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Objective <p>This study sought to explore the relationships between sex hormones and obesity-related markers, while utilizing Mendelian randomization (MR) to evaluate their causal links.</p> Methods <p>Data from 5179 participants of the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed. Multivariate linear regression and generalized additive models were utilized to examine linear and non-linear associations between sex hormones and obesity-related parameters. Causal inference was explored via a two-sample MR analysis, with inverse-variance weighting (IVW) as the primary approach.</p> Results <p>Cross-sectional assessments showed that in males, testosterone levels, SHBG, and T/E2 ratio were negatively correlated with obesity, while estradiol displayed a non-linear, inverted U-shaped relationship. In females, estradiol and SHBG had negative associations with adiposity measures. MR analysis revealed that genetically increased Bio-T was associated with lower obesity risk in males, while SHBG showed a negative correlation with visceral and waist obesity. In females, Bio-T and FAI were associated with higher visceral adipose tissue volume and waist circumference, findings consistent with potential causal effects.</p> Conclusions <p>Sex hormones show sex-specific associations with obesity. Testosterone is protective against obesity in males, whereas female hyperandrogenism elevates the risk of obesity, particularly central obesity. These results offer novel perspectives for obesity-related health interventions.</p>

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Associations between sex hormones and obesity-related indicators: results from the NHANES and Mendelian randomization study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月27日

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  • Yong Yuan,
  • Shuhao Cui,
  • Yingqi Hou,
  • Xiaofan Meng,
  • Yanqiu Huang,
  • Feng Xu,
  • Wentao Shi

摘要

Objective

This study sought to explore the relationships between sex hormones and obesity-related markers, while utilizing Mendelian randomization (MR) to evaluate their causal links.

Methods

Data from 5179 participants of the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed. Multivariate linear regression and generalized additive models were utilized to examine linear and non-linear associations between sex hormones and obesity-related parameters. Causal inference was explored via a two-sample MR analysis, with inverse-variance weighting (IVW) as the primary approach.

Results

Cross-sectional assessments showed that in males, testosterone levels, SHBG, and T/E2 ratio were negatively correlated with obesity, while estradiol displayed a non-linear, inverted U-shaped relationship. In females, estradiol and SHBG had negative associations with adiposity measures. MR analysis revealed that genetically increased Bio-T was associated with lower obesity risk in males, while SHBG showed a negative correlation with visceral and waist obesity. In females, Bio-T and FAI were associated with higher visceral adipose tissue volume and waist circumference, findings consistent with potential causal effects.

Conclusions

Sex hormones show sex-specific associations with obesity. Testosterone is protective against obesity in males, whereas female hyperandrogenism elevates the risk of obesity, particularly central obesity. These results offer novel perspectives for obesity-related health interventions.