Cardiovascular Outcomes and All-cause Mortality Following Measurement of Endogenous Testosterone Levels

Abstract

Although reduced testosterone levels are common in aging populations, the clinical consequences remain to be further explored. We examined whether low total testosterone levels are associated with stroke (ischemic and hemorrhagic), myocardial infarction (MI), venous thromboembolism (VTE), and all-cause mortality in adult men. We conducted a cohort study in the Central Denmark Region (2000 to 2015). We included all men with a first-ever laboratory testosterone result and computed the 5-year risks of cardiovascular outcomes and all-cause mortality. Propensity score-weighted hazard ratios were computed, comparing persons with normal versus low testosterone levels. Individuals were censored at testosterone treatment during follow-up (3%). We identified 4,771 men with low testosterone levels and 13,467 with normal levels. Persons with low testosterone levels were older (median ages, 55 years vs 50 years) and had more co-morbidities than men with normal testosterone levels. Persons with low testosterone had higher 5-year risks of stroke (2.4% vs 1.5%), MI (1.5% vs 1.2%), VTE (1.4% vs 0.9%), and all-cause mortality (17.8% vs 6.8%) than persons with normal testosterone levels. After propensity score-weighting, the associations with cardiovascular outcomes reached unity. The 5-year hazard ratios were 1.14 (95% confidence intervals [CIs] 0.87 to 1.49) for stroke, 0.95 (95% CI 0.70 to 1.30) for MI, 1.10 (95% CI 0.78 to 1.55) for VTE, whereas it was 1.48 (95% CI 1.32 to 1.64) for all-cause mortality. In conclusion, low testosterone level was a strong predictor for cardiovascular outcomes and all-cause mortality in unadjusted models, however only the association between low testosterone and all-cause mortality persisted after adjustment for age and co-morbidity.