What is PCOS

The Polycystic Ovary Syndrome is one of the most widespread endocrine pathology among reproductive age female population. PCOS, which has got genetic roots, is featured by a really heterogeneous phenotype, signs and symptoms, where the obesity plays an important role in increasing the prevalence and the severity of the symptoms [1].

Clinical features

Patients with PCOS present alterations of the endocrine, metabolic, gynecologic systems-especially; irregular period, infertility, hirsutism, acne, obesity, insulin-resistance, type 2 diabetes, disliphidemy, endometrial carcinoma, diabetes during pregnancy and pre-term labour and birth or high risk of miscarriage [2].

A glucidic alteration has been found in about 20-35 percent of the women with PCOS, whereas type-2 diabetes occurs in 7-8 percent of the American women with PCOS and in 2-3 percent of the Mediterranean ones [2].

Menstrual disorders are frequently found in patients sufferings from PCOS. Although 30 percent of the women have got a regular menses, 85-90 percent of the other patients show oligomenorrhea and the remaining ones present amenorrhea.

Symptoms connected to hyperandrogenism occurs in more than 80 percent of the women with PCOS: hirsutism is the most common clinical evidence and it affects about 70 percent of the patients [1]. A lot of women observe hair loss as well and 15 percent acne [3].

The evidence in the medical literature shows that PCOS is the most widespread cause of the anovulatory cycle and 40 percent of  PCOS women manifest infertility [3].


The diagnostic criteria have been modified significantly over the years [4].

Nowadays, they do not take into account insulin-resistance (IR), a very important feature of the syndrome which has been found to be connected to the hyperinsulinemia.

In the original  Stein-Leventhal syndrome, obesity was an essential standard to make the diagnosis. NHI and Rotterdam 2003 standards don’t take this clinical signal into consideration. Although obesity is often related to the syndrome, it occurs in only 50 percent of the cases [3]. About  28.3 percent of the overweight women suffer from PCOS and an experience of weight gain often foresee the onset of the clinical manifestation of the syndrome [4].

The typical distribution of fat mass in the body in overweight or obese patients with PCOS affects mainly the central part of the body [4], which is a typical feature of the hyperandrogenism [5],[6].

Numerous studies have highlighted the importance of the distribution of the fat mass in the body as a key  risk indicator of cardiovascular diseases and metabolic ones such as type 2 diabetes [7]. A fat mass distribution around the upper body (android distribution) is related to hyperinsulinism, alteration of the glucose tolerance, type 2 diabetes, increase in the endogenous production of androgens, decrease in the levels of sex binding globulin (SHBG) and an increase of the free testosterone and estradiol  [8],[9].

Adipocytes, obesity, insulin-resistance

Nowadays, fat tissue is considered as endocrinologically active point of view, this means that it is important to govern the lipid and glucose metabolism. Moreover, it has some meaningful influence on the levels of inflammation and on the immune, cardiovascular, and reproductive systems [10].

This pattern of features has been observed both in PCOS obese or overweight patients and in normal-weight ones.

In women with PCOS, studies have shown that visceral-located adipocytes have deviant metabolic and hormonal behavior: they have a reduced insulin activity which is related to altered glucose tolerance, hyperinsulinism, and insulin-resistance.

Although the connection between obesity, insulin-resistance, and PCOS endocrine disorders hasn’t been made clear yet, hyperinsulinemia is considered to be at the root of the pathogenesis and obesity is believed to be a worsening key factor of the clinical features as insulin stimulates the ovary production of androgens and it affects the follicular development [11].

Adipocytes carry out a really important role in the metabolism of the steroidal hormones. These ones, which are viscerally located at the level of the adipose tissue, are able to Δ-4 androstenedione in the testosterone activating the 17-βhydrossideidrogenasis, which fosters the visceral adiposity. Additionally, they are able to turn cortisone into cortisol, its active form, which increases itself the insulin-resistance [17],[12].


Together with the occurrences above described, hyperinsulininemia contributes to modify the balanced axis hypothalamus-hypophysis. The range and the frequency of the gonadotrophin peak is essential to a correct sequence of the ovary occurrences as the follicular recruitment, luteolysis, and the follicular atresia.

