https://gynecology.gr/userfiles/file/scientific-studies/eshr_asrm_pcos.pdf

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

/pdf/overweight-obesity-and-cancer-epidemiological-evidence-and-3aap682afc.pdf

Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.

Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding).1In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only non-hirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism.1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia.1-4 These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.3 5 6 

The presence of polycystic ovaries is necessary for the development of the syndrome but not all women with polycystic ovaries have PCOS. The typical …

Polycystic ovary syndrome.

Objective: The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. Participants: Participants included expert investigators in the field. Evidence: Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. Consensus Process: The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. Conclusions: Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that...

https://www.ae-society.org/pdf/guidelines/Criteria.pdf

Position statement: Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An androgen excess society guideline

Summary
objective Obese women with poiycystic ovary syndrome have a greater frequency of menstrual disturbance and of hirsutism than lean women with the syndrome. initial studies have demonstrated a marked improvement in endocrine function following a short-term, very low calorie diet. The purpose of this study was to examine the effect of long-term calorie restriction on clinical as well as biochemical abnormalities in obese women with polycystic ovary syndrome.

design We performed a wlthin-groupcomparison of ciinical and biochemical indices before and during dietary treatment.

patients Twenty-four obese women with polycystic ovary syndrome (mean weight 91·5 (SD 14·7) kg) were scheduled for treatment for 6–7 months with a 1000 kcal, low fat diet. Nineteen of the 24 had menstrual disturbances, 12 had infertility and 19 were hirsute.

measurements and results Thirteen subjects lost more than 5% of their starting weight (range 5·9–22%). in this group there was no significant change in gonadotrophin or total serum testosterone levels but there was a marked increase in concentrations of sex hormonebinding globulin (pretreatment: 23·6 (9·5); post-treatment 36·3 (11·8) nmol/l, P= 0·002) and a reciprocal change in free testosterone levels (77 (26) vs 53 (21) pmol/l, P= 0·009). These changes were accompanied by a reduction in fasting serum insulin levels (median (range) 11·2 (5·2–32) vs 2·3 (0·1–13·8) mU/l, P= 0·018) and the insulin response to 75 g oral glucose. There were no significant changes in these indices in the group who lost < 5% of their inltiai body weight.

Of the 13 women who lost > 5% of their pretreatment weight, 11 had menstrual dysfunction. Amongst these women, nine of 11 showed an improvement in reproductive function, i.e. they either conceived (five) or experienced a more regular menstrual pattern. There was a reduction in hlrsutism in 40% of the women in this group. By contrast, in the group who lost less than 5% of their initial weight, only one of the eight with menstrual disturbances noted an improvement in reproductive function and none had a signtficant reduction in hirsutism.

conclusions These data indicate that moderate weight loss during long-term calorie restriction is associated with a marked clinical improvement which reflects the reduction in insulin concentrations and reciprocal changes in SHBG. The improvement in menstrual function and fertility may therefore be consequent upon an increase in insulin sensitivity which, directly or indirectly, affects ovarian function.

Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome

Improvement in Endocrine and Ovarian Function During Dietary Treatment of Obese Women With Polycystic Ovary Syndrome

