Wang Kaiwen, Lou Yu, Tian Shunjie, Tao Zhihui
Department of Oncology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2025 Jan 29;16:1338701. doi: 10.3389/fendo.2025.1338701. eCollection 2025.
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.
There was no causal relationship between sex hormones and IBD in women ( > 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, = 0.0004), and for testosterone was 1.20 (95% CI: 1.04-1.39, = 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, = 0.0195) and testosterone (OR = 1.01, 95% CI: 1.00 -1.02, = 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.
本研究旨在通过两样本双向孟德尔随机化（MR）研究，探讨性激素与炎症性肠病（IBD）之间的双向因果关系。
基于欧洲人群中关于性激素结合球蛋白（SHBG）、总睾酮、生物可利用睾酮、雌二醇和IBD的全基因组关联研究（GWAS）汇总数据，我们使用单核苷酸多态性（SNP）作为工具变量进行两样本双向MR分析。我们使用逆方差加权（IVW）、加权中位数、加权众数和MR-Egger方法来评估性激素与IBD之间的双向因果关系。
女性中性激素与IBD之间不存在因果关系（>0.05），而男性中SHBG、睾酮与IBD之间存在因果正相关。SHBG的比值比（OR）为1.22（95%置信区间：1.09-1.37，P = 0.0004），睾酮的OR为1.20（95%置信区间：1.04-1.39，P = 0.0145）。IBD与女性性激素之间无显著相互作用，但导致男性SHBG降低（OR = 1.02，95%置信区间：1.00-1.04，P = 0.0195）和睾酮降低（OR = 1.01，95%置信区间：1.00 -1.02，P = 0.0200）。
女性性激素与IBD之间不存在因果关系，但男性SHBG和睾酮与IBD风险呈正相关，且IBD促使男性SHBG和睾酮水平升高，这表明性激素在不同性别的IBD患者中发挥不同作用。
