Systematic Review and Meta-Analysis on the Association Between Cadmium and Mercury, with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with multifactorial etiology. Cadmium (Cd) and mercury (Hg) are potent endocrine-disrupting metals, yet their association with PCOS remains inconsistent. These metals were targeted due to their high prevalence, established ovarian toxicity, and shared mechanistic pathways relevant to PCOS. Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Embase through December 2025 for observational studies comparing Cd/Hg concentrations between women with PCOS and controls. Quality was assessed via the Newcastle-Ottawa Scale; pooled standardized mean differences (SMDs) were calculated using random-effects models. Eleven studies (1,960 cases; 2,696 controls) were included. Women with PCOS exhibited significantly higher cadmium (SMD = 0.42, 95% CI: 0.09-0.75; I²=95.6%) and mercury (SMD = 0.57, 95% CI: 0.23-0.91; I²=95.8%) concentrations than controls. Egger's test indicated potential publication bias; trim-and-fill adjustment yielded corrected SMDs of 0.78 (95% CI: 0.34-1.22) for cadmium and 0.76 (95% CI: 0.41-1.11) for mercury, indicating slight underestimation of true effects. Meta-regression for mercury identified biological matrix (p = 0.002) and geographical location (p = 0.026) as significant moderators; bubble plots confirmed attenuation of the Hg-PCOS association when shifting from serum to whole blood or urine. No significant predictors explained cadmium's heterogeneity, suggesting unmeasured individual factors. This meta-analysis provides quantitative evidence linking Cd and Hg exposure to PCOS. The choice of biological matrix is a critical determinant in assessing mercury's impact. These findings advocate for standardized environmental exposure assessments and longitudinal studies to establish causality and inform preventive public health strategies.