Male hypogonadism

Male hypogonadism

Date updated: December 08, 2006
Content provided by MayoClinic.com

Male hypogonadism is a condition in which the body doesn't produce enough of the sex hormone testosterone. As many as 5 million men in the United Sates may not produce enough testosterone - the hormone that plays a key role in masculine growth and development during puberty.

Testosterone's effects begin after conception, stimulating the formation of male sex organs. The hormone continues to play an important role through puberty and adulthood by triggering male characteristics and maintaining sex drive.

You may be born with hypogonadism, or it can develop later in life from injury or infection. The effects - and what you can do about them - depend on the cause and at what point in your life hypogonadism occurs.

During fetal development, low testosterone can cause incomplete formation of sex organs. Low testosterone levels before puberty can permanently affect growth and development. After puberty, the development of hypogonadism is more likely to cause temporary problems that may improve with treatment. Some types of hypogonadism can be treated with testosterone replacement therapy.

Signs and symptoms

Hypogonadism can occur during fetal development, puberty or adulthood. Depending on when it develops, the signs and symptoms differ.

Fetal development
If the body doesn't produce enough testosterone during fetal development, growth of external sex organs may be impaired. Depending at when it develops, and how much testosterone is present, a child that is genetically male may be born with:

• Female genitals
• Ambiguous genitals (genitals that are neither clearly male or female)
• Underdeveloped male genitals

Puberty
During puberty, male hypogonadism may slow growth and affect development. It can cause:

• Decreased development of muscle mass
• Lack of deepening of the voice
• Impaired growth of body hair
• Impaired growth of the penis and testicles
• Excessive growth of the arms and legs in relation to the trunk of the body
• Development of breast tissue (gynecomastia)

Adulthood
In adult males, hypogonadism may alter certain masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include:

• Erectile dysfunction
• Infertility
• Decrease in beard and body hair growth
• Increase in body fat
• Decrease in size or firmness of testicles
• Decrease in muscle mass
• Development of breast tissue (gynecomastia)
• Loss of bone mass (osteoporosis )

Hypogonadism can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include:

• Fatigue
• Decreased sex drive
• Difficulty concentrating
• Hot flashes
• Irritability
• Depression

Causes

Male hypogonadism means the testicles don't produce enough of the male sex hormone testosterone. There are two basic types of hypogonadism:

• Primary. This type of hypogonadism - also known as primary testicular failure - originates from a problem in the testicles.
• Secondary. This type of hypogonadism indicates a problem in the hypothalamus or the pituitary gland - parts of the brain that signal the testicles to produce testosterone. The hypothalamus produces gonadotropin-releasing hormone, which signals the pituitary gland to make follicle-stimulating hormone (FSH) and luteinizing hormone. Luteinizing hormone then signals the testes to produce testosterone.

Either type of hypogonadism may be caused by an inherited (congenital) trait or something that happens later in life, such as an injury or an infection (acquired).

Primary hypogonadism
Common causes of primary hypogonadism include:

• Klinefelter 's syndrome. This condition results from a congenital abnormality of the sex chromosomes, X and Y. A male normally has only one X and one Y chromosome. In Klinefelter's syndrome, two or more X chromosomes are present in addition to one Y chromosome. The Y chromosome contains the genetic material that determines the sex of a child and related development. The extra X chromosome that occurs in Klinefelter's syndrome causes abnormal development of the testicles, which in turn results in underproduction of testosterone.
• Undescended testicles. Before birth, the testicles develop inside the abdomen and normally move down into their permanent place in the scrotum two months before birth. One or both of the testicles may not be descended at birth. This condition often corrects itself within the first few years of life without treatment. If not corrected in early childhood, it may lead to malfunction of the testicles and reduced production of testosterone.
• Mumps orchitis. If a mumps infection involving the testicles in addition to the salivary glands (mumps orchitis) occurs during adolescence or adulthood, long-term testicular damage may occur. This may affect normal testicular function and testosterone production.
• Hemochromatosis. Too much iron in the blood can cause testicular failure or pituitary gland dysfunction affecting testosterone production.
• Injury to the testicles. Because of their location outside the abdomen, the testicles are prone to injury. Damage to normally developed testicles can cause hypogonadism. Damage to one testicle may not impair testosterone production.
• Cancer treatment. Chemotherapy or radiation therapy for the treatment of cancer can interfere with testosterone and sperm production. The effects of both treatments often are temporary, but permanent infertility may occur. Although many men regain their fertility within a few months after treatment ends, preserving sperm before starting cancer therapy is an option that many men consider.
• Normal aging. Older men generally have lower testosterone levels than younger men do. As men age, there's a slow and continuous decrease in testosterone production. The rate that testosterone declines varies greatly among men. As many as 30 percent of men older than 75 have a testosterone level that's below normal.

