Associations of acrylamide biomarkers with reproductive lifespan: A cross-sectional study in U.S. women

Acrylamide (AA), a potential carcinogen mainly present in thermally processed carbohydrate-rich foods, and cigarette smoke, forms acrylamide-hemoglobin adducts (HbAA) and its metabolite glycidamide-hemoglobin adducts (HbGA). Female reproductive lifespan (from menarche to menopause) is the key to women's health management and disease prevention. The reproductive lifespan of US women has shifted, but epidemiological research on its causes is lacking. This cross-sectional study included 1275 naturally postmenopausal women from four cycles of the US National Health and Nutrition Examination Survey, with a mean age of 61 ± 12 years. We examined the associations between HbAA, HbGA, the ratio of HbGA to HbAA (HbGA/HbAA) with female reproductive lifespan using linear regressions, restricted cubic splines (RCS) models, and threshold effect analyses. Results showed that HbAA and HbGA levels below 36.6 and 44.7 pmol/gHb showed no significant association with reproductive lifespan, but above these levels, the negative associations with reproductive lifespan strengthened. After adjusting for all covariates, each 2.7 - fold increase (one ln unit) in HbAA and HbGA was associated with a reduction in reproductive lifespan of 1.4 years (P = 0.003) and 2 years (P = 0.007) respectively. Higher levels of HbAA and HbGA shorten reproductive lifespan, while HbGA/HbAA showed no significant association. CLINICAL TRIAL: not applicable.