The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a prior history of myocardial infarction (MI) is unknown. The objective of this study was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT. We retrospectively examined 1470 males with documented low TT levels and prior MI, categorized into Gp1: TRT with normalization of TT levels (N=755) Gp2: TRT without normalization of TT levels (N=542), and Gp3: no TRT (N=173). The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models. All-cause mortality was lower in Gp1 vs. Gp2 (HR 0.76, CI 0.64–0.90, P=0.002), and Gp1 vs Gp3 (HR 0.76, CI 0.60–0.98, P=0.031). There was no significant difference in the risk of death between Gp2 vs. Gp3 (HR: 0.97, CI 0.76–1.24, P=0.81). Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs. Gp3, HR 0.79, CI 0.12–5.27, P=0.8; Gp1 vs. Gp2 HR 1.10, CI 0.25–4.77, P=0.90; Gp2 vs. Gp3 HR 0.58, CI 0.08– 4.06, P=0.58). In conclusion, in a large observational cohort of male veterans with prior MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared to those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.
