Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age

Background In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-M & uuml;llerian hormone concentrations. Methods Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-M & uuml;llerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixedeffect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. Findings In our multivariable linear regression models we observed associations of higher urinary pregnancyaveraged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No signi fi cant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences - 0.07 (95% CI - 0.13, - 0.02), - 0.09 ( - 0.15, - 0.02), - 0.08 (95% CI - 0.14, - 0.02), and - 0.08 ( - 0.13, - 0.03) mu g/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). Interpretation We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).