Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance

Background: Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism.

Materials and methods: A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase.

Results: DHEAS was found to be higher in the nonobese patients as compared to the obese (p?=?0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IRp?=?.06).While the total testosterone (p?=?.044) and SHBG (p?=?.007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p?=?.005).

Conclusions: The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.     

Serum vaspin and C-reactive protein levels in women with polycystic ovaries and polycystic ovary syndrome

Objective.?Our aim was to evaluate C-reactive protein (CRP) and serum vaspin levels in women with polycystic ovary syndrome (PCOS) or polycystic ovaries (PCO).

Design.?Twenty-four women with PCOS and 23 women with PCO constituted the study groups. The control group comprised 24 healthy women.

Methods.?Homeostatic model assessment for insulin resistance (HOMA-IR), CRP and serum vaspin levels were measured. The receiver–operating characteristic curve (ROC) of vaspin for prediction of women with increased diabetogenic risk was constructed.

Results.?The three groups did not significantly differ in age and body mass index. HOMA-IR was significantly higher in the PCOS and PCO groups than in control group. Median CRP levels in the control, PCO and PCOS groups were 0.66, 1.28 and 3.2?mg/l, respectively (p?=?0.0001). Women with PCOS had significantly higher serum vaspin levels than the healthy controls [3.52?±?1.38 vs. 0.36?±?0.19?ng/ml, p?=?0.0001]. Serum vaspin could differentiate between women with and without increased diabetogenic risk at a cut-off value of 1.82?ng/ml with a sensitivity of 83.3% and a specificity of 66.1%.

Conclusion.?The results of our study showed that the presence of the increased vaspin, CRP and higher HOMA-IR levels in women with PCOS and PCO could contribute to increased diabetogenic and atherogenic risk in these patients.     

Perinatal outcomes in type 2 diabetic patients compared with non-diabetic patients matched by body mass index

Objective: Given that both type 2 diabetes and obesity are associated with adverse pregnancy outcomes and often coexist, we sought to determine if outcomes in type 2 diabetic patients are related to the presence of diabetes or to maternal obesity. Methods: This retrospective cohort study examined perinatal outcomes of type 2 diabetic and nondiabetic patients matched by prepregnancy body mass index January 2000 to July 2008. Chi-square, Fisher’s exact test, Mann-Whitney U and t-tests were used to compare groups. The association between type 2 diabetes and adverse perinatal outcomes was evaluated through logistic regression with adjustment for potential confounders. Results: 213 pairs of type 2 and non-diabetic patients were compared. Diabetic patients had overall worse composite pregnancy, delivery, fetal, and neonatal outcomes. Specifically, diabetic patients had higher rates of preeclampsia, poly- and oligohydramnios, cesarean delivery, shoulder dystocia, postpartum hemorrhage, preterm delivery, LGA infant, fetal anomaly, and neonatal hypoglycemia, hyperbilirubinemia, RDS, sepsis, intubation, and admission to the NICU. Diabetes remained a significant predictor of adverse delivery, fetal and neonatal composite outcomes when adjusted for confounders in logistic regression. Conclusions: Type 2 diabetic patients have a higher incidence of adverse perinatal outcomes than nondiabetic patients independent of obesity.     

Endogenous thrombin potential in polycystic ovary syndrome: the association to body mass index,insulin resistance,and inflammation

Abstract

Objectives: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria.

Design: Multicenter cross-sectional study.

Setting: Two major University Hospitals in the Capital region of Denmark.

Patients: Hundred forty-eight European women with PCOS were consecutively recruited during April 2010–February 2012. Clinical examination, blood sampling, and DEXA scan were performed.

Main outcome measures: Endogenous thrombin potential (ETP).

Results: PCOS women with phenotype BMI?>?25?+?IR have increased potential of thrombin generation. ETP is associated with total body fat mass, IR, and CRP.

Conclusions: Obese and insulin resistant women with PCOS have elevated level of ETP corresponding to increased risk of CVD. ETP is related to well-known CVD risk factors in PCOS but not in general to the Rotterdam criteria.     

