J Diabetes Metab Disord. 2026 Jul 31;25(2):220. doi: 10.1007/s40200-026-02036-w. eCollection 2026 Dec.
ABSTRACT
OBJECTIVE: The association between endogenous sex hormones and Cardiovascular-kidney-metabolic (CKM) syndrome remains incompletely elucidated.
METHODS: We performed a cohort study using clinical data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Restricted cubic spline Cox proportional hazards models and stratified analyses were employed to analyze the relationships between sex hormone-binding globulin (SHBG), free androgen index (FAI), testosterone-to-estradiol ratio (T: E), and mortality.
RESULTS: In a cohort of 2,545 patients with CKM (mean age 51.84 years; 63.65% male) followed for a mean of 4.78 years, stage 2 disease was the most prevalent (56.96%). A significant inverse correlation between advancing CKM stages and serum levels of testosterone-related parameters (all P < 0.05) was observed, alongside reduced estradiol and elevated SHBG. After multivariable adjustments, the association between FAI and all-cause mortality remained significant (HR = 0.46, 95% CI: 0.30-0.69, P < 0.001), whereas the effects of SHBG and the T: E ratio were diminished (P > 0.05). However, for CVD mortality, no significant results were observed in multivariable adjustments. In men aged > 60 years, elevated FAI (> 25.91 nmol/L) and T: E ratio (> 1.55) were each independently associated with reduced all‑cause mortality, with adjusted HRs of 0.24 (P = 0.02) and 0.51 (P = 0.01), respectively.
CONCLUSIONS: Cox proportional hazards analysis demonstrated an inverse relationship between serum FAI and all-cause mortality in the overall, postmenopausal and men (> 60 years) CKM subgroup. In addition, a higher T: E ratio was inversely associated with all‑cause mortality specifically in men aged > 60 years with CKM.
PMID:42542681 | PMC:PMC13427681 | DOI:10.1007/s40200-026-02036-w