First Trimester Urinary Bisphenol and Phthalate Concentrations and Time to Pregnancy: A Population-Based Cohort Analysis.

Background: Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogs, and phthalate metabolites with time to pregnancy (TTP). Methods: Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates [median gestational age, 12.9 weeks (interquartile range, 12.1, 14.4)]. We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested. Results: In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally [respective fecundability ratios per each natural log increase were 0.90 (95% CI, 0.81 to 1.00) and 0.88 (95% CI, 0.79 to 0.99)]. Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high-molecular-weight phthalate metabolites. Conclusions: We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004-5.

BACKGROUND: Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. OBJECTIVE: To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. METHODS: In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. RESULTS: Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). CONCLUSION: Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.

Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community.

BACKGROUND & AIMS: Endocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS). METHODS: We studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7±13.7y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n=184). RESULTS: While a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P<0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P<0.001). CONCLUSIONS: In Israel, a country whose inhabitants demonstrate exposure to EDCs comparable to that of the US and Canada, a voluntary lifestyle of vegetarianism and preference for organic food has a modest, but possibly valuable, impact on exposure to phthalates, while it is associated with a very steep increase in the exposure to phytoestrogens. Major reduction in exposure to EDCs will require regulatory actions.

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.

Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China.

BACKGROUND: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. METHODS: In this study, BPA and phytoestrogens in urine specimens (n = 256) collected from children in China were measured by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). RESULTS: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. CONCLUSIONS: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.

Effects of Korean red ginseng (Panax Ginseng Meyer) on bisphenol A exposure and gynecologic complaints: single blind, randomized clinical trial of efficacy and safety.

BACKGROUND: Korean red ginseng (KRG) is a processed ginseng from raw ginseng to enhance safety, preservation and efficacy, known having beneficial effects on women's health due to its estrogen like function. While estrogen supplementation showed some modulation of endocrine disrupting chemicals, bisphenol A (BPA) has been focused as a potential endocrine disrupting chemical. In this study, we examined the efficacy and safety outcomes of KRG against BPA, focusing on female quality of life (QOL). Individual variations in susceptibility to KRG were also investigated with the Sasang Typology, the personalized medicine used for hundred years in Korea. METHODS: We performed a single-blind randomized clinical trial. Study subjects were young women (N = 22), consumed 2.7 g of KRG or placebo per day for 2 weeks and filled up questionnaires regarding gynecologic complaints at the 4 time spots. We analyzed urinary total BPA and malondialdehyde (MDA), an oxidative stress biomarker, with GC/MS and HPLC/UVD respectively, and diagnosed their Sasang Typology with the questionnaire for the Sasang constitution Classification (QSCC II). RESULTS: KRG consumption decreased urinary BPA and MDA levels (ps < 0.05) and alleviated 'menstrual irregularity', 'menstrual pain', and 'constipation' (ps < 0.05). SoEum type (Lesser Yin person) among the Sasang types showed significant alleviation in insomnia, flushing, perspiration and appetite by KRG consumption, rather than other Sasang types. During the intervention, no one experienced any aggravated side effects. CONCLUSION: We suggest KRG is efficient for protection for female QOL and BPA- exposure and - related oxidative stress. However, individual variation in susceptibility to KRG should be further considered for identifying ideal therapy. TRIAL REGISTRATION: KCT0000920.

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel.

BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein. METHODS: In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND DISCUSSION: BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable. CONCLUSIONS: We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.