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Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.

ABSTRACT: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins.We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007).We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones.Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88-1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23-1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone.Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.

SUBMITTER: Wolff MS

PROVIDER: S-EPMC2920905 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.

Wolff Mary S MS Teitelbaum Susan L SL Pinney Susan M SM Windham Gayle G Liao Laura L Biro Frank F Kushi Lawrence H LH Erdmann Chris C Hiatt Robert A RA Rybak Michael E ME Calafat Antonia M AM

Environmental health perspectives 20100322 7

<h4>Background</h4>Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins.<h4>Objectives</h4>We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (20 ...[more]

PMID: 20308033

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Project description:Study questionAre in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls?Summary answerWe found some associations of altered pubertal timing in girls, but little evidence in boys.What is known alreadyCertain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies.Study design, size, durationData were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence.Participants/materials, setting, methodsPregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers.Main results and the role of chanceIn girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben.Limitations, reasons for cautionThese chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable.Wider implications of the findingsThis study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children.Study funding/competing interest(s)This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest.Trial registration numberN/A.

Project description:BackgroundAnimal studies suggest that phthalates and bisphenol A (BPA), endocrine-disrupting chemicals found in many consumer products, may impact the timing of puberty.ObjectivesWe aimed to determine the association of prenatal exposure to high-molecular-weight phthalates and BPA with pubertal timing in boys and girls participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study.MethodsWe quantified urinary concentrations of eight phthalate metabolites and BPA at two time points during pregnancy among participating mothers ([Formula: see text]) and conducted clinical Tanner staging of puberty on their children every 9 months between 9 and 13 y of age. We conducted accelerated failure time models and examined the role of child overweight/obese status in this association.ResultsThe sum of urinary metabolites of di(2-ethylhexyl) phthalate [Formula: see text], monobenzyl phthalate (MBzP), and BPA were associated with later onset of at least one of the three outcomes assessed in girls (thelarche, pubarche, or menarche) and with earlier onset of at least one of the two outcomes assessed in boys (gondarche and pubarche). We found that monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono(3-carboxypropyl) phthalate, and BPA were associated with later pubarche and menarche mostly among normal-weight girls but not overweight/obese girls. MBzP was associated with later thelarche in all girls, and [Formula: see text] was associated with later thelarche and menarche in all girls. BPA and all phthalate biomarkers were associated with earlier gonadarche and pubarche in all boys as well as in overweight/obese boys when stratified by weight. Among normal-weight boys, associations with BPA were also inverse, whereas associations with phthalate metabolites were close to the null or positive.ConclusionsSeveral high-molecular-weight phthalates and BPA were associated with later puberty in girls and earlier puberty in boys included in the CHAMACOS cohort study. Childhood overweight/obesity may modify these associations. https://doi.org/10.1289/EHP3424.

Project description:BackgroundEpidemiologic evidence suggests that environmental factors acting as endocrine disrupting chemicals (EDCs) are associated with mammographic breast density and the risk of breast cancer. Exposure to EDCs during puberty, a period of rapid breast development, may affect susceptibility to breast carcinogenesis.MethodsIn a cohort of 366 Chilean adolescents from the Growth and Obesity Cohort Study, we evaluated the relation between urinary concentrations of 15 suspected EDC biomarkers across three pubertal time points (Tanner breast stage 1 (B1), 4 (B4), and 1-year post-menarche) and breast fibroglandular volume (FGV; percent FGV [%FGV] and absolute FGV [aFGV]) and total breast volume (tBV) at 2-years post-menarche. We used linear mixed models to test differences in creatinine-corrected EDC biomarker concentrations at B4 and 1-year post-menarche compared to B1 and calculated intraclass correlation coefficients (ICC) of EDC concentrations across time points to appraise the consistency of measurements. We fit multivariable generalized estimating equations (GEEs) to evaluate windows of susceptibility for the association between log10-transformed EDCs and log10-transformed breast outcomes. GEEs were adjusted for age, body fat percentage, total caloric intake, and maternal education.ResultsUrinary EDC biomarker concentrations highly varied across pubertal time points (ICC range 0.01-0.30). For 12 EDCs, biomarker concentrations decreased over time. Triclosan measured at 1-year post-menarche was inversely associated with %FGV at 2-years post-menarche (β = -0.025, 95 % confidence interval = -0.041, -0.008). Mono(2-ethyl-5-carboxypentyl) phthalate and the sum of di(2-ethylhexyl) phthalate metabolite concentrations at B4 were positively associated with aFGV and tBV at 2-years post-menarche. No measured phenols were associated with aFGV and tBV, while no measured parabens were associated with %FGV and aFGV.ConclusionsOur study suggests relatively high variability in EDC biomarker concentrations across the peripubertal time period. We also found evidence to suggest that there may be pubertal windows of susceptibility to select EDCs for the association with adolescent breast density.

