Environmental Exposures and Anti-Müllerian Hormone: A Mixture Analysis in the Nurses’ Health Study II

Background: Previous studies have linked environmental exposures with anti-Müllerian hormone (AMH), a marker of ovarian reserve. However, associations with multiple environment factors has to our knowledge not been addressed. Methods: We included a total of 2,447 premenopausal women in the Nurses’ Health Study II (NHSII) who provided blood samples during 1996–1999. We selected environmental exposures linked previously with reproductive outcomes that had measurement data available in NHSII, including greenness, particulate matter, noise, outdoor light at night, ultraviolet radiation, and six hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter, formaldehyde, methylene chloride, and tetrachloroethylene). For these, we calculated cumulative averages from enrollment (1989) to blood draw and estimated associations with AMH in adjusted single-exposure models, principal component analysis (PCA), and hierarchical Bayesian kernel machine regression (BKMR). Results: Single-exposure models showed negative associations of AMH with benzene (percentage reduction in AMH per interquartile range [IQR] increase = 5.5%, 95% confidence interval [CI] = 1.0, 9.8) and formaldehyde (6.1%, 95% CI = 1.6, 10). PCA identified four major exposure patterns but only one with high exposure to air pollutants and light at night was associated with lower AMH. Hierarchical BKMR pointed to benzene, formaldehyde, and greenness and suggested an inverse joint association with AMH (percentage reduction comparing all exposures at the 75th percentile to median = 8.2%, 95% CI = 0.7, 15.1). Observed associations were mainly among women above age 40. Conclusions: We found exposure to benzene and formaldehyde to be consistently associated with lower AMH levels. The associations among older women are consistent with the hypothesis that environmental exposures accelerate reproductive aging.