Secondary hypogonadism
In secondary hypogonadism, the testicles are normal but function improperly due to a problem with the pituitary or hypothalamus. A number of conditions can cause secondary hypogonadism, including:

• Kallmann syndrome. Abnormal development of the hypothalamus - the area of the brain that controls the secretion of pituitary hormones - can cause hypogonadism. This abnormality is also associated with impaired development of the ability to smell anosmia.
• Pituitary disorders. An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the pituitary gland may cause testosterone or other hormone deficiencies. Also, the treatment for a brain tumor such as surgery or radiation therapy may impair pituitary function and cause hypogonadism.
• Inflammatory disease. Certain inflammatory diseases such as sarcoidosis, histiocytosis, tuberculosis and some fungal infections involve the hypothalmus and pituitary gland and can affect testosterone production, causing hypogonadism.
• HIV/AIDS. This virus can cause low levels of testosterone by affecting the hypothalamus, the pituitary and the testes.
• Medications. The use of certain drugs, such as opiate pain medications and some hormones, can affect testosterone production.
• Obesity. Being significantly overweight at any age may be linked to hypogonadism.

Risk factors

Risk factors for hypogonadism include:

• Kallmann syndrome
• Undescended testicles as an infant
• Mumps infection affecting your testicles
• Injury to your testicles
• Testicular or pituitary tumors
• HIV/AIDS
• Klinefelter's syndrome
• Hemochromatosis
• Previous chemotherapy or radiation therapy

Hypogonadism can be inherited. If any of these risk factors are in your family health history, inform your doctor. Be aware of and watch for signs and symptoms of hypogonadism.

When to seek medical advice

See a doctor if you have any symptoms of male hypogonadism. Establishing the cause of hypogonadism is an important first step to getting appropriate treatment.

You may need to consult an endocrinologist, a physician who specializes in the hormone-producing (endocrine) glands. If your primary care physician suspects the condition is present, he or she may refer you to an endocrinologist. Or, you may ask for a referral yourself.

Screening and diagnosis

Your doctor may test your blood level of testosterone if you have any of the signs or symptoms of hypogonadism. Early detection in boys can help prevent problems from delayed puberty. Early diagnosis and treatment in men offers better protection against osteoporosis and other related conditions.

Doctors base a diagnosis of hypogonadism on symptoms and results of blood tests that measure testosterone levels. Because testosterone levels vary and are generally highest in the morning, blood testing is usually done early in the day.

If tests confirm you have low testosterone, further testing can determine if a testicular disorder or a pituitary abnormality is the cause. Based on specific signs and symptoms, additional studies can pinpoint the cause. These studies may include:

• Hormone testing
• Semen analysis
• Pituitary imaging
• Genetic studies
• Testicular biopsy

Testosterone testing also plays an important role in managing hypogonadism. This helps your doctor determine the right dosage of medication, both initially and over time.

Complications

The complications of untreated hypogonadism differ depending on what age it first develops - during fetal development, puberty, or as an adult.

Fetal development. If hypogonadism begins during fetal development, a baby may be born with ambiguous or abnormal genitalia.

Puberty. If hypogonadism develops before puberty, a lack of body hair and impaired penis and testicle growth may occur.

Adult. Infertility, erectile dysfunction, decreased sex drive, fatigue, muscle loss or weakness, enlarged male breasts, decreased beard and body hair growth, and osteoporosis are possible complications of hypogonadism in adults.

Treatment

Adults
Treatment for male hypogonadism depends on the cause and whether you're concerned about fertility.

