HHS requests testosterone therapy label updates, citing new safety data

The US Department of Health and Human Services (HHS) is requesting class-wide updates to prescribing information for testosterone replacement therapy (TRT) products, including removal of a longstanding limitation of use for men with age-related hypogonadism and revisions to warnings related to prostate cancer and benign prostatic hyperplasia (BPH).¹

The proposed changes follow the agency’s review of newer clinical evidence, including the phase 4 TRAVERSE trial assessing cardiovascular outcomes.

“During Men’s Health Month, we are putting science back at the center of men’s health care,” said HHS Secretary Robert F. Kennedy, Jr., in the news release by the agency.¹ “By updating testosterone therapy labels to reflect current evidence, we are giving patients and physicians clearer information, supporting informed medical decisions, and improving care for millions of American men.”

Cardiovascular risk and idiopathic hypogonadism

These proposed changes represent one of the most significant updates to TRT labeling since the FDA’s 2015 safety actions, which added warnings regarding cardiovascular risk and emphasized that the safety and efficacy of testosterone products had not been established for idiopathic hypogonadism.

The agency stated that its review found the previous limitation of use for age-related hypogonadism is no longer supported by the available evidence. In 2023, the TRAVERSE trial (NCT03518034) results were published in The New England Journal of Medicine.² The study enrolled 5,246 men with symptoms of hypogonadism and preexisting or elevated risk of cardiovascular disease. Participants were randomly assigned to transdermal testosterone gel (n = 2601) or placebo (n = 2603) and followed for a mean of 33 months. The study demonstrated noninferiority for major adverse cardiovascular events (MACE), with rates of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke of 7.0% in the testosterone group and 7.3% in the placebo group (HR, 0.96; 95% CI, 0.78 to 1.17; P < .001 for noninferiority).

Based on these findings, the FDA previously removed boxed warning language regarding increased cardiovascular risk from testosterone products in 2025 while adding updated blood pressure warnings informed by ambulatory blood pressure monitoring studies.³ The current proposed change extends the label update to include a removal of the limitation of use stating that the safety and effectiveness of TRT in men with age-related hypogonadism have not been established.

Prostate-related warnings

The agency is also seeking to revise labeling language regarding prostate cancer risk, while maintaining recommendations for patient screening and monitoring during treatment. Current prescribing information generally states that testosterone products should not be used in men with known or suspected prostate cancer and includes warnings that therapy may increase prostate cancer risk.

Under the requested revisions, TRT would be contraindicated only in men with metastatic prostate cancer. The FDA stated that available clinical trial and epidemiologic evidence has not generally demonstrated an increased incidence of prostate cancer among men receiving testosterone therapy. However, the agency acknowledged that uncertainties remain because prostate carcinogenesis may occur over many years and available studies may not provide sufficient long-term follow-up.

As a result, the FDA continues to recommend prostate cancer risk assessment, screening, and ongoing monitoring in men receiving TRT.

Similarly, the agency is proposing revisions to labeling related to BPH. Existing product labels generally warn that testosterone therapy may worsen lower urinary tract symptoms in men with enlarged prostates. According to the FDA review, available clinical trial data have not shown worsening symptoms among men with mild to moderate BPH. Evidence remains more limited in patients with severe symptomatic disease, and the revised labeling would continue to recommend close monitoring in this population.

“As our understanding of testosterone therapy continues to evolve, prescribing information should reflect the best available science,” added Brian J. Christine, MD, Assistant Secretary for Health, in the news release.¹ “This action helps ensure patients and health care providers have accurate, up-to-date information when considering treatment options.”

REFERENCES

1. HHS announces requested updates to testosterone therapy product labels. News release. US Department of Health and Human Services. June 18, 2026. Accessed June 19, 2026. https://www.hhs.gov/press-room/fda-requests-updates-testosterone-therapy-labeling.html

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

3. FDA issues class-wide labeling changes for testosterone products. News release. FDA. February 28, 2025. Accessed June 19, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-class-wide-labeling-changes-testosterone-products