Dose-response of greenness, air pollution, and female reproductive aging: a community-based nationwide study in China

BACKGROUND: Greenness and air pollution may influence female reproductive aging; however, evidence remains limited especially for women in low- and middle-income countries. Besides, the dose-response relationship, critical effect window, and interaction modes are poorly understood. METHODS: We included 15,681 postmenopausal women with natural menopause and 4,569 premenopausal women with ovarian reserve assessment in a nation-wide survey of China. Residential greenness (normalized difference vegetation index, NDVI) and air pollution were assessed via satellite remote sensing. Biomarker of ovarian reserve (serum anti-Müllerian hormone, AMH) was measured by ultrasensitive chemiluminescence immunoassay assays. Using Cox regression nested with distributed lagged nonlinear models (DLNM), we evaluated dose-response associations between environmental exposures and early menopause. Generalized linear model was conducted to uncover the link between greenness and serum AMH levels. Interaction effects and diverse population subgroups were also explored to identify vulnerable population. RESULTS: Higher greenness reduced early menopause risk non-linearly, with significant effects of NDVI within 0.4. Conversely, air pollution linearly increased risk with no minimal threshold. At the 90th percentile, cumulative greenness, PM2.5, PM₁₀, and NO₂ exposure yielded HR (95 % CI) of 0.04 (0.02, 0.10), 2.68 (2.19, 3.27), 2.74 (2.33, 3.23), and 3.78 (2.97, 4.81) compared with reference level, respectively. In the molecular perspective, higher greenness exposure was also linked to elevated ovarian reserve biomarker for premenopausal women in a non-linear manner, showing a rapid increase at NDVI within 0.4. At the 90th percentile, greenness yielded serum AMH change of 1.24 (1.15, 2.33) compared with reference level. Time-lag patterns indicated heterogeneous effect windows for greenness and air pollution. Stronger associations occurred in women with low socioeconomic status, higher parity, and irregular menstrual cycle. Greenness-air pollution interaction analysis revealed stronger associations of air pollution and early menopause among women residing in areas with higher levels of greenness. CONCLUSIONS: Low greenness and high air pollution accelerate female reproductive aging in a dose-response manner, particularly in socially vulnerable groups. Targeted strategies to enhance greenness and air quality could delay female reproductive aging.