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Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort.

ABSTRACT: Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phytoestrogens and markers of early puberty. We investigated the association between in utero exposure to phytoestrogens and early menarche (defined as <11.5 years of age at onset) using data from a nested case-control study within the Avon Longitudinal Study of Parents and Children, a longitudinal study involving families living in the South West of England. Concentrations of six phytoestrogens were measured in maternal urine samples collected during pregnancy. Logistic regression was used to explore associations between tertiles of phytoestrogen concentrations and menarche status, with adjustment for maternal age at menarche, maternal education, pre-pregnancy body mass index (BMI), child birth order, duration of breastfeeding, and gestational age at sample collection. Among 367 mother-daughter dyads, maternal median (interquartile range) creatinine-corrected concentrations (in µg/g creatinine) were: genistein 62.1 (27.1-160.9), daidzein 184.8 (88.8-383.7), equol 4.3 (2.8-9.0), O-desmethylangolensin (O-DMA) 13.0 (4.4-34.5), enterodiol 76.1 (39.1-135.8), and enterolactone 911.7 (448.1-1558.0). In analyses comparing those in the highest tertile relative to those in the lowest tertile of in utero phytoestrogen exposure, higher enterodiol levels were inversely associated with early menarche (odds ratio (OR)=0.47; 95% confidence interval (CI): 0.26-0.83), while higher O-DMA levels were associated with early menarche (OR=1.89; 95% CI: 1.04-3.42). These findings suggest that in utero exposure to phytoestrogens may be associated with earlier age at menarche, though the direction of association differs across phytoestrogens.

SUBMITTER: Marks KJ

PROVIDER: S-EPMC5488334 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort.

Marks Kristin J KJ Hartman Terryl J TJ Taylor Ethel V EV Rybak Michael E ME Northstone Kate K Marcus Michele M

Environmental research 20170310

Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phytoestrogens and markers of early puberty. We investigated the association between in utero exposure to phytoestrogens and early menarche (defined as <11.5 years of age at onset) using data from a nested case-control study within the Avon Longitudinal Study of Parents and Children, a longitudinal study involving f ...[more]

PMID: 28259093

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Project description:BackgroundEvidence from experimental studies suggests that atrazine and its analytes alter the timing of puberty in laboratory animals. Such associations have not been investigated in humans.ObjectiveTo determine the association between in utero exposure to atrazine analytes and earlier menarche attainment in a nested case-control study of the population-based Avon Longitudinal Study of Parents and Children.MethodsCases were girls who reported menarche before 11.5 years while controls were girls who reported menarche at or after 11.5 years. Seven atrazine analyte concentrations were measured in maternal gestational urine samples (sample gestation week median (IQR): 12 (8-17)) during the period 1991-1992, for 174 cases and 195 controls using high performance liquid chromatography-tandem mass spectrometry. We evaluated the study association using multivariate logistic regression, adjusting for potential confounders. We used multiple imputation to impute missing confounder data for 29% of the study participants.ResultsDiaminochlorotriazine (DACT) was the most frequently detected analyte (58%>limit of detection [LOD]) followed by desethyl atrazine (6%), desethyl atrazine mercapturate (3%), atrazine mercapturate (1%), hydroxyl atrazine (1%), atrazine (1%) and desisopropyl atrazine (0.5%). Because of low detection of other analytes, only DACT was included in the exposure-outcome analyses. The adjusted odds of early menarche for girls with DACT exposures≥median was 1.13 (95% Confidence Interval [95% CI]:0.82, 1.55) and exposure<median was 1.01 (95% CI: 0.73, 1.42) compared to girls with exposure<LOD (reference). In the subset that excluded girls with missing data, the adjusted odds of early menarche for girls with DACT exposures≥median was 1.86 (95% CI: 1.03, 3.38) and exposure<median was 1.26 (95% CI: 0.65, 2.24) compared to the reference.ConclusionsThis study is the first to examine the association between timing of menarche and atrazine analytes. We found a weak, non-significant association between in-utero exposure to atrazine metabolite DACT and early menarche, though the association was significant in the subset of girls with complete confounder information. Further exploration of the role of these exposures in female reproduction in other cohorts is needed.

