Urinary phthalate metabolites and alternatives and serum sex steroid hormones among pre- and postmenopausal women from NHANES, 2013-16

Background: Exposure to phthalates is ubiquitous across the United States. While phthalates have antiandrogenic effects in men, there is little research on their potential impacts on sex hormone concentrations in women and that also take into account menopausal status. Methods: Cross-sectional data on urinary phthalate metabolites, serum sex hormones, and relevant covariates were obtained from the National Health and Nutrition Examination Survey 2013-14 and 2015-16. Women over the age of 20 who were not pregnant or breastfeeding and had not undergone oophorectomy were included (n = 698 premenopausal, n = 557 postmenopausal). Weighted multivariable linear and Tobit regression models stratified by menopausal status were fit with natural log-transformed phthalate concentrations and sex hormone outcomes adjusting for relevant covariates. Results: Phthalate metabolites were associated with differences in sex hormone concentrations among postmenopausal women only. Di-2-ethylhexyl phthalate (DEHP) was associated with lower serum estradiol and bioavailable testosterone concentrations. Specifically, a doubling of DEHP concentrations was associated with 5.9% (95% Confidence Interval (CI): 02%, 11.3%) lower estradiol and 62% (95% CI: 0.0%,12.1%) lower bioavailable testosterone concentrations. In contrast, 12-cyclohexane dicarboxylic acid di-isononyl ester (DINCH) was associated with higher free testosterone, bioavailable testosterone, and free androgen index. Finally, di-2-ethylhexyl terephthalate (DEHTP) was associated with a higher testosterone-to-estradiol ratio. None of these results retained statistical significance when adjusted for multiple comparisons. Conclusions: DEHP, DINCH, and DEHTP were associated with differences in serum sex hormone concentrations among postmenopausal women, highlighting the need for further research into the safety of these chemicals. (C) 2021 Elsevier B.V. All rights reserved.