doctor will order other tests to determine whether or how far the cancer has spread.

Bone Scans and X-Rays. Bone scans and x-rays may reveal whether the cancer has invaded the bones. To perform a bone scan, doctors inject low doses of a radioactive substance into the patient's vein, which accumulates in bones that have been damaged by cancer. A scanner then reveals how much of the radioactive material has accumulated. Arthritis and infections may also produce positive scans. Patients with PSA levels below 20 ng/mL are unlikely to have scans that show cancer in the bone.

A radiotracer is injected into a peripheral vein. As the radiotracer decays, gamma radiation is emitted and is detected by a Gamma camera. When the tracer has collected in the target organ the area is scanned. Radionuclide scans can detect abnormalities such as fractures, bone infections, arthritis, rickets, and tumors that have spread, among other diseases.

Computed Tomography and Magnetic Resonance Imaging. Computed tomography (CT) or magnetic resonance imaging (MRI) scans can further pinpoint the location of cancer that has spread beyond the prostate. Advanced MRI techniques are showing promise for staging and planning treatments.

Click the icon to see an image of a CT scan.

Click the icon to see an image of a MRI.

Bone Metastasis Markers. Researchers are investigating chemical markers, such as amino-terminal propeptide of type I procollagen (PINP), as early indicators of bone metastasis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also called active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

The choice between watchful waiting and treatment usually depends on a number of factors, such as urine flow rates, prostate size, and PSA levels. Men with BPH who develop symptoms at around age 50 are more likely to need treatment within their lifetimes than older men. Unfortunately, there is no current way to determine who specifically might be at risk for serious problems and need early treatment.

The development of the International Prostate Symptoms Score (IPSS) has made the evaluation of symptoms somewhat easier. This scoring service serves as a benchmark for determining severity. The decision to treat or not to treat is typically based on the guidelines described below, but the ultimate choice is often guided primarily by a man's perception of his own symptoms.

Mild, or No, Symptoms. Men with mild, or no, symptoms (IPSS scores of 7 or below) usually choose watchful waiting even if their prostates are enlarged. BPH eventually progresses to the point of needing treatment in about 15% of men with mild symptoms who wait.

Moderate Symptoms. The choice is most difficult for men with moderate symptoms (scores between 8 - 19) and may simply depend on a man's ability to tolerate them. Some studies have reported that up to 40% of men with moderate symptoms eventually seek treatment, and a quarter require surgery. In a small percentage of patients, symptoms improve.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-to-Severe Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms, eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery is also typically a reasonable option when BPH is clearly related to one or more of the following conditions:

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

The greatest improvements resulting from surgery are usually increased urinary flow and reduced urine retention. In one study, men who chose surgery reported more worry and depression before the procedure, but afterward they had less depression and anxiety than those who had chosen medication. Often, however, the benefits of surgery are not permanent.

Treatment Options by Staging and Grading

Stages indicate the extent of the cancer:

Stage I and stage II cancer are considered early stage. The cancer is localized and has not spread outside the prostate gland.
Stage III, locally advanced cancer, means that the cancer has spread into the seminal vesicles (glands at the base of the bladder, which are connected to the prostate gland and help produce semen).
Stage IV is advanced cancer. The cancer has spread to the lymph nodes and other tissues or organs.

Experts have devised treatments based on classification systems, including staging and tumor grade. However, there are no clear-cut answers on the best treatments for particular stages. In addition to staging, other factors must be considered. These factors include the patient’s age, overall health status, and personal preferences concerning side effects and quality of life. In addition to standard treatments, patients may also wish to consider enrolling in clinical trials of investigational treatments.

The U.S. National Cancer Institute recommends the following treatment options by cancer stage:

Tumors: T1a, N0, M0, G1, Stage A

Active surveillance
Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy after surgery
External beam radiation therapy
Implant radiation therapy (brachytherapy)
Clinical trial options include high-intensity focused ultrasound

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

Tumors: T1a - c, N0, M0, any G, Stage A2, B1, or B2

Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy after surgery
Active surveillance
External beam radiation therapy with or without hormone therapy
Implant radiation therapy (brachytherapy)
Clinical trial options include radiation therapy with or without hormone therapy; ultrasound-guided cryosurgery; hormone therapy followed by radical prostatectomy

Tumors: T3, N0, M0, any G, Stage C

External beam radiation with or without androgen deprivation therapy (hormone therapy)
Androgen deprivation therapy
Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy following surgery
Radiation therapy, androgen deprivation therapy or transurethral resection of the prostate (TURP) to relieve symptoms
Clinical trial options include ultrasound-guided cryosurgery

Click the icon to see an illustrated series detailing transurethral resection of the prostate.

Tumors: Any T, any N, any M, any G, Stage D1 - D2

Androgen deprivation therapy
External beam radiation therapy with or without androgen deprivation therapy
Radiation therapy or transurethral resection of the prostate (TURP) to relieve symptoms
Active surveillance
Clinical trial options include radical prostatectomy with surgery to remove both testicles (orchiectomy)

Treatment options are dependent on various factors, including prior treatment, site of recurrence, coexistent illnesses, and individual patient considerations.

Patients whose cancer recurs locally after prostatectomy: Radiation therapy, androgen deprivation therapy.
Patients whose cancer recurs locally after radiation therapy: Androgen deprivation therapy, prostatectomy (very select patients).
Patients whose recurrent cancer has spread: See treatment options for stage IV.

Treatment for Localized Prostate Cancer

Choosing the best treatment for localized prostate cancer (T1 or T2) is generally based on the patient's age, the stage and grade of the cancer, overall health status, and the patient's personal preferences for the risks and benefits of each therapy.

Patients have three main options:

Active surveillance, also called watchful waiting, involves monitoring the tumor for cancer progression to determine if and when treatment should be started.
Surgery (radical prostatectomy) removes the prostate gland. The vessels that carry semen and surrounding tissue may also be removed. Studies indicate that compared to watchful waiting, radical prostatectomy may lower the risk of cancer recurrence and death, particularly for younger men with aggressive tumors.
Radiation therapy targets the tumor either externally (external beam radiation) or internally (implanted “seeds”).

In 2007, the American Urological Association (AUA) released guidelines for the treatment of localized prostate cancer. The guidelines recommend that patients should be classified as low, intermediate, or high risk. Doctors determine the risk category by using criteria such as PSA tests, tumor aggressiveness, and the clinical stage of the tumor.

Among the AUA’s treatment recommendations:

Compared with active surveillance, radical prostatectomy may lower the risk of cancer recurrence and death.
For men at intermediate and high risk, adding androgen deprivation therapy to external beam radiation may improve survival. A higher dose of external beam radiation also improves the odds for survival.
Initial (first-line) androgen deprivation therapy is seldom recommended for localized prostate cancer except for the relief of symptoms in patients with poor prognoses. Androgen deprivation therapy can increase the risks for diabetes and heart disease.
Patients with localized prostate cancer should have the opportunity to enroll in clinical trials investigating new types of therapy.

Conflicting Data on Survival Rates. To date, neither treatment nor active surveillance has emerged with a definitive survival advantage. Several studies from 2005 and 2006 suggested that treatment provides a survival advantage over watchful waiting for some men with early-stage prostate cancer. A 2005 New England Journal of Medicine study reported that men who had a radical prostatectomy before age 65 had a reduced risk of death from prostate cancer, death from other causes, localized cancer progression, and metastases than men who chose watchful waiting.

Similarly, research presented at the 2006 Prostate Cancer Symposium found in a study of nearly 50,000 men with early-stage prostate cancer that men who had radiation or surgical treatment had a 30% lower risk of death than men who were randomly assigned to watchful waiting. However, a 2005 Journal of the American Medical Association study advised against aggressive treatment for localized low-grade prostate cancer. The study found that men with low-grade prostate cancer had a small risk of cancer progression even after 20 years of watchful waiting or hormonal drug therapy

Imperfection of Classification System. The classification systems are not perfect. Even if tumors are rated in low stages and grades and are treated accordingly, undetected cancer cells may escape and spread beyond the prostate. Other factors, such as the man's age and medical condition, must be included in determining whether aggressive treatments or conservative measures are appropriate.

Specialty Bias. Patients should be aware that doctors may be biased to prefer a specific treatment depending on their specialty. For example, in one study the following treatments were favored for patients who were generally appropriate candidates for either surgery, radiation, or watchful waiting:

93% of urologists recommended radical prostatectomy.
72% of radiation oncologists recommended radiation. (And 82% thought that radical prostatectomy was overused.)
Virtually none of the doctors recommended watchful waiting for higher-risk disease. When in doubt, patients should always seek a second opinion to help them make this important choice.

Quality of Life. Surgery and radiation both have potentially distressing side effects, including the possibility of impotence, incontinence, or both. A man must weigh his own emotional responses to the possibility of these side effects versus the possible stress of watchful waiting.

In general, differences in quality of life after surgery or radiation treatment have to do with the specific effects of each type of treatment:

Radiotherapy generally causes more bowel problems than surgery, 30 - 35% versus 6 - 7%, according to a 2001 study. In a 2003 review, the risk for impotence from radiotherapy varied from 25% with brachytherapy to 45% with external beam radiotherapy.
Prostatectomy causes more urinary incontinence (39 - 49% versus 6 - 7% for radiotherapy patients) than radiotherapy. Risks for impotence range from 66% after nerve-sparing prostatectomy to 87% after cryotherapy. In spite of these adverse effects, a 2002 study reported no meaningful differences in well-being or quality of life during a 4-year period for men who chose surgery versus those who chose watchful waiting.
Active surveillance could lead to cancer growth that eventually obstructs the urinary tract (which can happen with the treatments as well). It may also impose an emotional burden on men who live with the possibility of progressive cancer and its difficult treatments. Some who decide to wait become what some doctors refer to as the "walking worried," men who are constantly concerned with their PSA levels. Because aggressive treatment reduces such anxiety, some studies reported that years after surgery, about 75% of men said they would chose it again, in spite of the significant side effects.

Watchful waiting involves lifestyle change and careful monitoring for cancer progression. Over the last several years, watchful waiting has evolved into a strategy called “active surveillance” or “delayed surgical intervention.” With this approach, patients have a digital rectal exam and PSA blood test every 6 - 12 months. If test results indicate cancer progression, then treatment options (surgery, radiation, drugs) are considered. Patients should exercise and eat healthy foods. Patients should report symptoms such as weight loss, pain, urinary problems, fatigue, or impotence to their doctors.

Candidates. Active surveillance may be most appropriate for the following patients:

Men in their late 70s and older. More aggressive therapies (surgery and radiation) are usually recommended for men in their 50s and younger. The choice for men in their 60s and early 70s is more problematic. The general recommendation is that aggressive therapy is suitable for those who have a life expectancy of more than 10 years and who have localized but mid- to high-grade tumors. The tumor grade may be the best guide for determining the risks in choosing watchful waiting.
Elderly men with early-stage (T0 - T2) low-grade tumors.
Men with low-to-moderate (3 - 13 ng/mL) PSA levels.

Some experts think that because prostate cancer grows so slowly, it is likely that older men will die from causes unrelated to the cancer. There is therefore little potential benefit from surgery or radiation, with both posing a risk for impotence and incontinence. However, some recent surveys suggest that more men are choosing treatment (especially surgery) over active surveillance. The choice is a difficult one. It is important that patients find a doctor who can provide them with all the necessary information so that they can make an informed decision.

In men whose cancer is confined to the prostate, surgical resection (radical prostatectomy) offers the potential for cure. Cure rates from initial surgery in men with localized cancer are about 70%, depending on tumor stage, tumor grade, and PSA levels. Research suggests that surgery provides long-term cancer control. Most patients can consider themselves disease-free if their PSA levels remain undetectable 10 years after surgery.

