BACKGROUND AND AIM: During their reproductive years, females show lower serum PFAS concentrations than males, most likely due to menstrual excretion, previous childbirth with transplacental transfer of PFAS and breastfeeding. Also, females in pre-menopause age have lower levels of low-density lipoprotein cholesterol (LDL-C) and higher levels of high-density lipoprotein cholesterol (HDL-C) compared to males. So far, little is known of the impact of menopause on dose-response relationships. Given the possible role of estrogens in regulating lipid metabolism, there can be an interaction and the aim of our study is to evaluate if the associations of PFAS and serum lipids changes with aging, comparing women in pre- and post-menopausal age groups. METHODS: A cross-sectional analysis was conducted among highly exposed women, 14,155 mostly pre-menopausal and 4,165 mostly post-menopausal women, based on a cut-off of 50 years. Associations between four PFAS (PFOA, PFOS, PFHxS and PFNA) and non-fasting serum total cholesterol (TC), HDL-C and LDL-C, were assessed through weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models, adjusting for potential confounders. RESULTS:We observed that each PFAS in the WQS index was associated with an increase in the levels of TC in both groups, and pre-menopausal women showed a larger increase of TC per quartile increase of PFAS mixture (4.63, 95% CI 3.46-5.79) than post-menopausal women (β:1.84, 95% CI 0.30-3.38), mainly driven by the effect on LDL-C. WQS analyses revealed a major contribution of PFOS and PFNA to the association with cholesterol levels, although the larger contrast being in PFOA for both groups. CONCLUSIONS:Investigations of combined exposures to four PFAS showed a strong positive association with all three serum lipid parameters. The large differences between pre- and post-menopausal women may reflect complex relationships between PFAS, estrogens and cholesterol. Analysis on menopausal timing are ongoing. KEYWORDS: PFAS, Mixtures, Chemical exposure, Female