Insulin Resistance In Polycystic Ovary Syndrome Women Research Articles

The Relationship between Thyroid Hormones and Insulin Resistance in Polycystic Ovary Syndrome Women.

This study aimed to investigate the changes in thyroid hormones in the serum of patients with polycystic ovary syndrome (PCOS) and their correlation with insulin resistance. This is a retrospective study. 84 patients having insulin resistance and 76 patients without insulin resistance were included. 90 women without history of PCOS were selected as a healthy control group. This study was conducted at Shijiazhuang Fourth Hospital. Blood samples were collected from each group on days 3-5 of their menstrual cycle, and their triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were analyzed and compared between groups. We investigated the changes of serum thyroid hormones in patients with PCOS and their correlation with insulin resistance. We found that serum levels of T3 and T4 were significantly decreased, while TSH levels were significantly increased in PCOS patients compared with HCs. Moreover, we found that patients with insulin resistance had significantly lower levels of serum T3 and T4 and higher levels of TSH compared to those PCOS participants without insulin resistance. This study was a retrospective and single-center study, which had selection bias, information bias, and confounding variables may affect the accuracy and reliability of the conclusion. Insulin resistance negative correlates with their serum T3, T4, and positive correlates with their TSH levels. Our results develop a combined test model with the serum T3, T4, and TSH levels for the clinical diagnosis of insulin resistance in PCOS women.

The Efficacy and Safety of DLBS3233, A Combined Bioactive Fraction of Cinnamomum burmanii and Lagerstroemia speciosa Plants on The Endocrine-Metabolic Profile of Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).

A Cross-Sectional Study of Protein Changes Associated with Dementia in Non-Obese Weight Matched Women with and without Polycystic Ovary Syndrome.

Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between women with non-obese and non-insulin resistant PCOS compared to matched control subjects. We measured plasma amyloid-related proteins levels (Amyloid-precursor protein (APP), alpha-synuclein (SNCA), amyloid P-component (APCS), Pappalysin (PAPPA), Microtubule-associated protein tau (MAPT), apolipoprotein E (apoE), apoE2, apoE3, apoE4, Serum amyloid A (SAA), Noggin (NOG) and apoA1) in weight and aged-matched non-obese PCOS (n = 24) and control (n = 24) women. Dementia-related proteins fibronectin (FN), FN1.3, FN1.4, Von Willebrand factor (VWF) and extracellular matrix protein 1 (ECM1) were also measured. Protein levels were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Only APCS differed between groups, being elevated in non-obese PCOS women (p = 0.03) relative to the non-obese control women. This differed markedly from the elevated APP, APCS, ApoE, FN, FN1.3, FN1.4 and VWF reported in obese women with PCOS. Non-obese, non-insulin resistant PCOS subjects have a lower AD-associated protein pattern risk profile versus obese insulin resistant PCOS women, and are not dissimilar to non-obese controls, indicating that lifestyle management to maintain optimal body weight could be beneficial to reduce the long-term AD-risk in women with PCOS.

Comparative study of the efficacy of combined metformin–clomiphene citrate versus combined metformin–letrozole in induction of ovulation in overweight women with polycystic ovarian syndrome

Background Polycystic ovary syndrome (PCOS) is the common cause of infertility. Clomiphene citrate (CC) is the first-line treatment in ovulation induction. Metformin biguanide has been used in insulin resistance in PCOS women. Adding metformin to CC in the CC-resistant PCOS was highly effective in achieving ovulation in 68.6–77.7% of patients. Letrozole, aromatase inhibitor, its use in patients with CC-resistant PCOS achieved ovulation 54.6–84.4% of the time. Aim We aimed to compare the efficacy of combined metformin–CC to combined metformin–letrozole in ovulation induction in overweight infertile PCOS women. Patients and methods A prospective randomized study was conducted at Obstetrics & Gynecology Department in Tanta University Hospitals. In total, 40 infertile overweight cases with PCO were included. Cases were randomly allocated in two groups. Results The mean age was 26.40 ± 5.20 years for CC group and 26.50 ± 5.10 years for letrozole group. BMI was 27.50 ± 1.43 for CC group and 27.45 ± 1.36 for letrozole group. The duration of infertility was 2.90 ± 1.40 years for CC group and 2.88 ± 1.21 for letrozole group. There was insignificant difference in both groups as regards the follicles more than 18 mm and endometrial thickness. But, as regards progesterone level, there was a statistically significant increase in letrozole group than CC group (P<0.005). Concerning pregnancy rate, there was insignificant difference between two groups. Conclusion The present investigation demonstrated that both CC and letrozole are similarly viable in treatment of infertility in PCOS patients, when joined with metformin treatment.

