Sex difference of the associations of sex hormone and their related indicators with all-cause mortality

BACKGROUND: Sex hormones are critical health determinants in both sexes. Some studies have found the association between sex hormones and all-cause mortality. However, the evidence of these association is limited and there is a lack of comprehensive investigation of various sex hormones. METHODS: Our study included a total of 7,294 participants from the 2013 to 2016 National Health and Nutrition Examination Survey (NHANES). The total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were obtained from laboratory data, free testosterone (FT), free estradiol (FE2), free androgen index (FAI) and the ratio of TT to E2 (TT/E2) were calculated. Cox proportional hazards regression models and restricted cubic spline were used to analysis the association between various sex hormones and all-cause mortality, and stratified analyses according to age, sex, race, and history of diabetes and hypertension were performed. RESULTS: The final study sample included 3,473 male and 3,821 female from the NHANES. In the multivariate-adjusted model, male participants with higher FT and higher FAI had an obvious lower incidence of all-cause mortality [FT: HR, 0.41 (95% CI, 0.36-0.79); FAI: HR, 0.34 (95% CI, 0.25-0.92)], but these associations were not significant in female. And there was a positive correlation between SHBG concentration and mortality rate in both male and female participants, but the HR in males was higher than that in females [2.45 (95% CI, 1.69-6.23) vs 1.81 (95% 1.53-3.21)]. CONCLUSION: Our study found sex differences in the association of sex hormones and their related indicators with all-cause mortality, providing new insights for future research in this field.