Body mass index and sleep duration may regulate the effect of heavy metals on age at menopause

Heavy metals are known endocrine disruptors that can interfere with ovarian function, but there are few epidemiological studies studying the impact of heavy metals on menopause. In this cross-sectional survey, we recruited 414 naturally postmenopausal women in the early postmenopausal stage (12 months ≤ time since last menstruation ≤ 24 months). We collected information on women's menopausal age through questionnaires. Blood concentrations of five metals, including chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), and lead (Pb) were measured. General linear regression and Quantile g-computation model were employed to explore the individual and combined impact of heavy metals on the natural menopausal age. Finally, Bayesian kernel machine regression (BKMR) was utilized to assess the reproducibility of the result in the two aforementioned models. The study revealed that for each unit increase in the ln-transformed Cd, the average menopausal age was delayed by 1.3 years (β = 1.30, 95% CI: 0.12, 2.48), while Pb is associated with an average advancement in menopausal age by 1.25 years (β = -1.25, 95% CI: -2.43, -0.07). Metal mixtures had no significant association on natural menopause age in Quantile g-computation. BKMR findings were consistent with the above results. Further stratified analyses indicated that the associations of Cd and Pb on natural menopausal age were significantly lower in populations with BMI < 25 kg/m2 or sleep duration ≥ 7 h. Our study indicates that heavy metals can influence the natural menopausal age, and maintaining a healthy weight and ensuring sufficient sleep may mitigate these adverse associations. Given the cross-sectional design and reverse temporality, findings represent associations and should be interpreted with caution.