Nearly six months after an advisory panel to the Food & Drug Administration voted overwhelmingly in favor of revising the labels on testosterone drugs, the agency has followed through with a stark rebuke to makers of those drugs. The order—issued yesterday for
The FDA came to this recommendation after reviewing several studies that reported an increased risk of heart attack, stroke, or death in men taking testosterone treatments, according to a statement from the agency. Although the studies were sometimes contradictory, regulators were concerned that “testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging,” the statement said. “The benefits and safety of this use have not been established.”
Testosterone has actually been on the market since the 1950s, but it wasn’t all that widely used until the 2000s, when topical treatments like AndroGel and Axiron (applied under the arms) arrived on the scene. Then came those ubiquitous TV ads, many featuring graying but seemingly healthy guys complaining of symptoms that anyone over age 50 experiences from time to time: moodiness, lack of energy, loss of sex drive, and so forth.
AbbVie and Lilly spent a combined $105.6 million in 2012 and $151.8 million in 2013 on TV ads praising the virtues of testosterone replacement therapy, according to market-researcher Kantar Media. As a result, a lot of men talked to their doctors about testosterone—and nabbed prescriptions for it: 2.3 million prescriptions were handed out for testosterone in 2013, up from 1.3 million just three years earlier, the FDA’s data showed.
Sales of topical testosterone drugs increased 10% in 2013, to $2.2 billion, according to data from market-research firm IMS Health. AbbVie claimed more than 65% of the market.
But only half of the men who received testosterone prescriptions were diagnosed with hypogonadism, a legitimate disease that causes levels of the hormone to drop, according to the FDA. Remarkably, a quarter of them never even had their hormone levels tested.
The FDA is now requiring testosterone manufacturers to conduct a clinical trial to better define the potential cardiovascular risks. The agency says it would encourage the companies to work together on that trial but will accept separately gathered data.
“AbbVie received the U.S. Food and Drug Administration’s Drug Safety Communication as well as a class labeling change request for all prescription testosterone replacement therapies (TRT),” the company said in an e-mailed statement. “TRT is an important men’s health topic. AbbVie is committed to our patients and we continue to work with the FDA.”
A Lilly spokesperson said in an e-mail, “We’ve heard from the FDA and we’ll continue to work closely with the agency in the best interests of men who use testosterone therapy.”
In fact, Lilly already has its own post-marketing study of Axiron underway—a one-year trial involving 600 men. The study is designed to measure the impact of testosterone on energy level and libido, according to a spokesperson. It is not intended to answer questions about risk (a one-year trial would be too short to accomplish that anyway), but Lilly will assess any adverse events that are reported. The company expects to have results from that trial in the next quarter.
Neither Lilly nor AbbVie has yet outlined plans for complying with the FDA’s order that they conduct a trial to determine risks associated with testosterone drugs.
Sorting out testosterone’s risks has been far from easy. In 2003, a team of scientists led by the University of Pennsylvania proposed a six-year study to try to determine if testosterone raises the risk of prostate cancer. But officials at the Institute of Medicine—the health arm of the National Academy of Sciences—shot the idea down because they weren’t convinced testosterone supplements offered any benefits to men’s health. The organization recommended that the National Institutes of Health (NIH) sponsor shorter trials to determine the upsides of testosterone supplementation before trying to suss out the downsides.
Penn led the first of those efficacy trials, which enrolled 788 men. The double-blind, placebo-controlled trial was designed to measure the effect of testosterone on seven outcomes: physical function, vitality, sexual function, cognitive function, anemia, cardiovascular health, and bone health. But as is the case with the Lilly trial, the men will have only taken testosterone for a year, making long-term risks impossible to determine. Nevertheless, the researchers believe that if testosterone is shown to offer sufficient benefits, that could strengthen the case for designing and funding larger, longer trials to determine the risks.
The results of the NIH-sponsored testosterone trial are just now starting to emerge. In December, the research team published a paper concluding that naturally occurring testosterone in the body is positively associated with sexual function “albeit to a small degree,” they wrote. The hormone did not seem to affect vitality or physical function, however. They concluded, “the relationship between sex hormones and age-related alterations in older men is not clear.”
What is clear is that all this controversy has not been good for sales of testosterone drugs. Last year, sales of AbbVie’s AndroGel dropped nearly 10% to $934 million, with the company suffering a staggering 20% drop in sales just in the fourth quarter.
As for all those men on TV urging other aging guys to check out testosterone, they’re rapidly disappearing. Kantar’s data shows that in the first nine months of 2014—when the FDA was investigating potential heart risks linked to testosterone—Lilly’s and AbbVie’s ad spending dropped 36% year-over-year to $73.2 million.
