Scientific evidence linking testosterone replacement therapy to heart attack risk accumulated rapidly between 2010 and 2015. The TOM Trial — published in the New England Journal of Medicine — was stopped early when researchers found 54 adverse cardiovascular events in the testosterone group, compared to far fewer in the placebo group. Subsequent large database studies confirmed the signal at population scale.

The biological mechanism involves multiple pathways: testosterone raises hematocrit (red blood cell concentration), increasing blood viscosity and clot risk; it may accelerate atherosclerosis (arterial plaque buildup); and it can promote platelet aggregation. Men with pre-existing cardiovascular conditions — hypertension, prior MI, coronary artery disease — face dramatically elevated risk when adding TRT.