Experts urge FDA to revisit labeling for testosterone replacement therapy in men

On December 10, 2025, the FDA convened a panel of experts across urology, sexual health, and related fields to discuss the current labeling for testosterone replacement therapy (TRT) in men.¹

These experts argued that the current warning labels and contraindications for those with prostate cancer or suspected prostate cancer are not supported by contemporary evidence and should be removed. Further, they emphasized that the current classification of testosterone therapy as a controlled substance creates unnecessary barriers to care, contributes to stigma surrounding men’s health, and encourages men to seek care outside of traditional settings.

Overall, they encouraged the FDA to remove warning labels linking TRT with prostate cancer, discontinue treating testosterone as a controlled substance, and broaden the indication for TRT to align with current guidelines across professional societies.

Opening remarks

Marty Makary, MD, MPH, FDA Commissioner, opened the discussion by acknowledging the landmark FDA decision last month to remove the broad black box warning from hormone replacement therapy (HRT) for women. He noted that the debate leading up to that decision echoed elements of the current conversation—specifically, the long-held but outdated belief that HRT in postmenopausal women increases breast cancer risk, which he compared to today’s debate over TRT and prostate cancer risk in men.

Makary also addressed the longstanding stigma surrounding men’s health, particularly in relation to TRT, and emphasized the need for more open, evidence-based dialogue on the topic.

“According to the Journal of Clinical Endocrinology and Metabolism, 5.6% of men aged 30 to 79 which is most men, have low testosterone and symptoms,” he noted. “Why are we ignoring this topic? Why is it taboo to talk about it? We have to be vigilant about poor-quality products and drive-by-night operations that are selling unsafe products. That's the FDA’s job, to safeguard the public. But we can't avoid the topic.”

Contextualizing the issue

The discussion then turned to Mohit Khera, MD, MBA, MPH, who is a professor of urology at Baylor College of Medicine and served as an investigator on the TRAVERSE trial (NCT03518034). This study, he explained, pushed back against beliefs that TRT was associated with increased risks of prostate cancer and major adverse cardiovascular events (MACE).

“Today, we know that testosterone is not a carcinogen. It is not a cardiovascular risk factor. It's not mainly a lifestyle drug,” Khera explained. “What we do know is that testosterone plays a very important role across multiple organ systems throughout the body. In fact, testosterone deficiency negatively impacts health, reduces quality of life, [and] increases the risk for mortality. Testosterone therapy offers multiple clinical benefits, such as improvements in diabetes, obesity, and bone mineral density.”

Khera also referenced the FDA decision in February 2025 in which the agency recommended a removal of the black box warning related to an increased risk of adverse cardiovascular outcomes for all testosterone products. This decision was made on the basis of findings from the TRAVERSE trial, which is the largest randomized controlled trial on testosterone to date. In total, the study included 5246 men aged 45 to 80 years who had a preexisting or a high risk of cardiovascular disease at study entry.

Published in 2023 in the New England Journal of Medicine, the data showed that the incidence of MACE for men on testosterone was non-inferior to that of those on placebo. Specifically, a MACE occurred in 7.0% of patients taking testosterone vs 7.3% of patients taking placebo (HR, 0.96; 95% CI, 0.78 to 1.17; P < .001 for noninferiority).²

Khera also noted that the current FDA label is at odds with what is recommended by other professional guidelines, creating confusion for both patients and physicians.

He explained, “The FDA label says testosterone therapy is approved only for men with low testosterone caused by a certain medical condition of the testis or the brain. However, many professional societies guidelines, such as the American Urological Association and the Endocrine Society, have a different opinion. They state that testosterone therapy is recommended in men with both symptoms of low testosterone and low morning 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.”

Low testosterone as a biomarker for poor health

Khera then turned the conversation over to Helen L. Bernie, DO, MPH, who is an associate professor of urology and the Director of the Male Sexual and Reproductive Medicine Program at Indiana University. Bernie argued that routine screening of testosterone can greatly benefit men, helping to both prevent and identify a variety of negative health outcomes.

“If you knew that there was a simple test that could help identify a man at risk for cardiovascular disease, diabetes, or osteoporosis, if you knew it could help prevent your husband or your father or your son from premature death, wouldn't you want that test to be part of routine care?” she asked. “That test already exists. It's a serum testosterone, one of the most powerful yet underutilized biomarkers of men's health. And yet in the US, we do not screen for it—not routinely, not proactively, and not preventatively.”

Bernie also reflected on data from clinical studies confirming that testosterone therapy does not increase the risk for MACE nor the risk for prostate cancer. However, she said that the current classification for TRT treats testosterone as if it were a dangerous performance enhancing drug, reflecting outdated beliefs from the 1980s.

“We are failing men not because we lack science, but because we lack the policy, the screening and the permission to use that science,” she concluded. “If we want to improve the health of American men, if we want to close the mortality gap, we must recognize testosterone deficiency for what it is: a public health issue.”

The regulation of testosterone

Landon Trost, MD, founder of the Male Fertility and Peyronie's Clinic in Orem, Utah, then shared some deeper insights into the outdated classification of testosterone as a Schedule III drug, noting that this was the result of political motives rather than scientific ones.

The Anabolic Steroids Control Act of 1990 placed anabolic steroids under Schedule III of the Controlled Substances Act. Trost cited data from a University of Michigan study that found an initial decline in illicit use of these substances following passage of the Act, which rebounded and surpassed initial rates after 10 years.

“It's arguable as to whether or not this Act even had its intended purpose, which was to reduce the illicit use of these substances. But no question, it did have an effect on the 60-year-old man who was trying to do this legitimately,” Trost explained.

Trost went on the explain that the Schedule III classification creates barriers to care, both discouraging physicians from prescribing testosterone as well as dissuading patients from asking for it. As a result, Trost noted, we’ve seen a significant rise in “low T clinics,” which aim to fill this gap in care, yet come with substantial risks.

“Normally, the patient would be going to their primary care physician, their urologist, their endocrinologist, who would be following guidelines and best standards of care, but instead, they're going to just go wherever they can get the prescription filled,” He added. “It makes it much more likely that they're going to use less well-studied options like DHEA.”

Closing remarks

Overall, the panelists urged the FDA to consider revised labeling on testosterone products to reflect the current science.

Specifically, they argued that current prostate cancer contraindications are not supported by the evidence, and that testosterone should be removed from the Schedule III classification of drugs—both which contribute to stigma and fear surrounding TRT. Further, they recommended a broadening of the indications for TRT to include eligibility for men who have signs and symptoms of testosterone deficiency, along with documented low testosterone levels, regardless of the underlying cause.

REFERENCES

1. FDA Expert Panel on Testosterone Replacement Therapy for Men. US Food & Drug Administration. YouTube. Accessed December 10, 2025. https://www.youtube.com/live/BdAawJmQ9Fs

2. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107-117. doi:10.1056/NEJMoa2215025