FDA Expert Panel Calls for Testosterone Therapy Label Revisions Following Cardiovascular Safety Data
核心洞察
FDA Commissioner Martin Makary convened an expert panel on December 10, 2025, to discuss revising testosterone replacement therapy labeling, following the agency's recent removal of black box warnings from estrogen therapy (搜索) products.
Experts argued that current prostate cancer (搜索) contraindications and Schedule III controlled substance classification for testosterone are not supported by contemporary evidence and create unnecessary barriers to care.
The TRAVERSE trial, the largest randomized controlled trial on testosterone to date with 5,246 men, demonstrated non-inferiority for major adverse cardiovascular events compared to placebo (7.0% vs 7.3%).
The Food and Drug Administration convened a panel of nine experts on December 10, 2025, to examine potential revisions to testosterone replacement therapy (TRT) labeling, marking a significant step toward addressing what panelists described as outdated regulatory barriers based on insufficient evidence.
FDA Commissioner Martin Makary opened the discussion by drawing parallels to the agency's recent decision to remove black box warnings from estrogen therapy (搜索) products used in menopause. "There are far fewer research studies demonstrating the potential benefits of testosterone therapy. They are emerging," Makary noted, while acknowledging the longstanding stigma surrounding men's health discussions.
TRAVERSE Trial Challenges Cardiovascular Risk Assumptions
Dr. Mohit Khera, professor of urology at Baylor College of Medicine and TRAVERSE trial investigator, presented evidence challenging traditional safety concerns about testosterone therapy. The TRAVERSE study, published in the New England Journal of Medicine in 2023, represents the largest randomized controlled trial on testosterone to date, including 5,246 men aged 45 to 80 years with preexisting or high cardiovascular disease (搜索) risk.
"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. The trial demonstrated that major adverse cardiovascular events (MACE) occurred in 7.0% of patients taking testosterone versus 7.3% taking placebo (HR, 0.96; 95% CI, 0.78 to 1.17; P < .001 for noninferiority).
Based on these findings, the FDA recommended removing the black box warning related to increased cardiovascular risk for all testosterone products in February 2025.
Regulatory Discrepancies Create Clinical Confusion
Khera highlighted significant discrepancies between FDA labeling and professional society guidelines. "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 (搜索) and the Endocrine Society (搜索), have a different opinion," he said.
Professional societies recommend testosterone therapy for men with both symptoms of low testosterone and low morning serum testosterone levels, regardless of underlying cause. This regulatory disconnect creates confusion for patients and providers while serving as a barrier to treatment.
Testosterone as Health Biomarker
Dr. Helen L. Bernie, associate professor of urology and Director of the Male Sexual and Reproductive Medicine Program at Indiana University, advocated for routine testosterone screening as a health biomarker. According to the Journal of Clinical Endocrinology and Metabolism, 5.6% of men aged 30 to 79 have low testosterone and symptoms.
"If you knew that there was a simple test that could help identify a man at risk for cardiovascular disease (搜索), diabetes (搜索), or osteoporosis (搜索), 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?" Bernie asked. "That test already exists. It's a serum testosterone, one of the most powerful yet underutilized biomarkers of men's health."
Schedule III Classification Under Scrutiny
Dr. Landon Trost, founder of the Male Fertility and Peyronie's Clinic, criticized testosterone's Schedule III controlled substance classification under the Anabolic Steroids Control Act of 1990. He argued this classification resulted from political rather than scientific motives and cited University of Michigan data showing the Act's questionable effectiveness in reducing illicit steroid use.
"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.
The Schedule III classification creates barriers that discourage physicians from prescribing testosterone and dissuade patients from requesting it, leading to the proliferation of "low T clinics" that may not follow established guidelines and best practices.
Expert Recommendations
The panel unanimously recommended several regulatory changes:
- Remove prostate cancer contraindications not supported by current evidence
- Declassify testosterone from Schedule III controlled substance status
- Broaden indications to include men with signs and symptoms of testosterone deficiency along with documented low testosterone levels, regardless of underlying cause
- Align FDA labeling with professional society guidelines
Bernie emphasized the public health implications: "We are failing men not because we lack science, but because we lack the policy, the screening and the permission to use that science. If we want to improve the health of American men, if we want to close the mortality gap, we must recognize testosterone deficiency (搜索) for what it is: a public health issue."
The expert panel represents a significant step toward evidence-based regulatory reform for testosterone therapy, potentially improving access to treatment for millions of American men with testosterone deficiency (搜索).