FDA Requests Testosterone Therapy Label Updates After New Safety Review

The U.S. Department of Health and Human Services, through the U.S. Food and Drug Administration, announced that FDA is requesting updates to the prescribing information for testosterone replacement therapy products. The request follows a comprehensive review of new clinical data and existing scientific evidence.

The proposed updates would make several important changes to testosterone therapy labels. FDA is requesting updated information related to prostate cancer risk and revised warnings regarding benign prostatic hyperplasia, also known as an enlarged prostate.

Key Changes at a Glance

• Broader patient eligibility: FDA wants to remove older wording that limited consideration of testosterone therapy for men with age-related low testosterone. This does not mean treatment is right for everyone.
• Cardiovascular boxed warning removed: FDA removed the boxed warning about increased heart attack and stroke risk after a large study found no higher rate of major cardiovascular events compared with placebo.
• Prostate cancer warning updated: FDA is proposing that testosterone therapy be avoided specifically in men with prostate cancer that has spread to other parts of the body.
• BPH warning updated: Studies have not shown worsening symptoms in men with mild to moderate enlarged prostate, though men with severe symptoms should still be monitored.
• Blood pressure still requires monitoring: Testosterone therapy may raise blood pressure.
• Some changes are final, while others are proposed: The cardiovascular boxed-warning change is already in effect, while the age-related, prostate cancer, and BPH revisions are still being requested.

Why FDA Is Reconsidering the Labeling

In 2015, FDA required testosterone replacement therapy product labeling to include a limitation of use for men with signs and symptoms associated with idiopathic hypogonadism, a condition involving low testosterone levels without a known underlying cause. HHS said that limitation was added because evidence of benefit was limited at the time and concerns had been raised about possible cardiovascular risks.

Those concerns were not new. FDA’s 2025 labeling update notes that the agency first convened an advisory committee meeting in 2014 after increased reports of stroke, heart attack, and death in men taking FDA-approved testosterone products. FDA then recommended an industry-wide clinical trial to better assess safety in men with age-related hypogonadism.

The TRAVERSE Trial and Cardiovascular Risk

Since the 2015 labeling limitation, additional evidence has become available. One of the most important pieces of evidence is the TRAVERSE trial, a large clinical study designed to assess cardiovascular safety in men receiving testosterone therapy.

FDA’s Testosterone Information page says the TRAVERSE trial tracked serious major adverse cardiovascular outcomes, including cardiovascular death, nonfatal heart attack, and nonfatal stroke, in more than 5,200 men who received at least one dose of AndroGel 1.62%.

The results showed no meaningful difference in serious cardiovascular events between men who received testosterone therapy and men who received placebo. FDA reported that major adverse cardiovascular events occurred in 7.0% of men in the AndroGel group compared with 7.3% of men in the placebo group.

The American College of Cardiology summarized the TRAVERSE study similarly, noting that testosterone therapy in middle-aged and older men with hypogonadism did not increase major cardiovascular events compared with placebo.

However, ACC also noted that pulmonary embolism, acute kidney injury, and atrial fibrillation were higher in the testosterone therapy group, which means treatment decisions still need to be individualized and medically supervised.

Based on its review of TRAVERSE and other available evidence, FDA concluded that the limitation of use is no longer warranted.

What the Proposed Label Changes Mean

The proposed label updates do not mean testosterone therapy is right for everyone.

FDA states that testosterone products are approved only for men who have low testosterone levels in connection with an associated medical condition, such as problems involving the testicles, hypothalamus, or pituitary gland.

FDA also states that none of the approved testosterone products are approved for men with low testosterone levels who do not have an associated medical condition.

Instead, the requested updates are about making the prescribing information better reflect the evidence FDA has reviewed. The changes would remove older language saying that safety and effectiveness had not been established for age-related hypogonadism, while also updating prostate-related safety information and continuing to support risk assessment, screening, and monitoring during treatment.

Prostate Cancer and Enlarged Prostate Warnings

FDA is also requesting updates to longstanding safety information related to prostate health.

HHS said current labeling generally states that testosterone replacement therapy should not be used in men with known or suspected prostate cancer and warns that treatment may increase prostate cancer risk. Under the requested revisions, testosterone replacement therapy would be contraindicated only in men with metastatic prostate cancer.

HHS also said available clinical trial and epidemiologic data have not generally shown an increased risk of prostate cancer in men receiving testosterone replacement therapy.

However, the proposed labeling would still recommend that healthcare providers assess risk, screen patients before treatment, and monitor patients during therapy, because prostate cancer can take years to develop and some studies may not have followed patients long enough to detect long-term effects.

For benign prostatic hyperplasia, or enlarged prostate, FDA is requesting revised labeling as well.

Current labeling generally warns that testosterone replacement therapy may worsen BPH symptoms. FDA’s review found that available clinical trial data do not demonstrate worsening symptoms in men with mild to moderate BPH, although evidence remains limited for men with severe symptoms.

The requested labeling changes would continue to recommend monitoring patients with severe symptomatic disease during treatment.

Talk With a Medical Provider Before Starting or Changing Therapy

For patients, the main takeaway is that testosterone therapy labeling may soon become more aligned with newer safety evidence, especially after the TRAVERSE trial.

However, testosterone therapy is still a prescription treatment that should be evaluated carefully by a qualified medical provider.

Men who are concerned about symptoms of low testosterone, age-related hormone changes, prostate health, heart health, or enlarged prostate symptoms should not start, stop, or change testosterone therapy without medical guidance. A provider can review symptoms, lab results, health history, cardiovascular risk, prostate risk, medications, and other factors before deciding whether treatment is appropriate. This article is for educational purposes only and is not a substitute for medical advice, diagnosis, or treatment.


Sources:
https://www.hhs.gov/press-room/fda-requests-updates-testosterone-therapy-labeling.html
https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/testosterone-information
https://www.acc.org/latest-in-cardiology/journal-scans/2023/06/20/14/42/cardiovascular-safety-of-testosteronehttps://www.fda.gov/drugs/drug-alerts-and-statements/fda-issues-class-wide-labeling-changes-testosterone-products https://www.nejm.org/doi/full/10.1056/NEJMoa2215025