Expand Labeling for Testosterone Replacement Therapy, FDA Panel Says

 Members of an FDA expert panel urged the agency to expand labeling for testosterone replacement therapy and remove its classification as a controlled substance.

Like previous FDA expert panels, the group was convened by Commissioner Marty Makary, MD, MPH, and included a dozen like-minded experts and stakeholders representing perspectives from medicine, industry, and government. All panelists were supportive of testosterone replacement therapy -- a treatment for men whose bodies don't produce enough on their own -- and said that outdated concerns about prostate cancer and other health risks had left the therapy underutilized.

"There are 10 million men taking testosterone," said Makary during his opening remarks. "We don't talk about this stuff enough."

HHS Secretary Robert F. Kennedy Jr., for instance, has previously stated he takes testosterone replacement therapy as part of his "anti-aging protocol."

Makary drew comparisons between testosterone replacement therapy and menopausal hormone therapy, which was the topic of an earlier expert panel, stating that both topics faced medical dogma. The previous menopause panel was also like-minded and urged FDA to remove the boxed warning on menopausal hormone therapy, which the agency ultimately did. Many ob/gyns were pleased with this, but concerned about how it was done and how potential benefits were overstated by federal health regulators.

During Wednesday's panel, Makary referenced a 2007 study that found that 5.6% of men between age 30 and 79 had low testosterone and associated symptoms and said that men with low testosterone report increased depression and decreased vitality, strength, and libido. However, testosterone is a schedule III drug, alongside ketamine and anabolic steroids, because of past doping scandals, Makary said. He added that it's "time to revisit the scheduling of testosterone, given the potential clinical benefits and the barrier that that scheduling may present."

Makary said FDA didn't "have preconceived ideas" about testosterone replacement therapy for men and told panelists that FDA was "not promoting any medical recommendation or any product, but we are here to listen."

The discussion was led by Brian Christine, MD, assistant secretary for health; Richard Iorio, MD, principal medical advisor for FDA; and Mohit Khera, MD, MBA, MPH, professor of urology at Baylor College of Medicine in Houston.

Khera was first to present and explained that testosterone had been mainly thought of as a performance-enhancing and lifestyle drug.

He noted that in 2015, FDA both added a cardiovascular warning on testosterone and gave guidance for the TRAVERSE trial, of which Khera is a co-author. He said TRAVERSE was "the largest randomized placebo-controlled trial ever published on testosterone."

The pivotal trial was published in 2023 and found that men with hypogonadism treated with testosterone replacement therapy did not have an increase in adverse prostate events, including prostate cancers, putting to bed concerns about prostate risks. Khera said the study also found that testosterone did not increase heart attack risk or worsen lower urinary tract symptoms but did have benefits like improved libido and depression.

FDA removed the cardiovascular warning on testosterone products earlier this year as a result of the trial, though testosterone products are still only FDA-approved for men "who lack or have low testosterone levels in conjunction with an associated medical condition," according to the agency.

Khera said that guidelines from professional societies like the Endocrine Society and American Urological Association are more expansive, recommending testosterone therapy for men with symptoms of low testosterone and low serum testosterone levels.

"You can see that there's a discrepancy here between the FDA and professional guidelines, and this only leads to confusion for patients and providers, and is a further barrier to treatment," Khera said.

Other panelists, like John Mulhall, MD, MSc, director of sexual and reproductive medicine, urology service at Memorial Sloan Kettering Cancer Center in New York City, also brought up these medical society guidelines and said the current FDA labeling for testosterone was too limiting.

"Given the label restriction, we can make the argument that thousands of patients in need of testosterone therapy have been and are being deprived of it," Mulhall said. "In fact, in my practice, almost one half of all men who are diagnosed with testosterone deficiency who start on testosterone therapy do not technically meet the label requirements."

Another panelist, Helen Bernie, DO, MPH, associate professor of urology and director of the male sexual and reproductive medicine program at Indiana University in Indianapolis, sang the praises of testing serum testosterone.

"Serum testosterone is one of the most powerful yet underutilized biomarkers of men's health, and yet in the U.S., we do not screen for it -- not routinely, not proactively, and not preventatively," Bernie said. "Testosterone is still regulated as if it were a dangerous performance-enhancing drug from the athletic doping scandals of the 1980s, and because of this outdated classification, many physicians fear prescribing it or even screening for it."

As a whole, the panel resoundingly urged FDA to expand labeling and reconsider the scheduled drug classification of testosterone to make it easier for more men to access the therapy.

The single-mindedness of the panel was one of many concerns Gary Schwitzer highlighted on his Health News Review Substack.

"Maybe it is time to revise the labeling of testosterone products. But such self-congratulatory, conflicted, one-sided, hyperbolic performances are not an impressive pathway," he wrote.

PharmedOut, a project at Georgetown University Medical Center in Washington, D.C., also called out the panel as "highly biased" and said that "many presenters were clinicians expressing non-evidence-based opinions."

"These sham 'expert' panels, made up of people selected because they uphold Commissioner Makary's personally held opinions on hormones, are a shame," PharmedOut wrote. "The FDA can no longer be trusted to make decisions based on best evidence."

https://www.medpagetoday.com/urology/urology/118961