Why do testosterone levels among healthy men vary so much? Hayes speculates that some men may have highly efficient testosterone receptors—cellular traps that grab the free hormone in the blood—so that what appears to be an abnormally low testosterone level is all the hormone they need. But even an individual’s testosterone levels can be markedly different at different times.

One factor may be stress, which seems to reduce levels of sex steroids. Drug interactions, too, might alter testosterone levels in unpredictable ways. And much of the variation simply eludes explanation. Crowley studied several young men whose initial test results showed testosterone levels ranging from 150 to 200—well below the 300 cutoff—over twenty-four hours. “They had a perfectly normal testosterone profile,” Crowley says. “There can be a funny disconnect between one measurement and a later one”, which means that testosterone deficiency, may be easily over diagnosed.

Updated guidelines on diagnosis and treatment of hypogonadism in men reflect advances in treatment and more robust data about the short-term benefits of testosterone replacement therapy.

The guidelines, issued by the American Association of Clinical Endocrinologists (AACE), also urge additional research into the long-term use of the therapy and its possible effects on the risks of cancer and cardiovascular disease.

“Concern about long-term safety and efficacy remains an issue,” said Dr. Steven M. Petak, chair of the guidelines revision committee.

“Perhaps these new guidelines will stimulate some additional research into these issues,” said Dr. Petak, an endocrinologist at the Texas Institute for Reproductive Medicine and Endocrinology, Houston.

The National Institute on Aging has begun work on a 1-year study to evaluate the feasibility of conducting clinical trials of testosterone replacement therapy in older men. A task force will report on the known benefits and risks of the therapy, its potential public health impact, and the ethical issues involved in conducting such a clinical trial. The report is expected by November, said Dr. Stanley Slater, deputy director of the institute’s geriatrics and clinical gerontology program.