Introduction: Literature surrounding testosterone replacement therapy (TRT) and major adverse cardiovascular events (MACE) is conflicting. Currently, the Food and Drug Administration requires warnings regarding a possible increased cardiovascular risk for TRTs. This study sought to investigate the association between TRT and MACE using a large population based database.
Methods: A propensity-weighted, retrospective cohort study was conducted by accessing provincial health administrative databases. Eligibility criteria included men 18 years and older, with no prior TRT or MACE, who had at least 1 year of provincial health coverage from their index date between April 1st, 1995 to December 31st, 2018. TRT was defined as having at least two testosterone prescriptions filled within one year (including capsules, gels, patches, and/or injections). MACE was defined as myocardial infarction, coronary revascularization procedures, ischemic stroke, or hospitalizations for heart failure. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in the study group. Logistic regression model that included age, socioeconomic status, index year, diabetes, hypertension, dyslipidemia and renal disease was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. A cox proportional hazard model was used to examine our primary outcome of time to a MACE.
Results: Among 7095 men receiving TRT and 392,204 controls, men receiving TRT were associated with a 76% higher risk of a MACE (Hazard Ratio 1.76, 1.63 – 1.89) in unweighted and 27% higher risk (Hazard Ratio 1.27, 1.16 – 1.39) in weighted analyses. The median time to a MACE was 2828 and 2707 days in the study and control cohort, respectfully. The proportion of individuals with a MACE was 9.9% and 5.6% in men receiving TRT and controls, respectfully.
Conclusions: Our study demonstrates that men receiving TRT had a higher risk of MACE as compared to controls. Our study is limited by its retrospective nature and inability to capture for all confounders. Whether TRT itself increases the odds of MACE requires further elucidation. Nonetheless, men receiving TRT should be counselled about their increased rate of MACE and health care providers prescribing TRT should identify comorbid conditions to mitigate risk and discuss lifestyle modifications.
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