Project description:BackgroundMaternal exposure to environmental phenols is common in pregnancy and has been linked to preterm birth, preeclampsia, and reduced fetal growth. One potential mechanism may be through increased maternal oxidative stress.ObjectiveWe examined the associations between a panel of 10 urinary phenols, including dichlorophenols, benzophenone-3, parabens, triclosan and triclocarban, and bisphenol-S, and two urinary oxidative stress biomarkers, 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane. All exposure and outcome biomarkers were measured at 4 time points in pregnancy.MethodsWe used repeated measures models to examine the association between repeated exposure and outcome biomarkers. Additionally, we used adaptive elastic net (AENET) to identify non-null associations accounting for the correlation structure of exposures, both for phenols and urinary phthalate metabolites that were previously associated with the oxidative stress biomarkers in our study population.ResultsIn adjusted repeated measures models, we observed that dichlorophenols, benzophenone-3, triclosan, and some parabens were associated with increases in both oxidative stress biomarkers. The greatest effect estimates were observed for 2,5-dichlorophenol; an interquartile range (IQR) increase in this compound was associated with a 15.2% (95% confidence interval [CI] = 11.0, 19.6) increase in 8-OHdG and a 16.7% (95% CI = 9.66, 24.2) increase in 8-isoprostane. Bisphenol-S detection was associated with a clear increase in 8-isoprostane (18.5%, 95% CI = 7.68, 30.5) but a more modest increase in 8-OHdG (6.18%, 95% CI = -0.27, 13.1). However, AENET models did not consistently select any of the phenols as predictors of 8-OHdG or 8-isoprostane when phthalate metabolites were included in the model.ConclusionOverall, urinary phenols were associated with increases in biomarkers of oxidative stress in pregnancy but either to a lesser extent, or due to correlation with, urinary phthalate metabolites.

Project description:BackgroundPolycyclic aromatic hydrocarbons (PAHs), a class of chemicals produced as combustion by-products, have been associated with endocrine disruption. To understand exposure in children, who have been less studied than adults, we examined PAH metabolite concentrations by demographic characteristics, potential sources of exposure, and variability over time, in a cohort study of pre- and peri-pubertal girls in Northern California.MethodsUrinary concentrations of ten PAH metabolites and cotinine were quantified in 431 girls age 6-8 years at baseline. Characteristics obtained from parental interview, physical exam, and linked traffic data were examined as predictors of PAH metabolite concentrations using multivariable linear regression. A subset of girls (n = 100) had repeat measures of PAH metabolites in the second and fourth years of the study. We calculated the intraclass correlation coefficient (ICC), Spearman correlation coefficients, and how well the quartile ranking by a single measurement represented the four-year average PAH biomarker concentration.ResultsEight PAH metabolites were detected in ≥ 95% of the girls. The most consistent predictors of PAH biomarker concentrations were cotinine concentration, grilled food consumption, and region of residence, with some variation by demographics and season. After adjustment, select PAH metabolite concentrations were higher for Hispanic and Asian girls, and lower among black girls; 2-naphthol concentrations were higher in girls from lower income households. Other than 1-naphthol, there was modest reproducibility over time (ICCs between 0.18 and 0.49) and the concentration from a single spot sample was able to reliably rank exposure into quartiles consistent with the multi-year average.ConclusionsThese results confirm diet and environmental tobacco smoke exposure as the main sources of PAHs. Controlling for these sources, differences in concentrations still existed by race for specific PAH metabolites and by income for 2-naphthol. The modest temporal variability implies adequate exposure assignment using concentrations from a single sample to define a multi-year exposure timeframe for epidemiologic exposure-response studies.

Dataset Information

Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.

Publications

Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.

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