Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome. Context To assess the presence of early CVD markers in young, nonobese women with PCOS. Patients Forty women with PCOS and 50 healthy women with regular menstrual cycles, matched for age and body mass index (BMI). Measurements The following CVD markers were assessed by ultrasonography: common carotid artery (CCA) stiffness index (β), distensibility and intima–media thickness (IMT), and brachial artery flow‐mediated dilatation (FMD). Inflammatory markers, including interleukin (IL)‐6, tumour necrosis factor (TNF)‐α, homocysteine, C‐reactive protein (CRP), glycaemia, lipid profile and insulin, were also assessed. Results CCA β was higher in PCOS than in control women (3·72 ± 0·96 vs. 3·36 ± 0·96, P = 0·04) and CCA distensibility was lower (0·31 ± 0·08 vs. 0·35 ± 0·09 mmHg^?1, P = 0·02). Waist circumference, total testosterone and the Free Androgen Index (FAI) were higher in PCOS patients than in controls (78·2 ± 10·0 vs. 71·5 ± 7·2 cm, P = 0·001; 88·1 ± 32·4 vs. 57·1 ± 21·2 ng/dl, P < 0·01; 12·7 ± 15·7%vs. 4·7 ± 2·3%, P < 0·01, respectively), while SHBG was reduced (37·9 ± 19·1 vs. 47·8 ± 18·3 nmol/l, P = 0·01). The remaining variables did not differ between the groups. Conclusions Young women with PCOS exhibit changes in vascular elasticity even in the absence of classical risk factors for CVD, such as hypertension and obesity.     

Retinol-binding protein in nonobese women with polycystic ovary syndrome

Objective Although polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance, cardiovascular disease and various metabolic diseases, the mechanisms linking PCOS to metabolic changes are not fully understood. Retinol‐binding protein (RBP) was recently reported as an adipocytokine that may link insulin resistance and lipid metabolism. The aim of this study was to investigate the potential role of RBP in women with PCOS. Research design and methods Fifty women with PCOS and 40 healthy women, all of whom were age‐ and weight‐matched, were studied. Blood was obtained to determine RBP levels as well as metabolic and hormonal parameters, and the homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated for each subject. Results The RBP levels were higher (P < 0·01) in women with PCOS after adjusting for age, body mass index (BMI), mean blood pressure, triglyceride (TG), high density lipoprotein (HDL)‐cholesterol, low density lipoprotein (LDL)‐cholesterol, fasting glucose, fasting insulin, estimated glomerular filtration rate (GFR), LH/FSH, total testosterone and SHBG levels. PCOS status was the strongest predictor of elevated RBP levels. In both the PCOS and control groups, RBP levels were significantly correlated with HOMA‐IR (P = 0·03 in the PCOS group; P = 0·01 in controls). In addition, RBP levels were significantly correlated with total cholesterol, LDL‐cholesterol and TG levels in PCOS (P < 0·01, P < 0·01 and P = 0·01, respectively). Conclusions Higher RBP levels in the PCOS group, when compared to the non‐PCOS group, were observed, and this difference may play a role in the pathophysiology found in women with PCOS. Further studies are needed to clarify the role of RBP in these women.     

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS)

Background Polycystic ovary syndrome (PCOS) is a common female reproductive‐age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin‐resistance and low‐grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin‐sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Study design Prospective baseline uncontrolled clinical study. Methods One‐hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One‐hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS‐T (trained) group underwent 3‐month ET program, whereas PCOS‐UnT (untrained) group did not. At baseline and at 3‐month follow‐up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C‐reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. Results PCOS‐T showed a significant (P < 0·05) improvement in maximal oxygen consumption (VO_2max) and in post‐exercise HRR, and a significant (P < 0·001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS‐UnT. Multiple linear regression analysis showed that 3‐month HRR is linearly related to the inclusion in training group (β = 0·316, P < 0·001), VO_2max (β = 0·151, P = 0·032) and the ratio between glucose and insulin area under curve (AUC) (β = 0·207, P = 0·003), and inversely related to body mass index (β = –0·146, P = 0·046), insulin AUC (β = –0·152, P = 0·032), CRP (β = –0·165, P < 0·021), and WBCs count (β = –0·175, P = 0·039). Conclusions Exercise training improves autonomic function and inflammatory pattern in PCOS women.     

Prediction of insulin sensitivity in nonobese women with polycystic ovary syndrome

Insulin resistance is a frequent (although not constant) abnormality in both obese and nonobese women with polycystic ovary syndrome (PCOS). It plays a key role in the predisposition to type 2 diabetes, which is the most important health consequence of the syndrome. Identification of patients with insulin resistance is significant both for follow-up and for therapeutic reasons. The aim of the study was to evaluate the relationships between insulin sensitivity, measured by euglycemic clamp, and both endocrine and metabolic indices and to identify the best model for predicting insulin sensitivity. A total of 41 nonobese women fulfilling the diagnostic criteria for PCOS were enrolled in the study. None of the androgens correlated with the insulin sensitivity index. All clamp parameters correlated with SHBG, triglycerides, and body mass index, although no correlation was found with waist to hip ratio or waist circumference. The close relationship between insulin sensitivity and SHBG was documented by factor analysis and by its presence in all prediction models as the most significant (or even the single) predictor of the insulin sensitivity index. In conclusion: 1) a decreased level of SHBG can be used as a single reliable parameter in the prediction of insulin sensitivity in nonobese women with PCOS; and 2) waist to hip ratio, waist circumference, and androgen concentrations have no predictive value.     

