The etiology of PCOS, most likely a combination of genetic disposition and environmental factors, is not completely understood (23,24). While familial clustering of PCOS has been well documented, even including a male factor with higher androgen levels in first degree relatives of affected patients (25,26), the search for candidate genes has not come up with obvious culprits (27,28).
While not its cause, insulin resistance plays a pathogenic role in the development of PCOS. Hyperinsulinemia increases ovarian and adrenal steroid hormone production, alters luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, and decreases hepatic sex hormone-binding globulin (SHBG) production, thus increasing free androgen and estrogen levels (Fig. 1) (29). The unopposed estrogens stimulate the proliferation of adipose tissue, which is a source of aromatase and thus vice versa converts androgens into estrogens, further increasing their serum levels and leading to inappropriate gonadotropin secretion (30). Treatment to improve insulin sensitivity should thus be useful in PCOS patients, and, indeed, diet/lifestyle modifications, metformin, glitazone and d-chiro-inositol treatment are effective approaches (2).
The clinical appearances (hirsutism, acne, alopecia, obesity) and biochemical features of PCOS are highly variable in affected women. A case-control cross-sectional study of South Asian and Caucasian PCOS women (31) revealed ethnic differences, presenting more severe clinical manifestations (hirsutism, acne) and a higher insulin resistance in young Asian women, supporting the hypothesis, of ethnic variations in clinical and biochemical features of PCOS. A population of Indian women with PCOS also showed a higher insulin response to a glucose load than age-matched Caucasian PCOS patients (32). Significant differences related to ethnicity were also found in Caribbean-Hispanic and non-Hispanic white PCOS women (33). Hispanic women had an increased insulin resistance and a reduced metabolic clearance rate of insulin compared with non-Hispanics in euglycemic clamp tests. Mexican American women were also shown to be more insulin resistant than white women (34). Another study comparing Maori, Pacific Island and Europeans, found European PCOS women less obese, less insulin-resistant and less prone to present with lipid abnormalities than the two other ethnic groups (35). In addition, Pacific Island women only had little or no acne. A German PCOS cohort was comparable to other Caucasian populations (3).
Diagnosing a woman as having PCOS implies an increased risk for several severe health problems, including endometrial carcinoma, T2DM, dyslipidemia, hypertension and possibly cardiovascular disease (CVD). Furthermore, it has important familial implications for her mother (36) and sisters (37). The diagnosis of PCOS should thus not be assigned lightly, as it
FIGURE 1 Pathopysiology of PCOS. Hyperinsulinemia augments elevated luteinizing hormone (LH) secretion by the pituitary (P), ovarian and adrenal steroid hormone production, and the androgen-induced decrease in hepatic sex hormone binding-globulin (SHBG) synthesis, thus increasing the free fraction of estrogens and androgens. The elevated estrogens increase the proliferation of adipose tissue (AT), which converts androgens to estrogens with its aromatase activity. The unopposed estrogens further disturb gonadotropin regulation of the hypothalamus (HT) and the pituitary, thus creating a vicious cycle of hormonal dysregulation.
could imply life-long treatment and may negatively affect her ability to access healthcare coverage.
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