FDA has requested major updates to testosterone replacement therapy labels, removing a longstanding hypogonadism limitation and revising prostate safety warnings following review of new evidence, including the TRAVERSE trial.
Written By: Disha Jadhao, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA), under the Department of Health and Human Services (HHS), has requested significant labeling updates for testosterone replacement therapy (TRT) products after reviewing new clinical evidence and long-term safety data.
The proposed revisions would remove a decade-old limitation stating that the safety and effectiveness of TRT had not been established in men with age-related or idiopathic hypogonadism, while also updating warnings related to prostate cancer and benign prostatic hyperplasia (BPH).
The action reflects a notable shift in the regulatory view of testosterone therapy and follows the accumulation of evidence supporting its safety profile in appropriately selected patients.
Reassessing Testosterone Therapy Risks and Benefits
Testosterone replacement therapy is used to treat hypogonadism, a condition characterized by low testosterone levels that can cause fatigue, reduced libido, erectile dysfunction, loss of muscle mass, and mood disturbances. Over the past decade, concerns regarding cardiovascular and prostate-related risks have influenced prescribing practices and regulatory guidance.
In 2015, the FDA required manufacturers to include a limitation of use stating that the benefits and safety of TRT had not been established in men with signs and symptoms associated with idiopathic hypogonadism. The agency also cited concerns about potential cardiovascular risks, including heart attack and stroke.
Since then, several large studies have expanded the evidence base surrounding testosterone therapy.
TRAVERSE Trial Supported FDA Reassessment
A key factor in the FDA’s review was the TRAVERSE cardiovascular outcomes trial (NCT03518034), one of the largest testosterone safety studies conducted to date. The study enrolled more than 5,200 men with hypogonadism and evaluated the risk of major adverse cardiovascular events (MACE), including myocardial infarction and stroke.
The trial found no meaningful increase in cardiovascular risk among men receiving testosterone replacement therapy compared with controls. Based on these findings and other available evidence, the FDA concluded that the previous limitation of use is no longer supported by current data.
As a result, the agency has requested removal of language suggesting that the safety and effectiveness of testosterone therapy have not been established in men with age-related hypogonadism.
Updated Guidance on Prostate Health
The FDA is also seeking revisions to longstanding prostate-related warnings.
Current prescribing information generally cautions against TRT use in men with known or suspected prostate cancer and warns of a possible increased risk of developing the disease. Under the proposed changes, TRT would be contraindicated only in men with metastatic prostate cancer.
According to the agency, available clinical trial and epidemiological evidence has not shown a clear increase in prostate cancer risk among men receiving testosterone therapy. However, uncertainties remain because prostate cancer often develops over many years and existing studies may not have followed patients long enough to detect long-term effects. The proposed labeling continues to recommend risk assessment, baseline screening, and ongoing monitoring during treatment.
For benign prostatic hyperplasia, existing labels warn that TRT may worsen urinary symptoms. FDA’s review found no convincing evidence that testosterone therapy aggravates symptoms in men with mild-to-moderate BPH, although data remain limited in patients with severe disease. The requested labeling updates would recommend continued monitoring for men with severe symptomatic BPH who receive treatment.
Regulatory Path Forward
HHS officials said the proposed revisions are intended to align prescribing information with the best available scientific evidence and provide clinicians with clearer guidance when evaluating treatment options.
The FDA has asked manufacturers of testosterone replacement products to update prescribing information to reflect current evidence. If finalized, the changes could influence clinical practice by reducing uncertainty surrounding patient selection and safety monitoring while maintaining safeguards for prostate health assessment. The action reflects a broader FDA effort to ensure that prescribing information evolves alongside emerging scientific evidence and remains relevant to modern patient care.
Reference
HHS Announces Requested Updates to Testosterone Therapy Product Labels | HHS.gov
About the Writer
Disha Sanjay Jadhao (LinkedIn) is a pharmacy graduate and healthcare writer with a strong interest in clinical documentation and simplifying healthcare information for better reader understanding. She is enthusiastic, adaptable, and eager to take on new challenges while contributing to clear, accurate, and engaging medical and pharmaceutical content.