Injection Testosterone and Adverse Cardiovascular Events: A Case-crossover Analysis

Summary

Context

Exogenous testosterone administration may affect blood clotting, polycythemia, and may increase atherosclerosis, though any association with cardiovascular events is unclear. While the literature is inconclusive, some studies have suggested testosterone use may increase short-term risk of cardiovascular events and stroke, and injection testosterone may convey higher risks than other dosage forms.

Objective

We sought to evaluate the short-term cardiovascular risk of receiving injection testosterone.

Design

We conducted a case-crossover analysis comparing injection testosterone exposure in the seven days prior to an outcome event to referent windows in the past to estimate the acute association of cardiovascular outcomes with the receipt of testosterone injections.

Patients

We identified adult male testosterone users hospitalized with myocardial infarction (MI), stroke, or a composite of MI, stroke, or unstable angina in US commercial claims (2000-2013) or Medicare (2007-2010) databases.

Measurements

We identified testosterone use for the patients from pharmacy dispensing claims or in-office procedure codes in the insurance billing data.

Results

We identified 2,898 commercially-insured men with events and recent testosterone use, and 339 from Medicare. Injected testosterone was associated with an increased risk of adverse events (composite outcome of myocardial infarction, stroke, or unstable angina) in the immediate post-injection period for the older, Medicare population only: commercial insurance, OR=0.98 (95% CI: 0.86-1.12); Medicare, OR=1.45 (1.07, 1.98). This association was either greatly attenuated or not present when evaluating receipt of any testosterone dosage forms (injection, gel, patch, implant): commercial insurance, OR=1.01 (0.92, 1.11); Medicare, OR=1.26 (95% CI: 0.98-1.63).

Conclusions

Testosterone injections were uniquely associated with short-term risk of acute cardio- and cerebrovascular events in older adult men following injection receipt.

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