Environmental endocrine disruptors and endometrial cancer risk: a systematic review and meta-analysis of cadmium and polychlorinated biphenyls, with emerging evidence on PFAS, phthalates, and bisphenols.

Background: Environmental endocrine-disrupting chemicals (EDCs) have been implicated in hormone-related carcinogenesis, however, their associations with endometrial cancer risk remain unclear; therefore, this study aimed to systematically evaluate the relationship between multiple classes of EDCs and the endometrial cancer risk. Methods: The PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched for studies published up to November 30, 2025. Studies evaluating the association between EDCs exposure and endometrial cancer risk were included. When sufficient data were available, meta-analyses of cadmium and polychlorinated biphenyls (PCBs) were conducted using random-effects models, with subgroup and sensitivity analyses performed. Evidence on per- and polyfluoroalkyl substances (PFAS), phthalates, and bisphenols was summarized through a structured narrative review. All statistical analyses were performed using Stata 18.0. Results: A total of 14 studies were included. The meta-analysis showed that higher cadmium exposure was associated with an increased risk of endometrial cancer (RR = 1.22, 95% CI: 1.01-1.47), with considerable heterogeneity across studies (I²= 72.17%). Subgroup analyses suggested that the association was not statistically significant for dietary cadmium exposure or among women undergoing hormone therapy, and a marginally positive association was observed in postmenopausal women (RR = 1.27, 95% CI: 0.99-1.64). No significant association was identified between PCBs exposure and endometrial cancer risk (RR = 1.11, 95% CI: 0.79-1.56), and heterogeneity was low (I² = 0.0%). Findings from case-control studies and subgroup analyses stratified by PCBs functional classification (Estrogenic and Enzyme-inducing types) were consistent, with no significant associations detected. Owing to the limited number of available studies, quantitative synthesis was not feasible for PFAS, phthalates, or bisphenols. Conclusion: Current evidence suggests a potential link between cadmium exposure and endometrial cancer, though substantial heterogeneity warrants caution. No consistent association was observed for PCBs. Evidence on emerging EDCs, including PFAS, phthalates, and bisphenols, remains limited and exploratory. Well-designed prospective studies with improved exposure assessment and standardized confounder control are needed.