Grumpy Old Men: Maybe It's

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."

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?

"The moment you add the element of aging, you add the element of ageism. It's giving things for sex to old men," says John E. Morley, director of geriatric medicine at Saint Louis University, who, like other experts quoted here has worked with makers of testosterone products.

"Everybody agrees that testosterone deficiency should be treated in younger men. Why not treat it in older age groups?" says Ronald S. Swerdloff, chief of the endocrinology at Harbor-UCLA Medical Center.

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."

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