Associations of Phthalates and Phthalate Replacements With CRH and Other Hormones Among Pregnant Women in Puerto Rico

CONTEXT: Phthalates are endocrine-disrupting chemicals that may be associated with adverse birth outcomes. Dysregulation of maternal endocrine homeostasis could be a possible biological pathway between phthalates and birth outcomes. OBJECTIVE: Examine associations between 19 maternal urinary phthalate or phthalate replacement metabolites and 9 serum hormones measured over two time points during pregnancy. DESIGN: Longitudinal study conducted in the PROTECT pregnancy cohort. SETTING: Puerto Rico. PATIENTS: Six hundred seventy-seven women in the first trimester of pregnancy. MAIN OUTCOME MEASURES SERUM: CRH, estriol, SHBG, progesterone, TSH, total T3, free T4, total T4, and testosterone. RESULTS: T3 was significantly associated with most metabolites. CRH was inversely associated with mono carboxyisononyl phthalate [MCNP; percent change (%Δ), −4.08; 95% CI, −7.24, −0.804], mono-3-carboxypropyl phthalate (MCPP; %Δ, −5.25; 95% CI, −8.26, −2.14), mono-2-ethyl-5-carboxypentyl phthalate (MECPP; %Δ, −18.4; 95% CI, −30.4, −4.37), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; %Δ, −13.4; 95% CI, −22.7, −2.92), and mono-2-ethyl-5-oxohexyl phthalate (MEOHP; %Δ, −12.7; 95% CI, −22.2, −2.20). Positive associations were found between numerous phthalate metabolites and free T4, T4, and the T3/T4 ratio. Testosterone was positively associated with mono hydroxybutyl phthalate (MHBP; %Δ, 4.71; 95% CI, 0.27, 9.35) and inversely associated with monoethyl phthalate (MEP; %Δ, −14.5; 95% CI, −24.3, −3.42), and relationships with MCNP and mono carboxyisooctyl phthalate (MCOP) were significantly modified by study visit. Finally, an inverse association was found between mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP), a terephthalate metabolite, and progesterone at visit 3 only (%Δ, −13.1; 95% CI, −22.3, −2.75). CONCLUSIONS: These results indicate that exposure to phthalates may differentially impact the maternal endocrine system at different points during pregnancy, and that exposures to phthalate replacement chemicals may be particularly important to consider in future human health studies.