Injection testosterone and adverse cardiovascular events: A case-crossover analysis

Context: Exogenous testosterone administration may affect blood clotting, polycythaemia, 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 7 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 2898 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 postinjection period for the older, Medicare population only: commercial insurance, odds ratios (OR) = 0.98 (95% confidence intervals [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.