Does TRT Increase Heart Attack and Stroke Risk? What the TRAVERSE Trial Found in Men Over 45

Does TRT increase heart attack risk? In the TRAVERSE trial of 5,246 men aged 45 to 80 with heart disease or high cardiac risk, major cardiac events occurred in 7.0% of men on testosterone gel and 7.3% on placebo. Testosterone did come with more atrial fibrillation, pulmonary embolism and acute kidney injury, and a small rise in blood pressure.

Does TRT increase heart attack risk? In the largest randomized trial ever run on the question, it did not. The TRAVERSE trial, published by Lincoff and colleagues in the New England Journal of Medicine in 2023, gave 5,246 men aged 45 to 80 either testosterone gel or placebo. Heart attack, stroke or cardiovascular death occurred in 7.0% of men on testosterone and 7.3% of men on placebo.

That result changed FDA labeling in 2025, but it is not a blanket clean bill of health. TRAVERSE also recorded more atrial fibrillation, more pulmonary embolism and more acute kidney injury in men on testosterone, along with a small rise in systolic blood pressure. This guide walks through what the trial measured, who was in it, what it could not answer, and what the FDA did with the results. Every figure below comes from the published trial papers or the FDA-approved AndroGel 1.62% label.

TRT did not increase heart attack risk in the TRAVERSE trial. The primary end point combined cardiovascular death, nonfatal heart attack and nonfatal stroke, a standard bundle cardiologists call major adverse cardiac events, or MACE. MACE occurred in 182 men (7.0%) on testosterone and 190 men (7.3%) on placebo, a hazard ratio of 0.96 with a 95% confidence interval of 0.78 to 1.17.

TRAVERSE was designed as a noninferiority trial. The investigators set the bar in advance: testosterone would count as safe for the heart if the upper end of the confidence interval stayed below 1.5. The result of 1.17 cleared that bar comfortably. The abstract also reports that each separate component, death from cardiovascular causes, heart attack and stroke, appeared similar between the two groups, as did a secondary end point that added coronary revascularization.

TRT did not increase stroke risk in TRAVERSE. Nonfatal stroke was one of the three parts of the primary end point, and the trial authors reported that the incidence of each component appeared similar in the testosterone and placebo groups. The FDA summarized the trial as showing no increase in the risk of adverse cardiovascular outcomes in men using testosterone for hypogonadism.

One caveat applies to stroke in particular. Atrial fibrillation, which was more common on testosterone in TRAVERSE, is a known cause of stroke over many years. The trial ran for a mean of 33 months, so it could not show whether a higher rate of atrial fibrillation would eventually translate into more strokes over a decade of treatment. That longer-term question is not established in trials.

TRAVERSE enrolled men at high cardiac risk, which makes its reassuring result more meaningful, not less. Every man was 45 to 80 years old, reported symptoms of low testosterone, and had two fasting morning testosterone results below 300 ng/dL. Each also had either existing cardiovascular disease or a high risk of it. According to the AndroGel 1.62% label, the mean age was 63.3, mean BMI was 35, and about 69%, 84% and 93% of men had diabetes, high cholesterol and high blood pressure.

TRAVERSE used daily 1.62% testosterone gel, with the dose adjusted to keep blood levels between 350 and 750 ng/dL. Mean testosterone in the treated group rose from 220.4 ng/dL at baseline to 440.5 ng/dL at 12 months, then sat at 420.9 ng/dL at 24 months and 428.7 ng/dL at 36 months. Those are mid-normal levels, not the high peaks some men see on large weekly injections.

TRAVERSE found three safety signals outside the main heart attack and stroke end point: atrial fibrillation, acute kidney injury and pulmonary embolism. The NEJM abstract states that a higher incidence of all three was observed in the testosterone group. The FDA label for AndroGel 1.62% gives the rates. Atrial fibrillation occurred in 3.5% of men on testosterone versus 2.4% on placebo, and nonfatal arrhythmias that needed intervention occurred in 5.2% versus 3.3%.

Acute kidney injury occurred in 2.3% of men on testosterone versus 1.5% on placebo, according to the AndroGel 1.62% label. Venous thromboembolism, meaning blood clots in the veins, occurred in 1.7% versus 1.2%. That total included deep vein thrombosis in 0.6% versus 0.5% and pulmonary embolism in 0.9% versus 0.5%. The label calls the clot difference numerically higher, which means the trial was not built to prove it with statistical certainty.

One TRAVERSE analysis points to white blood cells. Gagliano-Jucá and colleagues, writing in the American Heart Journal in 2025, found that testosterone raised neutrophil and monocyte counts. A rise of one standard deviation in neutrophils was linked to an odds ratio of 1.32 for venous clots, and the same rise in monocytes to an odds ratio of 1.39. The authors suggested doctors consider these counts when judging clot risk in men on TRT. That is an association within the trial, not proof of cause.

The atrial fibrillation signal from TRAVERSE has not been consistently confirmed. A TriNetX database study by Greenberg and colleagues in the Journal of Sexual Medicine (2024) matched 2,134 men on topical testosterone with 2,134 similar men who were not. Men on TRT had a higher risk of acute kidney injury (relative risk 1.53) but no significant increase in new atrial fibrillation (relative risk 1.48, 95% CI 0.93 to 2.37).

A 2026 review by Maligireddy and colleagues in the Journal of the Endocrine Society notes that a 2024 meta-analysis of 106 randomized placebo-controlled trials found no significant pooled atrial fibrillation signal. The review describes a U-shaped relationship, where both low and high testosterone levels track with more atrial fibrillation. Its authors recommend mid-physiologic testosterone targets, stable formulations and structured monitoring until better data arrive.

