Hormone replacement therapy for men
Ronny G. Frischman
If the only urge a man feels in spring is a desire to climb out of his long underwear, it’s a sure sign that he’s getting on in years. Although there is no elixir to reverse aging, researchers are asking whether hormone supplements might restore a more youthful outlook and bolster the quality of life for aging men.
Although sex hormone levels start to decline in midlife for both men and women, only in women has this been considered a condition that warranted medical treatment. As a result, millions of menopausal women take hormone-replacement therapy (HRT) to relieve hot flashes and other symptoms of falling estrogen levels. HRT also may lower the risk for osteoporosis, heart disease, and Alzheimer’s.
In contrast, male hormone-replacement therapy (MHRT) has seldom been prescribed for healthy, older men. However, recent evidence suggests that men might be able to stay leaner, stronger, happier, and more virile longer if they took supplements to make up for the testosterone that is lost to advancing age.
With possible benefits extending from the bedroom to the boardroom, the appeal of testosterone-replacement therapy is obvious. There have been only limited scientific studies of its long-term effects, however, and experts remain concerned that hormone supplements might put mature men – who already are more vulnerable to prostate cancer and cardiovascular disease than younger fellows – at even greater risk.
Just starting out
As the principal masculinizing hormone (androgen), testosterone stimulates bone and muscle growth and promotes development of male genitalia. It begins shaping the male child in utero as early as 12 weeks into gestation and remains largely quiescent until puberty. At that point, acting on a signal from the brain’s hypothalamus, the pituitary gland tells specialized cells in the testes to kick testosterone production into high gear. This hormonal surge activates sex drive and sperm production, prompts the appearance of acne, facial and pubic hair, and deepens the voice. Not exclusive to men, testosterone is produced in much smaller quantities in women.
In adult men, the testes produce about 7 mg of testosterone daily, with output generally being higher in the early morning than at other times of the day. Most testosterone travels through the bloodstream in a biologically inactive form; only 1-2% interacts with tissue. A standard blood test that measures both types is used when doctors want to assess a man’s testosterone level.
Though the idea of male menopause, or male climacteric, has been tossed about for years, the fact is that hormonal shifts related to aging differ for men and women. Men simply don’t undergo the dramatic “change of life” that women do. Some time in their los or 50s, women stop menstruating – their ovaries literally cease to produce eggs or estrogen. In a wild attempt to restore flagging estrogen levels and ovary function, the pituitary releases huge amounts of gonadotropin hormones. The resulting hormonal turbulence accounts for the hot flashes, mood swings, and vaginal dryness that plague many menopausal women.
A slower decline
The male sex hormone doesn’t nosedive like estrogen. As men get older, the amount of testosterone in their blood gradually drops, and the peaks and valleys seen in younger men flatten out. By the age of 60, many men have testosterone levels hovering around the low end of normal. Although there is no failure in the sexual or reproductive system, the brain speaks less clearly to the pituitary gland, which in turn sends weaker signals to the testicles – where fewer cells are available to respond. Some studies suggest that men’s testosterone levels may fall 30-40% from their late 40s to early 70s.
Although physiologic changes occur in men, they are generally more subtle than those in women. For instance, men may see sexual function start to slide – the machinery still operates, but with less verve than the younger model. Muscles begin to atrophy, fat collects around the middle, and bones lose their density, leaving a man more prone to osteoporosis. Just how great a role the decline in testosterone plays in precipitating these changes is unclear.
Physicians have usually reserved testosterone replacement for men who have hypogonadism, a condition in which the testicles produce an inadequate amount of the hormone. Now that more men are living into their 70s, 80s, and beyond, scientists are testing the usefulness of MHRT in those who are testosterone impoverished, if not frankly deficient. “There is a lot of enthusiasm about hormone replacement, but we have to find out if there is a downside to it,” said Richard M. Spark, associate clinical professor of medicine at Harvard Medical School and director of the steroid research laboratory at Boston’s Beth Israel Hospital.
MHRT research is relatively new, and although most studies are small there are preliminary signs of benefit. In an experiment at Emory University School of Medicine in Atlanta, geriatrician Joyce S. Tenover gave injections of testosterone or a placebo to 13 men, ages 57-76, whose levels were at the low end of normal.
The hormone injections – 100 mg a week for three months – raised the participants’ testosterone levels to the middle of the normal range for young adult males. At the end of the study, the treated men showed significant increases in body weight and lean body mass. A urine test showed that they might be losing less bone mass than they had been, and a rise in hematocrit (red blood cell count) indicated an improve in the blood’s capacity to carry oxygen.
In terms of heart disease risk, treatment lowered levels of total cholesterol and harmful low-density lipoprotein (LDL); levels of beneficial high-density lipoprotein (HDL) declined slightly. On a more ominous note, the men’s level of Prostate specific antigen (PSA) rose – a change that could be linked to benign prostatic hyperplasia (a nonmalignant enlargement of the prostate) or to prostate cancer.
Particularly interesting was the effect of supplementation on the men’s mood and sexual function. During the three-month study, the men said they felt better when receiving testosterone than when the injections were inactive. In fact, 12 of the 13 could tell when they were getting the hormone. The tip-offs were enhanced libido, greater aggressiveness in business, and an overall sense of well-being. Dr. Tenover noted, however, that her study was short term and she advises against testosterone supplementation for older men until longer-term effects are known.
Until a few years ago, men who needed testosterone replacement had to have an injection every week or two. Testosterone pills are now available, but physicians seldom recommend them because they can cause serious liver damage.
The most exciting development is the availability of testosterone skin patches, which work like the estrogen patches that women have been using for years. One patch (Testoderm), which is worn on the scrotum, delivers either 4 or 6 mg of testosterone to the bloodstream daily. It must be changed every 22 to 24 hours to be effective. More recently, the Food and Drug Administration (FDA) approved another. preparation (Androderm), which comes with two patches that must be changed every evening but can be applied to the arms, thighs, back, or abdomen. Both products normalize blood levels of testosterone and even mimic the ebbs and flows typically seen in young, healthy men.
Advantages of the patches are their convenience and constant dosage; injections cause circulating testosterone level to start off extremely high and dwindle between treatments. The patches have a downside, of course. The scrotal patch will adhere only when the scrotum is shaved and the patch is preheated with a hair dryer. The body patches, on the other hand, must be moved around because they often cause local irritation and redness.
Cost also is a factor. While injections can cost as little as $8 a month, the testosterone patches run approximately $80 to $90 a month for the scrotal patch and about $100 a month for Androderm.
The jury is still out
The National Institute on Aging is underwriting large-scale studies that are expected to shed new light on the safety and effectiveness of MHRT. It will be several years before results are available, however. In the meantime, most physicians are cautious about hormone therapy for men. They worry that it might increase heart disease risk by lowering HDL cholesterol levels, aggravate prostate problems, or promote tumor growth. “We have to ask ourselves: will this help men live longer, or will it give them shorter but possibly happier lives?,” said Dr. Spark.
For now, men who are troubled by sexual dysfunction or a flagging quality of life should talk honestly with their physicians. Some problems may be due to slumping testosterone, but others may result from unrelated conditions. For example, atherosclerosis is the most common cause of impotence, and fatigue or depression may adversely affect sexuality. If laboratory tests confirm that testosterone level is low, men who use MHRT must have their cholesterol and PSA checked regularly.
Whatever the benefits of hormone replacement prove to be, it won’t turn back the clock or transform a frail octogenarian into Arnold Schwarzenegger. However, if future research yields good results and men have reasonable expectations, testosterone may provide some of them with a little extra steam as they chug up the hill.
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