Eleni Palioura

Endocrine Disruptors and Polycystic Ovary Syndrome (PCOS): Elevated Serum Levels of Bisphenol A in Women with PCOS

CONTEXT 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. OBJECTIVE 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. RESULTS 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). CONCLUSIONS 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.

Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs)

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure.

Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management.

Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins). Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification.

Impact of androgen and dietary advanced glycation end products on female rat liver.

Background/Aims: Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. Methods: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Results: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (γGT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (p<0.01) when compared to the respective low-AGE group, while aspartate aminotransferase (AST) levels were affected only in non-androgenized animals (p=0.0002). Androgenization per se constitutes an aggravating factor as demonstrated by the elevated γGT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007). Conclusion: The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions.

Endocrine disruptors and polycystic ovary syndrome: a focus on Bisphenol A and its potential pathophysiological aspects.

Abstract Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unknown etiology that may arise from a combination of a number of underlying genetic interactions and predispositions with environmental factors. Endocrine disruptors and, in particular, Bisphenol A may represent one of the many underlying causes of the syndrome as they are experimentally linked to metabolic and reproductive derangements resembling PCOS-related disorders. Exposure to endocrine-disrupting chemicals may act as an environmental modifier to worsen symptoms of PCOS in affected females or to contribute to the final phenotype of the syndrome in genetically predisposed individuals.

Developmental Exposure to Endocrine Disruptors and Ovarian Function

Τhe developing organism is particularly sensitive to environmental insults that can permanently reprogram normal physiology leading to long-term functional aberrations. With regard to the female gonad, any disruption of the complex regulatory mechanisms that control ovarian development/function could provoke disorders of normal steroidogenesis, folliculogenesis, ovulation, and, finally, female fertility. Endocrine-disrupting chemicals are among the factors that are incriminated to have an adverse impact on several aspects of ovarian biology. Through their capacity to mimic or antagonize natural hormones, this diverse class of chemicals is believed to interfere in the early stages of gonadal development. This chapter summarizes experimental evidence linking pre/peripubertal exposure (prenatal and/or early life until puberty exposure) to environmental chemical contaminants and perturbations in ovarian development and function.