Project description:This study examines the timing of menarche in relation to infant-feeding methods, specifically addressing the potential effects of soy isoflavone exposure through soy-based infant feeding. Subjects were participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers were enrolled during pregnancy and their children have been followed prospectively. Early-life feeding regimes, categorised as primarily breast, early formula, early soy and late soy, were defined using infant-feeding questionnaires administered during infancy. For this analysis, age at menarche was assessed using questionnaires administered approximately annually between ages 8 and 14.5. Eligible subjects were limited to term, singleton, White females. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess age at menarche and risk of menarche over the study period. The present analysis included 2920 girls. Approximately 2% of mothers reported that soy products were introduced into the infant diet at or before 4 months of age (early soy). The median age at menarche [interquartile range (IQR)] in the study sample was 153 months [144-163], approximately 12.8 years. The median age at menarche among early soy-fed girls was 149 months (12.4 years) [IQR, 140-159]. Compared with girls fed non-soy-based infant formula or milk (early formula), early soy-fed girls were at 25% higher risk of menarche throughout the course of follow-up (hazard ratio 1.25 [95% confidence interval 0.92, 1.71]). Our results also suggest that girls fed soy products in early infancy may have an increased risk of menarche specifically in early adolescence. These findings may be the observable manifestation of mild endocrine-disrupting effects of soy isoflavone exposure. However, our study is limited by few soy-exposed subjects and is not designed to assess biological mechanisms. Because soy formula use is common in some populations, this subtle association with menarche warrants more in-depth evaluation in future studies.

Project description:BackgroundIt remains unclear whether in utero and childhood exposure to air pollution affects pubertal development, particularly age of menarche in girls.ObjectiveThe aim of this study was to determine whether residential ambient particulate matter (PM) exposure in utero and during childhood is associated with age of menarche.MethodsWe studied 5,201 girls in the Growing Up Today Study 2 (2004-present) who were 10-17 y of age at enrollment (47.7% premenarchal; 52.3% postmenarchal). Exposure to three size fractions of PM [fine PM with aerodynamic diameter ≤2.5μm (PM2.5), PM with aerodynamic diameters between 2.5μm and 10μm (PM2.5-10), and PM with aerodynamic diameter 10μm (PM10)] was assigned based on maternal residential address, updated every 2 y, using nationwide spatiotemporal models. We estimated average PM exposure in utero, and time-varying windows: annual average exposure in the prior 1 and 2 y and cumulative average from birth. Age of menarche was self-reported on three surveys administered in 2004, 2006, and 2008. We calculated hazard ratios (HR) for menarche for an interquartile range (IQR) increase in PM exposure using Cox proportional hazard models adjusting for potential confounders.ResultsGirls attained menarche at 12.3 y of age on average. In the adjusted model, higher residential exposure to ambient PM2.5 during all time windows was associated with earlier age of menarche. The HRs of menarche for each IQR (4 μg/m3) increase in exposure to PM2.5 during the in utero period, 1 y prior to menarche, and throughout childhood were 1.03 [95% confidence interval (CI): 1.00, 1.06], 1.06 (95% CI: 1.02, 1.10) and 1.06 (95% CI: 1.02, 1.10), respectively. Effect estimates for PM10 exposure were similar, albeit attenuated, for all time windows. PM2.5-10 exposure was not associated with age of menarche.DiscussionAmong a large, nationwide, prospective cohort of U.S. girls, higher exposure to PM2.5 and PM10 in utero and throughout childhood was associated with an earlier age of menarche. Our results suggest that PM2.5 and PM10 may have endocrine-disrupting properties that could lead to altered timing of menarche. https://doi.org/10.1289/EHP12110.

Project description:BACKGROUND: Intelligence is a life-long trait that has strong influences on lifestyle, adult morbidity and life expectancy. Hence, lower cognitive abilities are therefore of public health interest. Our primary aim was to examine if prenatal bereavement measured as exposure to death of a close family member is associated with the intelligence quotient (IQ) scores at 18-years of age of adult Danish males completing a military cognitive screening examination. METHODS: We extracted records for the Danish military screening test and found kinship links with biological parents, siblings, and maternal grandparents using the Danish Civil Registration System (N = 167,900). The prenatal exposure period was defined as 12 months before conception until birth of the child. We categorized children as exposed in utero to severe stress (bereavement) during prenatal life if their mothers lost an elder child, husband, parent or sibling during the prenatal period; the remaining children were included in the unexposed cohort. Mean score estimates were adjusted for maternal and paternal age at birth, residence, income, maternal education, gestational age at birth and birth weight. RESULTS: When exposure was due to death of a father the offsprings' mean IQ scores were lower among men completing the military recruitment exam compared to their unexposed counterparts, adjusted difference of 6.5 standard IQ points (p-value = 0.01). We did not observe a clinically significant association between exposure to prenatal maternal bereavement caused by death of a sibling, maternal uncle/aunt or maternal grandparent even after stratifying deaths only due to traumatic events. CONCLUSION: We found maternal bereavement to be adversely associated with IQ in male offspring, which could be related to prenatal stress exposure though more likely is due to changes in family conditions after death of the father. This finding supports other literature on maternal adversity during fetal life and cognitive development in the offspring.

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Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort.

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Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort.

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