At first, FSH stimulates the folliculogenesis and the development of the ovum. During the development (follicular phase), the follicle starts producing an increasing quantity of estrogens, which, through a positive feedback control, releases the gonadotrophin-the LH starts the ovulation. After the ovulation, when the follicle opens and the oocyte is excreted, the luteal phases begins-the follicle turns into the corpus luteum which secretes steroids, especially, progesterone.  It plays an important role in the implantation and the development of the  fertilized ovum. Hyperinsulininemia interferes at this stage because it increases the range and the frequency of the pulsating secretion of the GnRH and LH which results in an increase in the production of synthesis of steroid hormones (especially androgens) in the ovary [13]. The increase of luteal hormone (LH) to value over 10 UI/l and of the ratio of the concentration of LH and FSH (≥3; normal 1-1,6) has been considered a key alteration in PCOS and it affects about 70-80 percent of the patients, in particular the normal weight ones [14].

High levels of insulin have been related to decreased levels of SHBG which govern the bioavailability of the androgens; the same occurs with high levels of glucose and fructose in the diet [15],[16]. To close this vicious circle, in PCOS context, the androgens themselves have been recently considered to be able to modify the frame and the functionality of the skeletal muscle: type 1 muscle fibers, which oxidize more and are more sensitive to the insulin, decrease. Type 2 muscle fibers, which are less glucose prone, increase [17],[18].

Irregular menses and anaovulatory cycles are more frequent and serious in obese women than in normal weight ones, the former  experience greater difficulties in the conception [19].


A diet poor in fibers and rich in fat has been related to hyperandrogenism and hyperinsulininemia with the increase in available free androgens [20]. Other mechanisms based on the diet, have need associated with some alterations of the ovarian functionality,

Advanced glycation end-products (AGEs) have been recognized  as toxic metabolites for the cells. These metabolites come from the metabolism of the carbohydrates and may position themselves in the ovarian tissue- they may provoke oxidative stress and modify ovarian frame and its functionality [21].

Lifestyle and weight-control

A change in lifestyle represents the first line management of PCOS [22] patients one of the main steps, along with a tailored pharmacological  therapy.

As PCOS patients show a significant risk of the onset of the type-2 diabetes, mainly caused by overweight or obesity,  weight loss is the first action to take, most of all for those patients whose weight is really significant.

PCOS patients tent to show a body mass index (BMI) beyond the normal range (19 -24.9 kg/m2).

The majority of the studies has underlined that an even slight reduction in weight of the 5-10 percent of the total body weight has a positive effect on the reduction in the CV risk, Type-2 diabetes, and PCOS endocrine parameters [23],[24]. Weight loss leads back to menstrual regularity in a high percentage of patients and to reduction of the levels of testosterone and free androgens as well [25],[26].

A weight loss is related to an improved general clinical condition as it may determine higher insulin sensitive [27],  reduction in hyperandrogenism [28], reduction in the ovarian volume and in the numbers of follicles [29], and improvement of the ovarian function with the restoration of the ovulation [30].

Findings don’t agree about the connection between weight reduction and LH secretion and hirsutim occurrences [31].

The reduction in the risk of CV has been clearly stated. Studies have shown that an even slight weight loss improves dyslipidemia [32], inflammation  markers [33], and arterial blood pressure [34].

The advantages of weight control in PCOS women has been clearly recognized, but there is no agreement about what the best diet may be, in term of composition of macro and micro-nutrients [35].

Moderate caloric restriction with low-fat macronutrients (about  30 percent of the energy, with about 10 percent of saturated fat  < 300 mg of cholesterol), moderate protein intake (about15 percent and a high content of carbohydrates (55 percent about) together with reasonable and regular exercise may manage obesity and commorbities [36].


Nowadays the concern about other strategies of losing weight has been increasing steadily: they consider, not only caloric restriction, but also a modification of the ratio of the macro-nutrients, with an increase in protein intake and a reduction or modification of type of carbohydrates in the diet.

A reasonable increase in protein intake may seem the most effective way to manage the feeling of satiety  [37], the ad libitum intake of food [38], the increase of postprandial thermo genesis and calorie consumption [39], and on preservation of the lean mass [40].