Candidates. Radical prostatectomy is a consideration for men who meet all of the following criteria:

In good health and with a life expectancy of 10 years or more. As average life expectancy in men has increased, more older men are becoming candidates for surgery. Complication rates are higher the older a man is, however.
The cancer has not spread beyond the prostate gland.
The cancer is potentially life threatening. (In general, a life-threatening tumor is indicated by volumes more than 0.2 cc and Gleason grade scores greater than 5.)

The procedure is more likely to cause incontinence (up to 50%) than radiation treatment but has fewer bowel complications. Impotence rates are about the same. Surgery for prostate cancer may be particularly difficult in men who have had transurethral resection of the prostate (TURP).

Radiation therapy (or radiotherapy) is administered as external beam radiation or as brachytherapy (radiation implants). It may be used as the sole primary treatment for localized prostate cancer; 5-year survival rates are similar to those of surgery.

Candidates. Radiation is considered for men with one or more of the following characteristics:

Being older and, particularly, having other medical problems.
Cancer has extended beyond the prostate capsule but has not spread to the lymph nodes or further.
Being a good surgical candidate, but having decided against an operation.

The risk for incontinence (less than 10%) is much lower than with surgery, although bowel problems occur in about a third of patients. Impotence rates are about the same.

Androgen Deprivation Therapy With Radiation. Hormonal (“androgen deprivation”) drugs combined with radiation therapy may improve survival rates in moderate- or high-risk groups. Patients may need to take these drugs long-term to improve outcomes. Hormonal drugs before radiation (neoadjuvant therapy) may be helpful in shrinking enlarged glands so that brachytherapy (radiation implants) can be used. Hormone therapy can also be given at the same time or following radiation.

An important study published in 2004 in the Journal of the American Medical Association (JAMA) found that for men with localized prostate cancer, a 6-month course of androgen deprivation therapy combined with radiation treatments produced greater survival rates than radiation treatment alone. Standard medical practice has generally indicated that hormone therapy should be given for 3 years; the JAMA study suggests that a shorter regimen may be equally beneficial for some patients and may help reduce the side effects that typically accompany androgen-suppressing drugs.

A 2005 JAMA study suggested that PSA velocity (PSAV) may help doctors decide which patients should receive androgen deprivation drugs along with radiation therapy. PSAV lets doctors calculate how quickly a patient’s PSA level has risen. Researchers found that men who had at least a 2.0 ng/mL increase in PSA levels during the year before their cancer diagnosis had a high risk of dying after external beam radiation therapy, even though they had low-grade prostate cancer. The study suggests that men with this particular PSAV history should consider combining radiation therapy with androgen deprivation drugs.

Surgery

Radical prostatectomy is the surgical removal of the entire prostate gland along with the seminal vesicles (the vessels that carry semen) and surrounding tissue. The incision can be made in one of the following regions:

Retropubicly (through the abdomen and under the pubic bone, exposing the entire surface of the prostate).
Through the perineum (the skin between the scrotum and the anus).

The gland and other structures are then removed. The operation lasts 2 - 4 hours. Advanced surgical techniques, such as minilaparotomy and laparoscopy, are being developed for radical prostatectomy. These techniques use smaller incisions, are less invasive, and may cause fewer complications.

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

Nerve-Sparing Techniques. Surgical procedures have been refined over the years, and many operations for localized low-grade prostate cancer now spare the nerves that control erection.

A bilateral nerve-sparing procedure saves the nerves on both sides of the sex organs.
A unilateral procedure saves nerves on only one side.

Nerve-sparing techniques can improve quality of life. The ability for sexual intercourse recovers in about a third of patients at 3 years and nearly 60% at 5 years after surgery. (Rates vary depending on certain factors, such as the patient's age -- the younger the better.) In cases where the tumor is bulky and undifferentiated, nerve-sparing techniques may not be appropriate.

Convalescence. Patients remain hospitalized for up to 2 weeks. A temporary catheter used to pass urine is kept in place when the patient is sent home and usually removed about 3 weeks after the operation. The convalescent period at home is about a month. In general, younger patients with early-stage cancers recover fastest and experience the fewest side effects.

Complication rates vary after radical prostatectomy and usually depend on the age of the patient and the experience of the surgeon and medical center. They can range from 4% in men in their 40s to 14% in men over age 70. Complication rates are 10 times higher in patients who have prostatectomy because of cancer recurrence after radiation treatment.

Complications include the usual risks of any surgery, such as blood clots, heart problems, infection, and bleeding. Complications specific to radical prostatectomy, (incontinence, impotence, and contracture of the bladder neck), are discussed below. The mortality rate is very low, about 0.4%.

Quality of life usually improves shortly after surgery, and recovery from certain complications, such as incontinence and sexual function, can continue to occur even over years.

Urinary Incontinence. Urinary incontinence is a common complication and a more distressing side effect of surgery for most men than sexual dysfunction. When the urinary catheter is first removed following surgery, nearly all patients lack control of urinary function and will leak urine for at least a few days and sometimes for months. Major medical centers report that continence returns within about 18 months for nearly all men younger than age 70 and in the great majority of men older than 70. The average time for return of continence in one center was just 1.5 months.

Click the icon to see an image of catheterization.

A number of approaches may help prevent or treat incontinence:

Nerve-sparing techniques can help prevent incontinence, although even in experienced centers, 8% of patients will have some postoperative incontinence, and this rate is much higher (up to 50%) in many community medical centers.
A procedure called endopelvic anterior urethral stitch (EAUS) used with prostatectomy appears to reduce urinary incontinence. In one small study, 75% of selected patients recovered continence in a month. The procedure requires a simple stitch at the front of the urethra.
Kegel exercises, contracting and relaxing the muscles used to shut off the urinary stream, strengthen the muscles on the pelvic floor and are reported to be very beneficial for many men.

If incontinence persists beyond a year, patients may require drug therapy or surgery. Collagen injections into the urethra, bladder neck suspension surgery, or a urinary sphincter implant may be helpful for men who have chronic incontinence. [See In-Depth Report #50: Urinary incontinence.]

Impotence. Studies suggest that about 40% of men have problems with erection after the procedure. In one study, however, more than 70% said they would have the procedure again. Nerve-sparing procedures are proving to be helpful in reducing impotence as well as incontinence.

Sildenafil (Viagra) may help restore potency on average in about a third of patients, but some men may do better than others. In one study, for example, 80% of younger men who were potent before surgery and had bilateral nerve sparing procedures responded to the drug. (Only 40% responded with only unilateral procedure.) Sildenafil is unlikely to be effective for men who had unilateral or no nerve sparing procedures. In those who respond, sildenafil may provide a benefit for years. Sildenafil may take 9 months or longer to become effective. Men who take it may benefit from alprostadil injections started right after surgery to preserve elasticity and help prevent scarring.

Early treatments with alprostadil injections may helpful in restoring erectile function in any case. This treatment maintains blood flow in the penis, and some research suggests that impotence after prostate surgery may be due in part to injury to these blood vessels. In one study, men administered injections every other night for 6 months. They then started taking sildenafil 3 months after surgery. At 6 months, 82% of these men achieved penetration compared to only 52% of men who took Viagra only. The vacuum pump may serve a similar purpose as the injections. [See In-Depth Report #15: Erectile dysfunction.]

Even when erectile function is preserved, men may experience other sexual problems:

Erections may not be as rigid as before the operation.
Orgasm and sexual sensation may be altered.
Patients who retain potency may suffer from retrograde ejaculation, also known as dry ejaculation. During ejaculation, semen travels backward into the bladder, causing infertility.

Fecal Incontinence. Radical prostatectomy can also cause fecal incontinence. The risk may actually be higher in men undergoing nerve-sparing procedures.

Contracture of the Bladder Neck. Another common postsurgical complication is contracture of the bladder neck at the point where it has been stitched to the remainder of the urethra. Contracture usually occurs within the first 3 months after the operation, causing a sharp decrease in urinary stream. The condition can be treated by dilation or surgery on the bladder neck, and rarely recurs.

Pelvic lymphadenectomy is the surgical removal of the pelvic lymph nodes. It is usually performed at the same time as prostatectomy. If the surgeon suspects that cancer has spread beyond the prostate, the surgeon will perform the lymphadenectomy as part of the operation. Some surgeons do this procedure as a matter of course when performing prostatectomy, since it has few complications and adds information on the state of the disease. The lymph nodes are removed through an incision in the lower part of the abdomen, using conventional surgery or laparoscopy, a less invasive variation. The nodes are immediately examined. If they show signs of cancer, metastasis has occurred. In such cases, the operation is usually stopped and the patient is offered radiation or hormone treatments.

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

Transurethral resection of the prostate (TURP) involves removing a section of the prostate with a surgical instrument (resectoscope) that is inserted through the urethra. TURP may be used to control urinary symptoms in men who are not good candidates for curative therapy due to advanced age, health status, or other reasons. TURP is also used as a treatment for benign prostatic hyperplasia (BPH).

Cryosurgery is an alternative to standard prostatectomy. The goal of cryosurgery is destruction of the entire prostate gland and possibly surrounding tissue. Steel probes are inserted through the skin between the anus and the rectum and into the prostate. Liquid nitrogen is pumped through the probes to freeze all prostate cells, both healthy and cancerous. For success, cryosurgery requires a uniformly frozen area. The dead cells are absorbed and eliminated by the body. Patients can leave the hospital in 2 - 3 days.

Candidates. Cryosurgery may be considered for patients with:

Early stage local cancer
Cancer that has recurred after radiation treatments
Large primary tumors that the surgeon wishes to reduce
Possibly tumors that have spread beyond the prostate if they have not yet reached the lymph nodes

Strong predictors of treatment failure include:

A history of both hormonal and radiation treatments
Tumor grades 8 and above
PSA levels of more than 10 ng/mL

Complications. Complications are similar to those of standard prostatectomy, but incontinence rates are much lower. Impotence rates, however, are much higher. Nevertheless, 96% of patients report that they are satisfied with the results. Incontinence and other side effects may be higher in patients who have had previous radiation treatments. Other significant complications include scarring and narrowing of the urethra, and fistulas (abnormal passages from internal organs to the skin or between two internal organs).

Radiation Treatments

The two major radiation treatments are:

External beam radiation
Brachytherapy (internal radiation)

Both treatments have generally equal success rates. Research presented at the 2006 Prostate Cancer Symposium indicated that the two therapies work equally well for treating localized prostate cancer. In some cases, both techniques may be used in high-risk patients.

In external beam radiation therapy, a doctor focuses a beam of radiation directly on the tumor for 35 3-minute treatments given 5 times a week over 7 weeks. 3-D conformal techniques use computers and a three-dimensional image of the prostate to target the tumor precisely, using high-dose radiation beams. It poses a lower risk for inflammation. Men who have had transurethral resection of the prostate (TURP) or have a history of lower urinary tract symptoms may be particularly good candidates for 3D conformal techniques.

According to the 2007 American Urological Association guidelines for treatment of localized prostate cancer, patients considering external beam radiation should know that higher radiation doses may reduce the risk for cancer recurrence and improve survival outcome.

Brachytherapy is an outpatient technique that implants radioactive "seeds" directly into the prostate. Implants can be temporary or permanent. Temporary implants are usually accompanied by external beam radiation. This procedure requires more skill than external beam radiation therapy and, even with experienced doctors, the distribution of radioactive seeds is uneven in 15% of cases, increasing the risk for insufficient doses.

