Examining the causal relationship between sex hormone-binding globulin (SHBG) and infertility: A Mendelian randomization study

Abstract

Background The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this relationship. Methods Risk factors for SHBG were extracted from European individuals within the UK Biobank using single-nucleotide polymorphism (SNP) data. Summary-level data for infertility outcomes were obtained from the FinnGen dataset. The causal relationship between SHBG and infertility was examined using inverse variance weighted, weighted model, weighted median, and MR-Egger regression analyses. Additionally, Cochran’s Q test and Egger intercept tests were used to confirm the heterogeneity and pleiotropy of identified instrumental variables (IVs). Results Our findings revealed a significant negative association between sex hormone-binding globulin (SHBG) levels and infertility, particularly with anovulation, a specific form of female infertility. However, SHBG did not exert a causal impact on male infertility or on female infertility of tubal origin. Conclusions SHBG expression offers protection against the development of certain types of female infertility, suggesting it is a potential therapeutic target for infertility.