By Melinda Beck

February 2008 | online.wsj.com

Printed in The Wall Street Journal, page D1, February 26, 2008

Tampa, Fla. They're bullish on testosterone here at the 6th Annual World Congress on the Aging Male.

Physicians and researchers from around the world gathered to review the latest findings on what low levels of the male hormone means for men, how replacing it might help and why it hasn't caught on broadly.

"If we had a drug that could restore sexual function in men, make them stronger, build their bones, reduce fat and get rid of the blues, you'd say, 'Oh my God, why doesn't everybody know about it?' " says Abraham Morgentaler, a urologist at Harvard Medical School and director of the Men's Health Boston clinic. "There is a drug like that -- but the public associates testosterone with cheating and illicit behavior and the fact that 40 years ago, it was thought to give people prostate cancer."

However, the testosterone level that defines androgen deficiency in aging men (ADAM) remains controversial, and its prevalence in men with ED has remained uncertain.

Whether it does or not is still an open question. But many studies have shown that low testosterone is associated with reduced muscle mass, bone density, sexual function and vitality, and increased fatigue, depression, Type II diabetes and obesity -- particularly belly fat. Evidence is accumulating that restoring testosterone to normal can alleviate many of those problems.

"Men with low testosterone are miserable to live with -- they fall asleep after dinner and snap at everyone," says David Greenberg, a general practitioner in Toronto. "You restore it and they say, 'Wow, I feel like myself again.' "

But there's debate over which of the three forms of testosterone to measure, what level constitutes "low" and, most importantly, at what age. Testosterone declines naturally after age 40. So is a 70-year-old man deficient or just aging?

Women lose estrogen much more abruptly in menopause, and replacing it to alleviate symptoms and maintain bone health has been standard practice for decades, though questions remain about the risk of breast cancer.

There are even more unknowns about the risks and benefits of testosterone replacement. For one thing, many of the symptoms of low testosterone are very common in older men and could be related to other conditions. Some, like obesity, may lead to low testosterone rather than vice versa.

And there is lingering concern that testosterone could fuel prostate cancer -- largely because drugs that reduce testosterone seem to shrink enlarged prostates and lower the risk of developing prostate cancer by 25%, according to the National Cancer Institute's Prostate Cancer Prevention Trial.

On the other hand, an analysis of 18 studies in the Journal of the National Cancer Institute last month concluded that there is no correlation between testosterone levels and prostate-cancer risk. Another study in the Journal of Clinical Endocrinology and Metabolism found that men with low testosterone had higher mortality rates in general than those with higher levels, regardless of other risk factors.

Some drug makers are testing oral variations of testosterone that would deliver the benefits without the potential prostate hazards. For now, testosterone is available mainly in injections, topical gels and patches. Nearly three million prescriptions were written in the U.S. in 2007, according to IMS Health, a health-information company.

Everyone here agrees that large-scale clinical trials are needed to evaluate the safety and effectiveness of testosterone therapy. One such trial has been proposed to the National Institutes of Health; and the New England Research Institutes is starting a registry of 1,000 patients, half in the U.S. and half in Europe, to follow for two years.

"In the meantime, some doctors are wary of treating older men until more is known. "If your patient is an old man who's grumpy and not the stud he used to be, you could give him testosterone for a few months and see what happens," says Elizabeth Barrett-Connor, chief of epidemiology at University of California, San Diego. "But no epidemiological results justify giving it to older men in general."

As The Wall Street Journal's new Health Journal columnist, Melinda Beck is returning to her love of reporting after a seven-year stint as the editor of Marketplace, the paper's second section. Before joining the Journal in 1996 as deputy Marketplace editor, Melinda was a writer and editor at Newsweek magazine, and wrote more than two dozen cover stories on topics ranging from the Oklahoma City bombing to the O.J. Simpson trial to liquid diets and the dilemmas of long-term care. She's malways found covering health-care issues particularly exciting, as evidenced by awards she's won for her stories from the Arthritis Foundation, the AARP, the American Society on Aging, the American College of Emergency Physicians, the National Institute of Health Care Management and the American College of Health Care Administrators. Melinda graduated from Yale University and lives in New York City with her husband and two daughters.