A prospective ultrasound study of whole blood metals and incidence of uterine leiomyomata

Background: Uterine leiomyomata (UL), hormone-dependent neoplasms, are a major source of gynecologic morbidity. Metals are hypothesized to influence UL risk through endocrine disruption, and their effects may vary by vitamin D status. Objective: We estimated associations of a metal mixture with incident UL, overall and by vitamin D status. Methods: We analyzed data from the Study of Environment, Lifestyle and Fibroids, a Detroit-area prospective cohort study of 1,693 Black women aged 23-35 years. We measured concentrations of 17 metals/metalloids in whole blood and 25-hydroxyvitamin D (25[OH]D) in serum collected at baseline (2010-2012). Participants underwent ultrasonography at baseline and after 20 months to detect UL. We used Bayesian Kernel Machine Regression to estimate adjusted associations (β) of the metal mixture with probit of incident UL. We also ran Cox regression models with interaction terms to estimate incidence rate ratios (IRR) by vitamin D status. Results: Among 1,132 UL-free participants at baseline, 832 (73%) had vitamin D deficiency (25[OH]D<20 ng/mL) and 117 (10%) developed UL within 20 months. Increasing all metals from their 50th to 75th percentiles was weakly positively associated with UL overall (β=0.06, 95% credible interval [CrI]: -0.03, 0.16) and among vitamin D-deficient participants (β=0.13, 95% CrI: 0.01, 0.24), driven by cadmium (overall and vitamin D-deficient) and mercury (vitamin D-deficient only). Increasing cadmium from its 25th to 75th percentile was positively associated with UL overall (β=0.03, 95% CrI: -0.05, 0.11) and among vitamin D-deficient participants (β=0.13, 95% CrI: 0.02, 0.24). In Cox models, cadmium (IRR=1.55, 95% confidence interval [CI]: 1.07, 2.24, per 1-unit increase in standardized concentration) and mercury (IRR=1.38, 95% CI: 0.99, 1.92) were positively associated with UL among vitamin D-deficient participants. Discussion: The metal mixture was positively associated with incident UL, but the association was weak and imprecise. We observed a stronger association among vitamin D-deficient participants that was driven by cadmium and mercury. https://doi.org/10.1289/EHP15218.