Testosterone replacement therapy and the risk of adverse cardiovascular outcomes and mortality

The risk of adverse cardiovascular events and mortality associated with testosterone replacement therapy is controversial. The purpose of this report was to evaluate the effect of testosterone replacement therapy (TRT) in men with secondary hypogonadism on the risk of myocardial infarction (MI), stroke (CVA) or all-cause mortality.

A retrospective cohort study was conducted using the Cleveland Clinic's electronic health record. Men ≥40 years of age, with at least two testosterone levels < 220 ng/dL, with one level obtained between 7 am and 10 am, were identified. Men with primary hypogonadism, secondary hypogonadism related to overt hypothalamic pituitary pathology, human immunodeficiency virus infection, metastatic cancer, and select contraindications to TRT, were excluded. Men exposed to TRT were matched to controls that were not exposed. A survival analysis was performed on the composite outcome of MI, CVA, or all-cause mortality.

One hundred sixty-five patients exposed to TRT (treatment group) were matched with 210 not exposed to TRT (comparison group). The prevalence of established cardiovascular disease (CVD) was 20.0% in the treatment group vs. 17.1% in the comparison group (P = 0.478). The median [interquartile range (IQR)] age (years) and BMI (kg/m²) were 55 (49, 62) and 35.6 (32.1, 40.1) in the treatment group, and 55 (49, 61.7) and 36.3 (32.1, 40.8) in the comparison group, respectively. There were 12 (7.3%) events observed in the treatment group, and 16 (7.6%) in the comparison group. The median time (years) to the composite event was 2.1 (IQR 0.9, 4.6) and 1.8 (IQR 0.6, 3.4) for treatment and comparison groups, respectively. No difference in the risk of the combined cardiovascular endpoint was observed between the treatment group vs the comparison group, hazard ratio (HR) 0.81 (95% Confidence Interval [CI]: 0.38-1.71; P = 0.57).

In hypogonadal men with a modest prevalence of established CVD, TRT was not observed to confer a protective or adverse effect on the risk of MI, CVA or all-cause mortality.