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Try out PMC Labs and tell us what you think. Learn More. Bisphenol A BPA is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals, yet human studies remain limited.

We estimated daily excretion of BPA among adults and examined hypothesized associations with serum estrogen and testosterone concentrations. Our study included adults between 20 and 74 years old. BPA concentrations were measured by liquid chromatography—mass spectrometry in hr urine samples. Geometric mean urinary BPA concentration was 3.

We found no associations with the other serum measures. We also found no associations with the primary outcomes among women, but we did find an association between BPA and SHBG concentrations in the 60 premenopausal women. Higher BPA exposure may be associated with endocrine changes in men. The mechanisms involved in the observed cross-sectional association with total testosterone concentrations need to be clarified.

Bisphenol A BPA is a synthetic compound that is a suspected endocrine disruptor—a compound capable of causing dysfunction to hormonally regulated body systems Talsness et al. Widespread and continuous daily exposure to BPA is believed to occur primarily through the diet Stahlhut et al. Most studies of the health effects of BPA have focused on its well-documented estrogenic activity, with reports of both estrogen agonist Lee et al. In addition, BPA has been reported to cause thyroid hormone disruption Moriyama et al. The potential for low-dose effects has prompted debate on revising the current legislation of recommended safe daily exposure levels Beronius et al.

Based on the animal and laboratory evidence, we ly hypothesized that Actual free sex Galloway urinary BPA concentrations would be associated with adverse human health effects. Using data from the U. National Health and Nutrition Examination Survey NHANES for —, the first large-scale population-based epidemiological data on urinary Actual free sex Galloway concentrations with sufficient power to detect low-dose effects, we showed for the first time a clear correlation between BPA exposure and disease in humans Lang et al.

Higher BPA concentrations in NHANES respondents were associated with diagnoses of cardiovascular disease and diabetes but not with other common diseases, which suggested specificity of the reported findings Melzer et al. The of this replication indicated that chance was an implausible explanation for our.

Studies to clarify the mechanisms of these associations are clearly a priority. A substantive literature documents the disruption of circulating reproductive hormone concentrations after BPA exposures in animal models reviewed by Richter et al. Studies of human populations have until now been limited to very small sample sizes. A Actual free sex Galloway, positive relationship was reported between circulating androgen concentrations and BPA exposure in a small study of 26 normal women and 47 women with ovarian dysfunction Takeuchi et al.

More recently, Meeker et al. Given these findings, we hypothesized that higher urinary BPA concentrations would be associated with altered reproductive hormone concentrations in serum. Because a limitation of studies has been their reliance on single spot urine samples, we based our current analysis on hr urine collections, to provide a direct measure of daily excretion rates.

Our analysis of the data from this sample provides the first report of daily BPA excretion levels in a large European cohort. Participants gave informed consent, or if they were unable to do so, a close relative provided surrogate consent. Because orally administered BPA is considered to be rapidly and completely excreted, urine is the body fluid Actual free sex Galloway appropriate for the biomonitoring assessment of BPA exposure see Calafat et al.

Two major advantages of the Symbiosis Pharma system are that a new SPE cartridge is used for every analysis and that one SPE cartridge is prepared while one is being analyzed. A linear calibration was obtained from 0.

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Participants who consented to donate a blood sample were asked also to collect the urine for 24 hr in a vessel containing 3 g boric acid as preservative. During the 3 days before blood and urine collection, the subjects consumed a diet free of meat and fish.

On the morning of the day before the blood samples were drawn, participants urinated and flushed away the first voided urine and then began the urine collection. During the day and night, all the produced urine was saved into the plastic bottle stored at room temperature or in the refrigerator. After 24 hr, bottles were weighed and the total volume measured in the clinic. First thing the next morning, after having been sedentary for 15 min, fasting blood samples were collected for routine blood examination.

Measurement of serum testosterone typically includes estimating total testosterone free plus boundfree testosterone not protein boundand bioavailable testosterone not SHBG bound. The minimum LOD was 0. Intraassay coefficients of variation CVs for three different concentrations ranged from 7. The intraassay CVs for three different concentrations were 1. Free testosterone was estimated from measured total testosterone, SHBG, and albumin 4.

The theoretical sensitivity was 2. Intraassay CVs across four different concentrations ranged from 6. Descriptive statistics of urinary BPA concentration and serum hormone levels were tabulated. We calculated geometric means and distribution percentiles of two different BPA measures. We performed multivariate linear regression analyses to study the association between BPA and a broad range of demographic covariates and possible confounders.

Because the concentrations of daily BPA excretion were not normally distributed, we used natural log transformation when BPA was considered the dependant variable. BPA values were not transformed when it was considered an explanatory variable in serum hormone examination.

In all analyses, an upper age cutoff was 75 years to minimize the problem of comorbidity. We adjusted our models by selecting different covariates. The variables included in our analyses were age, reported in years at the last birthday and used as a continuous variable; the two municipalities study sites where participants lived; waist circumference centimeters and weight kilograms ; and body mass index BMI was calculated as the weight kilograms divided by the square of height meters. We also considered smoking status, which appeared to be correlated to BPA in unadjusted models. Urinary creatinine concentration is commonly used to adjust within-day variation in metabolite analysis from single spot urine samples Barr et al.

