PMID- 32515996 OWN - NLM STAT- MEDLINE DCOM- 20201210 LR - 20201214 IS - 1552-9924 (Electronic) IS - 0091-6765 (Print) IS - 0091-6765 (Linking) VI - 128 IP - 6 DP - 2020 Jun TI - Urinary Concentrations of Phthalate Metabolite Mixtures in Relation to Serum Biomarkers of Thyroid Function and Autoimmunity among Women from a Fertility Center. PG - 67007 LID - 10.1289/EHP6740 [doi] LID - 067007 AB - BACKGROUND: Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women. OBJECTIVE: We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity. METHODS: This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005-2015). We quantified urinary concentrations of eight phthalate metabolites using 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 and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores. RESULTS: We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of fT4, TT4, fT3, and TT3 [absolute difference: - 0.62; 95% confidence interval (CI): - 0.12, - 0.01; p = 0.04; absolute difference: - 8.31; 95% CI: - 13.8, - 2.85; p = 0.003; absolute difference: - 0.37; 95% CI: 0.54, - 0.19; p < 0.0001; and absolute difference: - 0.21; 95% CI: - 0.32, - 0.10; p = 0.003, respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb. CONCLUSIONS: Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740. FAU - Souter, Irene AU - Souter I AD - Division of Reproductive Medicine and IVF, Department of Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Bellavia, Andrea AU - Bellavia A AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Williams, Paige L AU - Williams PL AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Korevaar, T I M AU - Korevaar TIM AD - Department of Internal Medicine and Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, Netherlands. FAU - Meeker, John D AU - Meeker JD AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. FAU - Braun, Joseph M AU - Braun JM AD - Department of Epidemiology, Brown University, Providence, Rhode Island, USA. FAU - de Poortere, Ralph A AU - de Poortere RA AD - Laboratory of Clinical Chemistry and Haematology, Maxima Medical Centre, Veldhoven, Netherlands. FAU - Broeren, Maarten A AU - Broeren MA AD - Laboratory of Clinical Chemistry and Haematology, Maxima Medical Centre, Veldhoven, Netherlands. FAU - Ford, Jennifer B AU - Ford JB AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. FAU - Calafat, Antonia M AU - Calafat AM AD - National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. FAU - Chavarro, Jorge E AU - Chavarro JE AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. AD - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. AD - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Hauser, Russ AU - Hauser R AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. AD - Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Minguez-Alarcon, Lidia AU - Minguez-Alarcon L AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. CN - Earth Study Team LA - eng GR - P30 ES000002/ES/NIEHS NIH HHS/United States GR - R01 ES009718/ES/NIEHS NIH HHS/United States GR - P30 ES017885/ES/NIEHS NIH HHS/United States GR - R01 ES022955/ES/NIEHS NIH HHS/United States GR - R01 ES024381/ES/NIEHS NIH HHS/United States GR - R01 ES028800/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200609 PL - United States TA - Environ Health Perspect JT - Environmental health perspectives JID - 0330411 RN - 0 (Biomarkers) RN - 0 (Environmental Pollutants) RN - 0 (Phthalic Acids) RN - 0 (Thyroid Hormones) RN - 6O7F7IX66E (phthalic acid) RN - 9002-71-5 (Thyrotropin) RN - C42K0PH13C (Diethylhexyl Phthalate) RN - EC 1.11.1.8 (Iodide Peroxidase) SB - IM MH - Adult MH - Autoimmunity/physiology MH - Bayes Theorem MH - Biomarkers/blood MH - Cross-Sectional Studies MH - Diethylhexyl Phthalate/urine MH - Environmental Pollutants/*urine MH - Female MH - Humans MH - Iodide Peroxidase/blood MH - Phthalic Acids/*urine MH - Thyroid Gland/*physiology MH - Thyroid Hormones/blood MH - Thyrotropin/blood MH - Women PMC - PMC7282564 EDAT- 2020/06/10 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/06/09 CRDT- 2020/06/10 06:00 PHST- 2020/06/10 06:00 [entrez] PHST- 2020/06/10 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/06/09 00:00 [pmc-release] AID - EHP6740 [pii] AID - 10.1289/EHP6740 [doi] PST - ppublish SO - Environ Health Perspect. 2020 Jun;128(6):67007. doi: 10.1289/EHP6740. Epub 2020 Jun 9.