Data_Sheet_1_Environmental Risk Factors for Endometriosis: An Umbrella Review of a Meta-Analysis of 354 Observational Studies With Over 5 Million Populations.docx

Background: The association between a diverse array of environmental risk factors and the risk of endometriosis is contradictory.Objective: To summarize the evidence of associations between environmental risk factors and the risk of endometriosis.Methods: Databases such as PubMed, EMBASE, Web of Science, and ClinicalTrial.gov were systematically searched in June 2020. Meta-analyses of observational studies investigated any environmental exposure (non-genetic) and endometriosis risk. For each article, we estimated the summary effect size, 95% CIs, and the 95% prediction interval (PI). We also estimated the between-study heterogeneity expressed by I2, evidence for small-study effects, and evidence of excess significance bias.Results: About 12 eligible articles (featuring 143,422 cases and 5,112,967 participants) yielded data on 40 unique environmental risk factors, including life styles (n = 16), reproductive factors (n = 3), early life factors (n = 4), and a range of other risk factors [e.g., phthalate metabolites, endocrine-disrupting chemicals, and body mass index (BMI)]. About 25 of these 40 associations (62.5%) were statistically significant (p < 0.05) under random-effects models. Evidence for an association was indicated for alcohol intake [relative risk (RR): 1.25; 95% CI: 1.11–1.41] and the exposure to endocrine disruptor chemicals (EDCs) (RR: 1.41; 95% CI: 1.23–1.60) while 15 associations presented only weak evidence.Conclusions: Our analyses showed that alcohol intake and exposure to endocrine-disrupting chemicals may be potential risk factors for endometriosis and supported by suggestive epidemiological evidence. However, it was evident that there was substantial heterogeneity and/or bias between the different studies featured in various meta-analyses included in this review; therefore, the outcomes of our analysis should be interpreted cautiously.