OBJECTIVE Insulin insensitivity is a recognized feature of polycystic ovary syndrome (PCOS) but previous studies have suggested that circulating insulin concentrations are normal in hyperandrogenaemic women with regular cycles. The aim of this study was to examine the relationship between insulin sensitivity and menstrual pattern in women with PCO. DESIGN A cross-sectional study of insulin sensitivity in a cohort of PCO subjects with oligomenorrhoea compared to women with PCO and regular menstrual cycles and a group of normal control subjects. SUBJECTS Seventy-two women with polycystic ovaries on ultrasonography were studied. PCO subjects had clinical and/or biochemical evidence of hyperandrogenism; 53 had oligo/amenorrhoea (olig) and 19 had regular menses (reg). Results were compared with 31 control subjects. The groups were matched for age, weight and ethnic origin. METHODS Glucose and insulin responses to 75 g oral glucose were measured. Insulin sensitivity was assessed by the decline in plasma glucose following intravenous insulin (0.05 U/kg). RESULTS Glucose area (mean +/- SEM) after oral glucose was increased slightly in both PCO groups compared with controls (olig 37.6 +/- 1.4, reg 36.0 +/- 1.8, control 33.7 +/- 0.9 mmol/l h, both P < 0.01). Insulin area median (interquartile range) in response to glucose was significantly greater in the oligomenorrhoeic group (346 (239-734) mU/l h), compared with both PCO with regular cycles (246 (148-355), P < 0.01) and controls (221 (147-277), P < 0.01). Insulin sensitivity was reduced (P < 0.01) in the oligomenorrhoeic group (147 +/- 9.2 mumol/l min) compared to controls (185 +/- 7.4) but was normal in PCO with regular cycles (182 +/- 12.5). Insulin sensitivity did not correlate significantly with plasma testosterone or with SHBG levels, but plasma insulin concentrations correlated negatively with SHBG levels (fasting insulin vs SHBG, r = -0.47, P < 0.01; insulin area vs SHBG, r = -0.41, P < 0.01). CONCLUSIONS Insulin insensitivity in polycystic ovary syndrome occurs when there is oligo/amenorrhoea but not when the menstrual cycle is regular. This is consistent with PCO and insulin insensitivity being separate abnormalities which when combined are associated with anovulation.

The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries.

OBJECTIVE Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history. DESIGN A cross-sectional study of insulin sensitivity and lipids in a cohort of PCO subjects compared to weight and ethnic group matched controls. PATIENTS AND METHODS We have therefore investigated glucose tolerance, plasma lipids and lipoproteins in 19 lean (LP) and 55 obese (OP) patients with PCO and compared the results with those in 22 lean (LC) and 15 obese (OC) control women. Insulin sensitivity was measured in the same subjects with a short insulin (0.05 U/kg i.v. insulin) tolerance test (LP, n = 18; OP, n = 20; LC, n = 19; OC, n = 11). RESULTS Results are expressed as mean +/- SEM or median (interquartile range). Fasting plasma glucose levels were similar in the four groups but the plasma glucose area was higher after oral glucose (75 g) in both the lean and obese PCOS groups than in their controls (LC 32.4 +/- 0.7 vs LP 35.2 +/- 1.2, P < 0.01; OC 34.7 +/- 1.8 vs OP 37.8 +/- 1.5 mmol/l/3 h, P < 0.01). Insulin sensitivity was significantly reduced in obese PCOS women (LC 196 +/- 9 vs LP 179 +/- 9, NS; OC 168 +/- 12 vs OP 133 +/- 9 mmol/l/min, P < 0.01). Total serum cholesterol levels were similar in the four groups but HDL2-cholesterol was reduced in both obese and lean PCOS (LC 0.42 (0.38-0.62), LP 0.31 (0.26-0.44), P < 0.05; OC 0.34 (0.21-0.47), OP 0.21 (0.12-0.32) mmol/l, P < 0.01). Total HDL-cholesterol was decreased significantly only in the obese PCOS group. Body mass index correlated significantly and negatively with total HDL-cholesterol and with HDL2-cholesterol levels both within the PCOS group and the control women. Using multiple regression insulin insensitivity contributes significantly beyond BMI to the low HDL-cholesterol in women with polycystic ovaries. CONCLUSION Polycystic ovary syndrome is associated with biochemical risk factors for premature vascular disease, which cannot be explained by obesity alone.

A. Bush

Papers

Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome

Improvement in Endocrine and Ovarian Function During Dietary Treatment of Obese Women With Polycystic Ovary Syndrome

The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries.

Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries

The role of nutrition and insulin in the regulation of sex hormone binding globulin.