Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction.

CONTEXT: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. OBJECTIVE: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. SETTING: The study was conducted in a fertility center in a teaching hospital. DESIGN: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. MAIN OUTCOME MEASURE: Live birth rates per initiated treatment cycle were measured. RESULTS: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. CONCLUSION: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations.

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

BACKGROUND: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.

Isoflavones in urine, saliva, and blood of infants: data from a pilot study on the estrogenic activity of soy formula.

In the United States, about 25% of infant formula sold is based on soy protein, which is an important source of estrogenic isoflavones in the human food supply. Nevertheless, few studies report isoflavone levels in infants. We did a partly cross-sectional and partly longitudinal pilot study to examine children's exposure to isoflavones from different feeding methods. A total of 166 full-term infants between birth and 1 year of age were recruited into soy formula, cow milk formula, or breast milk regimens according to their feeding histories. A total of 381 urine, 361 saliva, and 88 blood samples were collected at 382 visits. We used automated online solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for measuring three isoflavones (daidzein, genistein, and equol) in urine, and used similar LC/MS/MS techniques for saliva and blood spots. Concentrations of daidzein and genistein were undetectable in most blood or saliva samples from children fed breast milk or cow milk formula. The proportion of non-detectable values was somewhat lower in urine than in the other matrices. Concentrations of equol were detectable only in a few urine samples. For both daidzein and genistein, urine contained the highest median concentrations, followed by blood and then saliva. Urinary concentrations of genistein and daidzein were about 500 times higher in the soy formula-fed infants than in the cow milk formula-fed infants. The correlations between matrices for either analyte were strikingly lower than the correlation between the two analytes in any single matrix. We did not find significant correlations between isoflavone concentrations and the levels of certain hormones in children fed soy formula. Our results, based on much larger numbers of infants, strongly confirm previous reports, but whether phytoestrogens in soy formula are biologically active in infants is still an open question. We plan further longitudinal studies focusing on physical and developmental findings reflecting the effects of estrogen exposure.

Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls.

BACKGROUND: Hormonally active environmental agents have been measured among U.S. children using exposure biomarkers in urine. However, little is known about their variation by race, age, sex, and geography, and no data exist for newly developed biomarkers. OBJECTIVE: Our goal was to characterize relevant, prevalent exposures for a study of female pubertal development. METHODS: In a pilot study among 90 girls from New York City, New York, Cincinnati, Ohio, and northern California, we measured 25 urinary analytes representing 22 separate agents from three chemical families: phytoestrogens, phthalates, and phenols. Exposures occur chiefly from the diet and from household or personal care products. RESULTS: Participants represented four racial/ethnic groups (Asian, black, Hispanic, white), with mean age of 7.77 years. Most analytes were detectable in > 94% of samples. The highest median concentrations for individual analytes in each family were for enterolactone (298 microg/L), monoethylphthalate (MEP; 83.2 microg/L), and benzophenone-3 (BP3; 14.7 microg/L). Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.8-53.2 microg/L. After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile. Three phthalate metabolites differed by race/ethnicity [MEP, mono(2-ethylhexyl) phthalate, and mono-3-carboxypropylphthalate]. CONCLUSIONS: A wide spectrum of hormonally active exposure biomarkers were detectable and variable among young girls, with high maximal concentrations (> 1,000 microg/L) found for several analytes. They varied by characteristics that may be relevant to development.