A Prospective Ultrasound Study of Whole Blood Metals and Incidence of Uterine Leiomyomata.

Abstract

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 23-35 years of age. 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 ($\beta$) 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 $<20\text{\hspace{0.17em}ng}/\mathrm{mL}$] and 117 (10%) developed UL within 20 months. Increasing all metals from their 50th to 75th percentiles was weakly positively associated with UL overall [$\beta =0.06$; 95% credible interval (CrI): $-0.03$, 0.16] and among vitamin D-deficient participants ($\beta =0.13$; 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 ($\beta =0.03$; 95% CrI: $-0.05$, 0.11) and among vitamin D-deficient participants ($\beta =0.13$, 95% CrI: 0.02, 0.24). In Cox models, cadmium [$\text{IRR}=1.55$; 95% confidence interval (CI): 1.07, 2.24, per 1-unit increase in standardized concentration] and mercury ($\text{IRR}=1.38$; 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.