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Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic.

ABSTRACT: Human exposure to bisphenol A (BPA) is widespread. Animal studies have demonstrated that BPA can alter endocrine function, but human studies are limited. For the present study, we measured urinary BPA concentrations and serum thyroid and reproductive hormone levels in 167 men recruited through an infertility clinic. BPA was detected in 89% of urine samples with a median (range) of 1.3 (<0.4 - 36.4) ng/mL. In multivariable regression models adjusted for potential confounders, BPA concentrations in urine collected on the same day as a blood sample were inversely associated with serum levels of inhibin B and estradiol:testosterone ratio (E(2):T) and positively associated with follicle-stimulating hormone (FSH) and FSH:inhibin B ratio. Because BPA is metabolized quickly and multiple urine measures may better reflect exposure than a single measure, we also considered among a subset of the men the BPA concentrations in repeated urine samples collected weeks or months following serum sample collection. In these analyses, the effect estimates remained consistent for FSH and E(2):T but were somewhat weakened for inhibin B. In addition, we observed inverse relationships between urinary BPA concentrations and free androgen index (ratio of testosterone to sex hormone binding globulin), estradiol, and thyroid stimulating hormone. Our results suggest that urinary BPA concentrations may be associated with altered hormone levels in men, but these findings need to be substantiated through further research.

SUBMITTER: Meeker JD

PROVIDER: S-EPMC2823133 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic.

Meeker John D JD Calafat Antonia M AM Hauser Russ R

Environmental science & technology 20100201 4

Human exposure to bisphenol A (BPA) is widespread. Animal studies have demonstrated that BPA can alter endocrine function, but human studies are limited. For the present study, we measured urinary BPA concentrations and serum thyroid and reproductive hormone levels in 167 men recruited through an infertility clinic. BPA was detected in 89% of urine samples with a median (range) of 1.3 (<0.4 - 36.4) ng/mL. In multivariable regression models adjusted for potential confounders, BPA concentrations i ...[more]

PMID: 20030380

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Project description:BACKGROUND:We have previously investigated whether urinary concentrations of bisphenol A (BPA), parabens, and phthalate metabolites were individually associated with reproductive outcomes among women undergoing in vitro fertilization (IVF) treatment. However, humans are typically exposed to many man-made chemicals simultaneously. Thus, investigating one chemical at a time may not represent the effect of mixtures. OBJECTIVE:To investigate whether urinary concentrations of BPA, parabens, and phthalate metabolite mixtures are associated with reproductive outcomes among women undergoing IVF. METHODS:This prospective cohort study included 420 women contributing 648 IVF cycles who provided up to two urine samples per cycle prior to oocyte retrieval (N = 1145) between 2006 and 2017 at the Massachusetts General Hospital Fertility Center, and had available urine biomarker data. Urinary concentrations of BPA, parabens, and phthalate metabolites were quantified using isotope-dilution tandem mass spectrometry. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. Principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) were used to identify main patterns of BPA, parabens, and phthalate metabolites concentrations. We used generalized linear mixed models to evaluate the association between PCA-derived factor scores, in quartiles, and IVF outcomes, using random intercepts to account for multiple IVF cycles and adjusting for known confounders. Because of temporal trends in exposure, we conducted a sensitivity analysis restricted to women who underwent IVF cycles in the earlier years of study (2006-2012). RESULTS:Urinary concentrations of BPA, parabens, and most phthalate metabolites were significantly lower during the second half of the study period (2013-2017) than during the first half (2006-2012). None of the three factors derived from the PCA [di(2-ethylhexyl) phthalate (DEHP), non-DEHP, and paraben] was associated with IVF outcomes in the main analyses. Similarly, BKRM analyses did not identify any associations of individual urinary concentrations of BPA, paraben and phthalate metabolites with IVF outcomes while accounting for correlation between exposures. However, in sensitivity analyses restricted to women who underwent IVF cycles from 2006 to 2012, where concentrations of most phthalates and phenols were higher, there were decreases in implantation, clinical pregnancy, and live birth across quartiles of the DEHP factor. Specifically, women in the highest quartile of the DEHP factor had, on average, lower probabilities of implantation (-22% p, trend = 0.08), clinical pregnancy (-24% p, trend = 0.14), and live birth (-38% p, trend = 0.06) compared to women in the lowest quartile. Among this group of women, BKMR results did not identify any single contributor driving the decreased probabilities of live birth within the DEHP factor. CONCLUSIONS:We confirmed that women undergoing IVF are concurrently exposed to multiple endocrine disrupting chemicals (EDCs). While we found no overall significant associations, we observed diminished pregnancy success with specific clusters of chemicals among women who underwent IVF cycles in earlier years of study, when urinary concentrations of these EDCs were higher.

