High On Testosterone

Things weren't going well for Tristan Logan last winter, physically or mentally. The 55-year-old, an avid weight lifter with a black belt in tae kwon do, was tired and weak. The amount of iron he was able to pump during workouts was decreasing, after steadily increasing for years. Worse, the antidepressants he takes seemed to stop working, and his mood darkened. "I was going down the tubes," recalls Logan, of Nashua, N.H. Then, during a physical, his doctor checked Logan's testosterone level and discovered it was low. Logan was referred to a specialist, and after a workup that included tests for prostate cancer (results negative), he began receiving testosterone-replacement therapy (TRT). "I was going into a pretty bad depression right when I started the therapy," says Logan. "And man, I'll tell you, three days after I had that first shot it kicked me out of my depression like a mule." Seven months later, Logan continues to receive a testosterone shot every two weeks and, though no one really knows what the long-term health effects are, he has no plans to stop TRT. "I'm sold on it," he says.

Testosterone is hot, the hormone of choice for hundreds of thousands of middle-aged men determined to stave off the constellation of symptoms, including erectile dysfunction and loss of libido, that have come to be known by some as andropause, the male version of menopause. Doctors wrote more than 1.9 million prescriptions for testosterone in 2002, a 27 percent increase over 2001, according to IMS Health, which tracks the pharmaceutical industry. Nearly 1.3 million prescriptions were written in the first six months of 2003 alone. With 4 million to 5 million American men walking around with abnormally low testosterone, those numbers should continue to rise.

But as older men line up for TRT there is growing concern that they could suffer a fate similar to the millions of women who for years used hormone-replacement therapy (HRT) for the symptoms of menopause. They thought it was safe and even protected them from disease, until the summer of 2002, when a major study by the Women's Health Initiative was halted after it became clear that HRT actually increased a woman's risk of breast cancer and heart disease. In an effort to avoid a replay of that nightmare, the National Institutes of Health has created a special task force to study ways to assess the risks and benefits of TRT in older men. One option the task force could recommend: a big clinical trial like the one that revealed the dangers of HRT. The task- force report won't be released until November, but experts say the high cost of a large study--possibly $100 million or more--could be an obstacle. Another potential snag: it might be difficult to design a large-scale trial of TRT in older men without first doing more small-scale studies to gather additional data.

There's also an ethics question. Is it OK to give older men testosterone in a long-term study when there's a possibility that it could be harmful? Perhaps not, but lots of men--an estimated 819,000 in 2002, the majority (57 percent) between 46 and 65--are already using testosterone gels, patches, injections and pills. With that number sure to increase (it jumped 29 percent in a year), the question might be: is it ethical not to do a big study?

Testosterone, which circulates in the blood at levels that vary from hour to hour (normal range is from 300 to 1,200), has some traits that may make TRT risky. It's well known that testosterone can feed the growth of prostate cancer, which becomes more common as men age. It may also contribute to heart disease by facilitating blood clotting and reducing levels of HDL, the good cholesterol, says Dr. Todd Nippoldt, an endocrinologist at the Mayo Clinic. This raises the possibility that the decline in testosterone that accompanies aging might be one way nature protects older men against prostate cancer and heart disease.

But could the potential benefits of TRT outweigh the potential risks? Dr. Abraham Morgentaler, a professor at Harvard Medical School, has analyzed dozens of short-term TRT studies and is convinced the treatment is safe for men who don't have prostate cancer. "There is a good chance we're going to find out that testosterone is actually beneficial for health," says the urologist, who's treated thousands of men with testosterone. Besides restoring libido, TRT has been shown to improve bone density and muscle mass. And a small study done at Boston's McClean Hospital this year suggests that, when used in conjunction with antidepressants, testosterone may improve depression in difficult-to-treat men.

Morgentaler, whose new book, "The Viagra Myth," explores the social impact of the popular drug, doesn't think it's proper to withhold TRT from older men with symptoms of low testosterone because of "theoretical, unproven concerns." "There's a risk in not treating people," he says. "And the risk is that they may go through life with depressed mood, less energy. And if we have an opportunity to let men live satisfying, vital, loving lives, why shouldn't we do that?" A large-scale, long-term clinical trial of TRT might answer that question.