Polycystic Ovary Syndrome And Environmental Toxins
Karishma Deonarain
Dr. Gabriel Dugue
Polycystic Ovary Syndrome And Environmental Toxins Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder among reproductive age women. It is a “highly prevalent disorder affecting multiple aspects of a woman’s overall health, with long term affects that transcend well beyond the reproductive age” (Lizneva, Suturina, Walker, Brakta, Gavrilova- Jordan & Azziz, 2016). Patients with PCOS demonstrate reproductive abnormalities, marked insulin resistance (with increased risk for obesity), increased risk for type 2 diabetes mellitus, coronary heart disease, atherogenic dyslipidemia, cerebrovascular morbidity (higher blood pressure values, increased thrombotic activity), anxiety and depression. Common presentation of reproductive and endocrine abnormalities include hyperandrogenism (with hirsutism, alopecia, and acne), menstrual cycle dysfunction, chronic anovulation and infertility. The manifestations of PCOS can differ based on age, environmental or geographic factors and ethnic/ racial variations. Because of this, healthcare providers have often hesitated to make the diagnosis of PCOS (Lizneva et al., 2016).DiagnosisIn 2012, the National Institutes for Health undertook a PCOS Workshop in 2012 to create guidelines and criteria for PCOS diagnosis and definition. Building on the Rotterdam criteria they developed in 1990, [requiring the presence of two of the following three findings: 1) signs of clinical or biochemical hyperandrogenism (HA); 2) chronic ovulatory dysfunction (OD); and 3) polycystic ovarian morphology (PCOM), after exclusion of secondary causes], they depicted four phenotypical definitions for PCOS. These definitions are as follows: Phenotype A: HA (clinical or biochemical presence) + OD + PCOM; Phenotype B: HA + OD; Phenotype C: HA + PCOM; Phenotype D: OD + PCOM. Further research showed that patients with phenotype A and B were at highest risk for metabolic dysfunction. These definitions along with the Rotterdam criteria can help providers identify, anticipate, and tailor their treatment plan for patients with PCOS (Lizneva et al. 2016).Manifestations in adolescents and peri-/ postmenopausal women make it difficult to diagnose PCOS as their presentation may differ from those of adult women of reproductive age. According to Lizneva et al., (2016) the disorder in adolescents “could be considered on the basis of the presence of increased serum androgens levels and/or progressive hirsutism, in association with persistence oligo/amenorrhea for at least 2 years after menarche and/or primary amenorrhea by age 16 years, and/or an ovarian volume > 10 cm3, after exclusion of secondary causes”. Meanwhile, peri-/postmenopausal women with PCOS may gain “menstrual cyclicity, experience a decrease in the ovarian volume and number of ovarian follicles… and androgen levels tend to remain higher compared with similarly aged women” (Lizneva et al. 2016).CausesWhile it is important for us, as healthcare providers, to recognize the variable presentation and understand the diagnostic criteria for PCOS, it is also important for us to analyze the possible causes and risk factors of this disorder. The pathophysiology of PCOS is still unclear but current research are focused on evaluating the relationship between the clinical and biochemical features of PCOS and environmental and lifestyle factors. According to Rutkowska and Diamanti- Kandarakis (2016), “the heterogeneity of its features within ethnic races, geographic location, and families suggests that environmental and lifestyle are of prime importance”. Many researchers have focused on exploring the possible links between endocrine disrupting chemicals such as plasticizers and the pathogenicity of PCOS.Endocrine Disrupting Chemicals Endocrine disrupting chemicals (EDC) are “exogenous substances or mixtures that alter function(s) of the endocrine system and consequently cause adverse effects in an intact organism or its progeny or (sub) populations (European Workshop on the Impact of Endocrine Disruptors On Human Health And Wildlife, 1996). This group of molecules have the potential to interact with hormone receptors (like estrogen, androgen, thyroid), proteins that transport hormones (like sex hormone binding globulin), can easily mimic steroid hormones and “interfere with the synthesis, secretion, transport, mechanism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction and developmental process (United States Environmental Protection Agency, 1996). Because of these potential effects, they are considered risk factors in the development of many metabolic disorders, including PCOS.EDCs include persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane; plasticizers such as bisphenol