Association between bisphenol exposure and polycystic ovary syndrome risk: an integrated systematic review and meta-analysis

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with environmental endocrine-disrupting chemicals, particularly bisphenols (BPs) such as bisphenol A (BPA) and bisphenol S (BPS). BPs may disrupt reproductive and metabolic pathways through estrogenic, anti-androgenic, and obesogenic effects, contributing to the pathogenesis of PCOS. However, the epidemiological evidence remains inconsistent. Methods This PRISMA-guided systematic review and meta-analysis evaluated observational studies (cross-sectional, case-control, longitudinal) from PubMed and Web of Science up to December 2024. Seventeen studies involving 3, 010 women were included after screening. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models due to high heterogeneity (I² > 50%). Subgroup analyses were conducted to explore the sources of heterogeneity. Result The meta-analysis revealed significant positive associations between PCOS risk and serum BPA (SMD = 1.32, 95% CI: 0.83–1.82), urinary BPA (SMD = 2.69, 95% CI: 1.41–3.97), and serum BPS (SMD = 0.26, 95% CI: 0.07–0.46). Heterogeneity was high for BPA (I² = 95–99%) but absent for BPS (I² = 0%). Sensitivity analyses excluding lower-quality studies confirmed the robustness of the findings. Subgroup analyses utilizing the Rotterdam criteria slightly attenuated the associations for BPA. Funnel plots indicated no significant publication bias. Conclusion Exposure to BPs, represented by BPA and BPS, was significantly associated with an increased risk of PCOS, likely mediated by endocrine disruption, metabolic dysregulation, and epigenetic mechanisms. These findings underscore the necessity for regulatory policies aimed at reducing population-level exposure to BPs, the clinical integration of BPs biomonitoring in the management of PCOS, and further research on gene-environment interactions and non-monotonic dose effects. Addressing exposure to BPs may offer novel preventive and therapeutic strategies for PCOS. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , CRD42024578174.