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.
Project description:Bisphenol A (BPA) is an extensively used chemical with endocrine disrupting properties. Although animal and in vivo studies have suggested possible effects of BPA on levels of gonadotropic hormones, human studies are limited and inconclusive. The study examined whether environmental BPA exposure was associated with gonadotropic hormones levels in men. A total of 560 men aged 18-55 years were recruited from Sandu County, Guizhou Province, China. We collected urine samples for measurement of BPA, and blood samples for measurement of reproductive hormones. We examined serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T). Relative risk (RR) was obtained by log-binominal regression to explore the association between urinary BPA level and hormone levels. BPA was detected in 70.4% of urine samples, with a geometric mean of 0.50 ?g/gCr. Men with detectable levels of BPA had a 1.52-fold increased risk of having a high LH level (>75th percentile) when compared with men with undetectable levels of BPA, after adjustment for potential confounders (95% confidence interval (CI): 1.04-2.21). The association persisted and slightly intensified among current smokers (adjusted RR (aRR) = 1.76, 95%CI: 1.05-2.95), while it weakened among non-smokers (aRR = 1.17, 95%CI: 0.69-1.96). Urinary BPA level was associated with an increased FSH level among smokers (aRR = 1.64, 95%CI: 1.01-2.67). Urinary BPA level was inversely associated with total T level among males with body max index (BMI) ?25 kg/m2 although this association was of borderline significance (aRR = 0.52, 95%CI: 0.26-1.05). In conclusion, environmental exposure to BPA was associated with increased serum levels of LH and FSH in male smokers, along with decreased serum levels of total T in men with BMI?25 kg/m2. These findings suggest that the effects of environmental BPA exposure on hormone levels might be modified by smoking and BMI.
Project description:<h4>Background</h4>Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent.<h4>Objectives</h4>We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population.<h4>Methods</h4>Our 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.<h4>Results</h4>We 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.<h4>Conclusions</h4>The 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:This study aimed to examine whether endocrine-disrupting chemicals (EDCs), such as phthalates, para-hydroxybenzoic acids, and bisphenol-A (BPA), affect gonadal hormones and further link to the susceptibility to attention-deficit/hyperactivity disorder (ADHD). We recruited 98 boys with ADHD, 32 girls with ADHD, 42 boys without ADHD and any other psychiatric disorders, and 26 girls without ADHD and any other psychiatric disorders. Urine levels of EDCs, including mono-methyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoethylhexyl phthalate (MEHP), methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), and bisphenol A (BPA), were examined. Endocrine systems were evaluated by using the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, free testosterone, estradiol, progesterone, sex hormone-binding globulin (SHBG), and prolactin. We found that boys with ADHD had higher levels of MnBP and EP than control boys. There were no significant differences regarding EDCs between the females with ADHD and control groups. No significant differences in testosterone, free testosterone, FSH, LH, estradiol, progesterone, or SHBG were found between the ADHD group and controls among either boys or girls. Among boys with ADHD, urine MBzP and MEHP levels were positively correlated with serum testosterone levels. Among girls, urine MEP levels were positively correlated with serum LH, testosterone, and free testosterone levels. The findings suggest that the possibility of an adverse impact of EDCs on gonadal hormones and neurodevelopment may exist. However, the results could be subject to potential selection bias, and the findings in this study should be interpreted with caution.
Project description:To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA_Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (? = -0.34, 95% CI = -0.60, -0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.
Project description:Phthalates and BPA are known endocrine disruptors and exposure in pregnant mothers and children is ubiquitous. We explored the relationship of prenatal and childhood exposures with pubertal onset and sex hormones in boys (ages 8-14). Phthalate metabolites and BPA were measured in maternal 3rd trimester or childhood urine. Sex hormones DHEAS, estradiol, inhibin B, SHBG, and total testosterone were measured in serum. Adrenarche and puberty were assessed by pediatrician. Prenatal exposure to some phthalates was associated with decreased DHEAS and inhibin B levels, and with increased SHBG. Prenatal exposure to most phthalates and BPA was associated with greatly reduced odds of adrenarche (odds ratios [OR]=0.12-0.65) and slightly reduced odds of puberty (OR=0.50-0.98). Childhood exposure was not associated with adrenarche or puberty, but some phthalates and BPA were associated with increased SHBG levels and decreased total and free testosterone levels.
Project description:Measurement of endogenous hormones in early life is important to investigate the effects of hormonally active environmental compounds. To assess the possible hormonal effects of different feeding regimens in different sample matrices of infants, 166 infants were enrolled from two U.S hospitals between 2006 and 2009. The children were classified into exclusive soy formula, cow milk formula or breast milk regimens. Urine, saliva and blood samples were collected over the first 12 months of life. Estradiol, estrone, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels were measured in the three matrices. Lower estradiol and LH levels were found in urine and saliva samples of soy formula-fed boys compared to cow formula-fed boys. Higher LH level was found in urine samples of soy formula-fed girls compared to cow formula-fed girls. However, we found neither a neonatal testosterone rise in the boys nor a gender-specific difference in testosterone levels, which suggests that urinary testosterone levels may not accurately reflect blood levels during mini-puberty. Nevertheless, our study shows that blood, urine and saliva samples are readily collectible and suitable for multi-hormone analyses in children and allow examination of hypotheses concerning endocrine effects from dietary compounds.
