Public Citizen Petitions FDA for a Black Box Warning on Testosterone Products

Public Citizen today called on the U.S. Food and Drug Administration (FDA) to immediately add a black box warning about the increased risks of heart attacks and other cardiovascular dangers to the product labels of all testosterone-containing drugs available in the U.S.

The urgent petition is based on growing evidence of the risks of heart attacks and other cardiovascular dangers from many individual randomized studies going back as far as 2010 and a recently published overall analysis (meta-analysis) of 27 studies going back as far as 20 years. Although 13 of these studies, funded by the drug industry, collectively showed no increased risk, the 14 studies not funded by the industry collectively showed a highly significant increased cardiovascular risk.

More than five million U.S. prescriptions for testosterone products were filled in 2013. The most common of those, making up more than 90 percent of the testosterone prescriptions filled in 2013, include Androgel, Axiron, Testim and Fortesta.

The petition also was prompted by the most recent study, involving the experience of 55,000 men before and after starting testosterone. The risk of heart attacks among men 65 and older during the first three months of using the drug was twice the risk seen in the year before use. Further, the study found, for the first time, a 2.9-fold increase in heart attack risk among men under 65 with a history of heart disease who took testosterone.

The FDA-approved labeling for testosterone-containing products does not mention testosterone-induced cardiovascular risk.

Despite all of these studies, the FDA stated on Jan. 31 that it "has not concluded that FDA-approved testosterone treatment increases the risk of stroke, heart attack, or death."

"In the face of this accumulating evidence, this statement is reckless and is a betrayal of the FDA's role as an agency in the U.S. Public Health Service," said Dr. Sidney Wolfe, founder and senior adviser of Public Citizen's Health Research Group. "It is quite clear that testosterone treatment increases the risks of cardiovascular diseases, including heart attacks."

Although the FDA agrees that testosterone is "only for use in men who lack or have low testosterone levels in conjunction with an associated medical condition," the hyped-up nature of the low-T[estosterone] advertising campaigns, not adequately regulated by the FDA, assures that many men in the U.S. prescribed testosterone do not meet the FDA-specified criteria of both low testosterone levels and an associated medical condition due to hypogonadism. Evidence can be seen in the recent finding that almost 25 percent of men prescribed testosterone in this country had not previously had a blood test to even determine if their testosterone level was low.

"Unless the FDA immediately begins to provide strong, adequate black-boxed warnings about the risks of heart attacks and other cardiovascular diseases, the continuing toll of heart attacks, many in people who are not even candidates for testosterone, will continue," Wolfe said. "At the present rate of prescribing, almost 13,000 prescriptions a day are filled for testosterone products in this country. Each day of delay of the black box warning ensures much more exposure, too often for men who cannot benefit from the drug but will only be exposed to its risks."

In addition, the petition urges the FDA to delay its decision date on approving a new long-acting injectable testosterone product Aveed (testosterone undecanoate, Endo), now set for Feb. 28, because its approval, absent the new black box warning, would cause further cardiovascular damage to new users.

The petition is available at https://www.citizen.org/hrg2184.