Project description:BackgroundTriclosan, a widely-used antimicrobial in personal care products, has shown endocrine disrupting activity in experimental studies. However, there is limited evidence from epidemiologic studies on health effects.ObjectiveTo examine the association between urinary triclosan concentrations and semen quality.MethodsA total of 262 men enrolled in the Environmental and Reproductive Health (EARTH) Study provided 581 paired urine and semen samples (2009-2017). Urinary triclosan concentrations were quantified and semen analysis was evaluated according to WHO guidelines. We used linear mixed regression models to estimate the associations between specific gravity-adjusted urinary triclosan concentrations with semen parameters, with a random intercept to account for multiple samples per man and adjusting for age, body mass index (BMI), smoking, physical activity, sexual abstinence time, and season and year of samples' collection.ResultsMen had a mean (standard deviation) age of 36.6 (5.24) years and BMI of 27.9 (5.94) kg/m2. Seventy four percent of the samples had detectable (>2.3 μg/L) concentrations. We did not observe significant dose response trends between SG-adjusted urinary triclosan concentrations and semen parameters. However, in the adjusted analysis, compared to men with non-detectable triclosan concentrations in the lowest quartile, those in the second, third, and fourth quartiles had -1.32% (95%CI: -2.04, -0.59), -0.91% (95%CI: -1.63, -0.18), and -0.46% (95%CI: -1.25, 0.33) lower percent morphologically normal sperm, respectively. Similarly, a lower percentage of morphologically normal sperm was found among men with detectable triclosan concentrations, compared to men with non-detectable triclosan [-0.96% (95% CI: -1.57, -0.35)]. In sensitivity analyses, there was stronger negative associations on the percent morphologically normal sperm in the earlier time period due to the significant negative trend in detectable triclosan concentrations over time.ConclusionDespite the lack of observed dose response relationship, we found consistent patterns of lower percent morphologically normal sperm for men with urinary triclosan in the 2nd or 3rd quartile compared to undetectable concentrations.This association was stronger for samples obtained prior to 2013 when triclosan was more often detectable in urine.

Project description:Benzophenone-3 is used in a variety of cosmetic products as a sunscreen, and has shown weak estrogenic and antiandrogenic activity in animal and in vitro studies. Few studies have evaluated whether benzophenone-3 is associated with reproductive outcomes among women. We studied 304 women undergoing infertility treatment (2007-2017) in the prospective Environment and Reproductive Health cohort study and who underwent 449 treatment cycles (n = 788 urines). Generalized linear mixed models were used with random intercepts to account for multiple cycles, and adjusting for confounders including physical activity. Analyses were also stratified by self-reported moderate/heavy outdoor work. The cycle-specific median (IQR) urinary benzophenone-3 concentration was 147 (58, 462) μg/L, and 98% samples had detectable concentrations. Self-reported sunscreen use, physical activity, and time spent on moderate/heavy outdoor work were positively associated with urinary benzophenone-3. Adjusted probabilities of implantation, clinical pregnancy and live birth were higher in increasing quartiles of benzophenone-3, but these associations were restricted to women who reported spending time outdoors performing moderate/heavy work. Specifically, among these women, those in the highest quartile of benzophenone-3 concentrations had 51% higher implantation (p,trend = 0.02), 68% higher clinical pregnancy (p,trend = 0.01) and 75% higher live birth (p,trend = 0.02) adjusted probabilities than women in the lowest quartile. Benzophenone-3 was unrelated to these outcomes among women who did not report doing moderate/heavy work outdoors. These results confirm that sunscreen use is a source of benzophenone-3 exposure, and show positive associations between benzophenone-3 and pregnancy outcomes, especially among women who reported engaging in outdoor work. Since these associations may be subject to important residual confounding by lifestyle factors, further research is needed to confirm these novel results in other populations, and to investigate whether other factors may be affecting the relation of benzophenone-3 with fertility and other health outcomes.

Project description:BackgroundFew human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent.ObjectivesWe examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population.MethodsOur study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography-tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors.ResultsWe found that 98% of the men had detectable urinary levels of BPA. Median (5th-95th percentiles) BPA concentration was 3.25 ng/mL (0.59-14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile (p trend ? 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (-6.7 percentage points, 95% CI: -11.76, -1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results.ConclusionsThe pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic-pituitary-gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.

Project description:Study questionAre urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center?Summary answerUrinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic.What is known alreadyBisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal.Study design, size and durationThis prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673).Participants/materials, settings, methodsStudy participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis.Main results and the role of chanceThe specific gravity-adjusted geometric mean of BPA was 1.87 µg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (<37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (≥37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations.Limitations, reasons for cautionLimitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population.Wider implications of the findingsData on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction.Study funding/competing interestsThis work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Dataset Information

Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic.

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Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic.

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