妊娠期糖尿病孕妇体重指数变化与围产结局的关系

目的探讨妊娠期糖尿病(GDM)孕妇妊娠前体重指数(BMI)及妊娠期体重指数增幅与围产结局的关系。方法2006年1月至2007年12月间在浙江大学医学院附属妇产科医院产科门诊行常规检查并确诊为GDM的238例患者,按妊娠前体重指数分为正常组(18.5≤BMI<23)、超重组(23≤BMI<25)、肥胖组(BMI≥25),按早孕至终止妊娠前BMI的总增幅,分为A组(BMI总增幅<4),B组(4≤BMI总增幅≤6),C组(BMI总增幅>6),比较分析各组间围产结局的差异。结果肥胖组子痫前期、早产发生率均(26.0%,32.7%)显著高于正常组(11.9%,8.3%)及超重组(10.8%,13.7%),差异均有统计学意义(P<0.05)。正常组孕妇胎儿窘迫发生率(8.3%)显著低于超重组(23.5%)和肥胖组(23.1%),差异有统计学意义(P<0.05)。B组子痫前期(10.4%)、羊水过多(10.4%)、胎膜早破(10.4%)、胎儿窘迫(11.3%)和早产(8.0%)的发生率均明显低于C组(22.2%,23.8%,25.3%,30.2%,30.2%),差异均有统计学意义(P均<0.05)。C组胎膜早破发生率明显高...     

Serum brain natriuretic peptide and C-reactive protein levels in adolescent with polycystic ovary syndrome

Objective: Our primary aim was to investigate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) increases in adolescent with polycystic ovary syndrome (PCOS) compared with healthy controls and secondary aim was to determine whether metabolic and hormonal differences exist between groups. Methods: In this cross-sectional study, 25 adolescent patients with PCOS and 25 normal ovulatory control not suffering from PCOS were involved in the study. Fasting serum NT-proBNP, C-reactive protein (CRP), homocystein, insulin levels and biochemical and hormonal parameters were measured. Results: Serum NT-proBNP was not significantly different in PCOS subjects (0.62?±?0.80 vs 1.12?±?1.51?ng/mL, p?=?0.154). The mean serum fasting insulin levels (22.64?±?10.51 vs 13.32?±?3.97 mIU/mL, p?=?0.001) and Homeostasis Model Assessment Insulin–Resistance Index (HOMA-IR) levels (5.16?±?1.81 vs 2.97?±?0.89, p?=?0.001) were significantly high in the study group. The median serum CRP levels were not significantly different between groups (1 [1–12] vs 1 [1–19] g/dL, p?=?0.286). Conclusions: The present study demonstrated that the levels of BNP, CRP and homocystein were not different in PCOS subjects. Serum insulin levels and HOMA-IR were significantly higher in PCOS subjects. Possible serum markers for PCOS-related metabolic abnormalities and cardiovascular events, may not present in the adolescent years.     

Impact of pre-gravid body mass index and body mass index change on preeclampsia and gestational diabetes in singleton and twin pregnancies

Abstract

Objective: To examine pre-gravid body mass index (BMI) and gestational BMI change impact on preeclampsia and gestational diabetes mellitus (GDM).

Methods: Retrospective population-based cohort study. Data from Slovenian National Perinatal Information System were analyzed for the period 2002–2011. Three singleton controls were matched by parity and maternal age to each twin pregnancy delivered at >36 weeks. Student’s t test was used to compare pre-gravid BMI and gestational BMI change in different groups (p?<?0.05 significant).

Results: 2046 twin and 6138 singleton pregnancies were included. Twin and singleton patients with preeclampsia or GDM had higher pre-gravid BMI (p?<?0.001). Gestational BMI change was smaller in twins with GDM (p?<?0.001), and not associated with preeclampsia (p?=?0.07). Smaller gestational BMI change in singleton pregnancies was associated with GDM (p?<?0.001), and greater BMI change with preeclampsia (p?=?0.004).

Conclusions: Pre-gravid BMI is more strongly associated with preeclampsia and GDM in twin and singleton pregnancies than gestational BMI change. Smaller gestational BMI change in GDM pregnancies reflect the importance of dietary counseling.     

Markers of visceral obesity and cardiovascular risk in patients with polycystic ovarian syndrome

Background

Polycystic ovarian syndrome (PCOS) is one of most common endocrine disturbances in women of reproductive age. Besides its well known effects on reproductive health, it is also linked to increased cardiovascular risk in later life.

Objectives

The aim of this study was to investigate the link between some anthropometric indices of visceral obesity and surrogate markers of cardiovascular risk according to the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society consensus.