• Testosterone replacement therapy. For hypogonadism caused by testicular failure, doctors use male hormone replacement (testosterone replacement therapy, or TRT). TRT can restore sexual function and muscle strength and prevent bone loss. In addition, men receiving TRT often experience an increase in energy, sex drive and sense of well-being.

  If a pituitary problem is the cause, pituitary hormones may stimulate sperm production and restore fertility. Testosterone replacement therapy can be used if fertility isn't an issue. A pituitary tumor may require surgical removal, medication, radiation or the replacement of other hormones.

• Assisted reproduction. Although there's often no effective treatment to restore fertility in a man with primary hypogonadism, assisted reproductive technology may be helpful. This technology covers a variety of techniques designed to help couples who have been unsuccessful in achieving conception.

Boys

• Testosterone replacement therapy. In boys, testosterone replacement therapy (TRT) can stimulate puberty and the development of secondary sex characteristics, such as increased muscle mass, beard and pubic hair growth, and growth of the penis. Pituitary hormones may be used to stimulate testicle growth. An initial low dose of testosterone with gradual increases may help to avoid adverse effects.

Types of testosterone replacement therapy
Several testosterone delivery methods exist. Choosing a specific therapy depends on your preference of a particular delivery system, the side effects and the cost. Methods include:

• Injection. Testosterone injections are safe and effective. Injections are given in a muscle about every two weeks. Your symptoms may come and go between doses. You or a family member can learn to give TRT injections at home. If you're uncomfortable giving yourself injections, a nurse or doctor can give the injection.
• Patch. A patch containing testosterone (Androderm) is applied each night to your back, abdomen, upper arm or thigh. The site of the application is rotated to maintain seven-day intervals between applications to the same site to lessen skin reactions.
• Gel. You rub testosterone gel (AndroGel, Testim) into your skin on your lower abdomen, upper arm or shoulder. As the gel dries, your body absorbs testosterone through your skin. Gel application of testosterone replacement therapy appears to cause fewer skin reactions than patches do. Don't shower or bathe for several hours after a gel application to be sure it gets absorbed. A potential side effect of the gel is the possibility of transferring the medication to your partner. You can avoid this by avoiding skin-to-skin contact until the gel is completely dry or by covering the area after an application.
• Gum and cheek (buccal cavity). Striant, a small putty-like substance, delivers testosterone through the natural depression above your top teeth where your gum meets your upper lip (buccal cavity). This product quickly sticks to your gumline and, as exposed to saliva, softens into a gel-like form, allowing testosterone to be absorbed into your bloodstream. Side effects may include gum irritation or pain, bitter taste or headache.
• Oral. Taking testosterone orally is not recommended for long-term hormone replacement. Testosterone taken by mouth may cause liver problems, raise your cholesterol and increase your risk of heart disease.

Coping skills

Prevent osteoporosis. If hypogonadism occurs during adulthood, make lifestyle and dietary changes to prevent osteoporosis. Regular exercise and adequate amounts of calcium and vitamin D to maintain bone strength are important to reduce the risk of osteoporosis. The Recommended Dietary Allowance (RDA) for calcium is 1,000 milligrams (mg) for men younger than 65 and 1,500 mg a day for men older than 65. All men should get between 400 and 800 international units of vitamin D daily.

Learn about erectile dysfunction or infertility. These conditions caused by hypogonadism can cause psychological and relationship problems. Know what to expect from these conditions and what to do if new or uncomfortable feelings develop between you and your partner.

Reduce stress. Talk with your doctor about how you can reduce the anxiety and stress that often accompany these conditions. Many men benefit from psychological or family counseling. Support groups can help people with hypogonadism and related conditions cope with similar situations and challenges. Helping your family understand the diagnosis of hypogonadism also is important.

Allow time to adjust. Adolescents with hypogonadism may feel like they don't fit in. Testosterone replacement therapy can trigger puberty. When given at a slow pace that allows time for adjustment to physical changes and new feelings, it is an effective treatment.

Testosterone therapy: The answer for aging men?

Testosterone therapy: The answer for aging men?

Date updated: April 14, 2006
Content provided by MayoClinic.com

The possibilities are enticing - increase your muscle mass, sharpen your memory and mental focus, boost your libido, and improve your energy level. If you're an aging man, this may sound like the ultimate anti-aging formula. But such health benefits from testosterone therapy aren't quite so clear-cut.