Physical Activity, Rather Than Diet, Is Linked to Lower Insulin Resistance in PCOS Women-A Case-Control Study.

Insulin resistance (IR) is a prominent feature of polycystic ovary syndrome (PCOS). The importance of lifestyle interventions in the management of PCOS is strongly highlighted and it is suggested that diet and physical activity may significantly influence insulin sensitivity. Therefore, we evaluated the link between diet and physical activity and various indices of insulin resistance, including adipokines secreted by the adipose tissue in 56 PCOS and 33 healthy control women. The original food frequency questionnaire and Actigraph GT3X-BT were used to assess the adherence to the diet recommended in IR and the level of physical activity, respectively. We observed that higher levels of physical activity were associated with lower HOMA-IR and a greater chance of its normal value in PCOS group. No such relationship was observed for other IR indices and adipokines or for the diet. However, we noted a strong correlation between HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and HOMA-AD (Homeostatic Model Assessment-Adiponectin) in PCOS women. Additionally, when we used HOMA-AD we observed a higher prevalence of IR among PCOS women. Our study supports the beneficial role of physical activity in the management of insulin resistance in PCOS women. Moreover, our findings indicate that HOMA-AD may be a promising surrogate marker for insulin resistance assessment in women with PCOS.

Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial.

This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.

Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women.

Polycystic ovary syndrome (PCOS) is a disorder with an unknown etiology that features a wide range of endocrine and metabolic abnormalities that hamper fertility. PCOS women experience difficulties getting pregnant, and if pregnant, they are prone to miscarriage, gestational diabetes, pregnancy-induced hypertension and preeclampsia, high fetal morbidity, and perinatal mortality. Insulin, the pancreatic hormone best known for its important role in glucose metabolism, has an underrated position in reproduction. PCOS women who have associated insulin resistance (with consequent hyperinsulinemia) have fertility issues and adverse pregnancy outcomes. Lowering the endogen insulin levels and insulin resistance appears to be a target to improve fertility and pregnancy outcomes in those women. Berberine is an alkaloid with a high concentration in various medicinal herbs that exhibits a hypoglycaemic effect alongside a broad range of other therapeutic activities. Its medical benefits may stand up for treating different conditions, including diabetes mellitus. So far, a small number of pharmacological/clinical trials available in the English language draw attention towards the good results of berberine's use in PCOS women with insulin resistance for improving fertility and pregnancy outcomes. Our study aims to uncover how berberine can counteract the negative effect of insulin resistance in PCOS women and improve fertility and pregnancy outcomes.

Evaluation of endometrial immune status of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is described as a low-grade chronic inflammatory state. However, there are limited studies on the specific endometrial immune status of PCOS patients. Whether this endometrial immune cell pattern is intrinsic to PCOS or the consequence of PCOS-associated obesity is a subject of debate. This study retrospectively included one hundred women diagnosed with PCOS and ninety-five normal fertile controls, which further divided into four groups (normoweight PCOS; overweight PCOS; normoweight control; overweight control) based on body mass index. The percentages of endometrial CD68+ macrophages (1.97 % vs. 1.17 %; P < 0.001), CD163+ M2 macrophages (2.30 % vs. 1.83 %; P = 0.001), CD1a+ iDCs (0.044 % vs. 0.029 %; P = 0.002), CD83+ mDCs (1.72 % vs. 1.07 %; P < 0.001) and CD8+ T cells (2.82 % vs. 1.95 %; P < 0.001) were significantly higher in normoweight PCOS women than normoweight controls. The percentage of CD68+ macrophages (2.09 % vs. 1.15 %; P < 0.001) was significantly higher in overweight PCOS women compared with overweight controls. In multivariant linear regression analysis, participants’ PCOS status was the main predictors of endometrial CD68+ macrophages, CD163+ M2 macrophages, CD1a+ iDCs, CD83+ mDCs and CD8+ T cells in the whole study population. Additionally, in PCOS group, positive correlations were found between endometrial CD56+ NK, CD163+ M2 macrophages and QUICKI, indicating there was an association between endometrial immune cells and insulin resistance in PCOS women. Our study suggests that women with PCOS have altered endometrial immune cells, which may reflect a state of chronic low grade inflammation. The chronic inflammation, independent of obesity, may help understand the pathophysiologic mechanisms of intrinsic PCOS.

