Testosterone: Key to masculinity and more


From the first glance at the newborn, the evidence is obvious--a tiny penis and a scrotum enclosing the testes. No doubt about it; a male child.

But his gender wasn't always so clear. For the first six weeks or so of gestation, this new baby boy appeared identical to a girl. He had embryonic gonadal cells that looked like they could quite normally develop into ovaries. He had tissue apparently capable of forming fallopian tubes, a uterus, and vagina.

At about 7 weeks of gestational age, testes began to form from cells that otherwise might have become ovaries. The hormone testosterone, produced by the testes beginning in the eighth week, initiated a cascade of actions and reactions causing a remarkable change in embryonic cells that had been on the road to becoming female organs and tissue. Testosterone promoted development of the penis and scrotum, formation of the structures involved in sperm production, and regression of tissue that, without testosterone, would have become fallopian tubes, uterus, and vagina. The result is announced at birth.
"It's a boy!"

Testosterone (one of the masculinizing hormones called androgens) continues to exert a spectrum of influences-some-times quietly, sometimes furiously--throughout a lifetime. Little wonder that this powerful hormone has been ap-proved by the Food and Drug Administration for the treatment of serious health problems caused by a deficiency or absence of naturally occurring androgens and that physicians and scientists here and abroad are trying to demonstrate other beneficial uses for the hormone.
Fluctuating Hormones

At birth, baby boys normally have testosterone blood levels close to those of adolescent and young adult males. But the level soon falls and remains relatively low until puberty, when testosterone and other hormone levels rise sharply. About 99 percent of American boys begin puberty between 9 and 14 years of age.

The earliest sign of puberty is enlargement of the testes. Other changes--the appearance of pubic and other body hair, muscle and bone growth, deepening of the voice, and often acne--tell the world, to say nothing of the boy himself, that sexual maturation is well under way.

After puberty and into adulthood, a complex interaction among the testes, the adrenal glands (which also produce testosterone), and the pituitary and hypothalamus (located at the base of the brain) regulates levels of testosterone and other androgens. In adulthood, testosterone is thought to play a role, not only in sexual function, but in common adult male traits, such as loss of scalp hair and accumulation of abdominal fat--the all-too-familiar "spare tire." Testosterone levels decline with advancing age, but some men retain essentially youthful testosterone levels well into their 70s and 80s.

The presence of presumably normal amounts of testosterone is believed to be associated with some potentially dangerous changes in men. For example, it probably stimulates excessive growth of the prostate, which can lead to urinary disorders and prostate cancer, the second most common cancer in American men. (See "Prostate Cancer: New Tests Create Treatment Dilemmas" in the December 1994 FDA Consumer.)

A number of problems, collectively called "hypogonadism," result from failure of the testes to function normally because of genetic defect, illness, or injury. Unless an obvious abnormality is present at birth, delayed puberty may be the first indication that the testes are producing insufficient amounts of testosterone. If the malfunction occurs before the 12th week of gestation, male genitalia may not form fully or properly. When testosterone levels fall below normal after birth but before the normal onset of puberty, boys may begin puberty late or not at all, exhibit reduced growth of genitalia and body hair, retain a high-pitched voice, and show atypical bone growth and body proportions.

The consequences of hypogonadism beginning after puberty depend largely on the degree and duration of below-normal hormone levels. Typical effects are diminished libido, potency, sperm production, and overall strength. If the condition persists for a long time, the testes atrophy, fine wrinkles appear around the eyes and mouth, and body hair becomes sparse.
Testosterone Replacement

An estimated 150,000 to 200,000 boys and men in the United States are currently receiving testosterone to treat hypogonadism, although many more cases are thought to be undiagnosed and untreated. FDA has approved both oral and injectable testosterone products for use in hormone replacement therapy for boys and men who have hypogonadism. Testosterone is not readily absorbed and used by the body when taken by mouth. Most patients receive the drug by injection for their entire lives. An external patch that delivers the hormone through the skin of the scrotum has been approved by FDA for use in men 18 and older.

Carefully monitored testosterone replacement therapy, combined with other medical and psychological support, can help in cases of delayed puberty by inducing essentially normal growth and maturation. Mature men whose testosterone output is impaired because of illness, including chronic alcoholism, or injury also benefit from testosterone replacement and other medical treatment that can improve sexual and reproductive function.

Some scientists and physicians believe that testosterone therapy may help counter the effects of declining testosterone levels in older men--a normal consequence of aging. These investigators theorize that the decline of hormone levels is responsible for diminished sexual activity, bone and muscle loss, reduced vitality, diminished mental powers, and other physical and psychological deficits often seen in older men.

