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

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 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 with menarche status, with adjustment for maternal age at menarche, maternal education, pre- pregnancy BMI, child birth order, and duration of breastfeeding. Among 367 mother-daughter dyads, maternal geometric mean (95% confidence interval (CI)) creatinine-corrected concentrations (in µg/g creatinine) were: daidzein 184 (162 - 208), enterodiol 71.5 (64.6 - 79.1), enterolactone 755 (674 - 846), equol 5.65 (4.91 - 6.49), genistein 63.5 (54.9 - 73.4), and O-desmethylangolensin (O-DMA) 11.2 (9.34 - 13.5). In analyses comparing those in the highest tertile relative to those in the lowest tertile of in utero phytoestrogen exposure, only one statistically significant association with onset of menarche was found. Higher O-DMA levels were statistically significantly associated with early menarche (odds ratio (OR) = 2.36; CI: 1.26 - 4.43). O-DMA is an intestinal bacterial metabolite of daidzein; not all individuals harbor bacteria capable of metabolizing daidzein to O-DMA, and O- DMA may exhibit different biological actions than its parent compound. These findings suggest that in utero exposure to O-DMA, but no other phytoestrogens, may be associated with earlier age at menarche.

Table of Contents

CHAPTER I.........................................................................................................................1

Background/Literature Review.............................................................................................1

CHAPTER II......................................................................................................................17 Introduction.....................................................................................................................17 Methods...........................................................................................................................19 Results.............................................................................................................................23 Discussion........................................................................................................................26

CHAPTER III ....................................................................................................................32 Summary..........................................................................................................................32

Public Health Implications.................................................................................................32

Possible Future Directions..................................................................................................33 References.........................................................................................................................34 Tables...............................................................................................................................46

Table 1. Characteristics of the Avon Longitudinal Study of Parents and Children (ALSPAC) nested case-control study population (N=367 mother-daughter dyads). ................................... 46

Table 2. Gestational urinary phytoestrogen concentrations among mothers of girls with and without earlier age at menarche in the Avon Longitudinal Study of Parents and Children (ALSPAC) nested case-control study population (N=367 mother-daughter dyads). ................ 48

Table 3. Median and interquartile range of maternal isoflavone (genistein and daidzein) and lignan (enterodiol and enterolactone) concentrations by selected maternal and child characteristics in the Avon Longitudinal Study of Parents and Children (ALSPAC) nested casecontrol study population (N=367 mother-daughter dyads)........................................................ 49

Table 4. Associations of maternal urinary phytoestrogen concentrations with earlier age at menarche in the Avon Longitudinal Study of Parents and Children (ALSPAC) nested casecontrol study population (N=309 mother-daughter dyads)...............................................51 Figures...............................................................................................................................53

Figure 1. Flowchart of eligibility and exclusions. ...................................................................53 Appendix............................................................................................................................54

Supplementary Table 1. Adjusted associations of maternal urinary phytoestrogen concentrations with earlier age at menarche in the Avon Longitudinal Study of Parents and Children (ALSPAC) nested case-control study population (N=309 mother-daughter dyads).....................54

Supplementary Table 2. Gestational urinary phytoestrogen concentrations among mothers of girls in the Avon Longitudinal Study of Parents and Children (ALSPAC) nested case-control study population (1991-1992) (N=367) versus urinary phytoestrogen concentrations among white women aged 20 to 39 years old in the 2003-2006 National Health and Nutrition Examination Survey (NHANES) (N=277). ...............................................................................55

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Environmental Sciences Health Sciences, Epidemiology
Mot-clé	menarche phytoestrogens endocrine disrupting chemicals puberty
Committee Chair / Thesis Advisor	Hartman, Terry, Emory University
Partnering Agencies	University, college or educational institution (other than Emory) CDC

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