Per- and polyfluoroalkyl substances (PFAS) are commonly utilized in consumer products. While earlier studies have suggested potential impacts of certain PFAS on serum concentrations of vitamin D, these investigations were constrained to a limited set of conventional PFAS. Moreover, they did not specifically focus on populations with longer duration of PFAS exposure and potentially higher blood PFAS levels, such as older adults, and lacked adequate evidence to examine sex-related disparities. This observational investigation utilized cross-sectional data obtained from the U.S. NHANES spanning the years 2003 to 2018. Survey-weighted multiple regression models were employed to evaluate the relationship between PFAS exposure and vitamin D concentrations. Multi-pollutant models were employed to evaluate the association between PFAS mixtures and vitamin D concentrations. Subsequently, environmental risk scores (ERS) were constructed to gauge associations with vitamin D concentrations. ERS was computed through a weighted linear combination of PFAS, utilizing calculations from ridge regression and adaptive elasticity network (adENET) methodologies. All analyses were stratified by sex. The study encompassed 3,853 older adults. Our analysis revealed a negative association between PFOA, PFOS, PFNA, and MeFOSAA and serum vitamin D concentrations. In analyses examining mixed exposures, various models consistently indicated an inverse association between PFAS mixed exposure and vitamin D concentrations. Moreover, an increase in ERS of PFAS across the interquartile range was associated with a decrease in vitamin D concentrations (Q4 vs. Q1, adENET: β: -0.083, 95% CI: -0.117, -0.048; ridge regression: β: -0.077, 95% CI: -0.111, -0.042). Notably, these associations were exclusively observed within the female population. Our study indicates that heightened exposure to PFAS correlates with diminished serum vitamin D concentrations in females aged 60 years and older, evident in both single and mixed exposures. These findings find support in in vitro mechanistic studies, suggesting that PFAS may impact the metabolism of 25(OH)D, consequently affecting vitamin D concentrations.

Acute and chronic heat stress disturb sex hormone levels. However, epidemiological evidence on their associations remains lacking. We aimed to explore the relationship between chronic and acute heat exposure and female sex hormones. We conducted a longitudinal study including 19790 women receiving assisted reproductive technology from 2014 to 2020. We extracted participants' daily mean temperatures from a validated grid dataset. Chronic exposures were represented using the proportions of medium, high, and extreme heat days during the year before hormone measurement. Acute exposures were six different defined heatwaves during the week before measurement. To quantify their associations, we used linear mixed-effect models with subject-specific intercepts. Besides, we introduced the heat index (HI) to investigate the combined effects of heat exposure and humidity on sex hormones, and also explored potential modifying effects of greenness. For every 10% increase in the proportion of extreme heat days, E2 decreased by -15.1% (-19.2%, -10.7%), P decreased by -21.1% (-26.8%, -14.9%), T decreased by -9.9% (-13.8%, -5.8%), and LH increased by 28.6% (11.9%, 47.8%). Acute heatwave exposure across six definitions was all significantly linked to reduced E2 and elevated LH. Differing from heat exposure alone, chronic HI was associated with elevated E2 [28.1% (18.6%, 38.4%)] and P [20.4% (9.6%, 32.3%)], and acute HI was associated with elevated P [2.4% (1.3%, 3.5%)]. Besides, high greenness modified the negative impact of chronic heat exposure on P. Heat exposure may adversely affect female sex hormone homeostasis, with humidity and greenness playing a moderating role.