BPA vs BPF vs BPS Levels in Women with PCOS

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BPS (BPA substitute) levels found elevated in women with PCOS

Serum bisphenol A analogues in women diagnosed with the polycystic ovary syndrome – is there an association?

doi.org/10.1016/j.envpol.2020.115962

Background

Since the ban on bisphenol-A (BPA) use in polycarbonate feeding bottles by the European Commission, manufacturers have increased the use of alternatives (BPAF, BPE, BPF, BPS, BPP, BPZ, TBBPA and TCBPA), with similar chemical properties, known as BPA analogues.

Recent studies however have also found these alternatives to be hormonally active, meaning they can influence both estrogen and androgen levels, and lead to infertility or other sex-hormone dependent disorders such as PCOS.

However to date, the potential exposure of women with PCOS, to 2 of these main BPA analogues, bisphenol-S (BPS) and bisphenol-F (BPF), has not been investigated.

Aim

To evaluate a possible association between the exposure to BPA and its analogues, BPS and BPF, in the diagnosis of PCOS

Methodology

Women aged 18-40 years old and diagnosed with PCOS, according to the Androgen Excess and PCOS Society criteria, were actively recruited, alongside healthy eumenorrheic women with no signs of hyperandrogenism as the control group.

Any woman diagnosed with thyroid dysfunction, hyperprolactinaemia, potentially non-classical congenital adrenal hyperplasia, or taking medication / supplements which may interfere with hormonal and metabolic measurements, was automatically excluded from the study.

Participant demographics along with smoking and alcohol consumption was captured via a questionnaire.
Fasting blood samples was then collected between cycle day 6 and 10, for hormonal and biochemical analyses, with menstruation induced (5mg dydrogesterone) in women with irregular cycles or secondary amenorrhea.

Serum concentrations of BPA, BPS and BPF was measured using a triple quadrupole LC-MS/MS system, equipped with an electrospray ionization source (ESI), featuring a minimum limit of quantification (LOQ) and detection (LOD) for BPA, BPS and BPF of 0.028ng/mL and 0.009ng/mL, 0.067ng/mL and 0.022ng/mL, 0.037ng/mL and 0.012ng/mL, respectively.

Results

A total of 357 women (199 PCOS, 158 Control) satisfied the inclusion exclusion criteria.

Of the 199 women with PCOS, 24% presented with all three features (excess androgen, irregular cycles, polycystic ovaries), 54% with excess androgen and irregular cycles, and the remaining 22% with excess androgen and polycystic ovaries.

Initial analysis of participant characteristics showed that the PCOS group were significantly younger (26.6 vs. 31.2 years) and almost twice as likely to be smokers (14.6% vs 7.6%). However other variables such as BMI and alcohol consumption, were almost identical between the two groups. 

Homone test results showed no significant difference with respect to FSH, LH and TSH, however Prolactin, total testosterone and androstenedione was significantly higher, while E2 and SHBG was significantly lower, in the PCOS group as expected more or less.

Next, analysis of BPA, BPS and BPF levels detected BPA and BPS in 95% of women, while BPF was only detected in 71% of women.

Interestingly, BPA and BPF levels did not differ significantly between the 2 groups, however BPS levels were found to be significantly higher in the PCOS group (0.14 vs. 0.08 ng/ml).

On the other hand, (Spearman) correlation statistical analysis identified 2 statistically significant negative correlations, meaning as serum BPA levels increased, both total testosterone and HOMA-Insulin resistance decreased.

To test this finding further, serum BPA, BPS and BPF concentrations were grouped, according to the lowest, middle and highest tertile ranges, and the risk, or odds ratio (OR), of PCOS diagnosis calculated. Following crude and adjusted analysis, only BPS concentrations in the lowest tertile (<0.09ng/mL) was significantly associated with an increased risk of PCOS (OR, 1.21, adj. OR 1.12).

This preliminary finding may be explained by the increased polarity of BPS compared to BPA, however further studies are now required to confirm this finding.

SUMMARY: PCOS AND PLASTIC WATER BOTTLES

In this study of women with PCOS, bisphenol S (BPS), a common bisphenol A (BPA) substitute in plastic water bottles, was found significantly elevated (0.14 vs. 0.08 ng/mL) in women with PCOS compared to controls, while BPA levels on the other hand was not signifcantly different (P>0.4).

Limitations

  1. Single serum sample only, rather than multiple serum and urine samples, to better quantify real exposure levels

Funding

This study was funded by the Polish National Center for Science.

Glossary

Amenorrhea
Absence of menstruation.

Analogues
A compound with a molecular structure closely similar to that of another.

E2
Estradiol (oestradiol).

Eumenorrheic
Normal menstrual cycle.

FSH
Follicle-stimulating hormone.

Hyperandrogenism
High levels of androgens.

Hyperprolactinaemia
High levels of prolactin.

LH
Luteinizing hormone.

SHBG
Sex hormone-binding globulin.

Tertile
Any two points that divide an ordered distribution into three parts.

TSH
Thyroid-stimulating hormone.

Similar studies

Li A, et al. (2020). Serum concentration of bisphenol analogues in pregnant women in China. https://doi.org/10.1016/j.scitotenv.2019.136100

Vagi S J, et al. (2014). Exploring the potential association between brominated diphenyl ethers, polychlorinated biphenyls, organochlorine pesticides, perfluorinated compounds, phthalates, and bisphenol A in polycystic ovary syndrome: a case-control study. https://doi.org/10.1186/1472-6823-14-86


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