Only a few studies have made a comparison between the effects of a high-protein, moderate-carbohydrate diet and moderate-protein, high-carbohydrate one: the results have been equivalent in terms of weight reduction, basal insulin and hormonal parameters. A high protein diet has succeeded better in lowering the postprandial of the glucose, the index of the free androgens and in a lesser reduction of the cholesterol of the  high density lipoprotein during the weight maintenance period [41].

According to another study, a low-carb diet (about 20-30 gr a day) may guarantee and a more considerable weight reduction in individuals with hyperlipidemia, types 2 diabet, than a low calorie diet with the same calorie intake. But this type of diet is considered to have a low compliance and sustainability [42],[43]  as weight reduction isn’t likely to be maintained in a long term perspective (12-36 months).

Findings have stated that a change of type of carbohydrates in the diet-thus changing the glygemic index (GI) the glycemic load (GL), may lower the risk of cardiovascular diseases, guarantee the weight maintenance, and increase the feeling of satiety of the patients [44].

In overweight individuals without PCOS, but suffering from postprandial insulinemia, a low glycemic load (GL) diet has helped to lose weight and maintain the result [45]. So, a limited insulin stimulation after a meal has been considered to favor a greater fat oxidation longer after the meal, to lower the feeling of huger and as a consequence, to lower the exaggerate food intake [46] which take back to the original weight. As PCOS patients show a pronunced compensatory hyperinsulinemia after the carbohydrate intake, a low GI and GL diet may bring some advantages.

Conversely, Mavropoulos J. et al., have stated that ketogenetic diet-with a maximun of 20 gr of carbs per day for 6 months [47], brings about weight loss,  reduction circulating testosterone, reduction of the ratio LH/FSH, and reduction of basal insulin. This study, which has been carried out among a small number of individuals (5 women with PCOS and with BMI > 25), needs further in-depth analysis to understand clearly weather these advantages depends on the weight loss or the carb restriction.


Exercise represents up to 30 percent of the energy consumption of the body. It has been considered responsible for weight maintenance in the long term together with an adequate diet.

Thomson RL. et al. have compared the datas from the analysis of obese or overweight PCOS  which had been treated with: diet only, diet and aerobic exercise, diet and aerobic and endurance exercise. This study has highlighted that diet may reduce the weight, lower the risk of CV, improve the hormonal condition and the reproductive functionality. Diet and regular exercise don’t bring to any substantial improvements of the above stated benefits but they entail a better body composition with a reduction in the fat mass [48] by about 45 percent.

Recently, Vigorito et al have carried  out a well organized resistance training program with a large group of PCOS women: physical conditions have probed to be better, IR, BMI, waist circumference and inflammatory states have been lowered [49].

A few studies have evaluated that also the resistance exercise determine an improvement in the insulin sensitivity as a result of the increase in the muscle mass and the number of proteins which convey glucose (GLUT-4) [50], whereas the aerobic exercise increase the availability of the glucose with more capillaries in the skeletal muscle, improves the blood circulation and determines an improvement in the activity of the hexokinase and of the glycogenesis. It is clear that the endurance exercise (against the resistance) has been getting more and more acknowledged as further therapy-along with aerobic exercise, to  treat obesity and related metabolic anomalies. In the individuals with IR, mixed  training programs (aerobic and endurance) have led to a greater IR reduction than the only aerobic one [51], and to a greater reduction in the body fat mass, especially the abdominal visceral one, and at the same time, to a maintenance or an increase in the lean body mass.


In conclusion, the Polycystic Ovary Syndrome presents a complex clinical physiophatological condition which has been related to both reduced fertility, and-in the long term, also to the risk of developing cardiovascular or metabolic diseases such as type 2 diabetes.

Findings have all reported that a proper lifestyle, in terms of healthy diet and exercise, may exert beneficial effects on PCOS symptoms and may influence the onset of related disorders.

Although, guidelines about an appropriate diet for PCOS patients haven’t been drawn up yet, datas suggest that a dietary and nutritional treatment along with regular exercise (reduction in total energy intake, reduction in total fat intake, most of all the saturated one and cholesterol)  play a key role in improving the condition of the insulin-resistance and hyperandroginism [52].


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