Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive-aged women. Deranged luteinizing hormone levels and associated downstream signaling cascade mediated by its receptor luteinizing hormone chorionic gonadotropin receptor (LHCGR) are pivotal in the etiopathogenesis of PCOS. Genetic variations in the LHCGR have been associated with PCOS risk. However, the results are mixed and inconclusive. We evaluated the association of the LHCGR rs2293275 polymorphic variant with PCOS risk and its association with clinico-biochemical features of PCOS. 120 confirmed PCOS cases and an equal number of age-matched controls were subjected to clinical, biochemical, and hormonal investigations. Genotyping for rs2293275 was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models were used to calculate odds ratios (ORs) at 95% confidence intervals (95% CIs). In the current study, PCOS cases reported a lower number of menstrual cycles per year than respective controls. A significantly higher BMI, Ferriman Galway score, levels of serum testosterone, insulin, TSH, FSH, and fasting glucose were observed in cases than in controls (p < 0.01). Compared to GG carriers, we observed a higher risk of developing PCOS in the subjects who harbored GA (OR 10.4, p < 0.0001) or AA (OR 7.73, p = 0.02) genotype. The risk persisted in the dominant model (GA + AA) as well (OR 10.29, p = 0.01). On stratification, a higher risk of developing PCOS was observed in variant genotype carriers who had a family history of either type two diabetes mellitus (OR 117; p < 0.0001) or hirsutism (OR 79; p < 0.0001). We also found significantly elevated levels of serum LH levels in the subject harboring GA and AA genotypes when compared to GG carriers. In the present study, we report a significant association of the LHCGR rs2293275 variant with the PCOS risk.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.

Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue.

Women with type-2 diabetes (DM2) are at high risk of cardiovascular disease (CVD) which may be partly due to increased ovarian androgen production. Since the association of bilateral oophorectomy (BSO) with CVD remains controversial, we evaluated whether BSO is inversely associated with CVD among DM2.

Data were obtained from a national sample of 9599 postmenopausal women. Adjusted estimates and 95% confidence intervals (CIs) were calculated using logistic and Cox regression.

At baseline 2426 women had type-2 diabetes, of whom 580 had BSO. DM2 had adverse CVD risk profiles compared to women without diabetes, as did women with BSO with or without diabetes compared to those with intact ovaries. In DM2, BSO was positively associated with prevalent CVD (odds ratio: 1.63, 95%CI: 1.16-2.30). However, the higher odds were limited to women who had BSO before age 45 years (OR: 2.11, CI: 1.45-3.08). During a mean follow-up of 12.7 years, BSO in DM2 was positively associated with CVD mortality (hazard ratio: 2.23, CI: 1.25-3.99). Among women with BSO, those with family members who had MI before age 50 had elevated odds of CVD (OR: 2.29, CI: 1.56-3.37) compared to those without such family history (OR: 0.90, CI: 0.67-1.20), Pinteraction=0.04.

The risk of CVD is increased not decreased with BSO in DM2. Further, we propose that the association of BSO and CVD in young women with diabetes may partly reflect genetic susceptibility to CVD rather than an effect of ovarian hormones.

To evaluate insulin sensitivity and β-cell function in Chinese polycystic ovary syndrome (PCOS) women while taking into account the confounding variables including body mass index (BMI), blood glucose levels, ethnicity, medication history and a family history of type 2 diabetes.

Cross-sectional analysis.

Clinical research center in China.

76 PCOS women and 20 age-matched healthy control women.

No.

All subjects underwent botnia euglycemic-hyperinsulinemic clamp to assess their insulin sensitivity expressed as M value and β-cell function expressed as deposition index (DI).

Compared with age-matched controls, both DI and M (p < 0.05, respectively) value were lower in PCOS group with normal glucose regulation (NGR), and they (p < 0.05, respectively) were the lowest in PCOS group with impaired glucose regulation (IGR). The subgroup analysis showed that compared with normal-weight controls, DI (p = 0.072) was similar but M value (p < 0.05) was lower in normal-weight PCOS group with NGR, and DI (p < 0.05) and M value (p < 0.05) were lower in overweight PCOS group with NGR. DI and M value (p < 0.05, respectively) of overweight PCOS group with IGR were the lowest among all groups.

There was insulin resistance but not impaired β-cell function in Chinese normal-weight PCOS women with NGR. Insulin resistance may be an intrinsic factor prior to impaired β-cell function of PCOS.

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, P<0.05), lower M value but similar HOMA-βad index, while overweight/obese PCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, P<0.05) and PPG (6.15±0.84 vs. 5.44±0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-βad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-βad index in PCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

The "Barker hypothesis" suggests that low birth weight might predict future risk of developing obesity, cardiovascular disease, and type 2 diabetes. Identification of the causes of fetal growth restriction (FGR) is critical for preventive and management strategies. Some studies indicate that maternal carbohydrate metabolism might be involved in FGR development. We aimed to evaluate, in a large number of normotensive pregnant women with normal glucose tolerance, the effect of insulin sensitivity and β-cell function on unexplained fetal growth. A total of 1,814 Caucasian pregnant women with normal prepregnancy body mass index were tested with a 75-g, 2-h glucose load (24-28 gestation wk). Insulin sensitivity was evaluated with fasting (QUICKI) and dynamic index (OGIS) and β-cell function with a modified insulinogenic index as ΔAUC(insulin)/ΔAUC(glucose) and disposition index. FGR was a birth weight below the 5th percentile for gestational age. FGR developed in 99 (5.5%) pregnant women that showed significantly higher QUICKI, OGIS, insulinogenic, and disposition index with respect to women with normal-weight babies (P < 0.0001). By using multiple regression analysis in the FRG group, QUICKI and OGIS appeared as significant independent variables (P < 0.0001 and P < 0.0366, respectively). We conclude that elevated insulin sensitivity seems to be one of the factors involved in determining unexplained fetal growth retardation; its assessment, even only in the fasting state, could be useful to guide any possible monitoring and therapeutic strategies to reduce fetal complications.

To perform a review and metaanalysis of the studies evaluating the status of serum inflammatory markers in women with polycystic ovary syndrome (PCOS).

Systematic review and metaanalysis of articles published in English before January 2010 and identified using the PubMed search engine.

Academic hospital.

Women with PCOS and appropriate controls.

Measurement of serum concentrations of inflammatory markers by high-sensitivity techniques.

Metaanalyses of the mean difference in serum C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations among patients with PCOS and appropriate controls, applying random-effects models to limit interstudy variability, and using appropriate estimates of evidence dissemination bias.

Metaanalysis of the 31 articles meeting inclusion criteria showed that circulating CRP was 96% higher in women with PCOS compared to controls (95% confidence interval, 71%-122%; z = 7.32) without evidence of dissemination bias (Egger's regression intercept, 0.45; 95% confidence interval, -2.30 to 3.21). These findings persisted after excluding five studies with mismatches in body mass, frequency of obesity, or both, between women with PCOS and controls. Metaanalyses involving 10 studies of IL-6, and nine studies of TNF-α revealed no statistically significant differences between PCOS and controls.

Women with PCOS exhibit an elevation in circulating CRP that is independent of obesity. This finding corroborates existing molecular evidence of the chronic low-grade inflammation that may underpin the pathogenesis of this disorder.