Computerized systems are being developed to help oncologists optimize seed placement and allow precise treatment for each patient and higher radiation doses. Eventually, it could improve tumor control, reduce side effects, and cut costs.

It is common for PSA levels to temporarily rise, or "bounce," following seed implantation without it being a signal for cancer recurrence. This effect can produce anxiety and can interfere with the diagnosis of true recurrence.

Candidates. Studies suggest that brachytherapy is useful for select patients, specifically those with prostate volumes less than 60 mL and who have early-stage prostate cancer (T1 or T2 tumors, a Gleason grade lower than 7, and PSA levels below 10 ng/mL). It may be beneficial in patients with inflammatory bowel disease or with cancer close to the bowel. Poorer candidates for brachytherapy include men who have had TURP and patients with advanced cancer, high-grade tumors, or very enlarged prostate glands.

The side effects of radiation therapy include most of those of surgery, but the risks for impotence and incontinence are considerably lower. A 2000 study concluded that adjuvant radiation therapy (given right after surgery) in moderate doses does not increase the risk for long-term urinary incontinence or sexual dysfunction beyond that of surgery alone.

Gastrointestinal Complications. Complications in the gastrointestinal are common. Short-term effects include nausea and loss of appetite. Diarrhea is a very common side effect and can last for the duration of therapy. It is usually treated with Lomotil. A few patients have diarrhea flare-ups for years afterwards. Less than 1% suffer more serious intestinal problems.

There is potential for injury to the rectum with brachytherapy. Ulcers in the rectum occur in more than 10% of patients, but the risk decreases with greater experience in the technique.

Urinary Problems. The risk for incontinence is about 7 - 20%. Patients treated with radiation may experience a painful, but usually temporary, urinary tract inflammation. About 10 - 15% of patients develop a long-term urgent and frequent need to void their bladder. Brachytherapy carries a lower risk for urinary incontinence.

Scarring and narrowing of the urinary tract (stricture) may occur, particularly in men who had TURP performed within a short time before radiation treatment. In such men, radiation treatments should be delayed by 4 - 6 weeks. If the prostate has been injured or damaged or the bladder is easily irritated, side effects with brachytherapy may actually be worse than with other procedures.

Impotence. In a 2003 review, the risk for impotence following radiotherapy varied from 25% with brachytherapy to 45% with external beam radiotherapy. Still, very few studies on brachytherapy have lasted more than 2 years, so more research is needed.

Sildenafil (Viagra) may help many men experiencing impotence following radiation therapy for local prostate cancer. Early use of both alprostadil injections and sildenafil may be even more effective. Other treatments may also be useful. [See In-Depth Report #15: Erectile dysfunction.]

Investigators are testing radiation treatments that use a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard proton radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions.

High-Intensity Focused Ultrasound (HIFU). Studies are reporting promising results with an intensive ultrasound procedure called transrectal high-intensity focused ultrasound (HIFU). It allows for very precise minimally invasive removal of tissue in local prostate cancers. It may eventually prove to be an alternative to radiation therapy. More research, with long-term follow up, is needed.

Radiofrequency. Radiofrequency is being used to heat and destroy the prostate. Early studies suggest that this is a promising approach.

Options if Treatments Fail

Rising PSA Levels. If prostate cancer has been eliminated, PSA levels should drop to 0.5 ng/mL or less after treatment. A sudden rise or persistently elevated PSA levels after treatment are often indications that prostate cancer persists:

If PSA levels are above 2.0 ng/mL, then cancer is most likely still present.
If PSA levels are between 0.5 - 2.0 ng/mL, the situation is less clear. One study indicated that measuring free PSA may help determine the status of the cancer in such patients. An average free PSA of 27% indicated that cancer had been eliminated, while an average of 15% meant that cancer was still present.

Note: It is common for PSA levels to temporarily rise following radiation seed implantation without signaling cancer recurrence.

Rising PSA levels do not necessarily mean that the cancer has spread or even that the cancer will recur during a man's lifetime. An actual cure is still possible if the cancer is localized within the prostate. In one study, 64% of patients with rising PSA levels after surgery still had cancer confined to the prostate. Indications of a poorer outlook in this study included:

Cancer penetration of the prostate capsule
Positive surgical margins (microscopic evidence of cancer cells at the very edge of the resected specimen)
Invasion of nearby vessels or lymph nodes

Still, among the men in the study, after 7 years only 3% of patients had died of prostate cancer. After 15 years, only 19% had evidence of recurrence. Other markers for persistent cancer are under investigation. For example blood tests that show low levels of acid phosphatase (ACP) before treatments may predict a higher chance for recurrence-free survival.

Treatment for recurring cancer is not always clear-cut. If the cancer recurs locally, cure may still be possible:

Surgery and androgen deprivation therapy may be considered for patients who were first treated with radiation.
For patients who were initially treated with surgery, radiation or androgen deprivation therapy are both options.

If the disease has already spread or if the doctor suspects that it may have spread, the patient is typically given androgen deprivation therapy. Chemotherapy drugs in combination with hormonal drugs are being investigated for patients who fail surgery or radiation.

A 2005 study in the Journal of the American Medical Association suggested three factors that may help doctors and patients decide if additional treatment is needed if cancer recurs after surgery:

How quickly PSA levels double after surgery (shorter time equals higher risk)
How quickly the cancer recurred after surgery (shorter time equals higher risk)
Gleason score (higher score suggests more aggressive tumors and greater risk)

Patients at high risk are more likely to die from the recurrent cancer and should be considered for additional treatments. Patients at low risk face a lower likelihood of death from prostate cancer and probably do not require more treatment. The study found that for patients at low risk, the time to death after cancer recurrence was very long, generally lasting more than 16 years.

Androgen Deprivation Therapy. Androgen deprivation therapy, also called androgen suppression therapy or hormone therapy, involves blocking the effect of male hormones such as testosterone through medical (drugs) or surgical castration. Androgen suppression therapy is not recommended as a first-line approach for most men with localized prostate cancer. It is usually given to patients with recurrent, progressive, or advanced prostate cancer. It may also be given for a relatively brief time in combination with external beam radiation.

Although androgen deprivation therapy slows the growth of most prostate cancers, it can have serious side effects. The American Society of Oncology’s (ASCO) 2007 guidelines do not recommend the early use of hormone therapy. However, ASCO does recommend that patients start therapy once they begin to experience cancer symptoms. Patients who defer therapy should have regular doctor visits every 3 - 6 months to monitor their condition.

Salvage Prostatectomy. Salvage prostatectomy is sometimes performed after unsuccessful radiation treatment if the cancer is still local. The odds of the procedure's success are only 10 - 64%. Many experts recommend against salvage prostatectomy in most cases of radiation failure. Severe complication rates for salvage prostatectomy are very high: 10 times that of men who have not had radiation. For example, incontinence after salvage prostatectomy is often untreatable with medications, collagen implants, or other standard treatment measures.

Salvage Cryosurgery. Salvage cryosurgery may be effective in certain patients who fail external beam radiotherapy. The best candidates are those with Stage II cancer or less and PSA levels below 10 ng/mL.

Adjuvant and Salvage Radiation. Radiation is proving to help patients who still show detectable levels of PSA after surgery (generally 2 ng/mL or less). It may even be useful years after surgery if PSA levels rise. Depending on timing, radiation after treatment failure is referred to as either:

Adjuvant radiation is radiation therapy performed within 6 months after radical prostatectomy. One area of controversy is whether to use adjuvant radiation after surgery on patients whose PSA levels are very low or undetectable but who have other test results that indicate the cancer is likely to spread. Patients with adverse findings and low PSA have to weigh the potential complications of radiation therapy against the odds of recurrence without it, which are about 20 - 30%. A small 2006 study found that adjuvant radiation worked much better than salvage radiation for men with advanced (stage III or IV) local prostate cancer. However, a 2007 study indicated that adjuvant radiation in men with advanced cancer may reduce the risk of cancer recurrence but does not improve length of survival.
Salvage radiation is radiation therapy more than 6 months after surgery. A 2004 study suggested that salvage radiation could be more beneficial than previously thought, even for men with aggressive prostate cancer. Researchers studied 501 men who had undergone radical prostatectomy (surgical removal of the prostate gland) and subsequently received radiation treatment for recurrent cancer (as indicated by rising PSA levels). Men with lower Gleason scores and lower PSA levels benefited the most from salvage radiation. However, even men with higher-grade cancers were able to delay metastatic cancer progression as long as they received radiation at an early stage while their PSA levels were relatively low (less than 2.0 ng/mL).

Other Treatments

Male hormones (called androgens), particularly testosterone and dihydrotestosterone, determine male secondary sex characteristics and stimulate prostate cell growth. When prostate cells, both healthy and cancerous, are deprived of androgens, they no longer proliferate and eventually die.

Androgen deprivation therapy (also called androgen suppression therapy or hormone therapy) uses drugs or surgery (orchiectomy) to suppress or block male hormones (androgen) -- particularly testosterone and dihydrotestosterone -- that stimulate the growth of prostate cells. Androgen deprivation therapy is used for advanced and metastatic cancer and may be used if treatment for localized prostate cancer has failed and cancer recurs (as indicated by rising PSA levels). Side effects can include decreased bone density, decreased muscle mass, hot flashes, depression, fatigue, weight gain, enlarged breasts, and high cholesterol levels. Evidence also indicates that androgen deprivation therapy increases the risk for diabetes and death from heart disease.

There has been some debate about when androgen deprivation therapy should be initiated. In 2007, the American Society of Clinical Oncology (ASCO) published clinical guidelines for androgen deprivation therapy in patients with recurrent, progressive, or advanced prostate cancer. The guidelines recommend that hormone therapy should, in general, be delayed until patients begin to experience symptoms from their cancer. However, when therapy is deferred, patients should regularly visit their doctors every 3 - 6 months for careful monitoring of their condition.

ASCO recommends either removal of both testicles (bilateral orchiectomy) or injections with luteinizing hormone-releasing hormone (LHRH) as initial androgen deprivation treatments. Combining nonsteroidal antiandrogen drug therapy with orchiectomy or LHRH may also be considered.

Doctors vary widely on their opinions of androgen deprivation therapy. A 2006 study found that the decision to use hormonal therapy depends more on a patient’s urologist than on the patient’s tumor or other factors.

Androgen deprivation therapy includes:

Hormonal Drugs. The primary drugs used for suppressing androgens are called luteinizing hormone-releasing hormone (LH-RH) agonists.

Orchiectomy. Orchiectomy is the surgical removal of the testicles. It is the single most effective method of reducing androgen hormones, but it is considered an extreme procedure. Studies do not indicate that it significantly improves survival rates. Orchiectomy plus radical prostatectomy may delay progression in patients with cancers that have spread only to the pelvic lymph nodes. Combining orchiectomy with antiandrogen drug therapy adds a modest benefit.

The median survival rate after the operation is about 55% over a 40-month period. An estimated 25% of patients survive 5 years or more. Nevertheless, orchiectomy, although irreversible, may produce fewer adverse effects than hormonal drugs, and interestingly, many patients report significantly higher quality of life after orchiectomy than those who opt for hormonal treatment, particularly total androgen ablation. Because orchiectomy is irreversible, about 75% of patients with advanced prostate cancer choose hormonal therapy to block androgens. Like all androgen deprivation therapies, orchiectomy increases the risk for osteoporosis.

Many men can still achieve erection after orchiectomy, but there is almost always a decline in sexual drive. Men who cannot achieve erection may be candidates for a penile implant. Patients do not experience a reversal of sex characteristics; the voice does not change and body hair is not affected.

