Urinary Metal Mixtures and Hormone Levels during the Menopausal Transition: the Study of Women’s Health Across the Nation (SWAN)

Abstract

BACKGROUND AND AIM: Epidemiologic studies on associations between metal exposures and sex hormones in women have been limited, and results have been mixed. We assessed associations of urinary metals concentrations with longitudinal serum levels of follicle-stimulating hormone (FSH) and estradiol (E2). METHODS: We examined data from 1,355 women aged 45-56 years at baseline (1999-2000), followed through 2017, from the Study of Women’s Health Across the Nation. Baseline urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined. Serum levels of FSH and E2 were measured repeatedly over 17 years of follow-up. Linear mixed effects models were used to evaluate associations between individual metals and hormone levels. The least absolute shrinkage and selection operator (LASSO) penalized linear mixed effects models were used to evaluate associations between metal mixtures and hormone levels. An environmental risk score (ERS) was used to integrate metal mixture effects from LASSO results. RESULTS:After adjustment for confounders, one standard deviation increase in log-transformed baseline urinary metal concentrations were associated with 3.53% (95% CI: 0.42%, 6.73%) higher levels of FSH for cadmium, 5.61% (95% CI: 2.50%, 8.82%) higher levels for lead, and 3.06% (95% CI: -5.87%, -0.17%) lower levels for cobalt. For E2 levels, one standard deviation increase in log-transformed urinary metal concentrations were associated with 2.88% (95% CI: -5.31%, -0.38%) lower levels for mercury, 5.20% (95% CI: -7.56%, -2.78%) lower levels for lead, and 2.44% (95% CI: -4.74%, -0.09%) lower levels for tin. The ERS was associated with higher FSH and lower E2 levels. CONCLUSIONS:Results from this prospective cohort study of midlife women suggested that metals, including lead, cadmium, mercury, cobalt, tin, and metal mixtures were associated with serum FSH and E2 levels, consistent with findings that metal exposures affect reproductive aging. KEYWORDS: metals, mixtures, estradiol, follicle-stimulating hormone, cohort study