Will the FDA Tighten the Use of Testosterone Replacement Therapy?

A recommendation to narrow the official approval for testosterone replacement therapy has won generally favorable reviews from medical organizations, although questions remain about its ultimate impact.

Such treatments are currently indicated for any man with low testosterone, even if the only apparent cause is advancing age, but two of the US Food and Drug Administration’s expert panels have urged the agency to limit that indication to men whose low testosterone stems from an acute medical problem such as damaged testicles or thyroid disease.

If the FDA acts on the recommendation — and it typically does act on advice from its expert panels, particularly advice supported by 20 of 21 panel members — the decision will prohibit drug companies from advertising testosterone therapy as a treatment for age-related hormonal changes.

Such a decision would not, however, limit the ability of doctors to prescribe testosterone therapy as a treatment for age-related decline, so it would not necessarily eliminate such usage among patients who believe they benefit from testosterone therapy.

Experts who testified before the FDA panels argued in that there’s no clear evidence that testosterone therapy increases energy, improves mood, or even enhances erectile function over the long term in men with no obvious medical problems aside from advancing age.

Ronald Swerdloff, MD, professor at the David Geffen School of Medicine at UCLA who spoke on behalf of the Endocrine Society, said that testosterone treatment should thus be limited to men who have clinical manifestations of hypogonadism and consistently low testosterone levels.

Such testimony was largely supported by a review prepared by FDA staffers and a separate submission from several testosterone therapy makers, a submission that acknowledged a general lack of the sort of large, lengthy, randomized trials that would provide definitive answers about the true long-term costs and benefits of testosterone augmentation in aging men.

Panel members used this dearth of evidence to justify their recommendation to narrow product labeling.

"I think it should be very clear that it's just for the primary and secondary therapies and designated reasons and remove the indication for any of the age-related [hypogonadism],” said Michael Lincoff, MD, a panel member who is director at the Cleveland Clinic Coordinating Center for Clinical Research.

The panels’ recommendation has received praise from many quarters, including from some doctors whose practices revolve around testosterone supplementation.

“There is a right way and a wrong way to diagnose and treat low testosterone,” said William Reilly, MD, National Medical Director at Low T Center. “We are pleased that the FDA committee has finally recognized this difference.”

Still, many doctors and patients clearly think testosterone replacement provides some practical benefit for men whose testosterone levels are not particularly low or for men whose low testosterone levels stem from nothing but age. The number of patients with a testosterone prescription rose from 1.3 million people in 2010 to 2.3 million in 2013.

Randomized trials, moreover, have found testosterone augmentation to have all sorts of benefits in men with no obvious medical reason for hypergonadism, benefits that range from decreased obesity to improved heart health. But those trials have generally been small and short and prone to conflicting with other studies.

Analyses of large medical databases have also reached mixed results, with some linking testosterone replacement therapy to a wide range of significant health benefits, others linking it to bad outcomes and still others finding no effect whatever.

In an effort to settle some of those questions once and for all, the FDA’s expert panels made a second recommendation during their meeting this month.

They urged the agency to require the companies that make testosterone supplements to undertake a large, randomized trial that will definitively determine whether testosterone therapy increases or decreases the risk of heart attacks and stroke.

The results of that trial — and a large, ongoing trial of testosterone replacement as a treatment for age-related mental and physical decline — may have more effect on usage than any changes the FDA makes in product labeling.