Menopause-specific associations of organophosphate esters with sex hormones among US women.

Organophosphate esters (OPEs) may disrupt hormonal balance, but their specific effects in pre- and post-menopausal women have been underexplored. This investigation delves into the menopause-specific associations of OPEs with sex hormones in the National Health and Nutrition Examination Survey, 2013-2016. We included 817 premenopausal and 657 postmenopausal women. Survey-weighted multivariable linear regression, restricted cubic splines (RCS), principal component analysis (PCA), and quantile-based g computation (qgcomp) models were conducted to investigate the associations of OPE metabolites and OPEs mixture with sex hormones in pre- and postmenopausal women. In postmenopausal women, bis(2-chloroethyl) phosphate (BCEP) and Bis(1,3-dichloro-2-propyl) phosphate (BDCPP) were negatively associated with testosterone (T) (BCEP: β = -0.06 [-0.10, -0.01]; BDCPP: β = -0.07 [-0.13, -0.01]) and free androgen index (FAI) (BCEP: β = -0.08 [-0.13, -0.02]; BDCPP: β = -0.06 [-0.12, -0.01]). Diphenyl phosphate (DPHP) was also negatively associated with FAI (β = -0.08 [-0.14, -0.02]). RCS analyses revealed non-linear exposure-response relationships between DPHP and T, between BDCPP and estrogen (E2), and between BDCPP and DPHP and the T/E2 ratio. PCA and qgcomp analyses consistently found negative associations between the OPEs mixture and T and FAI. Conversely, in premenopausal women, BCEP was linearly and positively associated with sex hormone-binding globulin (SHBG) (β = 0.05 [0.01,0.09]), whereas DPHP showed a nonlinear relationship with SHBG, with a curve rising then plateauing. Overall, OPEs, alone or as mixtures, might lower T and FAI levels in postmenopausal women. In contrast, BCEP and DPHP might increase SHBG levels in premenopausal women.