Diets with lower carbohydrate concentrations improve insulin sensitivity in women with polycystic ovary syndrome: A meta-analysis

ObjectiveWomen with polycystic ovary syndrome (PCOS) are associated with increased levels of insulin resistance (IR). Other than treatment with insulin-sensitizing drugs, specialized diets have also been implemented to reduce the patient’s IR. However, the capacity of certain diets, concerning with the severity of the patient’s IR, to improve insulin sensitivity has not fully been explored. Therefore, we conducted a meta-analysis to determine in PCOS subjects from low to severe IR, if hypocaloric diets improve insulin sensitivity. Study DesignPubMed, SCOPUS, EBSCO, and LILACS databases and retrieved studies' bibliographies were searched for prospective studies that investigated the association between diets and IR in PCOS women until October 2018. Diet was defined as a modification of the patients’ nutrition intake according to caloric restriction, change in protein intake, or by using a specialized diet. IR measures (HOMA1-IR), pre- and post-intervention were extracted. Using Comprehensive Meta-Analysis software, depending on the level heterogeneity, determined by the ψ2-based Q-test and the I2-test, fixed-effects or random-effects models were used to calculate the pooled standard paired differences (SPD) and 95 %CI. Results20 publications (25 studies) fulfilled the inclusion criteria. Due to the heterogeneity of the diets, the random-effects model was used. In 48 % of the studies, the diets led to a decrease of IR, where 44 % had no effect. In 2 studies, the diets increased IR. Overall, the diets decreased IR (SPD=-0.58; 95 %CI: -0.81 to -0.36). Subjects with severe IR (HOMA1-IR>4.2) had a marked improvement (SPD=-1.22; 95 %CI: -1.61 to -0.84). Moreover, diets low in carbohydrate (<50 %) was also determined to improve IR (SPD=-0.86; 95 %CI: -1.23 to -0.50). ConclusionsHere, we demonstrate that diets are more likely to improve IR in PCOS women with severe IR. Therefore, it is crucial to determine a subject’s IR status before considering any intervention containing a diet.

The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal weight, obesity, insulin resistance, and PCOS; additionally, using an in vitro model of human endometrial cells exposed to an environment resembling hyperinsulinemic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by Western blot, immunocytochemistry, and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity (P < 0.05 vs. normal weight). In the in vitro model, PCOS conditions decreased p-AMPK levels, while they were restored with MYO (P < 0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism (P < 0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK-dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in vitro conditions. Consequently, MYO could be a potential insulin sensitizer through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.

Insulin Resistance and Its Associated Risk Factors in Nigerian Women with Polycystic Ovary Syndrome

