Testosterone Overview

Testosterone production declines naturally with age. Testosterone deficiency (TD) may result from disease or damage to the hypothalamus, pituitary gland, or testicles that inhibits hormone secretion and testosterone production, also known as hypogonadism. Depending on age, insufficient testosterone production can lead to abnormalities in muscle and bone development, underdeveloped genitalia, and diminished virility.

Testosterone is the androgenic hormone primarily responsible for normal growth and development of male sex and reproductive organs, including the penis, testicles, scrotum, prostate, and seminal vesicles. It facilitates the development of secondary male sex characteristics such as musculature, bone mass, fat distribution, hair patterns, laryngeal enlargement, and vocal chord thickening. Additionally, normal testosterone levels maintain energy level, healthy mood, fertility, and sexual desire.

The testes produce testosterone regulated by a complex chain of signals that begins in the brain. This chain is called the hypothalamic-pituitary-gonadal axis. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) to the pituitary gland in carefully timed pulses (bursts), which triggers the secretion of leutenizing hormone (LH) from the pituitary gland. Leutenizing hormone stimulates the Leydig cells of the testes to produce testosterone. Normally, the testes produce 4–7 milligrams (mg) of testosterone daily.

Incidence and Prevalence

Testosterone production increases rapidly at the onset of puberty and decreases rapidly after age 50 (to 20% to 50% of peak level by age 80). Approximately 8 million men in the United States experience testosterone deficiency; approximately 600,000 receive treatment.

Types and Causes

Hypogonadsim is classified by the location of its cause along the hypothalamic-pituitary-gonadal axis:

· Primary, disruption in the testicles
· Secondary, disruption in the pituitary
· Tertiary, disruption in the hypothalamus

Disease, injury, surgery, and drug side effects can cause hypogonadism and testosterone deficiency. Hypogonadism is congenital or acquired, depending on the nature of the underlying condition.

Congenital causes include the following:

· Anorchia (vanishing testes syndrome; causing primary hypogonadism)
· Cryptorchidism (failure of testicles to descend into scrotum; causing primary hypogonadism)
· Hormonal deficiency (e.g., deficiency of leutenizing hormone releasing hormone)
· Kallmann syndrome (insufficient hypothalamic GnRH production; causing tertiary hypogonadism)
· Klinefelter syndrome (underdeveloped testicles; causing primary hypogonadism

Acquired causes include the following:

· Chemotherapy
· Damage occurring during surgery involving the pituitary gland, hypothalamus, or testes
· Glandular malformation
· Head trauma (affecting the hypothalamus)
· Infection (e.g., meningitis, syphilis, mumps)
· Isolated LH deficiency (e.g., fertile eunuch syndrome)
· Radiation
· Testicular trauma
· Tumors (of the pituitary gland, hypothalamus, or testicles)

Signs and Symptoms

Signs depend on the age of onset and the duration of hormonal deficiency. Congenital hypogonadism is generally characterized by underdeveloped genitalia (testes that do not descend into the scrotum) and, occasionally, undeterminable genitalia. The development of hypogonadism near puberty can result in gynecomastia (enlargement of breast tissue), sparse or absent pubic and body hair, and underdeveloped penis, testes, and muscle. Adult men may experience diminished libido, erectile dysfunction, muscle weakness, loss of body hair, depression, and other mood disorders. Use the Testostene Deficiency HealthProviderr to evaluate your symptoms.

Complications

Testosterone deficiency has been linked to muscle weakness and osteoporosis. In one study, proximal and distal muscle weakness was detected in 68% of men with primary or secondary hypogonadism. Spinal, trabecular, and radial cortical bone density may also be significantly reduced in testosterone-deficient men. Thirty percent of men with spinal osteoporosis have long-standing testosterone deficiency, and one-third of men have subnormal bone density that puts them at risk for fracture.

Diagnosis

Serum and blood testing is done to determine the availability of testosterone and levels of leutenizing and gonadotropin-releasing hormones in the body. Men with low testosterone in whom normal or high gonadotropin levels are found typically have primary hypogonadism, which stems from a problem in the testicles. Secondary and tertiary types, caused by problems of the hypothalamus or pituitary gland, often result in low testosterone and low gonadotropin levels.

