Tens of thousands of American men are on testosterone despite long-standing concerns about long-term use, with some experts fearing it could fuel the growth of prostate cancer and possibly raise the risk of stroke and heart attack. Scientific evidence on testosterone's ability to preserve or restore age-related losses of sex drive, muscle mass and memory also has been mixed.
More than 200 men, ages 60 to 80, were randomly assigned to receive either testosterone or dummy pills, and neither participants nor researchers knew who got which. That design is considered the gold standard for medical experiments.
The investigators measured a range of outcomes, including functional mobility (such as how fast it takes to get up from a chair, walk a few feet and sit down again), hand and leg strength, body composition, bone mineral density, liver function, blood sugar, cholesterol and quality of life.
Like previous, smaller studies, this one found that men who took testosterone for six months developed more muscle mass and lost more fat than men who didn't take it. But the changes in body composition did not make them stronger.
No differences between the groups were detected on measures of prostate and heart health, nor were there differences in most quality-of-life measures.
The men taking testosterone had better insulin sensitivity, but lower levels of HDL or "good" cholesterol. There were no improvements in bone mineral density or cognitive function, which have been reported in some studies.
The study did find that men on testosterone had higher scores on a group of questions that included ability to tolerate stress, cope with anger and feel self-confident. The researchers did not look at sexual problems - one of the most common reasons doctors in this country prescribe testosterone.
The researchers, from Utrecht University in the Netherlands, invited more than 8,000 men, randomly selected from the municipal register, to participate. They screened nearly 2,000 who agreed to take part and excluded those with serious medical problems or whose testosterone levels were in the top half of the group.
Dr. Marielle Emmelot-Vonk and colleagues concluded that their findings "do not support a net benefit ... of modest testosterone supplementation in healthy men."
Dr. Laurence Levine, professor of urology at Rush University Medical Center and president of the Sexual Medicine Society of North America, welcomed the study, which he noted was the first to look at so many different parameters, adding: "I hope to see many more."
But he and other urologists said they were not surprised the study didn't show a greater benefit. The study subjects, they said, did not have symptoms of testosterone deficiency and would be unlikely to benefit.
"We don't necessarily see improvement because many of these men didn't have cognitive dysfunction, weakness, obesity, diabetes" - kind of aging-related issues testosterone might improve, Levine said.
Dr. Larry Lipschultz, professor of urology at Baylor College of Medicine in Houston, also questioned whether six months of testosterone was enough time to see real changes, and whether the dose was high enough.
"This doesn't answer the question: What happens if we give older men with low testosterone levels enough to get them back to the levels of younger men?" said Dr. Mitchell Harman, director of the Kronos Longevity Research Institute in Phoenix. "Maybe that will do nothing good and something bad, but we won't know until we do the study."
Testosterone is approved by the Food and Drug Administration for treating hypogonadism, a condition marked by inadequate testosterone production. But some physicians prescribe it "off-label" for patients whose hormone levels remain within normal limits.
Use of the hormone has increased with the development of new products - mainly gels and patches - that are more user-friendly than injections. Pharmacies filled 2.4 million testosterone prescriptions in 2004, more than twice the number filled in 2000, according to IMS Health, which tracks prescription drugs sales nationwide.
The pills used in the Dutch study (testosterone undecenoate, or Andriol Testocaps) are not available in the United States, where most men get testosterone supplements in the form of gels that are rubbed into the skin. The gels have not been shown to lower HDL cholesterol levels, a side effect of injections and pills, Lipschultz said.
Levine said more research is needed to learn exactly what testosterone replacement can do and who might benefit. "At least so far, well-designed studies have not shown any significant adverse effects," he said