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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1338701

Causal Relationship between inflammatory bowel disease and sex: a Mendelian randomization study

Provisionally accepted
Kaiwen Wang Kaiwen Wang 1Yu Lou Yu Lou 1Shunjie Tian Shunjie Tian 2Zhihui Tao Zhihui Tao 1*
  • 1 Seventh People's Hospital of Shanghai, Shanghai, Shanghai Municipality, China
  • 2 Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    The aim of this study was to investigate the bidirectional causal relationship between sex hormones and IBD through a two-sample bidirectional Mendelian randomization (MR) study.Based on Genome-Wide Association Study (GWAS) pooled data on SHBG, total testosterone, bioavailable testosterone, estradiol, and IBD in a European population, we performed two-sample bidirectional MR analyses using single nucleotide polymorphisms (SNPs) as instrumental variables. We used inverse variance weighting (IVW), weighted median, weighted mode, and MR-Egger to assess bidirectional causality between sex hormones and IBD.Results: There was no causal relationship between sex hormones and IBD in women (P > 0.05), and there was a causal and positive correlation between SHBG and testosterone and IBD in men.The OR for SHBG was 1.22 (95% CI: 1.09-1.37, P = 0.0004), and for testosterone was 1.20 (95% CI: 1.04-1.39, P = 0.0145 ).IBD did not significantly interact with female sex hormones but resulted in a decrease in SHBG (OR = 1.02, 95% CI: 1.00-1.04, P = 0.0195) and testosterone (OR = 1.01, 95% CI: 1.00 -1.02, P = 0.0200) in men.There is no causal relationship between female sex hormones and IBD, but male SHBG and testosterone are positively correlated with the risk of IBD and IBD promotes elevated levels of SHBG and testosterone in males, suggesting that sex hormones play different roles in IBD patients of different sexes.

    Keywords: sex hormone, IBD, Mendelian randomization, genome-wide association, biomarker

    Received: 08 Dec 2023; Accepted: 06 Jan 2025.

    Copyright: © 2025 Wang, Lou, Tian and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhihui Tao, Seventh People's Hospital of Shanghai, Shanghai, Shanghai Municipality, China

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