Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women

Abstract

Introduction Phenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)”. Methods Urinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16–20 weeks and 24–28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression. Results An IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI −18.31, −0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16–20 weeks), and suggestively positively associated with estradiol at the second time point (24–28 weeks). Conclusions Within this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required.

Systematic review of the literature on triclosan and health outcomes in humans

“…For example, Aker et al (2016) used data from a cohort study of pregnant women in Puerto Rico to examine associations between urinary TCS concentrations measured during three visits at [16][17][18][19][20][20][21][22][23][24], and 24-28 weeks gestation and serum levels of thyroid and sex hormones at visits 1 and 3.…”

“…Tier 2 included 13 publications. Twelve of those publications (Wolff et al , 2010(Wolff et al , 2015Philippat et al 2012Philippat et al , 2014Watkins et al 2015;Aker et al 2016;Ashley-Martin et al 2016;Buckley et al 2016;Lassen et al 2016;Smarr et al 2017;Geer et al 2017) were based on seven different cohorts assembled in France, Puerto Rico, Denmark, Canada, and various parts of the US. One paper ) presented a case-control study that used incident cases identified among members of a French cohort.…”

“…Similarly, three Australian papers (Cullinan et al 2012(Cullinan et al , 2015a(Cullinan et al , 2015b were based on the same study, as were two publications from Puerto Rico (Watkins et al 2015;Aker et al 2016), and three papers by Wolff et al (2008Wolff et al ( , 2010Wolff et al ( , 2015.…”

“…Of the 43 studies, 24 were conducted in North America (Wolff et al , 2010(Wolff et al , 2015Clayton et al 2011;You et al 2011;Buttke et al 2012;Savage et al 2012Savage et al , 2014Koeppe et al 2013;Lankester et al 2013;Buser et al 2014;Spanier et al 2014;Adgent and Rogan 2015;Li et al 2015;Ihde et al 2015;Shiue 2015aShiue , 2015bVelez et al 2015;Ashley-Martin et al 2016;Buckley et al 2016;Poole et al 2016;Scinicariello and Buser 2016;Smarr et al 2017;Geer et al 2017), two studies in the Caribbean (Watkins et al 2015;Aker et al 2016), 10 studies in Europe (Allmyr et al 2009;Chevrier et al 2012;Philippat et al 2012Philippat et al , 2014Bertelsen et al 2013;Buhl et al 2014;Den Hond et al 2013, 2015Geens et al 2015;Lassen et al 2016), four in Asia (Chen et al 2013;Wang et al 2015;Xue et al 2015;Zhu et al 2016), and three in Australia (Cullinan et al 2012(Cullinan et al , 2015a…”

“…The remaining five publications were assigned to Tier 1. Two of those (Watkins et al 2015;Aker et al 2016) were longitudinal cohort studies that included three samples obtained at different times and examined associations with health outcomes, taking all three TCS measures into consideration. Allmyr et al (2009) conducted an experimental study comparing health biomarker levels before and after intentional TCS administration and observed significantly higher plasma TCS levels following the 14-day study intervention (0.009-0.81 ng/g and 26-296 ng/g: ranges before and after exposure, respectively).…”