FDA Calls for New Clinical Trial on Testosterone Cardiovascular Outcomes

In January 2014, the FDA released a drug safety communication announcing they were investigating the risk of serious side effects—including stroke, heart attack, and death—in men taking testosterone replacement products. They released the warning in response to a couple of major studies that had indicated these drugs can increase risk of cardiovascular problems in men.

The FDA released a follow-up communication on March 3, 2015. They reminded doctors that these drugs were approved only for men with low testosterone levels caused by a medical condition. “The benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man’s symptoms seem related to low testosterone,” they stated.

They added that they had required manufacturers of AndroGel, Testim, Androderm, and other testosterone replacement therapies to include updated warnings alerting patients and doctors to the risk of cardiovascular side effects.

On August 20, 2015, the FDA published an article in the medical journal New England Journal of Medicine (NEJM), expressing its concerns about the widespread use of testosterone replacement drugs to address symptoms related to natural aging, like muscle loss, energy, and reduce libido. They also revealed that they are requiring testosterone manufacturers to conduct a controlled clinical trial to further investigate how testosterone replacement drugs may affect cardiovascular outcomes.

FDA Calls on Manufacturers to Work Together on New Data

Dr. Christine P. Nguyen, deputy director of Safety in the FDA’s Office of Drug Evaluation, is the lead author on the FDA’s article in NEJM, and is joined by five other health experts. As a representative of the FDA, Nguyen calls on testosterone drug manufacturers to show that their products are beneficial for men without “classic hypogonadism,” and that the benefits outweigh the risks of heart attacks and strokes.

In addition to requiring new data on the drugs, the FDA is also encouraging manufacturers to work together on one single trial, rather than conduct several separately. “We believe the health of American men will be well served by the presence of accurate drug labels and reliable data to inform clinical decision making,” the authors wrote.

Men Taking Testosterone Without Accurate Diagnosis

What’s concerning the FDA and other health experts is that many men are asking their doctors about testosterone replacement drugs because of aggressive advertisements that make it look like these medications address common symptoms of aging, and help men to feel more youthful.

A 2014 study, for example, reported that 40.2 percent of U.S. men did not have a testosterone test in the 180 days before beginning therapy, and 50 percent had only one test. A September 2014 FDA briefing report also noted that in their analysis, 28 percent of patients using testosterone therapy had no evidence of being tested for low testosterone prior to starting a prescription.

Testosterone Products in Older Men a Public-Health Concern

So far, there have been several studies indicating testosterone use may increase risk of heart attacks and strokes, but some other studies have found conflicting results. That’s why the FDA is calling on manufacturers to work together on a single trial to establish the cardiovascular safety of these drugs, particularly since so many men are using them for so-called “age-related” low-testosterone.

According to Nguyen and colleagues, because these drugs are so popular, and because we have little evidence supporting their use in men without classic hypogonadism, “the cardiovascular safety of testosterone products in older men remains an important public-health concern.”