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Objective <p>The association between endogenous sex hormones and Cardiovascular-kidney-metabolic (CKM) syndrome remains incompletely elucidated.</p> Methods <p>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.</p> Results <p>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 <i>P</i> &lt; 0.05) was observed, alongside reduced estradiol and elevated SHBG. After multivariable adjustments, the association between FAI and all-cause mortality remained significant (<i>HR</i> = 0.46, 95% CI: 0.30–0.69, <i>P</i> &lt; 0.001), whereas the effects of SHBG and the T: E ratio were diminished (<i>P</i> &gt; 0.05). However, for CVD mortality, no significant results were observed in multivariable adjustments. In men aged &gt; 60 years, elevated FAI (&gt; 25.91 nmol/L) and T: E ratio (&gt; 1.55) were each independently associated with reduced all‑cause mortality, with adjusted HRs of 0.24 (<i>P</i> = 0.02) and 0.51 (<i>P</i> = 0.01), respectively.</p> Conclusions <p>Cox proportional hazards analysis demonstrated an inverse relationship between serum FAI and all-cause mortality in the overall, postmenopausal and men (&gt; 60 years) CKM subgroup. In addition, a higher T: E ratio was inversely associated with all‑cause mortality specifically in men aged &gt; 60 years with CKM.</p>

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Association between endogenous sex hormones and cardiovascular-kidney-metabolic in US adults: a population-based study

  • 期刊论文

  • 发表日期：

    2026年7月31日

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  • Ruiyan Xie,
  • Jinxi He,
  • Yongqiong Zhang,
  • Pei Zou,
  • Shuo Xu,
  • Jiajing Zhong,
  • Tao Du

摘要

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.