Testosterone → Major cardiovascular events
A rise in Testosterone does not identify a change in Major cardiovascular events.
Lincoff 2023 found that daily testosterone gel was noninferior to placebo for a first major cardiac event among 5198 men aged 45 to 80 with hypogonadism and preexisting or high-risk cardiovascular disease (hazard ratio 0.96, 95% CI 0.78 to 1.17).
Randomized trial · Moderate · N=5198
Supported by an experiment or a tightly identified design. Read the caveats.
Mechanism
Lincoff, Bhasin, Flevaris and colleagues assigned 5246 men aged 45 to 80 with two fasting testosterone readings under 300 ng per deciliter, hypogonadal symptoms, and either established cardiovascular disease or three or more cardiac risk factors to daily 1.62 percent testosterone gel or matching placebo (TRAVERSE, NCT03518034). Dose was titrated to keep testosterone between 350 and 750 ng per deciliter. The primary safety end point was the first of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The safety population was 5198 men who received at least one dose. Mean treatment lasted 21.7 months. Mean follow-up lasted 33.0 months. A primary event occurred in 182 men on testosterone (7.0 percent) and 190 on placebo (7.3 percent). The hazard ratio was 0.96 (0.78 to 1.17). The trial called this noninferior if the upper 95 percent confidence limit sat below 1.5. That test passed (P<0.001). The secondary composite, which added coronary revascularization, was 269 (10.4 percent) versus 264 (10.1 percent), hazard ratio 1.02 (0.86 to 1.21). Each piece of the primary looked similar. This page is a safety contrast, not a claim that raising testosterone prevents heart attacks. The authors set out to test whether replacement raised major events in men already at risk. It did not, within that bound. Atrial fibrillation, acute kidney injury, and pulmonary embolism were more common on gel. Those are not the primary count. N=5198 is from the paper. Evidence grade is
Caveats
TRAVERSE enrolled US men 45 to 80 with low morning testosterone twice and a high cardiac load. About 55 percent already had cardiovascular disease. Mean body-mass index was about 35. About 70 percent had diabetes. About 80 percent were White. This is not young men, not eugonadal men, and not a shot or a pellet. It is a daily gel. The noninferiority margin of 1.5 is wide. A true 40 percent rise in events could still have passed. About 61 percent of both groups stopped the assigned gel. Mean time on treatment was under two years. Industry funded the trial. The paper is available here only as an abstract. Atrial fibrillation (3.5 percent versus 2.4 percent), acute kidney injury (2.3 percent versus 1.5 percent), and pulmonary embolism (0.9 percent versus 0.5 percent) were higher on testosterone. Those signals are not the MACE composite and do not flip this page to a claim that testosterone causes heart attacks. This is a journal entry, not medical advice and not a reason to start or stop a gel.
Effect
odds_ratio = 0.96. Lincoff 2023 TRAVERSE: HR 0.96 (0.78-1.17), 182 vs 190 events, N=5198. Noninferiority margin 1.5. Secondary +revasc HR 1.02 (0.86-1.21).
Nodes
Named confounders
Cite this page
What Causes What. “Testosterone → Major cardiovascular events.” https://whatcauseswhat.org/edges/e-t-cv (atlas updated 2026-09-02).
Papers
- Cardiovascular Safety of Testosterone-Replacement Therapy.
AM Lincoff, S Bhasin, P Flevaris, LM Mitchell, S Basaria, WE Boden, GR Cunningham, CB Granger · 2023 · The New England journal of medicine