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Sex-specific associations of circulating testosterone levels with all-cause and cause-specific mortality

Jiayu Wang  1 , Xikang Fan  2 , Mingjia Yang  3 , Mingyang Song  4 , Kai Wang  5 , Edward , et al.

Eur J Endocrinol. 2021 Mar 1;EJE-20-1253.R1.doi: 10.1530/EJE-20-1253. Online ahead of print.

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% confidence intervals (CI). 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 5,754 deaths in men, including 1,243 (21.6%) from CVD and 2,987 (51.9%) from cancer. In postmenopausal women, 2,435 deaths occurred, including 346 (14.2%) from CVD and 1,583 (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) versus the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 versus 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.