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Injection testosterone and adverse cardiovascular events: A case-crossover analysis
J Bradley Layton1,2, Dongmei Li1, Christoph R Meier3
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Insights
Testosterone injections may increase short-term cardiovascular risks, particularly in older men. This risk appears specific to injections, not other testosterone forms.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Pharmacology
Background:
- Exogenous testosterone administration's cardiovascular effects are debated, with some studies suggesting increased risks.
- Injection testosterone formulations may pose higher risks than other dosage forms.
Purpose of the Study:
- To evaluate the short-term cardiovascular risk associated with receiving testosterone injections.
- To compare risks across different testosterone formulations.
Main Methods:
- A case-crossover analysis was used to compare testosterone exposure within 7 days before an event to referent periods.
- Adult males hospitalized for myocardial infarction (MI), stroke, or unstable angina were identified in US insurance claims and Medicare data.
- Testosterone use was determined via pharmacy dispensing claims or in-office procedure codes.
Main Results:
- Testosterone injections were associated with an increased risk of adverse cardiovascular events (MI, stroke, unstable angina) in older men (Medicare population, OR=1.45).
- This association was not significant in the commercially insured population (OR=0.98).
- When considering all testosterone dosage forms, the increased risk was attenuated or absent across both populations.
Conclusions:
- Testosterone injections are uniquely associated with a short-term risk of acute cardiovascular and cerebrovascular events in older adult men.
- The findings suggest that the risk is specific to the injection method and the immediate post-injection period.
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.
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