Androgen Deprivation Therapy Before or With Radiation. Hormonal drugs combined with radiation therapy may improve survival rates in moderate- or high-risk groups. Patients may need to take these drugs long-term to improve outcomes. Hormonal drugs before radiation (neoadjuvant therapy) may be helpful in shrinking enlarged glands so that brachytherapy (radiation implants) can be used.

An important study published in 2004 in the Journal of the American Medical Association found that for men with localized prostate cancer, a 6-month course of hormone therapy combined with radiation treatments produced greater survival rates than radiation treatment alone. Standard medical practice has generally indicated that hormone therapy should be administered for 3 years; the JAMA study suggests that a shorter regimen may be equally beneficial for some patients and may help reduce the side effects that typically accompany androgen-suppressing drugs.

Androgen Deprivation Therapy Before or After Surgery. Some studies suggest benefits from using hormone therapy before surgery (neoadjuvant therapy) to reduce the tumor size, although it is not clear yet if this approach has survival benefits. Hormonal treatment may be useful after surgery in men who have high-grade tumors or tumors that have invaded the semen-carrying vessels or lymph nodes. Such men have a risk for failure after surgery of 50 - 80%.

The primary drugs used for suppressing androgens are called luteinizing hormone-releasing hormones (LHRH) agonists. They include:

Leuprolide (Lupron, Leuprogel). Studies report that disease progression is prevented in 72% of men taking daily leuprolide and up to 89% of those taking monthly injections. Certain men, however, may not respond to injections. Drug delivery using implants is under investigation.
Goserelin (Zoladex). Partial responses of 60 - 80% have been reported. A controlled release formulation has been developed that increases the time between injections from 4 weeks to 3 months.
Buserelin.

LHRH drugs block the pituitary gland from producing hormones that stimulate testosterone production. Patients must have injections of LHRH agonists for the rest of their lives.

Testosterone and PSA Surges. Treatment with LHRH agonists produces a testosterone surge in the first week, which may actually intensify symptoms. After this phase, testosterone levels drop to near zero. Leuprogel, a newer leuprolide, may pose a lower risk for this effect. Researchers are investigating other drugs, such as GnRH antagonists, that do not produce this surge.

LH-RH agonists can also cause PSA levels to rise temporarily. Administering flutamide, a drug known as an antiandrogen, for 2 weeks prior to LH-RH agonists may not only prevent PSA surge but also induce early declines in PSA levels.

Side Effects. Side effects include hot flashes and occasionally nipple and breast tenderness.

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary gland to release luteinizing hormone-releasing hormones (LHRH). GnRH antagonist drugs such as abarelix (Plenais) and histrelin (Vanta) block this action. They have two advantages over LHRH agonists:

They do not cause the same testosterone surge that can temporarily worsen cancer symptoms.
They seem to reduce testosterone levels more quickly.

Anti-androgens are drugs used to block the effects of testosterone. They are used alone or in maximal androgen blockage (MAB), in which they are combined with LHRH agonists or orchiectomy to completely block androgen hormones. Anti-androgens are either steroidal or nonsteroidal.

Nonsteroidal Anti-androgens. Nonsteroidal anti-androgen drugs include:

Flutamide (Eulexin, Drogenil). Flutamide has produced extended response in some patients. Side effects may include diarrhea and liver damage, which has been fatal in rare cases; liver function must be monitored closely.
Nilutamide (Nilandron). Nilutamide is associated with reversible interstitial pneumonitis, nausea, alcohol intolerance, and visual disturbances.
Bicalutamide (Casodex). Bicalutamide is effective and appears to have fewer severe side effects than other anti-androgens, including loss of sexual interest, osteoporosis, visual disturbance, and interstitial pneumonia. This drug is proving to have survival rates equal to those of maximal androgen blockage.

Steroidal Antiandrogens. Steroidal antiandrogens act like female hormones and include:

Megestrol uppresses androgen production, but incompletely, and is generally not used as initial therapy.
Cyproterone combined with estrogen may prevent the testosterone surge that occurs with LH-RH agonists.

Men often experience fatigue, loss of energy, and emotional distress from androgen suppression treatment. Hormonal therapy may significantly impair quality of life, particularly in men who had no symptoms beforehand and whose cancer has not metastasized. Common side effects of androgen suppression drugs include:

Osteoporosis, the loss of bone density. This risk is higher with orchiectomy than with androgen suppressants. Some androgen suppressants, such as bicalutamide, may cause less bone loss. The use of estrogens may actually be bone protective. A number of medications, especially bisphosphonates, are available to help prevent or reduce bone loss.
Diarrhea
Loss of muscle mass
Psychological disturbances
Fatigue
Loss of sexual drive and sexual dysfunction
Swelling of the breasts (gynecomastia)
Nausea and vomiting
Hair loss
Anemia

In addition, there is growing evidence that androgen deprivation therapy increases the risks for diabetes and heart disease.

Prostate cancer that does not respond to hormonal treatment is called hormone-resistant, or hormone-refractory, cancer. There are various drug treatments for hormone-resistant cancer:

Docetaxel and Other Chemotherapy. Chemotherapy drugs for prostate cancer include docetaxel (Taxotere), mitoxantrone (Novantrone), estramustine (Emcyt), and various platinum-based drugs, such as carboplatin. These drugs are often combined with other cancer drugs (such as 5-fluorouacil) or corticosteroids (such as prednisone).

Docetaxel-based drug regimens are emerging as the main chemotherapy treatment for hormone-refractory prostate cancer. In 2004, the FDA approved docetaxel injection in combination with prednisone for treatment of patients with hormone-resistant prostate cancer. Patients who received this drug combination survived on average 2.5 months longer than patients who received mitoxantrone and prednisone. Another 2004 clinical trial found that a docetaxel and estramustine combination worked better than mitoxantrone and prednisone for advanced resistant prostate cancer. Side effects can be serious and may include gastrointestinal problems (nausea, vomiting, or diarrhea), fatigue, low blood cell counts, and increased risk for blood clots.

Researchers are continuing to investigate docetaxel combinations and compare them to other chemotherapy regimens. A large 2006 study reported that docetaxel and prednisone worked better than mitoxantrone plus prednisone in improving quality of life, pain relief, and survival. Docetaxel is also being investigated in combination with vitamin D-related drugs. A 2006 trial found that men with advanced prostate cancer who took docetaxel plus high-dose vitamin D (calcitriol) lived about 8 months longer than men who received docetaxel and placebo. Calcitriol also appeared to protect against docetaxel’s side effects, especially gastrointestinal problems and blood clots.

Doctors are also studying other ways to help patients cope with docetaxel’s side effects. Research presented at the 2006 Prostate Cancer Symposium suggested that patients may be able to take periodic breaks from docetaxel treatment instead of having continuous therapy. In the study, patients with advanced prostate cancer were given the option of suspending docetaxel treatment if their PSA levels improved within a certain range. Researchers found that patients were able to take 16-week breaks and still show improvement once they resumed treatment. This approach may work best for patients who experienced a good initial response to docetaxel.

Bisphosphonates. These drugs prevent bone loss and reduce bone pain in metastasized cancers. They are of particular interest because they may inhibit prostate cancer cell growth in the bone. The bisphosphonates showing most promise in prostate cancer are newer drugs called nitrogen-containing bisphosphonates (pamidronate, zoledronic acid).

Immunotherapies. The prostate organ offers special possibilities for genetic therapies because it contains highly specific antigens (factors that the immune system can target). There are a number of approaches currently under investigation, including:

Genetically designed vaccines (Provenge, Gvaz, JBT 1001) inject factors into prostate cancer cells that trick the immune system into attacking the cancer cells.
Antisense therapy for prostate cancer blocks expression of a protein called BCL-2, which tends to be genetically overexpressed in some patients with androgen-independent prostate cancer. This protein prevents apoptosis (a natural process by which all cells, including cancer cells, self-destruct).
Monoclonal antibodies (MAbs) are genetically designed immune factors that target foreign compounds called antigens for attack by the immune system. Monoclonal antibodies are being designed to target prostate-specific antigens.

Angiogenesis Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis ). The spread of new blood vessels is controlled by compounds called growth factors, which may be important in cancer cell proliferation. Researchers are interested in drugs that turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In doing so, the drugs may be able to cut off cancer's life blood. Gefitinib (Iressa) and erlotinib (Tarceva) are angiogenesis inhibitors that target receptors of epidermal growth factors called tyrosine kinase. They are being used in lung cancer and are being investigated in a number of other cancers, include prostate cancer. Various drugs that inhibit angiogenesis in other ways (thalidomide, endostatin) are also under investigation.

Ketoconazole. Ketoconazole is an antifungal drug that blocks an enzyme that stimulates production of testosterone. It is effective in high doses but can have severe gastrointestinal effects, mainly nausea and anorexia. Long-term use can result in impotence, itchy skin, nail changes, and suppression of stress hormones. One center reported a consistent PSA response in more than 60% of patients who had failed other androgen deprivation treatments.

Aromatase Blockers. Aminoglutethimide (Cytadren) and similar drugs block aromatase, an enzyme important in estrogen production. Because the female hormone estrogen plays such a major role in the development of breast cancer, some experts think that blocking the small amount of estrogen found in men may also affect prostate cancer. Side effects include drowsiness and skin rash.

Atrasentan. Atrasentan is known as an ET(A)-receptor antagonist. It is showing promise in reducing bone loss and delaying progression of prostate cancer in men with advanced disease that no longer responds to hormone therapy. Side effects are relatively mild.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.prostatecancerfoundation.org -- Prostate Cancer Foundation
www.fightprostatecancer.org -- National Prostate Cancer Coalition
www.urologyhealth.org -- Urology Health
www.nccn.org -- National Comprehensive Cancer Network
www.cdc.gov/cancer/prostate -- CDC Cancer Prevention and Control
www.psa-rising.com -- PSA Rising: Prostate Cancer Survivor Info
www.ustoo.org -- Us Too! Prostate Cancer Education and Support
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):416-24.

Gudmundsson J, Sulem P, Manolescu A, Amundadottir LT, Gudbjartsson D, Helgason A, et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet. 2007 May;39(5):631-7. Epub 2007 Apr 1.

Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, et al. Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet. 2007 May;39(5):638-44. Epub 2007 Apr 1.

Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006 Sep 20;24(27):4448-56.

Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst. 2007 May 16;99(10):754-64.

Leman ES, Cannon GW, Trock BJ, Sokoll LJ, Chan DW, Mangold L, et al. EPCA-2: a highly specific serum marker for prostate cancer. Urology. 2007 Apr;69(4):714-20.

Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007 Apr 20;25(12):1596-605. Epub 2007 Apr 2.

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, et al. Guideline for the management of clinically localized prostate cancer: 2007update. J Urol. 2007 Jun;177(6):2106-31.

Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA. 2006 Nov 15;296(19):2329-35.

Walter LC, Bertenthal D, Lindquist K, Konety BR. PSA screening among elderly men with limited life expectancies. JAMA. 2006 Nov 15;296(19):2336-42.

Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May;39(5):645-9. Epub 2007 Apr 1.

Review Date:
6/27/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Benign prostatic hyperplasia

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Symptoms
Causes of Benign Prostatic ...
Causes of Lower Urinary Tra...
Risk Factors
Complications
Diagnostic Tests
Treatment
Lifestyle Changes
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Self-Management for Benign Prostatic Hyperplasia (BPH)

Men who receive training in lifestyle and behavioral approaches may be able to successfully manage BPH without drugs or surgery, suggests a 2007 study in the British Medical Journal. Men in the study were trained to self-manage their lower urinary tract symptoms (LUTS), a condition that often accompanies BPH. Self-management approaches included limiting daily fluid intake, avoiding caffeine and alcohol, and urinating at least once every 3 hours.