Other tests involve injecting GnRH or clomiphene citrate (an estrogen) to stimulate a diagnostic response within the hypothalamic-pituitary gonadal axis.

Rarely, testicular biopsy is done, usually in cases where sperm is absent from ejaculate despite normal testicle development. Biopsy, which involves using a needle to collect a sample of testicular tissue, may detect a malfunction in sperm production.

Treatment

Treatment involves hormone replacement therapy. The method of delivery is determined by age and duration of deficiency. Treatment for adults is aimed at maintaining secondary sex characteristics, improving energy, strength, mood, and feelings of well-being, and preventing bone degeneration. Modes of delivery include transdermal, injection, and oral.

Transdermal delivery (through the skin) is used to administer therapeutic agents for hormone replacement. Transdermal replacement therapy with a testosterone patch is becoming the most common method of treatment for testosterone deficiency in adults. It establishes and maintains adequate serum levels without causing significant side effects in as many as 92% of men treated. A patch is worn, either on the scrotum or elsewhere on the body, and testosterone is released through the skin at controlled intervals. Patches, like Testoderm® (scrotal) or Androderm® (nonscrotal), are typically worn for 12 or 24 hours and can be worn during exercise, bathing, and strenuous activity. The Androderm® patch is applied to the abdomen, lower back, thigh, or upper arm.
The most common side effects associated with transdermal patch therapy include itching, discomfort, and irritation at the site of application. Some men may experience fluid retention, acne, and temporary gynecosmastia.

Androgel® is a transdermal gel that is applied once daily to the clean dry skin of the upper arms or abdomen. It delivers testosterone for 24 hours when used properly. The gel must be allowed to dry on the skin before dressing and must be applied at least 6 hours before showering or swimming. It cannot be applied to the genitals. Side effects may include adverse reaction at the site of application, acne, headache, and alopecia (hair loss).

Kallmann syndrome in adults may be treated with chorionic gonadotropin, which can cure cryptorchidism and infertility.

Instramuscular injection is used less frequently because it is associated with erratic testosterone levels. Levels that get too high and then drop too low before the next dose may cause fluctuating moods, energy levels, and libido.

Children and adolescents with low testosterone and delayed puberty may be treated with low doses of testosterone through intramuscular injection (IM) to induce puberty. Adolescents may receive gradually increasing doses that last longer in the body, because, with age, there is less risk for affecting normal growth patterns.

Oral testosterone (methyltestosterone, Testred®) is prescribed sparingly, because it is associated with liver toxicity and liver tumors.

Testosterone Replacement for Women

"Although women authors including Gail Sheehy and Susan Rako, M.D. have described this deficient testosterone state in women, almost no one talks about it and almost no one does anything about it," states Dr. Lichten. "When women are placed on hormonal therapy, whether birth control of estrogen replacement, their testosterone levels drop dramatically." As physicians, we must listen to our women patients, ask them questions about their sexuality and day-to-day ability to function, and replace testosterone whenever appropriate.

Background Information:

Testosterone is recognized as the hormone of desire: it makes muscles for boys and turns them into sexually functional men. But testosterone is very important to a woman, too. She produces increased amounts of this hormone in her puberty, because testosterone is the precursor to estrogen. Without testosterone, there would be no "woman."

A woman's testosterone levels are highest in the early twenties. The decrease in sex drive we see thereafter is often due to oral contraceptives which suppress all sex hormone production (testosterone, estrogens and progesterone). The treatment is relatively simple: add back some testosterone. However, physicians see more effects from testosterone deficiency as a woman approaches and enters menopause. The ovaries produce the majority of testosterone and estrogens. With the cessation of 80% of hormonal production, a peri- menopausal woman suffers from estrogen, progesterone and testosterone deficiency. The replacement of estrogen alone does not correct an absent sex drive, loss of muscle tone and general lack of mental get-up-and-go.