FDA Testosterone Warning: What the 2015 Drug Safety Communication Means for TRT

Last Updated: March 2026

On March 3, 2015, the U.S. Food and Drug Administration issued a Drug Safety Communication requiring manufacturers of all approved prescription testosterone products to update their labeling. The communication addressed two issues: clarifying the approved uses of testosterone medications and adding warnings about a possible increased risk of heart attacks and strokes.

This page covers what that warning said, the evidence behind it, and how the regulatory landscape changed after the 2023 TRAVERSE trial.

What the FDA Communication Said

The FDA’s 2015 communication stated that:

• Prescription testosterone products are approved only for men who have low testosterone levels caused by certain medical conditions, specifically hypogonadism resulting from disorders of the testicles, pituitary gland, or brain
• The benefit and safety of testosterone therapy have not been established for the treatment of low testosterone levels due to aging alone
• There is a possible increased cardiovascular risk associated with testosterone use, based on available evidence from studies

The FDA noted that some studies reported an increased risk of heart attack, stroke, or death associated with testosterone treatment, while others did not. The agency concluded the evidence warranted labeling changes but fell short of concluding a definitive causal link existed.

This communication updated an earlier January 2014 FDA alert that had announced the agency was evaluating the risk of stroke, heart attack, and death with FDA-approved testosterone products.

Background: Why the FDA Acted

By 2014, the FDA had become aware that testosterone was being prescribed extensively to men with low testosterone levels attributable only to normal aging. That use had not been studied in the same rigorous clinical trials required for FDA approval.

Sales of testosterone products in the United States grew from approximately $324 million in 2002 to over $2 billion by 2012, with a substantial portion driven by direct-to-consumer advertising and off-label prescribing for age-related testosterone decline.

An FDA Advisory Committee meeting in September 2014 reviewed the available evidence. While the committee did not find definitive proof of cardiovascular harm, they concluded the risks warranted clearer labeling and that prescribers needed to understand the distinction between hypogonadism and normal age-related testosterone decline.

Two observational studies published in 2013 and 2014 drove much of the concern. A PLOS ONE study found a 29% increased risk of heart attacks in men who had used testosterone therapy within 90 days, and a study in JAMA Internal Medicine reported increased mortality and heart attack risk in veterans on testosterone. Both studies had methodological limitations, but the FDA determined the signal warranted action.

What the Labeling Change Required

Following the 2015 communication, testosterone product labels were required to:

1. Clarify approved indications — explicitly stating that testosterone is approved only for hypogonadism caused by a specific medical condition, not for age-related decline
2. Add cardiovascular risk language — informing patients and prescribers about the possible increased risk of heart attacks and strokes
3. Recommend patient awareness — instructing healthcare professionals to make patients aware of potential cardiovascular risks before initiating or continuing testosterone therapy

The FDA also recommended that patients experiencing symptoms of a heart attack or stroke while on testosterone — including chest pain, shortness of breath, weakness on one side of the body, or slurred speech — seek immediate medical attention.

The TRAVERSE Trial Changes Everything

In June 2023, the New England Journal of Medicine published results from the TRAVERSE trial, the largest randomized, placebo-controlled cardiovascular outcomes trial of testosterone therapy ever conducted. The study enrolled 5,246 men aged 45 to 80 with hypogonadism and pre-existing or high risk of cardiovascular disease.

Key findings:

• No significant increase in major cardiovascular events (heart attack, stroke, or cardiovascular death) in the testosterone group compared to placebo
• Testosterone was noninferior to placebo on the primary cardiovascular endpoint
• The trial did find a higher incidence of atrial fibrillation, pulmonary embolism, and acute kidney injury in the testosterone group, though these were secondary endpoints

The TRAVERSE trial provided the highest-quality evidence to date that TRT does not increase cardiovascular risk in hypogonadal men when properly prescribed and monitored.

What Changed in 2025

In February 2025, the FDA issued an updated class-wide labeling change for testosterone products based primarily on the TRAVERSE trial data. The update removed the black box warning about adverse cardiovascular outcomes that had been added following earlier observational studies.

The 2025 label revision required:

• Inclusion of TRAVERSE trial data in testosterone product labeling
• Continued monitoring recommendations for blood pressure and hematocrit
• Retained language clarifying that testosterone is approved for hypogonadism from a specific medical condition, not age-related decline

Key Takeaways for Patients and Prescribers

• Testosterone therapy is FDA-approved for hypogonadism — a clinical condition confirmed by lab tests showing low testosterone due to a specific medical cause
• From 2015 to 2025, all testosterone products carried cardiovascular risk warnings based on mixed observational study evidence
• The 2023 TRAVERSE trial provided robust randomized controlled evidence that TRT does not significantly increase major cardiovascular events in hypogonadal men
• The FDA updated testosterone labeling in 2025 to reflect the TRAVERSE data
• Healthcare professionals should still monitor patients on TRT for blood pressure changes, hematocrit elevation, and any signs of cardiovascular events

Sources

• FDA Drug Safety Communication (March 3, 2015): FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack and Stroke. Archived via Wayback Machine
• Lincoff AM, et al. (2023). Testosterone and Cardiovascular Risk in Men with Hypogonadism — TRAVERSE Trial. New England Journal of Medicine. doi:10.1056/NEJMoa2308836
• Finkle WD, et al. (2014). Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men. PLOS ONE. doi:10.1371/journal.pone.0085805
• Vigen R, et al. (2013). Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels. JAMA Internal Medicine. doi:10.1001/jamainternmed.2013.10787