Study design

The study included 36 normal weight (BMI < 25 kg/m²) and 19 obese PCOS subjects (BMI ≥ 30 kg/m²), aged between 18 and 40 years. Different anthropometric markers were compared as predictors for an adverse cardiometabolic profile and composite cardiovascular risk factors as defined by the AE-PCOS consensus.

Results

Both waist-to-stature ratio (WSR) (area under the curve 0.75, p = 0.002) and waist circumference (WC) (area under the curve 0.77, p = 0.001) but not waist-to-hip ratio (WHR) (area under the curve 0.62, p = 0.143) were shown to be good markers of increased cardiovascular risk, insulin resistance and dislipidemia in PCOS patients. The cut-off point for WSR of 0.50 is useful and the cut-off of 80 cm for WC is more appropriate than 88 cm in detecting cardiovascular risk in PCOS patients. Androgen levels and immunoreactive insulin during an oral glucose tolerance test had lower power for predicting increased cardiovascular risk than WC and WSR.

Conclusion

The study indicates that WSR and WC are better associated with composite cardiovascular risk factors as defined by the AE-PCOS consensus than WHR, and that the commonly used cut-off for WSR of 0.5 is useful for detecting cardiovascular risk in PCOS patients.     

Evaluation of asymmetric dimethylarginine,nitric oxide levels and associated independent variables in obese and lean patients with polycystic ovarian syndrome

Objective.?To evaluate the asymmetric dimethylarginine (ADMA) and nitric oxide (NO) levels in obese and lean patients with polycystic ovarian syndrome (PCOS) and find out their relation with hormonal and metabolic parameters.

Methods.?Twenty-two obese, 18 lean patients with PCOS and 11 obese, 24 lean healthy control patients were enrolled prospectively. Plasma ADMA and NO levels and arginine/ADMA ratio were evaluated on 3rd day of menstrual cycle after at least 10?h overnight fasting.

Results.?Plasma ADMA, NO levels and arginine/ADMA ratio were similar in the groups. ADMA level did not correlate with the hormonal and metabolic parameters in patients with PCOS. However, NO correlated inversely with fasting insulin (r?=??0.353, p?=?0.041) and homeostasis model of insulin resistance (HOMA-IR) (r?=??0.379, p?=?0.027). Arginine/ADMA ratio also correlated inversely with fasting insulin (r?=??0.339, p?=?0.050). In multinomial regression analysis the risk of low NO was associated independently with high fasting insulin (OR?=?1.19, 95% CI 1.001–1.42, p?=?0.049) and high HOMA-IR in patients with PCOS (OR?=?2.26, 95% CI 1.03–4.98, p?=?0.042).

Conclusions.?Insulin resistance may be the underlying mechanism of endothelial dysfunction through NO pathway in PCOS.     

Phenotypic expression, body mass index and insulin resistance in relation to LH levels in women with polycystic ovary syndrome

Objective

To evaluate LH levels in women with the classic (1990 criteria) and the newer (2003 criteria) PCOS phenotypes, and to examine the impact of BMI and insulin resistance indices on hormone levels.

Study design

In this controlled clinical study 936 women with PCOS, classified as classic (n = 729) and newer (n = 207), and 204 controls were included. All women were divided into normal-weight (BMI < 25 kg/m²) and overweight plus obese (BMI ≥ 25 kg/m²). Serum LH, FSH, anthropometrics, androgens, fasting insulin and glucose, HoMA-IR, number of follicles, and ovarian volume were assessed.

Results

Women with classic PCOS presented significantly higher LH and LH/FSH ratios, and lower glucose/insulin levels than those with the newer phenotype and controls. Overweight plus obese women of all groups had lower LH levels than normal-weight women. Independent positive correlations between LH and androgens and negative correlation between LH and BMI were found.

Conclusions

The higher LH concentrations of the classic phenotypes of PCOS could be attributed to the higher androgen levels, which desensitize the hypothalamus to the negative feedback regulation by progesterone. Moreover, the lower LH levels of overweight plus obese women of all groups could be attributed to the increased peripheral aromatization of androgens to estrogens in adipose tissue leading to suppression of LH secretion.

Condensation

Both normal-weight and overweight women with classic PCOS phenotypes present higher LH levels and LH-to-FSH ratios than women with similar BMI but the newer phenotypes.