1. Introduction

Polycystic ovary syndrome (PCOs) is the most common reason of androgen excess in reproductive-age women with a prevalence of 6.5–8% according to clinical appearance [1] or even up to 20% by sonographic evidence [2].

For the first time, Stein and Leventhal described it in the year 1935 [3]. Year after year, the description of the disease developed; in 1990, the National Institutes of Health (NIH) mentioned oligo-ovulation and hyperandrogenism with or without hyperandrogenemia (HA) must be together (of course, after exclusion of another causes of androgen excess) [4].

Another expert meeting in 2003 expanded the NIH definition of PCOs by adding the sonographic aspect of the disease (Rotterdam criteria) [5]. According to their criteria, two of three signs/symptoms are necessary for PCOs diagnosis; therefore, PCOs woman can be ovulatory with regular menstruation.

More recently, the Androgen Excess Society (AES) advocated that all of the signs and symptoms should be present for the confirmation of diagnose [6] (Table 1).

Contrary to physicians' and patients' belief, weight or body mass index (BMI) had never been a part of PCOs definition.

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3. Insulin and PCOs

diabetes mellitus (T2DM) [24].

lean PCOs.

background associated with this discrepancy.

For the first time in 1980, the relation between this syndrome and insulin was determinate [23]. Clinically insulin resistance (IR) is specified as inability of a known amount of endogenous or exogenous insulin to enhance glucose uptake and consumption. As a result of a misbelief that IR always accompanies with obesity, in clinical practice, IR is underestimated in non-obese PCO women. IR is a common character between obese and non-obese PCO patients and its overall prevalence is 50–75%. Up to 35% of PCOs women have IGTT and 7–10% are type 2

Lean Women with Polycystic Ovary Syndrome http://dx.doi.org/10.5772/intechopen.70621 25

At now, the most used IR indices are homeostasis-model assessment (HOMA) and insulinemic 2-h area under the curve (AUCi 2 h), both derived from oral glucose tolerance test (OGTT) [25]. The 120-min glucose and insulin evaluation (HOMA-M120) is the best IR index in lean PCOs women according to Morciano et al. study [26]. Meanwhile, there are several earlier studies about IR evaluation in lean PCOs women [27–29]. Although, a study in a large group of European lean PCOs patients displayed that this group had significantly less IR compared with obese PCO women [30]; but, instead of it, there is evidence that in American and Asian PCOs women, IR is independent from BMI [31]. It seems that dietary composition and ethnic

Owing to another recent study, the crucial role of insulin in PCO pathogenesis emphasized that IR shall be evaluated even in normal weight and lean PCOs patients [12].

As suggested in the earlier study [32], hyperinsulinemia stimulates ovarian P450c17 alpha activity in non-obese women with PCOs, which means more conversion of progesterone to androstenedione which is changed to testosterone. In granulosa cell, insulin intensifies their response to LH. Therefore, these cells experience premature arrest of follicular growth and abnormal differentiation, and thus anovulation. Also, elevated insulin resistance causes hyperglycemia which leads to hyperinsulinemia and it can increase LH action on theca cells and subsequent elevation in androgen level. Hyperinsulinemia, insulin resistance, and enhancement in androgen production are the famous pathophysiology triads in PCOs. From another side, elevated level of insulin prevents hepatic sex hormone-binding globulin (SHBG) production, which can lead to elevated free androgen and again elevated level of insulin, a positive feedback in an undesirable circle. Thus, IR and hyperinsulinemia are the principal pathological

As insulin resistance has fundamental role in non-obese PCOs patients, then metformin administration have a beneficial effect on them and regulate their menstruation cycle [33]. As well, there is a new therapeutic option: inositol, a precursor component of second messenger for follicle-stimulating hormone (FSH), thyroid - stimulating hormone (TSH), and insulin receptor. This drug can overcome IR from another way [34]. It is important to mention that only 15% of women with IR are having PCOs criteria; therefore, insulin resistance cannot be the only pathophysiologic pathway [35] and metformin administration may not be effective in all of

causes of this syndrome, and hyperandrogenemia is their consequence.

function, nonclassical adrenal hyperplasia, hyper prolactinemia, drug-induced androgen excess, androgenic neoplasm, Cushing syndrome, growth hormone excess).

1 European Society for Human Reproductive Medicine.

2 American Society for Reproductive Medicine.

Table 1. Different definition of polycystic ovary syndrome.

According to epidemiological data, there is a wide variation in the prevalence of obese and non-obese PCOs women: in Korean population 20%, in Europe 27–50.5%, and in USA 67% of PCOs woman are obese [7–11]. Regarding to different ethnicity, the prevalence of normal weight and underweight patients with PCOs has been reported 1.5–6.6% [12, 13]. Entirely, by using Rotterdam criteria, the overall prevalence of PCOs is increasing because ovulatory or non-hyper androgen PCO patients also are considered [14].

By definition, women with BMI ≤ 25 are non-obese and with BMI > 25 considered obese.

Although at now, we have a few reports about the prevalence of non-obese PCOs patients, but attention toward those patients and their metabolic and health problems are enhanced day by day.

The pathophysiology of PCOs is multifactorial and manifests the final effect of genetic, fetal, environmental, and metabolic factors. As a result of weakness or strength of each factor, clinical and subclinical character and their response to therapeutic efforts will be different.