Testosterone does raise blood pressure slightly, and the FDA now says so on every testosterone product. In TRAVERSE, mean systolic blood pressure rose by 1.0 mm Hg from baseline to 36 months on testosterone gel and fell by 0.5 mm Hg on placebo, a difference of 1.5 mm Hg. The FDA said in February 2025 that separate ambulatory blood pressure studies confirmed an increase in blood pressure with all testosterone products.

The current AndroGel 1.62% label warns that the drug can increase blood pressure, which can increase cardiovascular risk over time. It advises measuring blood pressure periodically and says testosterone is not recommended for men with uncontrolled hypertension. A home cuff makes this easy to track, and our guide to blood pressure for men over 40 explains how to read the numbers.

The biggest limit of TRAVERSE is that many men stopped treatment. According to the AndroGel 1.62% label, about 61% of all participants discontinued testosterone or placebo during the study. Mean treatment lasted 21.7 months, while mean follow-up was 33.0 months. The authors reported similar findings in sensitivity analyses that censored events after men stopped treatment, but heavy dropout weakens any trial's ability to detect slow-building harms.

TRAVERSE also tested only one product. Every treated man used 1.62% testosterone gel, which produces steadier blood levels than weekly or biweekly injections. The trial says nothing direct about injections, pellets or doses that push testosterone above the normal range. The study was funded by AbbVie, the maker of AndroGel, and others. Our comparison of TRT delivery methods covers how injections, gels and pellets differ.

On February 28, 2025, the FDA announced class-wide labeling changes for testosterone products based largely on TRAVERSE. The agency recommended adding the TRAVERSE results to every label and removing language from the Boxed Warning about an increased risk of adverse cardiovascular outcomes. At the same time, it added a class-wide blood pressure warning and kept the Limitation of Use for age-related hypogonadism.

The FDA went further in June 2026. Its testosterone information page says the agency requested removal of the limitation of use about age-related hypogonadism, along with revised safety information on prostate cancer and benign prostatic hyperplasia. Regulatory language is still shifting, so men should check the current label for their specific product rather than relying on older summaries.

TRT helped men in TRAVERSE in some ways and not in others. In the Sexual Function Study by Pencina and colleagues (Journal of Clinical Endocrinology and Metabolism, 2024), 1,161 men with low libido saw more sexual activity on testosterone, by 0.49 acts per day at 6 months and 0.47 at 12 months, with the effect maintained at 24 months. Testosterone improved sexual desire and hypogonadal symptoms but not erectile function.

Testosterone corrected anemia more often than placebo. In an analysis of 815 anemic TRAVERSE participants published in JAMA Network Open (2023), anemia corrected in 41.0% of men on testosterone versus 27.5% on placebo at 6 months, and in 45.0% versus 33.9% at 12 months. Anemia was defined as hemoglobin below 12.7 g/dL.

Other TRAVERSE substudies were less encouraging. In the fracture analysis by Snyder and colleagues (NEJM, 2024), clinical fractures occurred in 3.50% of men on testosterone and 2.46% on placebo, a hazard ratio of 1.43. In 1,175 men with prediabetes, Bhasin and colleagues (JAMA Internal Medicine, 2024) found no significant difference in progression to diabetes: 7.8% versus 10.7% at 12 months and 12.8% versus 15.8% at 36 months. Our article on testosterone and type 2 diabetes covers that result in detail.

This article is for educational purposes only and is not medical advice. It does not diagnose, treat, cure or prevent any disease. Speak with a licensed physician before starting, stopping or changing any hormone therapy, and seek urgent care for chest pain, sudden breathlessness, a racing irregular heartbeat or a swollen painful leg.

• Lincoff AM et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine, 2023. https://doi.org/10.1056/NEJMoa2215025
• AndroGel (testosterone gel) 1.62% Prescribing Information, revised 07/2025. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022309s022lbl.pdf
• FDA issues class-wide labeling changes for testosterone products. U.S. Food and Drug Administration, February 28, 2025. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-issues-class-wide-labeling-changes-testosterone-products
• Testosterone Information. U.S. Food and Drug Administration, updated June 2026. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/testosterone-information
• Snyder PJ et al. Testosterone Treatment and Fractures in Men with Hypogonadism. New England Journal of Medicine, 2024. https://doi.org/10.1056/NEJMoa2308836
• Pencina KM et al. Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Network Open, 2023. https://doi.org/10.1001/jamanetworkopen.2023.40030
• Pencina KM et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. Journal of Clinical Endocrinology and Metabolism, 2024. https://doi.org/10.1210/clinem/dgad484
• Bhasin S et al. Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism: A Substudy of the TRAVERSE Randomized Clinical Trial. JAMA Internal Medicine, 2024. https://doi.org/10.1001/jamainternmed.2023.7862
• Gagliano-Jucá T et al. Association of testosterone-induced increase in neutrophil and monocyte counts with thromboembolic events: The TRAVERSE trial. American Heart Journal, 2025. https://doi.org/10.1016/j.ahj.2025.04.004
• Greenberg DR et al. Association of testosterone replacement therapy with atrial fibrillation and acute kidney injury. Journal of Sexual Medicine, 2024. https://doi.org/10.1093/jsxmed/qdae138
• Maligireddy AR et al. Association of testosterone and testosterone replacement therapy with atrial fibrillation: an updated review. Journal of the Endocrine Society, 2026. https://doi.org/10.1210/jendso/bvag180

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