Testosterone therapy benefits elusive, major studies find

SAN DIEGO – Testosterone therapy for older men possibly could provide some benefit, but there are also signs it could cause harm, according to a major series of studies published Tuesday.

The five studies are published in the Journal of the American Medical Association and JAMA Internal Medicine. Four are the product of the Testosterone Trials, which examined the effect of testosterone gel on healthy men aged 65 and older who had age-related low testosterone levels.

The four 12-month, placebo-controlled studies won’t resolve the long-standing medical debate over the usefulness of testosterone replacement therapy. It has been marketed as a simple fix for low energy levels and loss of libido, along with health-protective benefits.

But previous studies have repeatedly failed to find rigorous proof of these claims, despite the vigorous advertisements aimed at convincing middle-aged and older men that they need testosterone to combat “Low T.”

Likewise, the new trials provide scant support for testosterone therapy unless low testosterone is disease-related, according to two editorials published along with the studies.

A total of 788 men took part in the Testosterone Trials, including controls who were given a placebo gel.

On the positive side, testosterone therapy significantly increased bone density in 211 men and corrected anemia in 126 men by increasing hemoglobin levels.

While the two studies in JAMA Internal Medicine hinted at health benefits, this remains to be demonstrated. For example, a larger and longer follow-up trial to the bone density study will be needed to determine if the therapy decrease the risk of fractures.

On the worrisome side, early signs of potential heart disease increased in 73 treated men compared with 65 who got a placebo gel. Non-calcified arterial plaque built up faster than in the controls.

And in another study, men who got the gel failed to show improvement in memory or cognitive function. Both trials were published in JAMA.

The studies were led by Peter J. Snyder, M.D., of the University of Pennsylvania’s Perelman School of Medicine along with numerous co-authors.

A fifth study, not part of the Testosterone Trials, found a lower risk of heart problems in men who were ever prescribed testosterone replacement therapy by injection, mouth or transdermally.

However, the study of 8,808 men was observational. Such studies are considered less reliable than randomized placebo-controlled studies, which can be scientifically designed to determine whether an apparent effect is actually causal.

“At this point, clinicians and their patients should remain aware that the cardiovascular risks and benefits of testosterone replacement in older hypogonadal men have not been adequately resolved,” wrote Dr. Eric Orwoll in an editorial published in JAMA Internal Medicine.

In a second editorial, researcher David J. Handelsman of the University of Sydney in Australia said the trials should deflate unwarranted enthusiasm for testosterone.

“Professional societies should revise guidelines that provide tacit, uncritical endorsement, which is too readily used for boosting testosterone as a panacea for male aging,” Handelsman wrote.

“Testosterone and synthetic androgens have valuable medical applications but a key lesson is that such novel indications should be established by efficacy and safety studies and not preceded by wide-scale, off-label adoption,” he wrote.