Diet and BPH

Eating lots of fruits and vegetables, especially those high in beta-carotene and vitamin C, may help protect against BPH, suggests a 2007 study in the American Journal of Clinical Nutrition. Another study, published in Urology, indicated that high consumption of cereal, bread, eggs, and poultry may increase the risk of BPH.

High Intake of Zinc Increases BPH Risk

High doses of zinc supplements may increase the risk for urinary problems, especially for men, indicates a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc. In general, the upper limit for zinc supplements should not exceed 40 mg/day.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe LUTS, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Botox for BPH?

Botulinum toxin A (Botox) is being investigated as a treatment for BPH. In research presented at the 2007 meeting of the American Urological Association, men who had Botox injected into their prostate glands experienced symptom relief and improved quality of life for up to a year after treatment.

Introduction

Hyperplasia is a general medical term referring to excess cell replication. Benign prostatic hyperplasia (BPH), also called benign prostate hyperplasia, is a noncancerous growth of the prostate gland. It is the most common noncancerous form of cell growth in men and usually begins with microscopic nodules in younger men. BPH, however, is not a precancerous condition. Prostate cancer usually occurs in the outer area of the prostate, called the peripheral zone.

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid that mixes with sperm to make semen. The urethra carries urine from the bladder and sperm from the testes to the penis.

As BPH progresses, overgrowth occurs in the central area of the prostate, called the transition zone, which wraps around the urethra (the tube that carries urine through the penis). This pressure on the urethra can cause lower urinary symptoms that have been the basis for diagnosing BPH. In 2000, an expert committee suggested that the impact of such symptoms on quality of life, including sexual activity, is also important in assessment of the disease.

Click the icon to see an image of BPH.

Description of the Prostate Gland. The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Glandular cells, which produce a milky fluid that liquefies semen.
Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen. Molecules called alpha adrenergic receptors stimulate the muscle cells.
Stromal cells (which form the structure of the prostate).

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

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland. The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate also secretes another substance that may have antibacterial properties.
The prostate gland also contains an enzyme called 5 alpha-reductase that converts testosterone to dihydrotestosterone, another male hormone with a major impact on the prostate.

Changes During the Lifespan. The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly. It reaches normal adult size and shape, about that of a walnut, when a man is in his early 20s. The gland generally remains stable until about the mid-40s, when, in most men, the prostate begins to grow again through a process of cell multiplication.

Hormonal changes also occur in the prostate gland. Testosterone levels fall while dihydrotestosterone remain at normal levels.

Symptoms

The symptoms commonly associated with BPH are collectively called lower urinary tract symptoms (LUTS). BPH is not always the cause of these symptoms. An enlarged prostate may be accompanied by few symptoms, while severe LUTS may be present with normal or even small prostates and are most likely due to other conditions. Many experts are now categorizing LUTS as either voiding or storage symptoms to help define the source of the problem.

Voiding symptoms, also referred to as obstructive symptoms, can be caused by an obstruction in the urinary tract. They are often due to BPH. Obstruction is the most serious complication of BPH and requires medical attention. Voiding symptoms include:

Weak or intermittent urinary stream
Straining when urinating
A hesitation before urine flow starts
A sense that the bladder has not emptied completely
Dribbling at the end of urination or leakage afterward
Painful urination
Hematuria (blood in the urine)

Storage symptoms, also referred to as irritative symptoms, include:

An increased frequency of urination, particularly at night
An urgent need to urinate
Bladder pain or irritation when urinating

The process of urination is more complicated than it appears:

It begins when waste fluids flow out of the kidneys into two long tubes called ureters.
The ureters empty into the bladder, which rests on top of the pelvic floor, a muscular structure similar to a sling running between the pubic bone and the base of the spine.
The brain regulates muscles in the urinary tract through a pathway of nerves. As the bladder fills to its capacity of 8 - 16 oz of fluid, the nerves send signals from the bladder to the brain that indicate how full the bladder is.
As the bladder swells, the muscles contract to prevent urination.
At the time of urination, the spinal cord initiates the voiding reflex. The detrusor muscles (which surround the bladder) contract, while the internal sphincter (a strong muscle encircling the neck of the bladder) relaxes.
When the internal sphincter is open, urine flows out of the bladder into the urethra (the tube that carries urine from the bladder out through the penis).

Causes of Benign Prostatic Hyperplasia

The causes of benign prostatic hyperplasia are not fully known. Several theories have been proposed to explain benign cell growth in older men.

Male Hormones. Androgens (male hormones) most likely play a role in prostate growth. The most important androgen is testosterone, which is produced throughout a man's lifetime. The prostate converts testosterone to a more powerful androgen, dihydrotestosterone (DHT). DHT stimulates cell growth in the tissue that lines the prostate gland (the glandular epithelium) and is the major cause of the rapid prostate enlargement that occurs between puberty and young adulthood. DHT is a prime suspect in prostate enlargement in later adulthood.

Estrogen. Some authorities believe that the female hormone estrogen may also play a role in BPH. (Some estrogen is always present in men.) As men age, testosterone levels drop, and the proportion of estrogen increases, possibly triggering prostate growth.

Another theory focuses on cells in a certain section of the gland that may become active late in life, signaling other prostate cells to replicate or causing them to be sensitive to growth-stimulating hormones.

This theory suggests that a process known as apoptosis, in which cells naturally self-destruct, goes awry and results in cell proliferation.

Some experts theorize that the blood vessels in the prostate gland may deteriorate as men age, causing abnormal blood flow and oxygen loss, which would stimulate cell growth. Such a theory is supported by the presence of heart and circulatory problems in many men with BPH.

Causes of Lower Urinary Tract Symptoms

Several structural or medical conditions, either independently or in conjunction with BPH, can cause lower urinary tract symptoms. In addition, prostate growth does not always explain symptoms normally attributed to BPH. Men with large prostates do not always have symptoms, and men with small or normal-sized prostates sometimes have symptoms that are more severe than in those with enlarged glands.

Abnormalities in the urinary tract can cause BPH-like symptoms in men with or without enlarged prostate glands. Such conditions can produce obstruction, impair or weaken the detrusor muscles surrounding the bladder, or cause other damage that impacts the urinary tract. They include:

Muscle contractions in the area where the bladder and urethra meet
A narrowing of the urethra
A weakened bladder
Overactivity in prostate muscles

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

The process of aging weakens the detrusor muscles that surround the bladder, which causes the bladder to become unstable and lose capacity. Unstable detrusor muscles may also impair bladder storage capacity, which then produce irritative or storage symptoms. Studies also indicate that as men get older they may produce more urine at night, although the total daily output of urine is similar to that in middle-aged men. It is not fully known why this occurs.

Prostatitis is an inflammation of the prostate gland. It can be caused by bacterial infection, which is the easiest cause to diagnose. However, the most common form of prostatitis is nonbacterial.

Bacterial Prostatitis. A prostatitis infection can occur abruptly (acute) or be long-term (chronic). Chronic bacterial prostatitis (CBP) is often subtle and may persist for weeks or months with low-grade symptoms, including an urgent need to urinate, frequent urination, and the need to urinate at night. Pain may occur in the lower back or rectum, or it may develop after ejaculation. Because the prostate isn't swollen, doctors may mistake chronic prostatitis for BPH. A urine culture should always be taken, which, in the case of both acute and chronic bacterial prostatitis, will reveal bacteria and confirm a diagnosis. Antibiotics are required to treat CBP. Fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim, Septra) are particularly effective, but prolonged treatment may be necessary.

Nonbacterial Prostatitis. In nonbacterial prostatitis, inflammation occurs, but no bacteria are present. It is 8 times more common than bacterial prostatitis. The causes of nonbacterial prostatitis have not been determined. In one study, alfuzosin, an alpha-blocker drug that is used for BPH, provided some modest relief in patients with prostatitis and chronic pain. The routine use of drug therapy does not seem to help this condition. More research is needed.

Prostatodynia. Although it is considered a form of prostatitis, prostatodynia is a noninflammatory disorder characterized by prostate pain, but neither inflammation nor bacteria are present. The causes of prostatodynia are unknown.

Congestion of the prostate, sometimes called prostatosis, is a benign condition in which the prostate seems to be swollen by excess fluid. It can cause frequent, slow, or uncomfortable urination, but it responds well to a program of frequent ejaculation and sitz baths.

On occasion, prostate cancer can mimic BPH, since both conditions may cause obstruction of the urethra. Bladder cancer can sometimes cause urinary bleeding, frequency of urination, or a sense of urgency, also symptoms of BPH.

Click the icon to see an image of prostate cancer.

Several other conditions can impair the lower urinary tract, including tumors, reactions to medications, and spinal cord injuries. Diseases that affect the nervous system, such as diabetes, multiple sclerosis, and shingles, can desensitize the nerves so that they fail to sense fullness and do not trigger the contraction of the bladder.

Risk Factors

About 5.5 million American men have benign prostatic hyperplasia (BPH) that could warrant medical attention. Age is the major risk factor. BPH occurs in about 60% of men over 60 years of age and over 80% of men over age 80.

A family history of BPH appears to increase a man's chance of developing the condition. One study reported that men with BPH who had three or more family members with the condition had much larger prostate glands than men with BPH without such a family history.

Some evidence suggests a higher incidence of benign prostatic hyperplasia -- particularly fast-growing BPH -- in men with obesity, heart and circulatory diseases, and type 2 diabetes. Diabetes and hypertension, in any case, worsen urinary tract symptoms in men with BPH. In one study, diabetes adversely affected flow rates, although residual urine volumes were not significantly greater.

Complications

The progression of symptoms in benign prostatic hyperplasia (BPH) is typically very slow, and additional symptoms, when they occur, often come and go. Individual response to these symptoms also varies widely. Some men can tolerate very uncomfortable sensations of abnormal urination, while other men seek relief from mild symptoms. BPH does not appear to impair sexual function. Problems with urination, however, can be very distressing and severely affect quality of life in some cases.

Click the icon to see an animation about BPH.

Men are more apt to tolerate voiding symptoms (intermittent flow, hesitancy before urinating) and seek help for storage symptoms (urgency, frequency, urination at night). Voiding symptoms, however, may indicate an obstruction blocking the bladder, which if extensive can severely reduce urine flow and cause other complications, some serious.

Acute Urinary Retention. Sometimes a man is unaware of an obstruction until he suddenly cannot urinate at all. This condition is called acute urinary retention. It is a dangerous complication that can damage the kidneys and may require emergency surgery. In general, BPH progresses very slowly, and long-term urinary retention is very uncommon. Men with BPH at highest risk for this problem tend to be elderly and to have moderate-to-severe lower voiding symptoms. Taking anti-hypertensive drugs (except for diuretics) or antiarrhythmic drugs may also increase the risk.

Other Complications. Bladder obstruction can also cause bladder stones, blood in the urine, urinary tract infection, and incontinence. It may also increase the risk for chronic kidney disease. Unfortunately, no current tests can accurately predict which men are at higher risk for complications, although men with a weak urine stream and larger prostates are at higher risk for urinary retention.

Click the icon to see an image of prostate cancer.

