- Question
- Is testosterone-replacement therapy cardiovascularly safe in middle-aged and older men with hypogonadism and preexisting cardiovascular disease or high cardiovascular risk?
- Design
- Multicenter, randomized, double-blind, placebo-controlled noninferiority trial of 5246 men. Mean treatment duration was 21.7 months and mean follow-up was 33.0 months.
- Population
- Men aged 45 to 80 years with preexisting or high risk of cardiovascular disease, symptoms of hypogonadism, and two fasting testosterone levels below 300 ng per deciliter.
- Intervention
- Daily transdermal 1.62% testosterone gel, dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter.
- Control
- Matching placebo gel once daily.
- Primary outcome
- First occurrence of any component of the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, analyzed as time to event; noninferiority required the upper limit of the 95% CI of the hazard ratio to be below 1.5.
- Results
- The primary event occurred in 182 patients (7.0%) on testosterone and 190 (7.3%) on placebo (HR 0.96; 95% CI, 0.78 to 1.17; P<0.001 for noninferiority). The incidence of the secondary composite end point and of each component of the primary end point appeared similar between groups.
- Safety
- A higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism was observed in the testosterone group.
- Conclusion
- In men with hypogonadism and preexisting or high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo for major adverse cardiac events.
- Why it matters
- It provided large-scale randomized evidence on the cardiovascular safety of testosterone in this population, although safety signals for other events need to be weighed when prescribing it.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026