Project description:JMJD1C, a member of the Jumonji-domain containing histone demethylases protein family, has been associated with levels of sex-hormone binding globulin (SHBG) and testosterone in men, and knock-out rodent models show age-dependent infertility. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) nearby JMJD1C are associated with pubertal onset in boys and with male reproduction. 671 peri-pubertal boys, 1,027 young men, 315 fertile men, and 252 infertile men were genotyped for two JMJD1C SNPs (rs7910927 and rs10822184). rs7910927 and rs10822184 showed high linkage. Boys with the rs7910927 TT genotype entered puberty 3.6 months earlier than their peers (p?=?2.5?×?10-2). In young men, the number of T alleles was associated with decreased levels of SHBG, follicle-stimulating hormone (FSH), testosterone, and testosterone x luteinizing hormone, as well as increased levels of Inhibin B, Inhibin B/FSH ratio, and testis size. No significant associations with semen parameters were observed and the genotype distribution was comparable among fertile and infertile men. In conclusion, genetic variation in the vicinity of JMJD1C had a surprisingly large impact on the age at pubertal onset in boys as well as levels of reproductive hormones and testis size in men, emphasizing the relationship between JMJD1C and reproductive functions.
Project description:The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, -211 bp from the mRNA start) and significantly reduced male serum FSH.In the current study, the T-allele carriers of the FSHB -211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action.We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center.Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10(-6); T-allele effect, -0.41 IU/liter), inhibin-B (P = 2.16 × 10(-3); T-allele effect, -14.67 pg/ml), and total testosterone (P = 9.30 × 10(-3); T-allele effect, -1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10(-4); TT genotype effect, -9.47 ml) and increased serum LH (P = 2.25 × 10(-2); TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations.We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential.
Project description:OBJECTIVE:To compare the serum inhibin B, anti-Müllerian hormone (AMH) and leptin concentrations in girls with idiopathic central precocious puberty (CPP) to their concomitant characteristics and evaluate the capacity of each of these hormones to predict the age at first menstruation in those who were untreated and who completed their puberty. METHODS:This single-center study included 94 girls selected from a cohort of 493 girls seen between 1981 and 2012 and diagnosed with idiopathic CPP for whom a remaining serum sample collected at the initial evaluation was available. Of these 25 were untreated and completed their puberty. RESULTS- CORRELATIONS AT INITIAL EVALUATION:In the whole cohort the inhibin B concentration displayed significant positive correlations with the age at the onset of puberty and at initial evaluation; bone age; breast Tanner stage; serum basal estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and AMH concentrations, LH peak and LH/FSH peak ratio. The AMH concentration displayed a significant positive correlation with serum estradiol and a negative correlation with basal FSH concentration. The leptin concentration displayed significant positive correlations with the age at initial evaluation, bone age, and body mass index and a negative correlation with the FSH peak. RESULTS- PREDICTION OF AGE AT FIRST MENSTRUATION:In 25 untreated girls, the inhibin B concentration was negatively correlated with the age at first menstruation (r = -0.61, p = 0.001) and the time between the onset of puberty and first menstruation (r = -0.59, p = 0.002). Inhibin B concentrations <30 pg/mL were associated with a time between the onset of puberty and first menstruation ?3 years in 14/15 patients with a sensitivity of 0.67 and a specificity of 0.75. The age at first menstruation was estimated using a formula: min (11.15-0.510 LH/FSH peak ratio, 11.57-0.025 inhibin B)available at: http://www.kamick.org/lemaire/med/girls-cpp18.html. CONCLUSION:We established formulas based on the serum inhibin B concentrations and LH/FSH peak ratio at the initial evaluation, alone or in combination, to predict the age at first menstruation in girls with CPP. These formulas can assist with determining the indications for treatment in CPP.
Project description:Activins and estrogens participate in regulating the breakdown of ovarian germ cell nests and follicle assembly in mammals. In 1994, our group reported elevated frequencies of abnormal, multioocytic ovarian follicles in 6 month old, environmental contaminant-exposed female alligators after gonadotropin challenge. Here, we investigated if maternal contribution of endocrine disrupting contaminants to the egg subsequently alters estrogen/inhibin/activin signaling in hatchling female offspring, putatively predisposing an increased frequency of multioocytic follicle formation. We quantified basal and exogenous gonadotropin-stimulated concentrations of circulating plasma steroid hormones and ovarian activin signaling factor mRNA abundance in hatchling alligators from the same contaminated (Lake Apopka) and reference (Lake Woodruff) Florida lakes, as examined in 1994. Basal circulating plasma estradiol and testosterone concentrations were greater in alligators from the contaminated environment, whereas activin/inhibin betaA subunit and follistatin mRNA abundances were lower than values measured in ovaries from reference lake animals. Challenged, contaminant-exposed animals showed a more robust increase in plasma estradiol concentration following an acute follicle stimulating hormone (FSH) challenge compared with reference site alligators. Aromatase and follistatin mRNA levels increased in response to an extended FSH challenge in the reference site animals, but not in the contaminant-exposed animals. In hatchling alligators, ovarian follicles have not yet formed; therefore, these endocrine differences are likely to affect subsequent ovarian development, including ovarian follicle assembly.