Debate is ongoing over whether BPH and prostate cancer have any association. Both occur in men in the same age groups, and BPH causes prostate enlargement. Most evidence finds no significantly higher risk for prostate cancer in men with BPH. For one reason, the two conditions develop in different parts of the prostate:

BPH occurs in the inner transition zone, while
Cancer tends to develop in the peripheral outer zone

A 10-year study found no higher risk for prostate cancer in men with BPH. Unsuspected prostate cancer is detected during surgery in about 15% of BPH patients, but the risk of this slow-growing cancer is high in all older men. Some estimates suggest that up to a third of men over age 50 have at least microscopic prostate cancer.

Still, there is some evidence that men with fast-growing BPH may be at higher than average risk for prostate cancer. This prostate condition is also associated with obesity, heart disease, and diabetes. Some experts suspect that insulin resistance may be the common factor in all of these conditions, including prostate cancer.

Diagnostic Tests

An indexing tool called the International Prostate Symptoms Score (IPSS) can help evaluate the key lower urinary tract symptoms. As opposed to laboratory tests or other objective tests, this scoring system measures the patient's own experience. The higher the score, the more severe the conditions. It is useful for many reasons:

The patient's score on this test gives a highly accurate assessment of the effect of lower urinary tract symptoms on the quality of a man's life.
It is a reasonable basis from which the patient and doctor can discuss treatment options.
The index is also often used to gauge treatment outcomes and may be a better indicator of success than objective tests, such as the measurement of the prostate gland or the rate of urine flow.

Limitations. The IPSS is useful only as a measure of symptom severity, and has the following limitations:

Other conditions can produce similar scores, so the test is not used as a diagnostic tool for BPH.
The index does not include other urinary symptoms, such as dribbling and incontinence or sexual health, that are important for quality of life. At the very least, the patient should have a frank discussion with his doctor if such symptoms are present and affect his life.
It also does not reflect regional or ethnic differences that can vary the responses to these symptoms.


Symptoms over past month	Never	Less than 1 time in 5	Less than half the time	About half the time	More than half	Almost always
Sensation that the bladder is not empty after urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to urinate within two hours of a previous urination	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to stop and start again several times while urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Have a weak urinary stream	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to strain to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Number of times during the night awakened by the need to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Circle appropriate number. Totals of 7 or less = mild symptoms; 8-19 = moderate; 20-35 = severe.

Other indexing systems, such as Symptom Problem Index (SPI) and the BPH Impact Index (BII), which gauge different quality-of-life and disease issues, are being used in addition to the IPSS to help assess the patient.

Digital Rectal Exam. The digital rectal exam is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate to estimate its size and to detect nodules or tenderness. The exam is quick and painless, but embarrassing for some, and far from infallible. The test helps rule out prostate cancer or problems with the muscles in the rectum that might be causing symptoms, but it generally underestimates the prostate's size. It is never the sole diagnostic tool for either BPH or prostate cancer.

Other Physical Examinations. The doctor will usually press on and manipulate (palpate) the abdomen and sides to detect signs of kidney or bladder abnormalities. The doctor will also check for signs of anemia or swelling in the legs and arms. Certain procedures that test reflexes, sensations, and motor response may be performed in the lower extremities to rule out possible neurologic causes of bladder dysfunction.

To determine whether the bladder is obstructed, an electronic test called uroflowmetry measures the speed of urine flow. The test cannot determine the cause of obstruction, which can be due not only to BPH but possibly also to problems in the urethra, weak bladder muscles, or other causes.

The patient is instructed not to urinate for several hours before the test and to drink plenty of fluids so he has a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that the patient remains still while urinating to help ensure accuracy, and that he urinates normally and does not exert strain to empty his bladder or attempt to retard his urine flow.
Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend then that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for several reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.
The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

A urinalysis can detect signs of bleeding or infection. A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. Although urinary infection is uncommon in younger men, it occurs more frequently in older men, particularly those with BPH. A urinalysis also helps rule out bladder cancer.

To rule out prostatitis (infection or inflammation of the prostate gland), a simple test called the Pre and Post Massage Test (PPMT) is about 90% accurate. This test requires two cultures and microscopic examinations of urine samples, taken before and after massage of the prostate gland. To massage the prostate the doctor simply inserts a gloved finger into the rectum and presses several times on the prostate. The following results are indicated by findings on cultures after massage:

Category II prostatitis (Chronic bacterial). Bacteria are found on post-massage.
Category IIIA prostatitis (Inflammatory chronic pelvic pain syndrome). Leukocytes or other cells are found that indicate inflammation.
Category IIIB prostatitis (Noninflammatory chronic pelvic pain syndrome). No signs of inflammation or bacteria.

In men with symptoms, blood tests can measure a substance called serum creatinine, which is a marker for kidney trouble. Kidney problems exist in an average of 13.6% of BPH patients. Studies have reported rates as high as 30% and as low as 0.3%.

A PSA test measures the level of prostate-specific antigen (PSA) in the patient's blood. It is the standard screening test for prostate cancer. A PSA is recommended annually for all men over 50 years old and for men over age 40 who are at high risk for prostate cancer.

BPH itself can also raise PSA levels, but the test has generally been optional for men with suspected BPH. One 2000 study indicated that PSA levels may be good predictors of future prostate growth in men with BPH. In the study, men with the lowest PSA level groups (0.2 - 1.3 ng/mL) had prostate growth rates of only 0.7 mL per year while those in the high PSA groups (3.3 - 9.9) had growth rates of 3.3. mL per year. Other research has detected a specific molecular form of PSA, called BPSA because it may be a specific marker for BPH. Such findings could eventually lead to a shift from focusing on symptoms and flow rates for diagnosis to a more specific and possibly preventive approach.

Certain treatments for BPH, including the drug finasteride (Proscar) and the surgical procedure transurethral resection of the prostate (TURP), can reduce PSA levels and possibly mask the existence of prostate cancer.

A more recent test identifies so-called free PSA, which is found in lower levels when prostate cancer is present and in higher levels with benign prostate hyperplasia. This may be more accurate than total PSA, regardless of whether a man is taking finasteride or not.

One of the important tests for urinary incontinence is the postvoid residual urine volume (PVR), the amount of urine left after urination. Normally, about 50 mL or less of urine is left; more than 200 mL is a definite sign of abnormalities. Measurements in between require further tests. The most common method for measuring PVR is with a catheter, a soft tube that is inserted into the urethra within a few minutes of urination. PVR can also be measured using transabdominal ultrasonography.

Ultrasound of the prostate does not require a catheter and gives an accurate picture of the size and shape of the prostate gland. Ultrasound is very beneficial when planning surgery and determining treatment options and gauging their effectiveness. Ultrasound may also be used for detecting kidney damage, tumors, and bladder stones. Ultrasound tests of the prostate generally use one of two methods:

Transrectal ultrasonography (TRUS) uses a rectal probe for assessing the prostate. TRUS is significantly more accurate for determining prostate volume. It can sometimes detect cancer.
Transabdominal ultrasonography uses a device placed over the abdomen. It can give an accurate measure of postvoid residual urine and is less invasive and expensive than TRUS.

Filling cystometry, also called cystometrography, is usually used for patients who cannot urinate and in whom nerve damage or injury of the bladder is suspected. The test is used to determine the absence or presence of a condition called uninhibited detrusor contractions (UDC), which often occurs in men with storage urinary tract symptoms. The detrusor is the group of muscle fibers that cover the outside of the bladder. The test does not add much information to results from less invasive tests and is not used routinely.

A urethrocystoscopy, also called cystourethroscopy, may be performed in men diagnosed with BPH, particularly if they are surgical candidates or if other urinary tract problems are suspected. Such problems include blood in the urine, infection, interstitial cystitis, bladder cancer, or prior surgery or injury. The doctor can determine the presence of a number of structural problems, including enlargement of the prostate, obstruction of the urethra or neck of the bladder, anatomical abnormalities, or the presence of stones.

Procedure. In this procedure, a flexible or rigid fiberoptic tube (an endoscope) is inserted into the urethra to allow doctors to view the lower urinary tract.

Complication. The procedure is not without risks. Complications are uncommon but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

An x-ray called an intravenous excretory urography (IVU) is an invasive test that is used only when complications in the upper urinary tract, particularly in the kidney, are suspected. Alternatively, an abdominal ultrasound plus a normal x-ray may be as useful as IVU for most patients with suspected upper urinary tract problems.

Complications and Side Effects. If there is any danger of kidney failure, the test should not be performed, since it can exacerbate the condition. Severe side effects of the test occur in 0.1% of patients.

Some doctors believe that a number of men may be incorrectly diagnosed with BPH when they have interstitial cystitis (an inflammation of the bladder that may be associated with allergic or autoimmune response). The potassium sensitivity test is sometimes used to diagnose IC. Some experts believe this test missed too many IC patients, although a 2001 study concluded that a combination of potassium sensitivity and urodynamic tests is useful in distinguishing between BPH and interstitial cystitis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also known as active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-Severe-Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

Lifestyle Changes

Certain lifestyle changes can help relieve symptoms and are particularly important for men who choose to avoid surgery or drug therapy. A 2007 study found that men who were educated on behavioral and lifestyle management of BPH were less likely to require surgery or drug therapy. Men should limit daily fluid intake to less than 2,000 mL (about 2 quarts) and, in particular, avoid alcohol and caffeine intake. Men should try to urinate at least once every 3 hours. “Double-voiding” may also be helpful -- after urinating, wait and try to urinate again. Cold weather and immobility may increase the risk for urine retention. Keeping warm and exercising may be useful. Stress reduction techniques may also help.

Studies have suggested the following:

Avoid fluids after your evening meal.
Coffee has been associated with a higher risk for BPH. Some evidence suggests that drinking green tea, however, may benefit the prostate.
Moderate alcohol consumption may be protective. (Heavy alcohol consumption, however, may increase the risk for lower urinary tract symptoms, and, in any case, is harmful.)
Genistein, a chemical found in soy, reduced the growth of BPH tissue in the laboratory. Although Asians have a low incidence of BPH and prostate cancer and also have diets rich in soy, it is not yet known if eating soy products will reduce the risk of BPH or improve any symptoms.
Fruits and vegetables rich in beta-carotene and vitamin C may help protect against BPH. Conversely, high consumption of cereals, bread, eggs, and poultry may increase the risk for BPH.
High doses of zinc supplements may increase the risk of BPH.

Decongestants and Antihistamines. Men with BPH should avoid, if possible, the many medications for colds and allergies that contain decongestants, such as pseudoephedrine (Sudafed). Such drugs, known as adrenergics, can exacerbate urinary symptoms by preventing muscles in the prostate and bladder neck from relaxing to allow urine to flow freely. Antihistamines, such as diphenhydramine (Benadryl), can also slow urine flow in some men with BPH.

Diuretics. Men who are taking diuretics, which increase urination, may want to talk to their doctor about reducing the dosage or switching to another drug. These are important drugs for many people with high blood pressure, with a proven track record for saving lives. No one should go off these medications without medical supervision.

Other Drugs. Other drugs that may worsen symptoms are certain antidepressants and drugs used to treat spasticity.

Some, but not all, research suggests that moderate exercise can reduce urinary tract problems associated with BPH.

Kegel (pelvic floor muscle) exercises, first developed to help women with childbirth, can also help men prevent urine leakage. They strengthen the pelvic floor muscles that both support the bladder and close the sphincter.

Performing the Exercises. Since the muscle is internal and sometimes hard to isolate, doctors often recommend practicing while urinating:

The patient is asked to contract the muscle until the flow of urine is slowed or stopped. He attempts to hold each contraction for 20 seconds.
He then releases the contraction.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Medications

The two primary drug classes used for BPH are:

Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Uroxatral). Alpha-blockers help relieve BPH symptoms, but they do not reduce the size of the prostate. The can help improve urine flow and reduce risk of bladder obstruction. They are often the first choice, especially for men with smaller prostates.
5-alpha-reductase inhibitors. Finasteride (Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs are better for men with significantly enlarged prostates. In addition to relieving symptoms, they increase urinary flow and may even help shrink the prostate. However, patients may have to take these drugs for up to 6 - 12 months to achieve full benefits.