"We just can't predict all the potential harmful effects of taking hormones even though on the surface they may seem beneficial."

Todd Nippoldt, M.D.
Mayo Clinic Rochester

Testosterone therapy has been used successfully for years to treat men with abnormally low testosterone levels - a medical condition called male hypogonadism. More recently, healthy, aging men have taken the hormone to boost waning testosterone levels. But not enough is known about the effects of testosterone therapy for this purpose. No long-term studies have weighed the potential benefits against the possible risks, including infertility and prostate problems.

Despite the lack of scientific evidence, testosterone therapy is growing in popularity. Pharmacies filled 2.4 million testosterone prescriptions in 2004 - more than twice the number filled in 2000, according to IMS Health, a company that tracks pharmaceutical sales. Though the number appears to be growing, there are no data that track who's filling these prescriptions - men or women - and for what purpose.

At the core of the controversy is whether gradually declining testosterone levels are a natural phenomenon or a health problem. And the practical question for men and their doctors is whether to treat it, particularly in the absence of scientific evidence. Before you buy into the tempting claims, find out what's known - and not known - about testosterone therapy so that you can make the best decision for you and your long-term health.

The natural decline of testosterone

Starting around age 40, a man's body produces less testosterone. Testosterone is the main male hormone that maintains muscle mass and strength, fat distribution, bone mass, sperm production, sex drive, and potency.

Many call this progressive decline of hormones "male menopause" or "andropause" and equate it to women's menopause. But this isn't a valid comparison, says Todd Nippoldt, M.D., an endocrinologist at Mayo Clinic, Rochester, Minn. "In women, ovulation ceases and female hormone production plummets over a relatively short time frame," says Dr. Nippoldt. "In men, there's a gradual decline in the production of male hormones."

For most men, testosterone levels naturally decline but still remain within the normal range throughout their lifetimes, causing no significant problems. But about two in 10 men age 60 and older have testosterone levels below the normal range (testosterone deficiency).

Testosterone deficiency can have several effects on the body, including:

• Decreased energy
• Reduced muscle mass and strength
• Decreased cognitive function
• Less sexual interest or potency
• Depressed mood

If you experience these signs or symptoms, you may have testosterone deficiency. Other medical conditions - such as liver disease, hypothyroidism and depression - can cause these effects as can certain medications, including beta blockers, painkillers and certain drugs for depression or anxiety. In addition, some healthy men encounter these changes as a part of the aging process, possibly because of declining hormones other than testosterone.

Talk to your doctor if you're experiencing these signs and symptoms. He or she can help determine the likely cause and suggest the best treatment plan, if any.

Potential benefits and risks

In men with testosterone deficiency, testosterone therapy can restore sexual function and muscle strength, prevent bone loss and protect against heart disease (atherosclerosis). Also, some men taking testosterone therapy report an increase in energy, sex drive and well-being.

Some anti-aging enthusiasts claim that increasing the level of testosterone in older and healthy men provides these same benefits. Though potentially beneficial for some of these men, testosterone therapy isn't risk-free. High doses of testosterone may result in sleep apnea, infertility and excess blood production, which could increase the risk of stroke.

Increasing testosterone levels may also pose problems for the prostate, a small male gland that produces most of the fluids in semen. Testosterone naturally stimulates the growth of the prostate. Long-term testosterone treatment could cause prostate gland enlargement. Also, doctors are concerned that testosterone therapy might fuel the growth of prostate cancer that is already present. This is especially worrisome since prostate cancer is common in older men, and many men may have prostate cancer that is undiagnosed.

In addition, scientists have linked testosterone therapy to breast cancer in men. Breast cancer, like prostate cancer, is a hormone-dependent cancer. Because long-term testosterone treatment could cause breast enlargement in men (gynecomastia), doctors are concerned that testosterone therapy might also fuel the growth of breast cancer that is already present.

All men, especially those with a family history of prostate or breast cancer, should discuss the potential benefits and risks of testosterone therapy with their doctors before beginning treatment.

