What About Men?
Tired? Got the blues? Maybe testosterone can help. Or not.
When Joe Marcklinger hit his 50s, he found himself feeling tired and blue--way too often. He tried taking antidepressants but had a hard time accepting one of the drugs' most common side effects--sexual dysfunction. Then Marcklinger's wife, Maureen, a psychiatric nurse, heard about research using the male sex hormone testosterone to treat depression. She urged her husband to check it out. "Within a few days I started feeling mentally better," says Marcklinger, 57. "I started feeling more energy." He now finds it easier clambering over fences while on the job with his surveying business in Sudbury, Mass., and has better muscle tone. "You know how older guys look weak? I'm not like that." Things are better in the bedroom, too.
In the past few years, the number of men taking supplements of the male sex hormone testosterone has soared, fueled by baby boomers feeling the slights of middle age. The market has also been boosted by the availability of skin gels that are much easier to use than the unpleasant injections or dangerous pills of years past. The number of men taking "testosterone replacement therapy" increased 29 percent from 2001 to 2002, when nearly 2 million prescriptions were written, and the Internet is awash with ads selling the sex hormone--despite the fact that testosterone is available only by prescription. The Web site for AndroGel, one of the leading treatments, shows the needle of a gas gauge drooping at Empty. "Fatigued? Depressed mood? Low sex drive?" the site asks. With "testosterone restored," the needle leaps to "Full."
Risks. Only one problem: There's no clear proof that testosterone replacement therapy combats fatigue, depression, or low sex drive in healthy men. In fact, there's little proof of either the benefits or the risks of supplemental testosterone, because no large, long-term studies have been done. Although there are intriguing hints that testosterone may reduce age-related bone and muscle loss, there are also ominous suggestions that extra testosterone could be life threatening. The No. 1 concern: prostate cancer. Suppressing testosterone slows both prostate cancer and benign prostatic hyperplasia, and about half of men over age 50 have undetected cancer cells in their prostate glands. Adding testosterone may also increase the risk of stroke-causing blood clots, cardiovascular disease, and sleep apnea. But no one knows for sure. "It could be that testosterone therapy may have an important preventive role," says Evan Hadley, an associate director at the National Institute on Aging. "Right now we just don't know." The NIA recommends testosterone therapy only for the relatively few men with extreme deficiencies, saying that it's otherwise "not deemed appropriate therapy for most men at this time."
But that's not stopping Marcklinger and lots of other men with relatively normal testosterone levels. Well aware of the controversy surrounding testosterone therapy and prostate cancer, he underwent a prostate biopsy to look for cancerous cells before starting treatment and has his PSA level checked every six months. He says he'd undergo a biopsy again in a minute if that's what it would take to stay on the drug. "I went to [talk] therapy for depression, or midlife crisis, and found that helped. But this really is a fix."
Skeptics. More than a few researchers worry that American men risk repeating the sorry tale of the nation's women, who for decades took estrogen supplements after menopause in the belief it would protect them against heart disease. Only recently, through new research from the Women's Health Initiative, have they discovered that the opposite is true. Add in the huge marketing push for "testosterone replacement therapy" by the pharmaceutical companies hawking the stuff, which has waxed just as enthusiasm for women's hormone replacement therapy has waned, and there's more than a little reason to be skeptical. "Because of what we've learned from the Women's Health Initiative, it's very important to be cautious and not assume that a single hormone can be therapeutic," says Linda Fried, director of the Center on Aging and Health at Johns Hopkins University. Fried served on an Institute of Medicine panel that called last year for more research on testosterone therapy--and extreme caution in using it until the research is done. Because so little is known, the IOM panel said, scientists should look first at frail men over 65 with clear testosterone deficiencies, because they would be the most likely to see benefits. Those studies will take at least four years to yield information, according to NIA's Hadley. Research on the much larger cohort of healthy men, ages 50 and up, who may be interested in using testosterone to fight symptoms of aging, would take longer. That research would also be more controversial, because the men involved would face potential long-term risks with less clear benefit.
Few physicians would argue that a man with very low testosterone, which can cause infertility, enlarged breasts, and muscle wasting, should seek treatment. The larger question is whether "male menopause" should be treated--or if it even exists. Where a woman's production of estrogen plummets at menopause, ending fertility, men's testosterone levels subside very gradually, declining by about 1 percent a year starting around age 30. But an individual's testosterone levels can fluctuate a great deal through adulthood, and men in their 70s are still capable of fathering children. There is no "pause" in "andropause." Even diagnosing clinical testosterone deficiency--the technical name is hypogonadism, which affects 2 million to 4 million men in the United States--is tricky, since the blood tests most commonly used aren't very reliable. (A total serum testosterone level below 200 is considered deficient, while 30-year-olds have a mean level of 600, compared with 400 at age 80.) And the symptoms listed for andropause, which include decreased sex drive, fatigue, loss of strength and muscle mass, and difficulty concentrating, could apply at some point to just about every older man--or older woman for that matter.
"The resistance to the idea of testosterone is that it's very common for all sorts of things to decline as we grow older," says Abraham Morgentaler, a urologist at Beth Israel Deaconess Medical Center in Boston, who reviewed existing studies on testosterone's safety in a recent New England Journal of Medicine. Although Morgentaler monitors his patients for prostate cancer with biopsies and blood tests, he describes himself as a "cheerleader" for testosterone therapy, saying it treats the biggest sex organ of them all--the human brain. "If a man comes in with low sexual desire and fatigue, there's a good chance that testosterone will be a home run for him."
But aging is a complex process, involving many physical processes and hormones. Testosterone, a steroid that affects many organs and tissues, is just one of them. Studies that gave healthy men over 65 enough testosterone to raise their blood levels to that of a man in his 20s found that the men gained, on average, 4 pounds of muscle and lost 6 pounds of fat but gained no improvement in muscle strength or bone density. And more isn't always better. Although testosterone is universally associated with virility, giving a man too much causes testicular atrophy and sterility. The normal decrease in testosterone associated with aging may well confer some yet-to-be-understood physiological benefit (aside from making an office less like a high school locker room). Or it may be possible to develop drugs that deliver the benefits of testosterone without the risk, much as drugs such as raloxifene have been developed to give women the bone-protecting benefits of estrogen without the cancer risk, according to Glenn Cunningham, a testosterone researcher at the Baylor College of Medicine. "The symptoms that are associated with low testosterone in younger men are clearly a lot of the symptoms that occur in the setting of aging," Cunningham says. "I believe there is a potential benefit. I just don't know what the risk is."
Do Men Have an 'Andropause'?
Unlike women, men don't experience a sharp drop in sex hormones in midlife.
[Chart labels]
Peak hormone levels
Men
Women
10 yrs.
30
50
70
90
USN&WR
This story appears in the March 15, 2004 print edition of U.S. News & World Report.