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

Abstract

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.

Figure 1. Spearman correlation coefficients among measures of surrounding greenness, particulate air pollution, noise, LAN, UV, and HAPs

The shade of each ellipse on the upper panel indicates the absolute value of the correlation coefficient. When an ellipse is leaning towards the left, this suggests the correlation between two variables are negative; when an ellipse is leaning towards the right, this suggests the correlation between two variables are positive. Abbreviations: NDVI, normalized difference vegetation index; PM_10–2.5, particulate matter with an aerodynamic diameters between 10 to 2.5 microns; PM_2.5, particulate matter with an aerodynamic diameters less than or equal to 2.5 microns; L50, median anthropogenic noise; LAN, light at night; UV, ultraviolet radiation; HAPs, hazardous air pollutants.

Figure 2. Component loadings for measures of surrounding greenness, particulate air pollution, noise, LAN, UV, and HAPs

The direction of the triangles denotes the direction of the loading (upward: positive, downward: negative). Abbreviations: NDVI, normalized difference vegetation index; PM_10–2.5, particulate matter with an aerodynamic diameters between 10 to 2.5 microns; PM_2.5, particulate matter with an aerodynamic diameters less than or equal to 2.5 microns; L50, median anthropogenic noise; LAN, light at night; UV, ultraviolet radiation; HAPs, hazardous air pollutants.

Figure 3. Exposure–response curve for surrounding greenness (NDVI), benzene, and formaldehyde with AMH (A) and overall association (percentage change and 95% credible intervals) of the exposure to environmental factors with AMH (B).

Abbreviations: NDVI, normalized difference vegetation index; AMH, anti-Müllerian hormone. All exposures in the mixture matrix were standardized. All models were adjusted for age (in natural cubic spline with 3 degrees of freedom), body mass index, race–ethnicity, parity, spouse education status, pre-tax household income, Census tract median income, smoking, and other environmental exposures (PM_10–2.5, PM_2.5, daytime L50, nighttime L50, and UV). Overall association was computed by comparing when all exposures are fixed at different quantiles to the median.

Figure 4. Overall association (percentage change and 95% credible intervals) of the exposures with AMH among women under (A) and above age 40 (B).

Abbreviations: NDVI, normalized difference vegetation index; AMH, anti-Müllerian hormone. All exposures in the mixture matrix were standardized. All models were adjusted for age (in natural cubic spline with 3 degrees of freedom), body mass index, Census tract median income, smoking, and other environmental exposures (PM_10–2.5, PM_2.5, daytime L50, nighttime L50, and UV). Overall association was computed by comparing when all exposures are fixed at different quantiles to the median.