Per- and Polyfluoroalkyl Substances and Endometriosis: A Systematic Review and Meta-Analysis

Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals implicated in reproductive dysfunction. Epidemiologic evidence examining their association with endometriosis remains inconsistent. Thus, we conducted a PRISMA-compliant systematic review and meta-analysis using PubMed, Embase, EBSCO Host, and Google Scholar databases. RStudio software was used for all analyses. Random-effects or fixed-effects model was applied to estimate pooled odds ratios (ORs) and standardized mean difference (SMD) in PFAS levels between endometriosis patients and controls. Heterogeneity was assessed using I² statistics. Publication bias was evaluated using funnel plots, and Egger's and Begg's tests. Twelve studies met the inclusion criteria for the systematic review and eleven were included in the quantitative synthesis. Overall, PFSAs (OR: 1.50; 95% CI: 1.12-2.00) and PFCAs (OR: 1.46; 95% CI: 1.12-1.90) were significantly associated with increased odds of endometriosis, particularly PFOS and PFOA. However, analyses of pooled SMD did not demonstrate consistent concentration differences between endometriosis cases and controls. Heterogeneity was moderate to high for most compounds. Funnel plot symmetry and Egger's and Begg's tests suggest no publication bias. Exposure to PFASs, particularly PFOS and PFOA, may be associated with increased odds of endometriosis. Further prospective studies incorporating mixture modeling and emerging PFASs are warranted.