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

The association between a diverse array of environmental risk factors and the risk of endometriosis is contradictory. To summarize the evidence of associations between environmental risk factors and the risk of endometriosis. 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 , evidence for small-study effects, and evidence of excess significance bias. About 12 eligible articles (featuring 143,422 cases and 5,112,967 participants) yielded data on 40 unique environmental risk factors, including life styles ( = 16), reproductive factors ( = 3), early life factors ( = 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 ( < 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. 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.