**4. Metabolic syndrome and polycystic ovary syndrome**

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including impaired fasting glucose, central obesity, dyslipidaemia and raised blood pressure [30]. Ever since the metabolic syndrome was described by Reaven in 1988 [31], at least six diagnostic definitions have been published by different organizations. In this respect, although there is a general agreement regarding the main components of the MetS including abnormalities in glucose metabolism (insulin resistance, hyperinsulinemia, glucose intolerance, diabetes mellitus), central obesity, and cardiovascular risk factors (hypertension, increased triglyceride, de‐ creased HDL cholesterol), this variation requires different cut-off points and inclusion criteria [30]. Table 1 shows most important definition of MetS according to World Health Organization (WHO) [32], and International Diabetes Federation (IDF) [33] criteria.

It has been shown that the combination of different components of MetS may predict a higher risk for cardiovascular than individuals and insulin resistance plays as a common link between these coexisting abnormalities [34].

The MetS affects roughly 25% of adults over the age of 20 y and up to 45% over age 50 y [35-37]. Some studies reported that during the last decade, the prevalence of MetS has increased in the general population, especially among young women [38]. However, this incremental trend may be attributable not only to anthropometric differences between diverse ethnicity, but also to differences in the criteria used for MetS diagnosis. Mechanisms underlying the metabolic syndrome are not completely clear. There is no single etiology of the MetS. Hyperinsulinemia, the most accepted and unifying hypothesis and a cornerstone of the syndrome [30],, results from interplay between environmental and genetic factors. Excess caloric intake and lack of physical exercise, combined with a predisposition to visceral adiposity, play a key role in the development of a pro-inflammatory insulin-resistant state that generates the clinical features of the MetS [37, 39]. However, the relationship between PCOS and MS is possibly mutual [34]. Majority of women with PCOS present clinically with at least one component of the metabolic syndrome [40]. In this respect, the prevalence of MetS among PCOS women is 43%-53%; approximately 2-fold higher that general women population [40]. However, the pathophysi‐ ology that may link are not fully understood. Possible hypothesis regarding the association include: (I) insulin resistance underlies the pathogenesis of both the metabolic syndrome and PCOS; (II) obesity and related adipose tissue factors, independently of insulin resistance, are the major pathogenic contributors to both conditions; and (III) vascular and coagulation abnormalities are the primary pathogenic contributors to both conditions.

liver, as a result lead to increase in free androgen level. Third, insulin may affect ovarian follicle

Decrease in SHBG level affected the concentration of estron and free estradiol in women with PCOS. Due to none fluctuated production of estrogen, pituitary receive both positive feedback for LH secretion and negative feedback for secretion of FSH. As a result, the LH-FSH ratio increases. LH has pulsatile pattern. In women with PCOS, the frequency of LH secretion is increase. This change happens in response to receiving stmilution by GnRH and increase bioavailabilty of LH. The high level of LH, lead to ovarian hyperplasia and production of androgen from ovarian stromal and tecal cells. This condition fixes the chronic anovulation. It is not clear that the impairment in hypothalamic-pituitary-ovarian axis leads to PCOS or this

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including impaired fasting glucose, central obesity, dyslipidaemia and raised blood pressure [30]. Ever since the metabolic syndrome was described by Reaven in 1988 [31], at least six diagnostic definitions have been published by different organizations. In this respect, although there is a general agreement regarding the main components of the MetS including abnormalities in glucose metabolism (insulin resistance, hyperinsulinemia, glucose intolerance, diabetes mellitus), central obesity, and cardiovascular risk factors (hypertension, increased triglyceride, de‐ creased HDL cholesterol), this variation requires different cut-off points and inclusion criteria [30]. Table 1 shows most important definition of MetS according to World Health Organization

It has been shown that the combination of different components of MetS may predict a higher risk for cardiovascular than individuals and insulin resistance plays as a common link between

The MetS affects roughly 25% of adults over the age of 20 y and up to 45% over age 50 y [35-37]. Some studies reported that during the last decade, the prevalence of MetS has increased in the general population, especially among young women [38]. However, this incremental trend may be attributable not only to anthropometric differences between diverse ethnicity, but also to differences in the criteria used for MetS diagnosis. Mechanisms underlying the metabolic syndrome are not completely clear. There is no single etiology of the MetS. Hyperinsulinemia, the most accepted and unifying hypothesis and a cornerstone of the syndrome [30],, results from interplay between environmental and genetic factors. Excess caloric intake and lack of physical exercise, combined with a predisposition to visceral adiposity, play a key role in the development of a pro-inflammatory insulin-resistant state that generates the clinical features of the MetS [37, 39]. However, the relationship between PCOS and MS is possibly mutual [34]. Majority of women with PCOS present clinically with at least one component of the metabolic syndrome [40]. In this respect, the prevalence of MetS among PCOS women is 43%-53%; approximately 2-fold higher that general women population [40]. However, the pathophysi‐

maturation, lead to ateresia, and increase level of androgen [22].

82 Contemporary Gynecologic Practice

disturbance happen as an outcome of PCOS [21, 22, 27-29].

**4. Metabolic syndrome and polycystic ovary syndrome**

(WHO) [32], and International Diabetes Federation (IDF) [33] criteria.

these coexisting abnormalities [34].


**Table 1.** Definitions of MBS for women, according to WHO, NCEP ATP III and IDF criteria

Insulin resistance is the major underlying pathophysiologic abnormality linking the metabolic syndrome and PCOS. Indeed, the co-morbidities associated with insulin resist‐ ance are well-known to be common to both conditions [41, 42]. Nevertheless, it is likely that a combination of various factors interacts with or results from insulin resistance to manifest the metabolic abnormalities of the metabolic syndrome and PCOS. In addition, genetic susceptibilities and genetic polymorphisms or mutations likely contribute to the expression of these manifestations [43].

Although PCOS and MetS often coexist, several factors have been shown to predict the risk of metabolic syndrome among women with PCOS. Among these factors fasting insulin, obesity and family history of diabetes have the capacity for prediction of metabolic syndrome in women with PCOS [44, 45].

It seems that it is reasonable to assess the components of MetS in women with PCOS; however there is no consensus on the methods and interval of these assessments [43]. Assessments of blood pressure, waist circumference and/ BMI, fasting lipid profile, Fasting glucose and glucose tolerance by a 2-hour oral glucose tolerance test have been suggested and aboratory studies for cardiovascular risk markers such as C-reactive protein and homocysteine are recommend [46, 47]. There were therapeutic overlap between PCOS and MetS. *Weight loss with life-style modification* is the safest and cheapest therapy that has shown benefit both in MetS and PCOS.

Reduction of insulin resistance is the primary goal for Weight loss in women with PCOS. Lifestyle modification through increased physical activity and reduction in body weight, especially waist circumference, represents the first-line therapy for MetS in PCOS. Successful mainte‐ nance of exercise and weight loss can lower blood pressure, central adiposity, and very low density lipoprotein cholesterol while improving lipid profile and insulin sensitivity [21, 48]. *Medical therapies for insulin resistance* with pharmacological approaches like metformin improve insulin sensitivity, glucose control and even reproductive abnormalities. Also metformin could decreases weight and BMI, blood pressure and LDL cholesterol [49, 50].

However, evidence has demonstrated that a combination of metformin and lifestyle modifi‐ cation improves the metabolic profile in women with PCOS to a greater degree than either measure alone [51].
