PCOS, BPA and Endocrine Disruptors
by Jeffrey Dach MD
At the May 16 A4M Meeting in Orlando, Felice Gersh MD gave an excellent talk on PCOS, which I will attempt to summarize in this article. Dr. Gersh in an integrative OB/Gyne in Irvine California.
What is PCOS ?
Poly Cystic Ovary Syndrome – PCOS
PCOS is characterized by anovulatory cycles, increased testosterone and DHEA levels causing hirsutism and acne, insulin resistance, and increased inflammation in the body. In addition, recent studies show dysfunctional Estrogen Receptors (ER alpha and ER Beta) and Progesterone receptors.(1)
Dr Gersh was very blunt about the cause of PCOS, linking neonatal exposure to the endocrine disruptor chemical BPA (Bisphenol-A) to the increasing epidemic of PCOS affecting 10-20% of the female population.(1-7)
Dr Gersh pointed out that in experimental animals, neonatal exposure to BPA (Bisphenol-A) results in a PCOS-like syndrome in
adulthood. In addition, there is elevated BPA levels in PCOS patients.(6) Genetic studies show polymorphism or genetic mutations in the Estrogen receptors.(4)
The altered Estrogen Receptors leads to altered follicle development and explains the anovulory cycles.
Bis-Phenol-A Physiologic Effects
1) Reduces the number of oocytes
2) Lowers successful number of births
3) Changes gene expression – differences only apparent after
4) Reduces the function of Estrogen Receptor Beta
5) Negatively affects mitochondrial function
6) Alters hypothalamic pituitary- gonadal axis Increases testosterone,
7) lowers progesterone,
8) alters GnRH secretion
9) Increases glucocorticoids,
10) heightens response to stress, elevates levels of anxiety
BPA is Everywhere !
Bisphenol A is found in plastics and in the plastic lining of canned foods (see above image) and we are unfortunately exposed to huge quantities of it in our everyday life.
Early Environmental Pioneers
Early pioneers in the field who warned us about the effects of endocrine disrupting chemicals in the environment were Rachel Carson in her 1962 book, Silent Spring, and Theo Coburn in her book, Our Stolen Future: Threatening Our Fertility.
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
PCOS part three references
Estrogen Receptors altered in PCOS
Estrogen receptor expression altered in PCOS follicles
17 December 2002. Journal of Clinical Endocrinology and Metabolism 2002; 87: 5532–8
The fertility problems associated with polycystic ovary syndrome (PCOS) may be partly due to abnormal granulosa cell expression of estrogen receptors (ERs) in women with the condition, a study shows.
Noting that high estrogen concentrations are “a defining characteristic of dominant follicles,” Dr. Denis Magoffin (Ceders-Sinai Medical Center, Los Angeles, California, USA) and co-investigators examined whether abnormal expression of ERs could contribute to poor follicular development and ovulatory failure in women with PCOS.
They obtained follicles from 12 polycystic ovaries from women with PCOS, and 23 normal ovaries from women with regular menstrual cycles.
Expression of ER-alpha mRNA was similar in control and PCOS follicles in the granulosa cells, but in the theca cells, ER-alpha concentrations were significantly increased in the PCOS samples, compared with the controls. ER-beta mRNA expression was higher in small antral than in dominant follicles from the control ovaries, and was observed at an intermediate level in PCOS follicles. Interestingly, however, ER-beta protein was detected at similar levels in the PCOS follicles and control dominant follicles.
“The results of this study demonstrate that there are significant alterations in the expression of ER-alpha and ER-beta in PCOS that may be related to abnormal follicular development,” Magoffin et al conclude.
3) Ovarian Actions of Estrogen Receptor-β: An Update Ann E. Drummond, Ph.D.1 Peter J. Fuller, B.Med.Sci., M.B.B.S., Ph.D., F.R.A.C.P.1 1Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia Ovarian_Actions_of_Estrogen_Receptor_β_ Drummond_2012
Fertil Steril. 2010 Apr;93(6):1942-7. doi: 10.1016/j.fertnstert.2008.12.
Estrogen receptor beta gene +1730 G/A polymorphism in women with polycystic ovary syndrome. Kim JJ1, Choi YM, Choung SH, Yoon SH, Lee GH, Moon SY.
To investigate whether the +1730 G/A polymorphism in the estrogen receptor (ER)-beta gene is associated with susceptibility to polycystic ovary syndrome (PCOS).
University Department of Obstetrics and Gynecology.
PATIENT(S): Women with (n = 138) or without (n = 290) PCOS.
INTERVENTION(S): Genotyping was performed by polymerase chain reaction-restriction fragment-length polymorphism analysis.
MAIN OUTCOME MEASURE(S): Genotype distribution and allele frequency of the +1730 G/A polymorphism in the ER-beta gene.
