Environmental exposures and anti-Müllerian hormone: a mixture analysis in the US based Nurses’ Health Study II (NHSII)

Abstract

BACKGROUND AND AIM: Previous studies have linked exposures such as air pollution and greenness with anti-Müllerian hormone (AMH), a marker of ovarian reserve. However, the association of multiple environment factors has not been addressed. We aimed to assess the impact of a mixture of environmental exposures on AMH. METHODS: A total of 2,449 premenopausal women in the NHSII, a US nationwide prospective cohort who provided blood samples for AMH assay were included. Exposure to greenness, particulate matter, noise, outdoor light at night (LAN), ultraviolet radiation, and 6 hazardous air pollutants (HAPs) (1,3-butadine, benzene, diesel particulate matter, formaldehyde, methylene chloride, and tetrachloroethylene) were available at all residential addresses since 1989. We first estimated associations with AMH in single exposure models adjusting for relevant covariates and then explored patterns of exposure using principal component analysis (PCA). Hierarchical Bayesian kernel machine regression (BKMR) was used to select key exposures and estimate the joint associations. We further conducted subgroup analyses by age at blood draw. RESULTS:Median age at blood collection was 40. Single exposure models showed negative associations of AMH with benzene (percentage reduction in AMH per interquartile range (IQR) increase = 5.44%, 95%CI=1.05, 9.62) and formaldehyde (percentage reduction in AMH per IQR increase = 6.04%, 95%CI=1.72, 10.17) but not the other exposures. PCA identified four major exposure patterns and only the one with high exposure to HAPs and LAN was associated with lower AMH. Hierarchical BKMR selected benzene, formaldehyde, and greenness as important exposures, and suggested an inverse joint association with AMH (percentage reduction comparing all exposures at the 75th percentile to median= 8.12%, 95%CI=0.54, 15.12). The observed associations were mainly found among women aged above 40. CONCLUSIONS:We found exposure to benzene and formaldehyde to be consistently associated with lower AMH levels. Older reproductive aged women were the most susceptible, suggesting these exposures may accelerate reproductive aging. KEYWORDS: multi-pollutant, mixtures analysis, reproductive outcomes