Phthalate Exposure in Relation to Maternal Thyroid and Reproductive Hormone Levels during Pregnancy

Abstract

There is increasing evidence that exposure to phthalates during pregnancy may elevate the risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal thyroid (thyroid-stimulating hormone [TSH], free thyroxine [FT4], and free triiodothyronine [FT3]) and reproductive (sex hormone-binding globulin [SHBG], progesterone, and estradiol) hormone levels at multiple time points during pregnancy. Preliminary data (n=106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We measured 11 urinary phthalate metabolite concentrations in urine samples collected up to three visits per subject during pregnancy (18±2, 22±2, and 26±2 weeks of gestation; N=293 total samples). We also measured thyroid and reproductive hormone concentrations in serum collected at up to two time points per subject during pregnancy (18±2 and 26±2 weeks of gestation). In adjusted linear mixed models, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations in the third visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP), and between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP) compared to the corresponding results for the first visit. Negative effect estimates for MEP and progesterone were similar between study visits. Urinary phthalate metabolites may be associated with altered maternal thyroid and reproductive hormone levels during pregnancy. In particular, the potential thyroid-disrupting effects of phthalates may be more profound during the latter half of gestation.