Sex-Specific Associations Of Circulating Testosterone Levels With All-Cause And Cause-Specific Mortality

Objective: Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined.Methods: We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154 965 men and 93 314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% CIs. Given multiple testing, P < 0.005 was considered statistically significant.Results: Over a median follow-up of 8.9 (inter-quartile range: 8.3?9.5) years, we documented 5754 deaths in men, including 1243 (21.6%) from CVD and 2987 (51.9%) from cancer. In postmenopausal women, 2435 deaths occurred, including 346 (14.2%) from CVD and 1583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75?0.91) and 0.80 (95% CI: 0.73?0.87) for the highest (Q5) vs the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 vs Q1 = 1.20, 95% CI: 1.06?1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03).Conclusions: Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.