| Title: | Sex-specific associations of SHBG, testosterone, and obesity with cholecystectomy risk: a population-based cohort study |
| Journal: | Biology of Sex Differences |
| Published: | 23 Mar 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41872976/ |
| DOI: | https://doi.org/10.1186/s13293-026-00884-y |
Publication 18231
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Abstract
BackgroundGallstone disease exhibits a marked sex difference. While obesity and female sex hormones are known risk factors, the role of sex hormone-binding globulin (SHBG) and testosterone in gallstone-related risk, and whether they mediate the association between obesity and gallbladder disease, remain unclear.MethodsWe included 176,909 men and 160,147 women from the UK Biobank. Serum SHBG and testosterone were measured using immunoassays. Incident cholecystectomy cases were identified through hospital records. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Mediation analyses were performed to assess the contribution of SHBG and testosterone to the obesity-cholecystectomy association.ResultsA total of 2,877 men and 4,607 women underwent cholecystectomy. Higher SHBG levels were associated with a lower risk of cholecystectomy in both sexes, with a stronger association in women (HRQ4 vs. Q1 = 0.40, 95% CI: 0.36-0.43) than in men (HRQ4 vs. Q1 = 0.67, 95% CI: 0.59-0.77). Elevated testosterone levels were associated with an increased risk of cholecystectomy only in women (HRQ4 vs. Q1 = 1.28; 95% CI: 1.18-1.38). Obesity exhibited a stronger association with cholecystectomy in women than in men. In women, SHBG mediated 14.7% and 20.0% of the associations between general and abdominal obesity and cholecystectomy, respectively, whereas testosterone mediated smaller proportions (2.7% and 1.8%). No significant mediation was observed in men.ConclusionsSHBG levels are inversely associated with risk of cholecystectomy in both sexes, whereas higher testosterone levels are associated with a higher risk of cholecystectomy only in women. SHBG and, to a lesser extent, testosterone accounted for a modest proportion of the obesity-cholecystectomy association in women.</p>
14 Keywords
- Adult
- Aged
- Cholecystectomy
- Cohort Studies
- Female
- Gallstones
- Humans
- Male
- Middle Aged
- Obesity
- Risk Factors
- Sex Characteristics
- Sex Hormone-Binding Globulin
- Testosterone
7 Authors
- Jie-Qiong Lyu
- Yi Luo
- Yu-Wen Qian
- Ji-Mei Gu
- Meng-Yuan Miao
- Guo-Chong Chen
- Guo-Jian Yin
1 Application
| Application ID | Title |
|---|---|
| 90087 | Role of environmental and host factors and their interplays in the development and progression of chronic diseases |
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