Associations between exposure to air pollution and sex hormones during the menopausal transition

Menopause is a significant milestone in a woman's life, characterized by decreasing estradiol (E2) and increasing follicle-stimulating hormone (FSH) levels. Growing evidence suggests that air pollution may affect reproductive health and disrupt hormone profiles, yet the associations in women undergoing menopausal transition (MT) remains underexplored. We examined the associations between annual air pollutant exposures and repeated measures of E2 and FSH in 1365 women with known final menstrual period (FMP) date from the Study of Women's Health Across the Nation. Air pollution was calculated as the annual averages of 24-h average PM_2.5 levels, daily one-hour maximum NO₂ levels, and daily 8-h maximum O₃ levels. Linear mixed models with piece-wise linear splines were used to model non-linear trajectories of E2 and FSH in three distinct time periods: up to 2 years before the FMP (early MT), within 2 years before and 2 years after FMP (transmenopause), and >2 years post-FMP (postmenopause). In the transmenopausal period, an interquartile (5 μg/m3) increase in PM_2.5 was associated with a significant decrease in E2 levels (-15.7 %, 95 % CI: -23.7, -6.8), and a 10 ppb increase in NO₂ was associated with a significant decrease in E2 levels (-9.2 %, 95 % CI: -16.2, -1.7). A higher PM_2.5 was also associated with an accelerated rate of decline in E2. Regarding FSH, a 10 ppb increase in NO₂ was associated with decline in FSH levels (-11.7 %, 95 % CI: -21.8, -0.1) in the early MT and accelerated rates of decline in the postmenopause (-1.1 % per year, 95 % CI: -2.1, -0.1). Additionally, inverse associations between O₃ and FSH were observed in the transmenopause and postmenopause. Our study suggests that increases in PM_2.5, NO₂, and O₃ exposures are linked to significant declines in E2 and FSH levels across menopausal stages, suggesting the detrimental impact of air pollutants on women's reproductive hormones.