Because these two types of drugs work in different ways, researchers are investigating combinations of the two for selected patients. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, published in 2003, reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. The combination treatment may work best for high-risk patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.

General Guidelines for Alpha-Blockers.Alpha-adrenergic antagonists, commonly called alpha-blockers, were originally used to treat high blood pressure. They are prescribed for BPH to relax smooth muscles in the prostate. The muscle cells in the prostate are stimulated by molecules called alpha adrenergic receptors. This can cause lower urinary tract symptoms.

Drugs that block these receptors relax the muscles in and around the prostate, increase urinary flow and improve symptoms, sometimes significantly. Improvement occurs within days to weeks. Because these drugs are short-acting, symptoms return very quickly once a man stops taking the medication. They neither affect PSA levels nor shrink the size of the prostate. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct. Investigators are studying whether these drugs may help prevent the development of prostate cancer.

Alpha-blockers are prescribed for most men with BPH symptoms whose prostates are not significantly enlarged. Even men with moderately enlarged prostates might try alpha-blockers before more intense treatments because these drugs work fairly quickly, have no effect on sexual drive, and are the least expensive treatment for BPH. Some experts now recommend alpha-blockers as first-line treatment for patients with moderate-to-severe symptoms.

These drugs are generally referred to as either nonselective or selective alpha-blockers. Drugs in both categories are similar in effectiveness for reducing symptoms and improving urinary flow. There are some differences, however. Patients should discuss the appropriate alpha-blocker for their individual condition with their doctors.

Nonselective Alpha-Blockers. Nonselective alpha-blockers (also referred to as alpha-specific antagonists) include terazosin (Hytrin), doxazosin (Cardura), and alfuzosin (Uroxatral). Alfuzosin is the newest drug and can be taken once a day. They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These drugs work within a few weeks, are inexpensive, and produce long-lasting benefits. Alfuzosin begins to improve urine flow within hours.

Side Effects. Nonselective alpha-blockers can reduce blood pressure, which may cause dizziness, headache, rapid heartbeat, and fatigue. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects. (Alfuzosin's extended-release formulation appears to pose a much lower risk than the other drugs.) Alpha-blockers can also cause headache, sore throat, and weakness. Nasal congestion occurs in about 2% of cases. Men may also experience a decreased ejaculate. (Impotence is not a common side effect of alpha-blockers, as it is with finasteride.)
Long-Term Effects. These drugs slow the progression of BPH but do not help prevent urinary retention.
Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems and especially those with hypertension, high cholesterol levels, or both. However, alpha-blockers can exacerbate heart failure symptoms in men with this condition.

Selective Alpha-Blockers. Tamsulosin (Flomax) is the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved for treatment of BPH. Naftopidil is a similar drug under investigation. These drugs target receptors that affect only the smooth muscles of the prostate. Tamsulosin seems to work as well as nonselective alpha-blockers. It is not clear if it reduces long-term complications of BPH.

Selective alpha-blockers appear to be very safe, even for years. Side effects are minimal. Most common ones include nasal congestion. The risk for low blood pressure and dizziness is lower than with the nonselective alpha-blockers. They may pose a higher risk for problems in ejaculation than nonselective alpha-blockers, but do not appear to cause impotence or reduce sexual drive as finasteride does. These drugs can interact with certain medications, including calcium channel blockers (particularly verapamil).

Researchers are studying the combination of tamsulosin and tolteridine (Detrol). Tolteridine is an anticholinerogic medication used to treat urinary incontinence. Tamsulosin targets the prostate while tamsulosin helps inhibit involuntary contractions of the bladder. A 2006 study in the Journal of the American Medical Association found that a combination of tolterodine and tamsulosin worked better than either drug alone for men with lower urinary tract symptoms (LUTS), including overactive bladder.

Specific Benefits. The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Finasteride (Proscar) and dutasteride (Avodart), known as a 5-alpha-reductase inhibitors, block this enzyme and thus reduce dihydrotestosterone in the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but it can be helpful. Follow-up studies have reported that the drug is safe and effective over the long-term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing symptoms in men with large prostates. (Men with larger prostates and high PSA values may also benefit from combination therapy of finasteride and the alpha-blocker doxazosin.) In such cases, studies on finasteride also suggest it reduces the risk of acute urinary retention and the need for surgery. It also helps control bleeding in the urine that is related to BPH. A side benefit of finasteride is reduction of hair loss related to male hormones and in some cases hair growth in men with mild-to-moderate male pattern baldness.

Dutasteride (Avodart) is a newer drug that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. A 4-year study reported sustained improvements in urinary symptoms and prostate volume reduction. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride. Researchers are also investigating whether dutasteride can help prevent the development of prostate cancer.

Candidates. Some experts recommend 5-alpha-reductase inhibitors for men of any age who have all three of the following conditions:

Very large prostates (40 mL or larger)
Low urinary flow rates
Prostate enlargement related primarily to hormone-stimulated overgrowth of glandular tissue

Finasteride is also proving to be helpful for patients who have hematuria (blood in the urine) related to BPH.

Dosing. Finasteride and dutasteride are taken once a day. It may take as long as 6 - 12 months for a man to notice a change in symptoms.

Effects on PSA. Finasteride and dutasteride decrease prostate-specific antigen (PSA) levels, which are measured for screening prostate cancer. Lower PSA levels may mask the presence of the cancer. Doctors calculate PSA levels in men taking these drugs by doubling the PSA values. Studies confirm that this doubling equation helps provide an accurate measurement.

Side Effects. Finasteride has been associated with:

Sexual dysfunction, including low sexual drive and impotence, in about 6 - 19% of patients. Such problems appear to occur only during the first year of use and diminish over time in most men who take finasteride.
Reductions in energy.
Breast tenderness.
Possible weight loss in some men.

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but they can reduce sexual drive and are much more likely to cause impotence. Flutamide is an anti-androgen that may be an alternative to surgery in certain patients with BPH who have physical or mental disorders.

Popular herbal treatments for BPH include:

Saw Palmetto. Saw palmetto is one of the most popular herbal remedies for BPH. It comes from the berry of the plant Serenoa repens. A major 2006 study in the New England Journal of Medicine found that saw palmetto had no benefit for treating BPH. The study enrolled 225 men with moderate-to-severe BPH. The men received either placebo or 160 mg of saw palmetto twice daily. After 1 year, there were no differences in symptom improvement between the placebo and saw palmetto groups.

Beta-Sitosterol. Beta-sitosterol preparations come from South African star grass, Hypoxis rooperi, and other plant species. Some studies have shown beta-sitosterol to improve urinary symptoms and flow. They may increase the risk for impotence, however.

Pygeum Africanum. The herbal Pygeum africanum is an extract from the bark of an African plum tree. In an analysis of 18 trials, the herb provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were short in length, however.

Cernilton. Cernilton is prepared from rye grass pollen. Studies have been limited, but some suggest it may help improve symptoms, including nighttime urinary problems. Other studies have found no benefit.

Other popular herbs include nettle root extract (Urtica dioica) and pumpkin seed oil (Cucurbita peponis). There is no scientific evidence that any of these remedies help treat BPH.

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

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including BPH. Preliminary studies are showing promising results in improving urine flow and reducing urinary retention. Research, presented at the 2007 annual meeting of the American Urological Association, reported that men with BPH who had Botox injected directly into their prostate gland had symptom relief and improved quality of life for up to a year after treatment.

PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors can treat erectile dysfunction (ED). They include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Because lower urinary tract symptoms (LUTS) and ED often occur together in older men, researchers are investigating whether PDE5 inhibitors may help improve BPH symptoms. Research presented at the 2006 American Urological Association meeting suggested that sildenafil improves urinary symptoms in men who have both ED and LUTS. Another study indicated that a combination of sildenafil and the alpha-blocker alfusozin (Uroxatral) worked better for treating LUTS and ED than either drug alone.

Other Areas of Investigation. Researchers are looking at several different drugs for future BPH therapies. Most drugs being researched for BPH, such as arylpiperazines, target molecules in the prostate that may help suppress cell growth. Some efforts are focusing on drugs that affect the central nervous system or nerve fibers in the bladder and urethra to reduce urinary tract symptoms.

Other Treatments

Several surgical approaches are now available for treating BPH.

Invasive Procedures. The most effective surgical procedures, transurethral resection of the prostate (TURP) and open prostatectomy, are also the most invasive. They carry the highest risks for significant complications, including impotence and incontinence. Greater surgeon experience with TURP, however, has reduced complications and hospital stays. Because it is more effective than less invasive procedures, TURP remains the procedure of choice for many doctors. When considering invasive surgery, the patient should be sure his surgeon performs at least 50 of these procedures each year. The complication rates of the surgeon should be no higher than 1% for incontinence and 4% for impotence. Transurethral incision of the prostate (TUIP) is an alternative to TURP for men with smaller prostate glands.

Less Invasive Procedures. Minimally invasive procedures use some form of heat to destroy excess prostate tissue. The heat may be delivered by:

Radio frequency: transurethral needle ablation (TUNA)
Microwave: transurethral microwave thermotherapy (TUMT)
Electrical current: transurethral electrovaporization (TUVP)
Ultrasound: high-intensity focus ultrasound (HIFU)
Hot water: water-induced thermotherapy (WIT)
Laser: interstitial laser coagulation (ILC) and holmium laser enucleation of the prostate (HoLEP)

One laser procedure, photoselective vaporization (PVP), is typically done as an outpatient procedure. The patient goes home on the same day. However, there is no long-term data for this procedure.

None of the other minimally invasive procedures have proven superior to TURP to date, but they vary by complications. Some may be appropriate for certain patients, such as the following:

Younger men. (Many of the less invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk for TURP is not high.)
Debilitated elderly patients
Patients with severe medical conditions, including uncontrolled diabetes, cirrhosis, active alcoholism, psychosis, and serious lung, kidney, or heart disease
Men who are on blood-thinning drugs

Transurethral resection of the prostate (TURP) involves surgical removal of the inner portion of the prostate where BPH develops. It is the most common surgical procedure for BPH, although the number of procedures has dropped significantly over the past decades because of the availability of effective medications.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

Procedure. TURP usually requires a 1 - 3 day hospital stay. The surgeon inserts a fiberoptic endoscope, which is a thin tube, into the urethra. No incision is needed. The surgeon uses the endoscope to cut away excess prostatic tissue, and water solutions are used to flush away the excised matter.

Risk of Water Intoxication. If the fluids used during TURP build up, water intoxication can develop, which can be serious. This condition is referred to as the transurethral resection (TUR) syndrome and includes abdominal cramps, nausea, vomiting, lethargy, and dizziness. Patients who undergo TURP for longer than 1 hour and those with larger prostate glands seem to be at greater risk for this complication. An irrigation system that uses a mechanical valve may reduce the risk.

Postoperative Catheterization. A Foley catheter generally remains in place for 3 - 5 days after surgery to allow urination. This device is a tube inserted through the opening of the penis to drain the urine into a bag. The catheter can cause bladder spasms that can be painful, but they eventually cease.

Some studies have suggested that in selected patients the catheter can safely be removed within 24 - 48 hours, allowing patients to go home earlier. Early catheter removal is not appropriate for patients with intense urine retention, signs of infection, bleeding, or other complications.

