Time-varying testosterone level and risk of myocardial infarction and stroke among hypogonadal men: a longitudinal study in Germany

Background and objective: Findings on the association between testosterone and cardiovascular risk in men have been inconsistent. Previous studies investigated this association based on testosterone level measured at one single point in time (e.g., testosterone level at the baseline visit), which might not be relevant for the future cardiovascular events that occurred many years later, given the dynamic changes of testosterone level over time. Additionally, as compared to patients without prior cardiovascular history, those with prior cardiovascular events are more likely to have pathological changes in coronary or peripheral vasculature, and therefore more susceptible to cardiovascular events when exposed to risk factors. However, whether time-varying testosterone level affects differently between patients with prior cardiovascular events and those without is unknown. The objective of this study was to investigate the association between time-varying testosterone level and risks of myocardial infarction and stroke, and compared the associations stratified by patient's prior cardiovascular event history. Material and methods: We used data of 376 hypogonadal men from a registry study in Germany with up to 11 years' follow-up and applied Cox proportional hazards regression models to investigate the proposed association. Results: No association was found between baseline testosterone level and risks of myocardial infarction and stroke. When taking into account the changes of testosterone level over time and including testosterone as a time-varying covariate in the model, the adjusted hazard ratio (HR) for myocardial infarction associated with 1 nmol/L increase in testosterone level was 0.78 (95% CI: 0.64, 0.97); no association between time-varying testosterone level and stroke was found. The associations between testosterone level and cardiovascular risk were not different among patients with prior cardiovascular event history and those without. Conclusion: One baseline measurement of testosterone level may be insufficient to predict one's future risk of cardiovascular events; regular monitoring of testosterone levels may be useful to assess the short-term cardiovascular risk in men.