The U.S. Food and Drug Administration on Tuesday directed makers of prescription testosterone products to revise their labels to warn about the risk of heart attack and stroke, and to clarify the approved uses.
Testosterone supplements are approved only for men with low levels of the hormone due to birth defects, chemotherapy, or other known causes. But over the last 15 years, the quintessential male hormone has become a $2 billion market, with nearly 3 percent of men over 40 using it for low energy, low libido, low mood - what marketers call "Low T."
"Testosterone is being used extensively to relieve symptoms in men who have low testosterone for no apparent reason other than aging," said the FDA announcement. "The benefits and safety of this use have not been established."
Although the link between testosterone use and cardiovascular problems is not conclusive, the FDA decided that labels should warn about it and clinicians "should make patients aware of this possible risk." Manufacturers also must conduct clinical trials to address whether testosterone promotes heart attacks and strokes.
The announcement was praised by law firms suing on behalf of men who believe they were harmed by using testosterone.
"Requiring warning label changes that specifically reference increased risks of heart attacks and strokes will be pivotal in the already existing testosterone litigation nationwide," said Matthew Casey of the Philadelphia firm Ross Feller Casey. The firm has 230 testosterone clients, including some who are part of mass tort litigation consolidated before a federal court in Illinois.
The FDA action did not surprise University of Pennsylvania endocrinologist Peter J. Snyder, leader of a federally funded study designed to see whether "Low T" really is a pathological condition in some older men.
His team is still analyzing and preparing to publish results from the $50 million study, completed last June. But Snyder gave a talk to the FDA advisory committee in September that recommended the tougher labeling.
"My opinion, based on the evidence available right now, is that one has to be much more cautious in prescribing testosterone for men whose blood testosterone is low for no obvious reason other than age," Snyder said. "And that's what the FDA is saying as well."
However, Snyder added, this is not the final word. The "T trial" put 788 men, average age 72, on testosterone or a placebo for a year to see if the hormone improved walking, vitality, sexual function, bone density, artery hardening, or red blood count.
Snyder said he is sure that the FDA will reevaluate its position when new information becomes available.
Prescription testosterone has been approved in the United States since the 1950s to treat "hypogonadism" - little or no testosterone, usually caused by disorders of the testicles, pituitary gland, or brain.
The concept of age-related testosterone deficiency remains controversial. Unlike estrogen, the primary female hormone, testosterone ebbs but doesn't bottom out in middle age. And even long-term menopausal estrogen supplementation - marketed for decades as a virtual youth elixir - was finally discredited by the 2002 results of a landmark federal study.
The explosion in the testosterone market has been mostly driven not by science but by the introduction of aggressively marketed, convenient, rub-on products, starting in 2000 with AndroGel, developed by Solvay Pharmaceuticals and now sold by AbbVie. Before that, men had to take the hormone in the form of pills, which were not readily absorbed, or as unpleasant shots.
AndroGel now has competition from Testim, Axiron, and other topical products. Surveys suggest that many men obtain a prescription without even having their blood testosterone level checked.
Although Snyder said he would still prescribe testosterone if careful testing showed a "severely low" level, he applauded the new conservatism.
"My prediction is that it will lead to reduced use of testosterone for elderly men because the change in labeling will cause insurance companies not to cover the prescriptions," he said, unless doctors can document an approved use.