A (BPA), bisphenol F, bisphenol S, and phthalates; pesticides such as atrazine and vinclozin; and flame retardants. These compounds are found in common household items; hence human exposures to EDCs are variant but innumerable. Phthalates, for example, can be found in building materials, household furnishings, clothing, medical devices, dentures, cosmetics, personal care products, pharmaceuticals, nutritional supplements, paint, nail polish, children’s toys, food, dietary supplements, cleaning materials and insecticides; while BPA can be found in items such as baby bottles, water/drink bottles, plastic bags, food containers, cans, dental sealants, medical devices, daily care products (soaps, lotions, shampoo, sunscreen and nail polish) and toys. Although these are all sources of potential BPA exposure, studies have shown that diets high in canned meats and/or vegetables and beverages contained within plastic bottles are the main sources of BPA exposure (Giulivo et al., 2016). These beverages and food items may become contaminated with EDCs when their plasticizer bonds break down with exposure to intense heat. Environmental Toxins and Polycystic Ovary Syndrome Epidemiological and experimental studies as well as clinical evidence and meta-analyses have suggested a correlation between EDCs and major health risks for humans. EDCs can disrupt the body’s hormonal balance because of their molecular similarity to endogenous steroid hormones. Research focused on reproductive repercussions have concluded that there are two possible mechanism of EDC hormonal disruption on female ovulation: 1) by directly affecting the female gonad; and 2) indirectly, by affecting the hypothalamic-pituitary ovarian axis (HPO Axis). BPA, specifically, can affect ovarian steroidogenesis, disrupt the intrafollicular environment and impair maturation of oocytes. Ehrlich et al. (2012) found that higher urinary BPA correlated with reduced maturation of oocytes. Other research have shown that EDC may also be involved in the pathogenesis of anovulation. In human studies of women with PCOS, there was an association between increased serum BPA levels and elevated androgen levels –total testosterone (T), free T, androstenedione and dehydroepiandrosterone (DHEA) (Rutkowska & Diamanti-Kandarakis, 2016). Researchers Hanioka, Jinno, Nishimura and Ando (1998) hypothesized that BPA causes elevated androgens synthesis through stimulation of ovarian theca-interstitial cells while also inhibiting T catabolism, leading to an overall elevation in androgen levels.In addition to length and concentration of EDC exposure, the timing of EDC exposure is crucial to determining health risks. Studies have shown that “fetuses, babies, and/or young children are the most susceptible groups, especially in the early developmental periods. Thus exposure of pregnant women to EDCs possess a high specificity and binding affinity to estrogen-related receptors-gamma, which are highly expressed in the placenta, developing fetus and neonate” (Takeda et al., 2009). In other words, exposure to EDCs pose a potential risk as early as fetal development; BPA from the mother can cross the placenta and affect the development of the fetus. In experimental studies with rats, neonatal exposure to BPA caused endocrine and reproductive alterations resembling PCOS in adulthood (Fernandez, Bourguignon, Lux- Lantos and Libertun, 2010).Other correlation studies showed: 1) significant positive association between increased urine BPA concentrations and higher prolactin and progesterone levels in BPA exposed and unexposed Chinese women (Miao et al., 2015); and 2) elevated BPA levels in PCOS adolescents compared with controls (Akin et al., 2015). BPA has also been implicated in the development of insulin resistance and obesity (which is also manifested in PCOS patients). The environmental obesogenic hypothesis suggests that environmental chemicals contribute to development of metabolic disorders in humans, including obesity, insulin resistance, type 2 diabetes, hepatic injury, dyslipidemia and cardiovascular diseases (Giulivo et al., 2016). For the specific theories on the proposed mechanism of action see table 1. These studies have generated an awareness of the possible negative health impact of EDCs, specifically phthalates and BPA. They have also created a movement towards greater restriction of EDCs in products for specific populations. For example, as a result, the European Commission began to restrict the use of BPA in plastic baby bottles in the European Union. With more research, health care providers can better understand PCOS, and develop treatment and prevention options with regards to EDCs. We can begin to promote public health awareness about the possible negative effects of BPA products.