**2. Pathogenesis**

The pathogenesis of PCOS are not fully understood, it seems that there are many different factors are associated with PCOS.

## **2.1. Gene's role**

Some studies suggest that genetic plays an important role in pathogenesis of PCOS. The high prevalence of women with PCOS and the wide range of phenotypes can be explained by the interaction of key genes with environmental factors [18, 19]. There are some evidences showed that there are association between cytochrome P450 17-hydroxylase/17, 20-desmolase (CYP17) and PCOS. Cytochrome P450 side-chain cleavage enzyme (CYP11A) is another candidate gene that some studies find a role for it in PCOS. This gene encodes the cholesterol side-chain cleavage enzyme. Mutation in cytochrome P450 21-hydroxylase (CYP21) gene has found to have a role in PCOS in studies. This gene encodes 21-hydroxylase, which is responsible for most cases of congenital adrenal hyperplasia (CAH) [20].

#### **2.2. Obesity-insulin**

Approximately 50% of women with PCOS are overweight or obese and most of them have the android obesity. Obesity may play a pathogenetic role in the development of the PCOS in women through disturbances in insulin and androgenesis.

Accumulation of adipose tissue mass around abdomen increases the availability of metabo‐ lites, which are able to affect the secretion, the metabolism, and peripheral action of insulin. Insulin, together with liver, adipose tissue and muscles, plays a role in the regulation of ovary. At ovarian level, insulin stimulates ovarian steroidogenesis by interacting with insulin and insulin growth factor type I receptors, in granulosa, thecal and stromal cells. Insulin increases 17-hydroxylase and 17-20 lyase activity and stimulates the expression of 3-hydroxysteroid dehydrogenase in granulosa cells. In addition, insulin seems to increase the sensitivity of pituitary cells to gonadotropin releasing hormone (GnRH) action and by increase the number of the luteinizing hormone (LH) receptor, increase the ovarian steroidogenic response to gonadotropins. Also, insulin is able to reduce sex hormone binding globulin (SHBG) synthesis in liver and ovary. IGFBP-1 regulates ovarian growth and cyst formation and adrenal steroi‐ dogenesis [21].

## **2.3. IGFs**

disorders [10]. These criteria reflected differences in defining PCOS which could affect

Despite PCOS being considered the most common endocrine disorder, the estimation of its prevalence is highly variable, ranging from 2.2% to 26.7% [11-13], due to differences in the presentation of PCOS phenotype methods [12]. In a study in Iran, a total of 646 reproductiveage women were assessed by Rotterdam, Androgen Excess Society, and NIH criteria, the prevalence of PCOS were 14.1%, 12%, and 4.8% respectively [14]. In a study from china, levels of luteinizing hormone and higher luteinizing hormone/follicle-stimulating hormone ratios were used for defining PCOS for 915 women in reproductive age, the results demonstrated 2.2 % prevalence [14]. In a study from china, levels of luteinizing hormone and higher luteinizing hormone/follicle-stimulating hormone ratios were used for defining PCOS for 915 women in reproductive age, the results demonstrated 2.2 % prevalence [11]. The prevalence based on NIH criteria in an unselected population black and white women in the southeastern United States were 3.4% and 4.7% respectively [15]. Using same criteria, the prevalence of PCOS was

The pathogenesis of PCOS are not fully understood, it seems that there are many different

Some studies suggest that genetic plays an important role in pathogenesis of PCOS. The high prevalence of women with PCOS and the wide range of phenotypes can be explained by the interaction of key genes with environmental factors [18, 19]. There are some evidences showed that there are association between cytochrome P450 17-hydroxylase/17, 20-desmolase (CYP17) and PCOS. Cytochrome P450 side-chain cleavage enzyme (CYP11A) is another candidate gene that some studies find a role for it in PCOS. This gene encodes the cholesterol side-chain cleavage enzyme. Mutation in cytochrome P450 21-hydroxylase (CYP21) gene has found to have a role in PCOS in studies. This gene encodes 21-hydroxylase, which is responsible for

Approximately 50% of women with PCOS are overweight or obese and most of them have the android obesity. Obesity may play a pathogenetic role in the development of the PCOS in

Accumulation of adipose tissue mass around abdomen increases the availability of metabo‐ lites, which are able to affect the secretion, the metabolism, and peripheral action of insulin.

reporting, diagnosis and treatment of it.

almost 6.5% between Caucasian and Greek women [16, 17].

most cases of congenital adrenal hyperplasia (CAH) [20].

women through disturbances in insulin and androgenesis.

**1.1. Epidemiology**

80 Contemporary Gynecologic Practice

**2. Pathogenesis**

**2.1. Gene's role**

**2.2. Obesity-insulin**

factors are associated with PCOS.

IGF-I and IGF-II may be involved in the pathogenesis of the hyperandrogenism in the women with PCOS. IGFs are able to stimulate ovarian progesterone and estrogen secretion and increase the aromatase activity. In normal weight PCOS women, IGF bioavailability seems to be increased. But, in obese women with PCOS, IGF-1 bioavailability has been reduced. It could be suggested that insulin resistance and hyperinsulinemia may play a central role in obese PCOS patients; however disturbance of the IGF-IGFBP system may be important in normalweight PCOS women [21-23].

#### **2.4. SHBG**

Sex hormone binding globulin (SHBG) is a glycoprotein that regulate circulating concentra‐ tions of free sexual steroid hormones and their transport to target tissues [24]. The concentra‐ tions of SHBG are regulated by a number of factors such as cortisol, estrogens, iodothyronines and growth factors, and decreased by androgens, insulin, prolactin and IGF-I [25]. SHBG concentration reduced specially in women with PCOS influence by hyperinsulinemia. Therefore, the free androgens increase at the level of peripheral tissues [21].
