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Updated: Apr 29, 2026
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Genetic Association Between Sex Hormones, Serum Urate, and Gout: A Comprehensive Mendelian Randomization Study
Shiwei Li1, Mengjuan Zhang1, Xuemei Wang1
1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, China, tjmugh.com.cn.
International Journal of Endocrinology
|April 22, 2026
Summary
Sex hormones impact urate metabolism differently in men and women. Higher total testosterone in women is linked to increased serum urate, partly mediated by a specific metabolite, suggesting sex-specific gout interventions.
Area of Science:
- Endocrinology
- Genetics
- Metabolic Diseases
Background:
- Observational studies suggest a link between sex hormones and hyperuricemia (HUA) and gout risk.
- Causal relationships and underlying mechanisms remain unclear, particularly regarding sex-specific effects.
Purpose of the Study:
- To investigate the causal relationship between sex hormones and HUA/gout.
- To explore sex-specific mechanisms in European populations.
- To identify potential mediating factors in urate metabolism.
Main Methods:
- Utilized sex-specific genome-wide association study (GWAS) data from European populations.
- Employed linkage disequilibrium score regression (LDSC) for genetic correlation analysis.
- Conducted two-sample Mendelian randomization (MR) and mediation analyses to assess causality and metabolite effects.
Main Results:
- Genetic correlation analysis showed moderate associations between sex hormones and serum urate/gout.
- MR analysis revealed a significant association between genetically predicted total testosterone (ToT) and increased serum urate in women.
- Mediation analysis identified androstenediol (3β, 17β) disulfate (2) as a partial mediator (28.4%) of ToT's effect on serum urate.
Conclusions:
- Sex hormones significantly influence urate metabolism with distinct sex-specific differences.
- Findings support tailored interventions for HUA, especially for European women with hyperandrogenism.
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