Feb. 26, 2003 -- Many were shocked last summer when a large government study confirmed the potential health risks of estrogen replacement therapy -- once lauded as the Fountain of Youth for aging women. Now similar claims are being made about testosterone replacement for aging men. A growing legion of users say the therapy helps turn back the clock, but experts counter that there is little scientific evidence to back that up.
Proponents say testosterone replacement therapy restores youth by improving sex drive, sexual performance, energy, and mood. It is also said to help build muscle mass and bone, and there have been claims that it lowers cholesterol and protects against heart disease. But research is limited to relatively small studies, and those findings are far from conclusive.
In the Feb. 26 issue of The Journal of the American Medical Association, Brian Vastag raises concerns about the lack of knowledge surrounding testosterone replacement. A large study, similar to the estrogen trial in women, is the only way to determine the safety and effectiveness of testosterone replacement therapy in aging men, experts say.
A special committee of the National Academy of Science's Institute of Medicine is considering the question and is expected to report its findings late this year.
"We don't know whether testosterone replacement therapy actually does many of the things that it is supposed to do," committee member and epidemiologist Elizabeth Barrett-Connor, MD, tells WebMD. "The only thing we are fairly sure of is that it gives older men some energy and helps build a little muscle. Those are desirable things, but we don't know what price these men are paying for it."
She says there is some evidence that, instead of preventing heart disease, testosterone replacement increases the risk of heart attacks and strokes in older men. In addition, there is a big concern that hormone therapy increases the risk of prostate cancer. Barrett-Connor is chief of the division of epidemiology at the University of California San Diego.
"We don't have the answers, but a large number of men are out there taking testosterone anyway," she says. "We really need to do trials to determine if it is safe."
It is not known how many older men are on testosterone replacement, but the numbers are believed to have increased dramatically since the FDA approved an easy-to-apply testosterone gel in the spring of 2000. News reports noted that sales of the gel quadrupled the following year.
The usefulness of the treatment for men with abnormally low testosterone levels is unquestioned. But it is less clear whether testosterone therapy offers benefits to aging men with naturally declining levels of the male sex hormone, says National Institute on Aging deputy director Stanley Slater, MD.
"We know that in most men, testosterone levels drop by about a third by the time they reach 65, but this is not the case for all men," Slater tells WebMD. "The question is, does it matter in terms of health whether a man has 30% less testosterone? And nobody knows the answer to that."
Slater says a good trial to determine if testosterone therapy increases the risk of prostate cancer would need a minimum of 6,000 men and would cost in excess of $100 million. A similarly large study would be needed to determine if testosterone replacement promotes or protects against heart disease.
In his editorial, Vastag writes that a Baylor College of Medicine researcher has proposed just such a study. But any plans to move forward are on hold -- pending conclusions from the Institute of Medicine special panel. In light of this delay, the study would not even begin until mid to late next year, with results expected at the end of the decade.
"Small studies have suggested that testosterone replacement therapy increases bone density and promotes lean body mass and less fat," Slater says. "These things are indicative of youth and health, but they are not the same thing. The real measures of health are whether there is sickness and loss of functionality. For these measures, we don't yet know if testosterone is helpful."