Older men with relatively low testosterone levels may be at greater risk of frailty than those with higher levels of the hormone, new research suggests.

In a study of more than 3,600 Australian men age 70 and older, researchers found that those with lower-than-average testosterone levels were more likely to be frail or to become frail over the next several years.

The findings, published online April 21 in the Journal of Clinical Endocrinology and Metabolism, add to evidence connecting testosterone loss to health problems in older men. But the question of what, if anything, to do about it remains open.

"It's too early to recommend testosterone therapy at this stage," lead researcher Dr. Zoe Hyde, of the University of Western Australia in Perth, told Reuters Health by email.

"Large-scale, clinical trials are needed first to see if testosterone can prevent or treat frailty," she said, "and to assess the benefits and risks of therapy."

For the current study, Dr. Hyde and her colleagues assessed frailty and testosterone levels in 3,616 men, ages 70 to 88. They were able to reassess 1,586 of those men four to seven years later.

At the first exam, 15% of the men were considered frail, based on the presence of at least three of the following: chronic fatigue; difficulty climbing a flight of stairs; difficulty walking more than one block; more than five major medical conditions; or an unintentional weight loss of more than 5% over several years.

In general, men with total testosterone levels below the median were more likely to be frail. Moreover, lower levels of free testosterone were tied to a greater risk of becoming frail over the next four to seven years.

But, Dr. Hyde said, "We can never be certain of causality," because men with certain conditions may develop lower testosterone levels before their diseases make themselves known.

However, she added that because the study followed men prospectively and linked lower testosterone to a greater risk of becoming frail over time, the findings do suggest that the hormone may be directly involved in the frailty process.

"It is also biologically plausible," Dr. Hyde said, "as testosterone is important for maintaining bone density and muscle."

Still, no one knows whether testosterone replacement can prevent or treat frailty. There are also safety concerns about giving older men supplemental testosterone. Testosterone could, for instance, trigger an enlargement of the prostate gland or fuel the growth and spread of any existing prostate tumors. In addition, researchers are unsure what effect the hormone could have on older men's heart disease risk.

http://jcem.endojournals.org/cgi/content/abstract/jc.2009-2754v1

J Clin Endocrinol Metab 2010.

Amy Norton • Reuters Health Information © 2010