To carefully weigh the potential pros and cons for you, consider the following:

Potential benefits

Potential risks

Improve muscle mass and strength Increase bone mineral density Thicken body hair and skin Improve sexual desire Boost energy Decrease irritability and depression Improve cognitive function

Cause skin reactions Cause fluid retention Cause baldness Cause or aggravate sleep apnea (brief, repeated cessation of breathing during sleep) Stimulate noncancerous (benign) growth of the prostate and cause or worsen urinary symptoms Stimulate growth of prostate cancer that's already present Enlarge breasts (gynecomastia) Stimulate growth of breast cancer that's already present Cause testicle shrinkage (testicular atrophy) Limit sperm production (infertility) Stimulate excess blood production (polycythemia) Cause acne

Learning from experience
Men aren't the only ones evaluating the benefits and risks of hormone therapy. For years, women have wrestled with the decision whether to take hormone therapy for the treatment of menopausal symptoms. They've had to assess the pros and cons based on the available scientific evidence. Dr. Nippoldt says that men should learn from women's experience.

"Early studies suggested that taking hormone therapy might protect postmenopausal women from heart disease. But a large, long-term study found just the opposite results," he says. "We learned from these studies that we just can't predict all the potential harmful effects of taking hormones even though on the surface they may seem beneficial."

Who should take testosterone therapy?

Testosterone therapy is clearly beneficial for men whose testicles fail to produce sufficient levels of testosterone (male hypogonadism). For this group of men, it can restore sexual function and muscle strength and prevent bone loss.

Few studies have evaluated possible benefits and risks of testosterone therapy for healthy aging men. And those that have been done provide conflicting results. Many questions remain unanswered, particularly the extent and the duration of the beneficial effects, which men might benefit, and the possible long-term risks.

In November 2003, the Institute of Medicine (IOM) reviewed the current evidence surrounding testosterone therapy and reported that this treatment is appropriate only for men who produce little or no testosterone. The IOM concluded that the long-term effects of supplemental testosterone on otherwise healthy men aren't known. And until more studies have been done, the institute recommends that testosterone therapy not be used to prevent or relieve the physical or psychological effects of aging.

Types of testosterone therapy

Several types of testosterone therapy exist. Choosing a specific therapy depends on your preference of a particular delivery system, the side effects and the cost. Types include:

• Injection. Intramuscular testosterone injections (Delatestryl, Depo-Testosterone) are safe and effective. Injections are given approximately every two weeks. You may experience fluctuations in symptom relief between doses. You or a family member can learn to administer this method of testosterone replacement therapy at home. If you're uncomfortable administering injections, a nurse or doctor can give the injection.
• Patch. A patch containing testosterone (Androderm) is applied each night to your back, abdomen, upper arm or thigh. The site of the application is rotated to maintain seven-day intervals between applications to the same site to lessen skin reactions.
• Gel. You rub testosterone gel (AndroGel, Testim) into your skin on your lower abdomen, upper arm or shoulder. As the gel dries, your body absorbs testosterone through your skin. Gel application of testosterone replacement therapy appears to cause fewer skin reactions than patches cause. Avoid showering or bathing for several hours after an application to ensure adequate absorption. A potential side effect of the gel is the possibility of transferring the medication to your partner. You can avoid this by avoiding skin-to-skin contact until the gel is completely dry or by covering the area after an application.
• Gum and cheek (buccal cavity). Striant, a small putty-like substance, delivers testosterone through the natural depression above your top teeth where your gum meets your upper lip (buccal cavity). This product rapidly adheres to your gumline and, as exposed to saliva, softens into a gel-like form, allowing testosterone to be absorbed directly into your bloodstream. Side effects may include gum irritation or pain, bitter taste or headache. A recent study found this form of testosterone therapy may deliver a steadier dose of testosterone throughout the day.
• Oral. Taking testosterone orally (Android, Testred, Virilon) is not recommended for long-term replacement. Testosterone taken by this method may cause an unfavorable cholesterol profile and increase your risk of blood clots and heart and liver problems.

The debate continues

There's no question a man faces emotional and physical challenges as he gets older. Changes at home, at work and within his body all can affect a man's general health. If you're concerned that you might have a hormone deficiency, talk to your doctor. A decline in testosterone that falls below normal values may be a reason to take supplemental testosterone. But it remains unclear whether restoring the testosterone levels to those of youth benefits older men.

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