Associations of Maternal Urinary Concentrations of Phenols, Individually and as a Mixture, with Serum Biomarkers of Thyroid Function and Autoimmunity: Results from the EARTH Study

Abstract

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009–2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography–tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols—both individually and as a mixture—and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT3 (mean difference for a 1 log unit increase in concentration: −0.088; 95% CI [−0.151, −0.025]) and TT3 (−0.066; 95% CI [−0.112, −0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT3 concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: −0.19, 95% CI [−0.35, −0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system.