25-hydroxyvitamin D and Endometriosis: A bidirectional Mendelian randomization study

Numerous studies have demonstrated a correlation between serum 25-hydroxyvitamin D (25OHD) and endometriosis. However, the precise nature of this association remains elusive. The causal connection between 25OHD and endometriosis remains uncertain, as it is yet to be determined whether one directly influences the other. The objective of our research was to investigate the cause-and-effect connection between 25OHD and endometriosis. The study employed Mendelian randomization (MR) in a bidirectional two-sample investigation to examine the causal relationship between 25OHD and endometriosis. The analysis utilized the most recent publicly accessible statistics from the genome-wide association study (GWAS) encompassing 25OHD, endometriosis, and its five subtypes. The primary analytical approach employed was Inverse-Variance Weighting (IVW), accompanied by supplementary analysis methods including weighted median, MR-Egger, simple mode, and weighted mode. Furthermore, sensitivity analyses were conducted to assess the potential influence of heterogeneity and pleiotropy on the MR outcomes. MR primary analysis showed no significant causal effect of 25OHD on endometriosis (OR = 0.892, 95%CI = 0.745 ~ 1.068, P = 0.213). Similarly, there was no evidence to support a causal relationship of endometriosis on 25OHD (IVW Beta = 0.005, 95%CI = 0.993 ~ 1.018, P = 0.406). However, when conducting MR analysis on different subtypes of endometriosis and 25OHD, we found a positive correlation between endometriosis of ovary and 25OHD level (IVW Beta = 0.012, 95%CI = 1.002 ~ 1.022, P = 0.024). This study indicates that there is no causal relationship between serum 25OHD and endometriosis. However, it is important to note that serum 25OHD levels will increase in patients with endometriosis of the ovary. Further observational studies and clinical trials are indispensable. Similar content being viewed by others Data Availability The supporting figures and tables can be found in the article/Supplementary Material, and the original datasets can be obtained from the first author or corresponding author upon request. Code Availability Codes for data analysis are available upon request.

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Thanks to all the teachers and colleagues for their help, as well as the home of researchers. Author information Authors and Affiliations Contributions The study's conceptualization and design were the responsibility of DP and PL. DP and PL were responsible for data collection. DP, PL, XD and SX conducted data analysis and interpretation. DP completed the writing of the manuscript. DP, XD and SX reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version. Corresponding author Ethics declarations Ethics Approval In this MR study, we used published studies or shared datasets that have been ethically approved. We did not need to obtain an additional ethics statement. Consent to Participate In this MR study, we used published studies or shared datasets that informed consent has been obtained. We did not need to obtain an additional consent. Consent for Publication All authors agree to the manuscript submitted and agree to be published in this journal. Conflicts of Interest/Competing Interests The author declares that there is no conflict of interest or competition in this article. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Pan, D., Li, P., Dai, X. et al. 25-hydroxyvitamin D and Endometriosis: A bidirectional Mendelian randomization study. Reprod. Sci. 32, 693–701 (2025). https://doi.org/10.1007/s43032-024-01517-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-024-01517-8