Recuperation. Urine flow is stronger almost immediately after most TURP procedures. After the catheter is removed, patients often experience some pain or sense of urgency as the urine passes over the surgical wound. These sensations gradually subside. Complete healing takes about 2 months. The following are some tips for hastening recovery and avoiding complications:

During recuperation at home, the patient should avoid driving, operating heavy equipment, lifting, sudden movements, and straining the muscles in the lower tracts, such as during a bowel movement.
Drinking 8 glasses of water a day after surgery is important to flush the bladder and help healing.
Foods that help prevent constipation, such as fruits and vegetables, are important. A laxative may be needed if constipation occurs.
Kegel exercises can help reduce incontinence. Performing three to four sets of 30 contractions daily is recommended. In one study, improvement due to Kegel exercises was significant within a month after surgery.

Postoperative Complications. Complications after TURP can be high, depending on the skill of the surgeon and other factors, but their incidence has decreased considerably over the past decades because of advances in surgical technique and more widespread expertise.

Bleeding. Some blood and small clots appear in the urine after surgery, and if the bladder is flushed with water, the urine may turn red. Such bleeding is normal. Occasionally, the scab on the surgical wound loosens, causing a sudden appearance of blood in the urine that can be alarming. Usually this stops after a rest, but the patient should notify the doctor at once if he is concerned about abnormal bleeding or clotting or has unusual feelings of discomfort. Rarely, hemorrhage may occur, requiring a transfusion.
Infection. Urinary tract infections occur in 5 - 10% of TURP patients. The risk is particularly high if a catheter is required. Antibiotics may be given to prevent infections, although often a doctor will choose to monitor a patient and administer antibiotics only if an infection is evident.
Incontinence. Temporary stress incontinence (urine leakage after activities such as sneezing, coughing, or lifting) occurs in most surgical patients. Urge incontinence is the involuntary loss of urine following an uncontrollable urge to urinate. About 2.1% of TURP patients experience stress incontinence, and nearly 2% have urge incontinence. In general, however, there is no significant risk for incontinence. [See In-Depth Report #50: Urinary incontinence.]
Sexual Dysfunction. Some men report certain sexual differences after the procedure, particularly low volume of fluid at ejaculation. Studies, however, do not report any significant risk for impotence. For most men who report this complication, sexual function returns in short order. (In some men it may take up to a year for complete recovery.) If potency was diminished before the operation, the procedure will not restore it. [See In-Depth Report #15: Erectile dysfunction.]
Retrograde Ejaculation and Low Semen. Many TURP patients report a lower volume of semen after the procedure. Between 66 - 75% of these patients experience retrograde ejaculation, in which semen is forced backward into the bladder instead of forward out of the urethra during orgasm. During most invasive procedures, the muscle that blocks off the bladder may be cut in order to widen the outlet. In such cases, the semen flows back through the wider opening rather than out of the penis. This condition can impair fertility and is of particular concern in younger men. Neither retrograde ejaculation nor the operation itself typically affects orgasm, although it takes many men some time to emotionally adjust to these conditions.
Low PSA Levels. PSA levels may be lowered after TURP, which might cause a doctor to miss a diagnosis of prostate cancer during routine screening.

Repeat Operations. Symptomatic relief is usually maintained for at least 15 years after surgery, but BPH may return or patients may need a second operation for other reasons. Up to 10% of TURP patients require a repeat operation within 10 years. In some cases, scarring in the bladder severe enough to cause obstruction occurs within a year of the procedure and may require transurethral incision (TUIP). More often, the urethra is scarred and narrows, but usually this condition can be corrected by a simple stretching procedure performed in the doctor's office.

In transurethral incision of the prostate (TUIP), the surgeon makes only one or two incisions in the prostate, causing the bladder neck and the prostate to spring open and reduce pressure on the urethra.

Candidates. TUIP is generally used only for men with minimally enlarged prostates (30 grams or less) who have obstruction of the neck of the bladder. Some experts believe TUIP is not performed enough and could benefit many patients, particularly those with severe medical conditions who are not good candidates for more invasive surgeries and men who want to lessen their risk for sterility.

Postoperative Complications. TUIP is less invasive than TURP, has a lower rate of the same complications, particularly retrograde ejaculation, and usually does not require a hospital stay. More studies are still needed, however, to determine whether they are comparative in long-term effectiveness.

In open prostatectomy, the enlarged prostate is removed through an open incision in the abdomen using standard surgical techniques. This is major surgery and requires a hospital stay of several days. Open prostatectomy is used only for severe cases, about 2 - 3% of BPH patients, when the prostate is severely enlarged, the bladder is damaged, or other serious problems exist. Up to 14% of patients require a second operation because of scarring. In making a decision about prostatectomy, it is essential that the doctor explains the consequences of a diminished sexual capacity that occurs after this procedure. When the situation of the patient does not constitute an emergency, prostatectomy should be considered a last resort if the patient still has an active sex life. Other complications are similar to those of TURP.

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

Procedures. Laser technology is used for removal of prostate tissue. Laser procedures can usually be done as an outpatient procedure, and there is little risk for bleeding. Different procedures are used to provide different degrees of thermal cell destruction that range from coagulation to complete vaporization:

Interstitial laser coagulation (ILC) involves insertion of a scope through the prostate. A fiberoptic tip is threaded through the scope to direct a diode laser emission to targeted areas of the prostate. The coagulated tissue is naturally absorbed back into the body. Approved in 1998, this procedure is being performed less frequently as urologists turn to newer laser technologies (HoLEP, PVP).
Holmium laser enucleation of the prostate (HoLEP) is a newer technique that can actually cut and vaporize the tissue. Vaporization is effective immediately and also may pose lower risks for prolonged urinary retention and reoperation rates than coagulation. The Holmium laser is showing very good results with low complication rates in small studies, and trials have reported benefits lasting more than four years. (HoLEP is actually proving to be better than TURP or even open prostatectomy for removing very large prostate glands.)
Photoselective vaporization of the prostate (PVP) uses a potassium-titanyl-phosphate (KTP) laser ("green-light" laser) to vaporize prostate tissue. The procedure is virtually bloodless and may be a better option for men taking anticoagulant medication. Results from several recent clinical trials report sustained improvement up to 1 year after the procedure. More studies are needed to confirm long-term efficacy.

Complications. The laser procedure carries a lower risk for incontinence than TURP or TUVP, another minimally invasive procedure. Studies have been mixed on whether laser surgery poses any risk for sexual dysfunction. In one study, TURP had a lower risk for sexual dysfunction, although the risk from either procedure was very low and it wasn't clear that lasers had even been responsible for this complication. After laser procedures, and especially after coagulation, the prostate often temporarily enlarged and caused obstruction and irritation. Sometimes these symptoms were severe. Most men require a temporary catheter to drain urine after laser procedures. Newer laser procedures may significantly reduce these adverse effects.

Transurethral Microwave Thermotherapy (TUMT). Transurethral microwave thermotherapy (TUMT) delivers heat using microwave pulses to destroy prostate tissue. Studies have found that between 60 - 80% of men respond favorably to the treatment and the benefits seem to last. A 2001 study reported that it remained effective for at least 18 months and was superior over the long-term to the alpha-blocker drug terazosin. Improvement is not as complete as with TURP, but TUMT has fewer complications.

Candidates. TUMT may be beneficial for men with larger prostates and moderate to severe bladder obstruction, including those who require indwelling catheters. A 2000 study, for example, concluded that is was a safe and effective therapy for treatment of urinary retention. In general, the procedure should not be performed on men who have pacemakers, defibrillators, or any metal implants. One possible exception, the Targis System, was approved for use for patients with hip or penile implants that are located at least 1.5 inches from the urethra. Men who have had previous radiation therapy to the pelvic area are at higher risk for injuries from this procedure.
Procedure. A microwave antenna is inserted through the urethra with ultrasound used to position it accurately. The antenna is enclosed in a cooling tube to protect the lining of the urethra. Computer-generated microwaves pulse through the antenna to heat and destroy prostate tissue. When the temperature becomes too high, the computer shuts down the heat and resumes treatment when a safe level has been reached. The procedure takes 30 minutes to 2 hours, and the patient can go home immediately afterward. About 30% of patients experience some pain during the procedure. The patient should report any pain that appears to be unusually severe, however, since this could indicate improper application.
Complications. Swelling in the urinary tract often occurs later, which prevents urination and requires the use of a temporary catheter for about 3 days until the swelling subsides. There have also been reports of serious injuries to the penis and urethra from overheating due to improper application. It is important to note that TUMT does not significantly affect sexuality or cause incontinence or retrograde ejaculation, which are risks with some other prostate procedures.

Transurethral Needle Ablation. Transurethral needle ablation (TUNA) is a simple, safe, and relatively inexpensive procedure using needles to deliver high-frequency radio waves that heat and destroy prostate tissue. The procedure usually requires only a local anesthetic. One study reported that improvement was maintained in most patients after 2 years, although older men (over 70) had slightly worse symptoms and quality-of-life scores. Although small clinical studies have reported that TUNA is as effective as TURP, some experts believe that in actual medical practice TURP is still more effective.

Some studies have reported urinary retention, blood in the urine, retrograde ejaculation, and painful urination after the procedure, although in general TUNA has few or none of TURP's severe side effects. TUNA poses a very low to no risk for incontinence and impotence, and may be a good option for younger men.

Transurethral Electrovaporization. Transurethral electrovaporization (TUVP) uses high voltage electrical current delivered through a resectoscope to combine vaporization of prostate tissue and coagulation that seals the blood and lymph vessels around the area. Deprived of blood, the excess tissue dies and is sloughed off over time. Patients who have TUVP may be able to have their catheter removed within hours after the procedure compared to normal removal time of 3 - 5 days after TURP. A 5-year study reported that it was as effective as TURP over the long-term and had a similar complication rate.

Ultrasound. High-intensity focus ultrasound (HIFU) is a heat procedure under investigation that uses ultrasound to destroy specific prostate tissue. The principles are similar to transurethral microwave thermotherapy, but ultrasound techniques may destroy excess tissue without damaging other parts of the urethra.

Water-Induced Thermotherapy. A device called Thermoflex, which circulates heated water through a catheter to destroy prostatic tissue, has been approved for treating BPH. Another technique uses a balloon filled with hot water to destroy tissue around the urethra. Water-induced thermotherapy (WIT) does not require anesthesia and can be completed during a single outpatient visit.

Prostatic stents used for BPH are flexible mesh tubes that are inserted into the urethra. They are made of special alloys that do not cause reactions in the body. Typically, the insertion procedure takes only 15 minutes and requires only regional anesthetic and mild sedation. It usually requires minimal recuperation and no overnight hospital stay. Unfortunately, long-term studies are reporting high rates of dissatisfaction. Between 8 - 37% of the stents need to be removed later because of poor placement or complications, including irritation when urinating, urinary tract infections, and treatment failure. At this point stents seem to be best suited for high-risk surgical patients and those with a limited life expectancy. Stents composed of new materials and properties may increase their role.

Resources

www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.urologyhealth.org -- American Urological Association

References

Bravi F, Bosetti C, Dal Maso L, Talamini R, Montella M, Negri E, et al. Food groups and risk of benign prostatic hyperplasia. Urology. 2006 Jan;67(1):73-9.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Rohrmann S, Giovannucci E, Willett WC, Platz EA. Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am. J. Clin. Nutr. 2007 Feb;85(2):523-9.

van der Meulen J, Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, et al. Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ. 2007 Jan 6;334(7583):25. Epub 2006 Nov 21.

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

A.D.A.M. Copyright

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