Association between co-exposure to phenols and phthalates mixture and infertility risk in women

Background Exposure to phenols and phthalates has been separately linked to increased risks of infertility in women of reproductive age. However, the combined effect of phenols and phthalates exposure on infertility has not been explored. Methods Data from the National Health and Nutrition Examination Surveys (NHANES) were used. A total of 857 women of reproductive age (18–45 years) with available information on urinary phenol and phthalate metabolites, reproductive questionnaires, and covariates were included in the present study. The definition of infertility was based on self-reports. Multivariable logistic regression, principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) with stratified variable selection were applied to determine what associations were found between combined exposure to these mixtures and risk of infertility among women of reproductive age. Results After adjusting for potential confounders, bisphenol A (BPA), mono(3-carboxypropyl) phthalate (MCPP) and four di(2-ethylhexyl) phthalate (DEHP) metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)] were positively associated with infertility. PCA revealed that the DEHP-BPA factor's PC score was significantly positively related to the likelihood of infertility [adjusted odds ratio (aOR) = 1.45; 1.08, 1.82]. The DEHP-BPA component consistently had the highest group posterior inclusion probability (PIP) in BKMR models. The BKMR model also found that MEOHP, MEHHP, and BPA were positively associated with infertility risk when the remaining combination concentrations were held at their median values. In addition, we observed that the probability of infertility increased dramatically as the quantiles of total mixture concentration increased. Conclusion Our findings indicate that a combination of phenol and phthalate metabolites is linked to infertility among reproductive-age women. BPA and DEHP, in particular, are significantly related to the risk of infertility.