RESULT(S): There was a significant difference in the genotype distribution between the patients with PCOS and controls (non-GG rates were 22.1% for patients with PCOS and 36.6% for controls). There was also a significant difference in the G and A allele frequencies between these two groups (11.7% in patients vs. 19.1% in controls with A allele). But in patients with PCOS there were no significant differences in the serum levels of hormones, biochemical variables, or ovarian morphology between GG and non-GG genotypes.
The ER-beta gene +1730 G/A polymorphism may be associated with pathophysiologic aberrancies involved in PCOS.
PLoS One. 2013; 8(5): e64801. Published online May 21, 2013.doi: 10.1371/journal.pone.0064801
Genome-Wide Methylated DNA Immunoprecipitation Analysis of Patients with Polycystic Ovary Syndrome Hao-ran Shen,1 Li-hua Qiu,1 Zhi-qing Zhang,2 Yuan-yuan Qin,1 Cong Cao,2,* andWen Di1,*
Elevated Levels of BPA in PCOS
J Clin Endocrinol Metab. 2011 Mar;96(3):E480-4. doi: 10.1210/jc.2010-1658. Epub 2010 Dec 30. Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS. Kandaraki E1, Chatzigeorgiou A, Livadas S, Palioura E, Economou F, Koutsilieris M, Palimeri S, Panidis D, Diamanti-Kandarakis E.
Bisphenol A (BPA) is a widespread industrial compound used in the synthesis of polycarbonate plastics. In experimental animals, neonatal exposure to BPA results in a polycystic ovary-like syndrome (PCOS) in adulthood. A bidirectional interaction between androgens and BPA levels has been disclosed.
To determine BPA levels in PCOS women as well as the association between BPA and hormonal/metabolic parameters compared to a control group.
DESIGN, SETTING, AND PARTICIPANTS:
Cross-sectional study of 71 PCOS (National Institutes of Health criteria) and 100 normal women, age- and body mass index-matched, in a University hospital setting.
MAIN OUTCOME MEASURES:
Anthropometric, hormonal, metabolic parameters and BPA blood levels were determined. Patients (PCOS) and controls (C) were further subdivided according to body mass index into lean and overweight subgroups, respectively.
BPA levels were significantly higher in the total PCOS group compared with the controls (1.05±0.56 vs. 0.72±0.37 ng/ml, P < 0.001). PCOS women, lean (PCOS-L) and overweight (PCOS-OW), had higher BPA levels compared to the corresponding control group lean (C-L) and overweight (C-OW): (PCOS-L = 1.13±0.63 vs. C-L = 0.70±0.36, P < 0.001) (PCOS-OW = 0.96 ± 0.46 vs. C-OW = 0.72 ± 0.39, P < 0.05). A significant association of testosterone (r = 0.192, P < 0.05) and androstenedione (r = 0.257, P < 0.05) with BPA was observed. Multiple regression analysis for BPA showed significant correlation with the existence of PCOS (r = 0.497, P < 0.05). BPA was also positively correlated with insulin resistance (Matsuda index) in the PCOS group (r = 0.273, P < 0.05).
Higher BPA levels in PCOS women compared to controls and a statistically significant positive association between androgens and BPA point to a potential role of this endocrine disruptor in PCOS pathophysiology.
7) Semin Reprod Med 2012; 30:32–38 .
Ovarian_Actions_of_Estrogen_Receptor_β_ Drummond_2012, Ph.D. 1 Peter J. Fuller, B.Med.Sci., M.B.B.S., Ph.D., F.R.A.C.P. 1 1 Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia
Polycystic Ovarian Syndrome
Polycystic ovary syndrome (PCOS) is a common endocrine
disorder characterized by anovulation, elevated levels of
androgen, hirsutism, and insulin resistance.64,65 Folliculogenesis is arrested at the antral stage of development, and it is the accumulation of these follicles that gives the ovary its
characteristic morphology of a necklace-like pattern of fol
follicles in the periphery. Because estrogen has been shown to be
essential for folliculogenesis beyond the antral stage, it is
perhaps not surprising that ERβ mRNA and protein are
reduced in granulosa cells and theca cells from PCOS patients. 11,66
We hypothesized that changes in the ratio of ERβ
το ERα may result in abnormal follicular development. Similarly,
in a rodent model of PCOS, levels of ERβ protein were
decreased in the granulosa layers of cystic follicles.67 Idiopathic
ovulatory dysfunction has been found to be associated
with a G/A (1730) polymorphism in ERβ.2. Given that ovulatory
dysfunction is a key feature of PCOS, one group investigated
a cohort of PCOS patients to determine if there was an
association with this polymorphism.68 They reported significant
differences in the genotype distribution and allelic
frequencies between controls and PCOS patients that supported a correlation with the G/A polymorphism.68 To date,
the underlying mechanism has not been established.
header image courtesy of Earth Times
BPA in every day products courtesy of Milwaukee Sentinel
BPA in plastics making us sick courtesy of Health Environment Alliance
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
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