Background: The etiology of polycystic ovary syndrome (PCOS) is not completely understood; however one condition that correlates closely with the pathogenesis of PCOS is insulin resistance (IR). The objective of this study was to determine the prevalence of insulin resistance (IR) and the association of such abnormality with potential risk factors in women with PCOS. Method: 116 women with confirmed PCOS attending a reproductive clinic at the University of Benin Teaching Hospital in Benin City were studied. IR was determined by homeostatic model assessment (HOMA) ≥ 2 and pre-diabetes by fasting plasma glucose between 110 and 125 mg/dl and/or plasma glucose value between 140 and 200 mg/dl at 2 hours during an oral glucose tolerance test (OGTT) after ingestion of 75 g oral glucose load. Results: Forty-two women were insulin resistant among the 116 women with PCOS. The prevalence of IR was 36.2% (95% CI 26.6 - 46.2). The prevalence of impaired fasting glucose (IFG) showed 1.7% (95% CI 0.97 - 2.03), impaired glucose tolerance (IGT) was 2.6% (95% CI 1.97 - 3.03) and diabetes mellitus (DM) was 1.7% (95% CI 0.97 - 2.03) in the 116 PCOS women. Of these 42 insulin resistant PCOS women, 23.8% (n = 10) were obese and 40.5% (n = 17) were overweight. Multivariate analysis revealed that total cholesterol (OR, 1.07; 95% CI, 1.04 - 1.10), triglycerides (OR, 1.08; 95% CI, 1.04 - 1.13) and LDL-cholesterol (OR, 1.08; 95% CI, 1.04 - 1.12) were statistically significant independent risk factors for IR. Conclusion: The prevalence of IR was high in women with PCOS, and there was a significant association between IR, obesity, and dyslipidemia. However, the prevalence rates of impaired glucose tolerance and DM were low in women with PCOS compared to other studies. Since women with PCOS are at risk of IR and dyslipidemia, early screening, detection, intervention, and lifestyle modification would ameliorate the financial burden of DM and cardiovascular disease (CVD).

Association of leptin and insulin resistance in PCOS: A case-controlled study

Endocrine abnormalities related to polycystic ovary Syndrome (PCOS) are important problems. To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance (IR) and to evaluate the association between leptin and IR in PCOS group. This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI), several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used. Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m2) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (p<0.001) and to age in non-PCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (p<0.001), QUICKI (p<0.001), FI (p=.002), and FBS (p=0.02). BMI and IR have positive association with serum leptin in PCOS infertile women. HOMA-IR followed by FI and QUICKI is the most sensitive test for detection of IR.

Adipokines and soluble cell adhesion molecules in insulin resistant and non-insulin resistant women with polycystic ovary syndrome

Introduction: Insulin resistance (IR) is closely associated with increased atherogenic risk.Objective: To investigate leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and their relationship with each other and metabolic parameters in women with polycystic ovary syndrome (PCOS).Methods: The study included 76 PCOS women divided into insulin resistant and non-insulin resistant. Anthropometric parameters, glucose and lipid parameters, leptin, adiponectin, sICAM-1 and sVCAM-1 were determined. Homeostasis model of IR index(HOMA-IR), atherogenic index of plasma(AIP) and leptin/adiponectin ratio were calculated. HOMA-IR > 2.5 and/or fasting plasma glucose/immunoreactive insulin ratio < 0.333 were used as markers for IR.Results: Non-insulin resistant PCOS had significantly higher adiponectin and sVCAM-1 levels. AIP was significantly higher in insulin resistant PCOS. Adiponectin showed a positive correlation with sVCAM-1 and sICAM-1.Conclusion: Insulin resistant PCOS women were at higher atherogenic risk compared to non-insulin resistant group. sVCAM-1 data confirms the necessity of further investigations for clarifying its role in IR.

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women.

American Association Of Clinical Endocrinologists, American College Of Endocrinology, And Androgen Excess And Pcos Society Disease State Clinical Review: Guide To The Best Practices In The Evaluation And Treatment Of Polycystic Ovary Syndrome - Part 2