Linear regression analysis using Actual free sex Galloway outcome hormone measures as the dependant variable was performed first considering all the subjects and then considering men and women separately. The geometric mean urinary concentration of BPA was 3. Based on the hr urine collection, the daily excretion rate of BPA had a geometric mean of 5. The distribution was skewed, with a 10th percentile of 2. We obtained identical both with and without correction for creatinine. In models adjusted for age, sex, and study site Table 2we found no associations between daily BPA excretion and years of education or smoking status.

Geometric mean GM and Actual free sex Galloway population percentiles of urinary BPA concentrations and daily excretion of the study sample. Geometric means GMs of BPA excretion, by covariate status, plus age, sex, and study site using adjusted regression estimates of association. To explore further the association with testosterone in men, we examined associations with the derived measure of free testosterone, based on SHBG Actual free sex Galloway. In the models that tested hormone associations with BPA excretion among women Table 4we found no ificant associations for either estradiol or total testosterone.

Both SHBG concentration and the derived measure of free testosterone showed ificant associations with BPA excretion in premenopausal women, although it should be noted that the method used direct measure of free testosterone by RIA and calculation of the free androgen index was not deed for measuring androgen concentrations in women, where the concentrations involved are at the very lowest LODs Miller et al. Post hoc analyses for bioavailable testosterone showed patterns similar to those reported for free testosterone data not shown.

Associations with estradiol: testosterone ratios were nonificant. In this study, we have reported for the first time the daily excretion levels of Actual free sex Galloway among European adults in a large-scale and high-quality population-based sample. After adjusting for potential confounders, we have shown that higher BPA daily excretion was associated with an increase in serum total testosterone concentration in men. These are important because they provide the first report, using data from a large-scale human population, of associations between elevated exposure to BPA and alterations in circulating hormone levels.

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They also illustrate that the extent of exposure to BPA is similar in this European urban and rural population to exposures seen in the general adult population of the United States Calafat et al. studies of the relationship between human exposure to BPA and endocrine function are sparse and involve reported alterations in androgens gonadotrophins or testosterone in urine or serum in both men and women, although the s of participants were small Hanaoka et al.

Hanaoka et al. In a later study of men recruited through an infertility clinic Thuillier et al. Because FSH and inhibin B are the two hormones considered most predictive of semen quality, Thuillier et al. In an animal study, rats exposed to BPA in utero did not show ificant changes in circulating testosterone levels in adulthood, which suggests normal functioning of Leydig and Sertoli cells Actual free sex Galloway et al.

Because estrogens and androgens can exert differential effects in function depending on the cell type and its stage of development, the consequences of BPA exposure on adult reproductive and somatic tissues merits further attention.

The reported by Meeker et al. Mendiola et al. Plausible explanations for our finding of an increase in total testosterone include a reduction in aromatase activity Akingbemi et al. Lee et al. In our study, associations with the derived measure of free testosterone narrowly missed statistical ificance. Alternatively, there could be differential effects of BPA on the metabolism of testosterone and estrogen. A study of steroid hormone production in rat ovarian cells showed that BPA increased both testosterone synthesis and the mRNA expression of steroidogenic enzymes Zhou et al. The possibility that BPA could interfere with the RIA used to quantify serum testosterone is unlikely given the low cross-reactivity shown by the anti-testosterone antibody used in the assay and is further discounted by mathematical modeling studies showing negligible effects of xenoestrogens on the displacement of bound hormone and tracer Actual free sex Galloway binding and extraction steps in vitro Heringa et al.

It is also plausible that an androgenic environment le to alterations in the metabolism of BPA, that is, reverse Actual free sex Galloway. The level of both UGT activity and transcription has been shown to be downregulated by androgens Guillemette et al. However, it is unlikely that such metabolic change could alter hr urinary BPA excretion in the context of repeated ingestion of BPA at the population level and the limited increase in testosterone concentrations evident in our analysis. This concentration is lower than the mean value presented here, 3.

Here, we used hr urine collection to calculate a mean daily excretion rate of 5.

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In an earlier Japanese study, Arakawa et al. However, there are no actual in vivo data on the rate at which unconjugated BPA is converted to BPA-glucuronide in humans, only estimates. BPA is lipophilic with a log octanol—water partition coefficient log K ow between 2. Given the correlations Actual free sex Galloway BMI and waist circumference seen here, a true estimation of exposure rates remains a priority. There are limitations to this study that should be borne in mind when interpreting the.

First, replication is required in an independent study population to exclude chance as an explanation, although the small p -value in fully adjusted models and the broad consistency with work suggest this is unlikely. Second, the analysis is based on a single day of BPA excretion, which is Actual free sex Galloway not a perfect measure of longer term exposure given that human health effects are most likely associated with long-term low-dose exposure. However, using the hr urine specimens is likely to be more accurate than ly published work, which has been based on spot urine samples with post hoc adjustment to try to correct for concentration effects.

Misclassification due to this single-day snapshot of excretion will have resulted in a smaller diluted estimate of the strength of association between BPA and total testosterone concentrations: the true associations are likely to be much stronger. Third, the cross-sectional nature of the association reported here needs to be treated with caution. It is also theoretically possible, for example, that those with higher testosterone concentrations alter their diet in such a way as to increase BPA exposure, or, as noted above, that higher testosterone concentrations are themselves responsible for altering metabolism of BPA.

It is unclear, however, why altered metabolism would alter our measure of hr excretion systematically, because all BPA is thought to be excreted in the urine in humans sooner or later. We ly reported positive associations between urinary BPA and prevalence of cardiovascular disease Lang et al.

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