A number of studies in the United States, Europe, and Asia suggest that testosterone replacement therapy may counteract or retard these effects of aging. But they also confirm that using testosterone in this way can cause or aggravate undesirable growth, including cancer, of the prostate gland. Such treatment can also be very dangerous in patients with heart, liver or kidney disease. FDA has not approved the use of testosterone to treat conditions associated with aging. In this country, the only approved use for testosterone in males is treatment of hypogonadism. Androgenic hormonal drugs, including methyltestosterone, are approved for treating postmenopausal women with advanced inoperable breast cancer that has spread to skeletal bone.
Testosterone Replacement in Women?

There is a good deal of scientific uncertainty about the possible usefulness of testosterone replacement therapy in postmenopausal women, despite the claim by some authorities that it could have a role in women's health. Although usually thought of as the "male" hormone, small amounts of testosterone are produced in the female body as well--chiefly by the ovaries and adrenal glands. Wide variations are common, but on average a woman's blood has about 5 to 10 percent as much testosterone as a man's. Along with levels of the hormones estrogen and progesterone, women's testosterone levels fluctuate during the menstrual cycle. They are highest at the time of ovulation. (Similarly, in men, the adrenal glands produce low levels of estrogens, the "female" hormones. See "Estrogen: Friend or Foe?" in the April 1995 issue of FDA Consumer.)

The role of testosterone and other androgens in female development and health is not well understood. Androgenic hormones, including testosterone, cause the growth of pubic and underarm hair in men and women and influence normal bone and muscle growth in both sexes. If androgens reach unusually high levels in an adolescent girl, they may produce effects ordinarily seen in pubescent males--excessive growth of facial and body hair, deepening of the voice, and worsening of acne.

In adult women, higher-than-normal testosterone levels have been associated with elevated blood pressure and increased risk of heart disease, diabetes,. and uterine cancer, although these possible health effects have not been thoroughly studied.

There is some medical and scientific interest in using testosterone to treat certain symptoms in postmenopausal women. Some researchers speculate that among the problems for which testosterone may be beneficial are diminished sexual interest and response, loss of bone and muscle tissue, depression, and other physical and psychological changes--a spectrum of conditions not unlike that for which testosterone is being studied in older men. (The skin patch testosterone preparation, Testoderm, is not approved for use in women.)

Testosterone in the treatment of women has not been well studied in the United States, and data from other countries is sparse. Testosterone is used along with estrogen in some postmenopausal women receiving hormone replacement therapy at the Chelsea and Westminster Hospital in London. A similar treatment approach is followed in other European and Asian countries. FDA has not ap-proved any applications for such uses in this country, however, and the vast majority of U.S. physicians do not prescribe it for this use as there is no substantial evidence that it provides any important health benefit or that its risks are acceptable in women.

Testosterone replacement therapy for men for conditions associated with normal aging is being studied, but is far from standard practice in the United States. But estrogen replacement therapy in women, though commonplace today, was once an unproven subject of research. Research has shown that estrogen can be used safely and effectively in the treatment of menopausal hot flashes and the prevention of postmenopausal osteoporosis in women. Whether science can establish a role for testosterone in the treatment of older men (and perhaps women as well) is a question that awaits further research.

ILLUSTRATION: The Waiting Womb...

PHOTO (BLACK & WHITE): A man opens a package containing a testosterone patch that he will place on the scrotum. Absorbed through the skin, the hormone treats hypogonadism.

GRAPH: Approximate Testosterone Blood Levels in Human Males (in nanograms per deciliter)


By Ken Flieger

Ken Flieger writer in Washington, D.C.


Testosterone exerts powerful effects on human bodies, helping make them stronger and bigger. It also increases sex drive and function in men (and, according to some studies, in women--although this possibility is still uncertain). Not surprisingly, some young American men obtain testosterone illegally. And so, it seems, do athletes, including both men and women Olympic competitors who apparently use the hormone to improve performance. This use violates Olympic rules--and it's dangerous.

Androgens, such as testosterone, taken by injection or by mouth during early puberty can cause abnormal bone growth, including premature growth stoppage. At inappropriate doses, testosterone can disturb fluid and mineral balances; cause nausea and other gastrointestinal problems, including life-threatening liver disease and tumors; induce male breast enlargement; interfere with blood clotting; cause increased or decreased libido, headache, anxiety, and depression; raise cholesterol levels; and--especially if taken over a long period--suppress normal testosterone production.

Like anabolic steroids, many testosterone products, including the skin patch formulation known as Testoderm, are schedule III controlled substances because of the potential for abuse. Testosterone is nothing to fool around with.

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