Polycystic ovary syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists and the Androgen Excess Society aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2014. Insulin resistance is believed to play an intrinsic role in the pathogenesis of PCOS. The mechanism by which insulin resistance or insulin give rise to oligomenorrhea and hyperandrogenemia, however, is unclear. Hyperinsulinemic-euglycemic clamp studies have shown that both obese and lean women with PCOS have some degree of insulin resistance. Insulin resistance is implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic-pituitary-ovarian axis. Given the association with insulin resistance, all women with PCOS require evaluation for the risk of metabolic syndrome (MetS) and its components, including type 2 diabetes, hypertension, hyperlipidemia, and the possible risk of clinical events, including acute myocardial infarction and stroke. Obese women with PCOS are at increased risk for MetS with impaired glucose tolerance (IGT; 31 to 35%) and type 2 diabetes mellitus (T2DM; 7.5 to 10%). Rates of progression from normal glucose tolerance to IGT, and in turn to T2DM, may be as high as 5 to 15% within 3 years. Data suggest the need for baseline oral glucose tolerance test every 1 to 2 years based on family history of T2DM as well as body mass index (BMI) and yearly in women with IGT. Compared with BMI- and age-matched controls, young, lean PCOS women have lower high-density lipoprotein (HDL) size, higher very-low-density lipoprotein particle number, higher low-density lipoprotein (LDL) particle number, and borderline lower LDL size. Statins have been shown to lower testosterone levels either alone or in combination with oral contraceptives (OCPs) but have not shown improvement in menses, spontaneous ovulation, hirsutism, or acne. Statins reduce total and LDL cholesterol but have no effect on HDL, C-reactive protein, fasting insulin, or homeostasis model assessment of insulin resistance in PCOS women, in contrast to the general population. There have been no long-term studies of statins on clinical cardiac outcomes in women with PCOS. Coronary calcification is more prevalent and more severe in PCOS than in controls. In women under 60 years of age undergoing coronary angiography, the presence of polycystic ovaries on sonography has been associated with more arterial segments with >50% stenosis, but the relationship between PCOS and actual cardiovascular events remains unclear. Therapies for PCOS are varied in their effects and targets and include both nonpharmacologic as well as pharmacologic approaches. Weight loss is the primary therapy in PCOS--reduction in weight of as little as 5% can restore regular menses and improve response to ovulation- inducing and fertility medications. Metformin in premenopausal PCOS women has been associated with a reduction in features of MetS. Clamp studies using ethinyl estradiol/drosperinone combination failed to reveal evidence of an increase in either peripheral or hepatic insulin resistance. Subjects with PCOS have a 1.5-times higher baseline risk of venous thromboembolic disease and a 3.7-fold greater effect with OCP use compared with non-PCOS subjects. There is currently no genetic test to screen for or diagnose PCOS, and there is no test to assist in the choice of treatment strategies. Persistent bleeding should always be investigated for pregnancy and/or uterine pathology--including transvaginal ultrasound exam and endometrial biopsy--in women with PCOS. PCOS women can have difficulty conceiving. Those who become pregnant are at risk for gestational diabetes (which should be evaluated and managed appropriately) and the microvascular complications of diabetes. Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for gestational diabetes--and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption. Women should be screened and treated for hypertension and diabetes prior to attempting conception. Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor.

Frequency of Insulin Resistance in Egyptian Women with Polycystic Ovary Syndrome

Objectives:To evaluate the prevalence of insulin resistance in polycystic ovary syndrome (PCOS) women and to compare the findings (clinical and laboratory) of PCOS in insulin resistance (IR) to non-IR PCOS women. Patients and methods: Fifty PCOS women included in this cross sectional comparative study. Studied women underwent complete physical examination with calculation of BMI, assessment of hirsutism and measurement of blood pressure. Hormonal and lipid profiles of the studied PCOS women also evaluated. Fasting glucose/insulin (G/I) ratio calculated and a ratio < 4.5 was predictive of IR in PCOS women above 18 years old. Studied PCOS women divided into two groups according to presence or absence of IR to evaluate the prevalence of IR in PCOS Egyptian women and the findings of PCOS in IR to non-IR PCOS women. Results:IR (G/I ratio 8) was significantly more common in IR compared to non-IR PCOS women (20 (86.95%) versus 5 (18.5%)). There was no significant difference between IR and non-IR PCOS studied women regarding; mean age, blood pressure, age of menarche, menstrual regularity acne and baldness. In addition, there was no significant difference between the IR women and non-IR PCOS studied women regarding; ultrasound ovarian findings, hormonal and lipid profiles. Conclusion: The prevalence of IR in PCOS Egyptian women is about 46%, BMI was significantly high in IR compared to non-IR PCOS women and the hirsutism was significantly more common in IR compared to non-IR PCOS women.

Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women.

Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an insulin resistance (IR) state, like obesity and type 2 diabetes mellitus (T2DM). Although previous studies have suggested a correlation between irisin and the metabolic parameters associated with obesity and T2DM, the results have been inconsistent. Our objective was to (1) determine circulating irisin levels in women with PCOS and control subjects, (2) examine the relationship of irisin and conventional markers of insulin resistance, and (3) examine irisin changes with interventions modulating IR in PCOS women. This study was comprised of a series of cross-sectional and interventional studies of 178 PCOS and 123 healthy women from the general population and outpatients of the Internal Medicine Department at the Second Affiliated Hospital, Chongqing Medical University, China. Forty seven women with PCOS were randomly assigned to 6 months of oral metformin (850 mg bid). The oral glucose tolerance test (OGTT) and the euglycemic-hyperinsulinemic clamp (EHC) were performed to assess glucose tolerance and insulin sensitivity. Outcome measures were IR (AUC(Insulin) and M values) on an OGTT and EHC, irisin levels, and metabolic markers. Circulating irisin was significantly higher in both overweight/obese (body mass index [BMI] ≥ 25 kg/m(2)) and PCOS women (P < .01). Circulating irisin levels correlated with BMI, WHR, FAT%, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), AUC(Insulin), homeostasis model assessment of insulin resistance (HOMA2-IR), M values, and free androgen index (FAI). During EHC, short-term hyperinsulinemia exhibited an inhibitory effect on irisin levels. After 6 months of metformin treatment, there was a significant decrease in circulating irisin in PCOS women following improved IR. These data suggest that irisin may be a useful marker of IR in PCOS women.

The LIPT-Study: On Risk Markers of Vascular Thrombosis in Polycystic Ovary Syndrome. A Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Liraglutide

Overweight and insulin resistance (IR) are central pathogenic features of the Polycystic Ovary Syndrome (PCOS), and weight loss is the main treatment option. PCOS is also associated with signs of a chronic inflammation, activation of the coagulation system, defect endothelial function and increased arterial stiffness, all regarded as risk factors or markers for the development of cardiovascular disease. These factors are not taken into account in the definition of the syndrome, which is based on the 3 Rotterdam criteria. An uncertainty of the clinical risk of cardiovascular disease (CVD) in these relatively young women has led to many studies on surrogate markers of CVD in PCOS, including the search for new markers with additional information of the arteriosclerotic burden in PCOS. GLP-1 analogues, originally developed for the treatment of diabetes, induce weight loss also in non-diabetic people. We therefore questioned whether treatment with the GLP-1 analogue Liraglutide to women with PCOS in doses used for diabetes could induce weight loss and improve IR and through this action, or independently, improve markers of vascular thrombosis in women with PCOS. Thus, 70 overweight and/or insulin resistant PCOS women were planned treated for 26 weeks in a placebo controlled randomized trial with the following effect parameters to be evaluated: Changes in Thrombin generation time, Adrenomedullin, Atrial natriuretic peptide, body fat composition (DEXA), liver fat content (MRI), BMI, IR, sex hormones and ovarian morphology. The protocol and the background for the study are brought in this report.

Total body fat and central fat mass independently predict insulin resistance but not hyperandrogenemia in women with polycystic ovary syndrome.

Obesity is a common feature of women with polycystic ovary syndrome (PCOS). The aim of this study was to assess the role of body fat on insulin resistance and androgen excess in these subjects. One hundred sixteen consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, total fat mass and fat distribution were assessed by dual-energy x-ray absorptiometry, serum-free T by liquid chromatography mass spectrometry and equilibrium dialysis and insulin sensitivity by the glucose clamp technique. Total fat mass and truncal fat were significantly higher in insulin-resistant than in insulin-sensitive PCOS subjects (+89% and +127%, respectively, both P < .001), and both tended to be higher in hyperandrogenemic than in normoandrogenemic women (+22% and +28%, respectively, P = .087 and P = .090). All parameters of adiposity correlated inversely with insulin sensitivity (P < .001) and directly with serum-free T (P ≤ .001). A statistically significant inverse relationship was observed between insulin sensitivity and serum-free T concentrations (r = -0.527, P < .001). In a multiple regression analysis, either total fat mass or truncal fat, in addition to serum-free T and age, were independent predictors of insulin sensitivity. However, insulin sensitivity, but not total fat mass or truncal fat, was an independent predictor of free T concentrations. These data suggest that body fat contributes to determining insulin resistance in PCOS women. However, the association between body fat and hyperandrogenism seems to be to a large extent explained by insulin resistance.