大样本中国人PCOS临床特点分析

目的 为多囊卵巢综合征(PCOS)的临床诊治提供依据.方法 回顾性分析1 040例PCOS患者的临床特征及内分泌、血糖、血脂、胰岛素等检查指标.结果 ①1 040例PCOS患者中,月经稀发占62.60%,闭经占19.71%,所有成年患者的月经紊乱史均可追溯到青春期初潮后;450例存在肥胖(259例为腹部型);158例存在黑棘皮症(肥胖型103例,非肥胖型55例).②PCOS患者中高甘油三酯血症占5.58%、高胆固醇血症占7.02%、HDL异常占0.10%、LDL异常占12.69%,其中肥胖患者胆固醇、低密度脂蛋白明显高于非肥胖患者,P＜0.05.173例符合糖尿病诊断标准,179例糖耐量减低(IGT),27例空腹葡萄糖异常(IFG),9例IFG IGT;平均空腹及口服葡萄糖耐量试验(OGTT)30、60、120和180 min血糖超过正常范围的人次分别为19、74、110、42和12,如果不取空腹血糖值有10例患者被漏诊,分别略去30、60、120和180 min的血糖值,依次有16、50、28和1例被漏诊,5次抽血及3次抽血(空腹 60 min 120 min)的血糖及胰岛素曲线下面积有显著差异;体质量指数(BMI)和腰臀比(WHR)均与胰岛素抵抗指数(HOMA-IR)呈正相关(r=0.29987、P＜0.01,r=0.12441、P＜0.000 1).结论 PCOS患者肥胖发生率较高,肥胖型PCOS患者较非肥胖型存在更严重的内分泌及代谢紊乱;阻断肥胖、IR,打破内分泌代谢间的恶性循环,不但对阻断PCOS的进程具有重要意义,更是预防2型糖尿病、心血管疾病等远期并发症的关键.     

Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS)

Objective To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels. Design Prospective case–control study. Setting Endocrine clinics in the community. Patients Forty‐four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1·645] with PCOS; 16 were lean (BMI SDS <1·036) with PCOS; and 14 were lean (BMI SDS <1·036) without PCOS. Intervention Blood samples were collected from all girls between 8 and 11 am , after an overnight fast. Main outcome measures Serum levels of adiponectin, leptin, insulin, Müllerian‐inhibiting substance, luteinizing hormone, follicle‐stimulating hormone, testosterone, 17‐alpha‐hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17β‐oestradiol. Results Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10·5 ± 5·5 μg/ml) compared with that in lean girls with or without PCOS (16·9 ± 8·64 and 18·0 ± 7·4 μg/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12·3 ± 12·2 vs. 4·5 ± 2·9, P < 0·05), and compared with that in normal weight PCOS adolescents (7·4 ± 4·9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin. Conclusions Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.     

Long term complications of polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease affecting 10 to 15% of women. Menstrual disorders, hyperandrogenism and ultrasonographic aspect of ovaries are typical of the disease and are established diagnostic criteria. But PCOS has also long term complications frequently forgotten and underestimated. During pregnancy, gestational diabetes and gestational hypertensive disorders can occur. At an older age, metabolic disease such as glucose intolerance, type 2 diabetes or dyslipidaemia are frequently described. Women with PCOS have increased classical cardiovascular risks and increased subclinical cardio-vascular disease without proven increase of cardiovascular morbidity and mortality. Finally, endometrial cancer seems to be more frequent in women with PCOS. Therefore, PCOS have numerous long-term health risks and a life-long follow-up is necessary for these women “at-risk” to detect and prevent complications as soon as possible.     

Association of insulin resistance with anti-Mullerian hormone levels in women without polycystic ovary syndrome (PCOS)

Objective  To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS).
Design/patients/measurements  We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles.
Results  Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH.
Conclusion  An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.     

Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS

BACKGROUND: The phenotypic spectrum of PCOS has been broadened but the prevalence and clinical significance of PCOS phenotypes continue to challenge the scientific community. OBJECTIVE: Analysis of the phenotypic spectrum of PCOS and determination of the association between metabolic, hormonal and new ultrasonographic criteria. DESIGN: Clinical prospective study. PATIENTS: Six hundred and thirty-four women with PCOS (18-35 years) and comparable body mass index (BMI), diagnosed by ESHRE/ASRM criteria, were categorized into two major groups of phenotypes: classic (NIH) and nonclassic (ESHRE/ASRM), and then subdivided into phenotypes with all possible combinations of diagnostic characteristics. One hundred and eight healthy women of reproductive age, matched for BMI, were recruited as the control group. MEASUREMENTS: Ultrasonographic (ovarian follicle number and volume), hormonal and metabolic parameters. RESULTS: Classic PCOS phenotype was more frequent (85.96%) than the nonclassic phenotype (14.04%). The patients were also classified according to the presence of biochemical (80.60%) or clinical hyperandrogenaemia (12.62%), and, in the newly introduced group, to absence of evidence of hyperandrogenaemia (6.78%). Subjects with classic PCOS with biochemical hyperandrogenaemia (74.76%) were more insulin resistant than controls. In women with PCOS, follicle number was positively related to both insulin resistance and biochemical hyperandrogenaemia. Additionally, women with PCOS had a 6.58-fold increased relative risk (RR) of > 12 follicles on intravaginal ultrasound and a 2.94-fold increased RR of ovarian volume > 10 cm(3) compared to controls. CONCLUSION: The most frequent PCOS phenotype is the subgroup with biochemical hyperandrogenaemia only within the classic phenotype, which is more insulin resistant than the control group. The follicle number, a newly introduced ultrasonographic marker, is related to both metabolic and hormonal features of PCOS.     

Should physicians prescribe metformin to women with polycystic ovary syndrome PCOS?

1. Metformin is not efficient enough in order to regulate menstrual cycles.2.Metformin is not efficient enough in order to treat hyperandrogenism.3. Metformin should not be used as a first-line treatment in order to treat infertility. Clomiphene citrate (CC) is the reference treatment.4. Metformin in addition to CC is not recommended as a second line treatment, after the failure of CC alone.5. Metformin should not be used during pregnancy in non diabetic women with PCOS, in order to prevent the risk of gestational diabetes.6. Metformin should be prescribed to PCOS women when they are diabetic, in order to prevent their cardiovascular risk, after lifestyle modification.7. Metformin should not be used in PCOS non diabetic women in order to lose weight. Metformin should not be used in order to treat dyslipidemia in women with PCOS.8. In PCOS women, without diabetes, but with fasting hyperglycemia or carbohydrate intolerance, metformin should be prescribed if: BMI > 35.     

Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS).Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function.     

Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome

Women with the polycystic ovarian syndrome (PCOS) carry a number of cardiovascular risk factors, including insulin resistance, lipid abnormalities, and an altered pattern of sex steroid exposure. Noninvasive measurements of endothelial function, which can demonstrate abnormalities well in advance of clinically apparent disease, have not been previously reported in this patient group. We undertook a cross-sectional evaluation of endothelium-dependent and -independent vascular function using brachial artery ultrasound. We studied healthy women with clinical and laboratory evidence of PCOS (n = 18) and age-matched controls (n = 19), not taking any antihypertensive, cholesterol-lowering, or hormonal therapies. Laboratory parameters of insulin resistance, glycemia, cholesterol status, and hormone levels were also measured. Despite marked differences in glucose/insulin ratio [6.1 +/- 1.1 mmol/pmol (PCOS) vs. 9.9 +/- 0.6 (controls)] and free androgen index [11.9 +/- 2.3 (PCOS) vs. 3.7 +/- 0.6 (controls); normal, <5], we did not find evidence of impaired endothelial function in our patients with PCOS. Both endothelium-dependent (8.7 +/- 3.1%) and endothelium-independent (23.2 +/- 3.4%) vascular responses were normal, and practically identical to the responses seen in the control group (endothelium-dependent, 9.0 +/- 0.7; endothelium-independent, 23.0 +/- 1.2%). The PCOS women were more obese, but baseline brachial arterial diameters were not different between groups. There was no correlation between degree of insulin resistance or hyperandrogenism and the brachial response. This group of healthy obese young women with insulin resistance and hyperandrogenism due to PCOS had normal endothelium-dependent and -independent vascular responses compared to age-matched controls. The factors resulting in preservation of these response are unclear and warrant further investigation.     

Predictors of endothelial dysfunction in young women with polycystic ovary syndrome

CONTEXT: Women with polycystic ovary syndrome (PCOS) may be at increased risk for cardiovascular disease. Endothelial dysfunction is an early marker of atherosclerosis. OBJECTIVES: The objectives of this study were to 1) compare endothelial function in young women with PCOS and regularly menstruating control women, and 2) to identify the determinants of endothelial function and investigate its relationship with body mass index in women with PCOS. DESIGN: This was a cross-sectional study. SETTING: This study was conducted at a tertiary cardiovascular research center. PATIENTS: Sixty-two young women with PCOS (mean age, 22.7 yr) and 17 control women, matched as a group for age and body mass index, were studied. Twenty-three women with PCOS were lean, 21 were overweight, and 18 were obese. MAIN OUTCOME MEASURES: Endothelium-dependent and -independent vascular function was assessed by measuring flow-mediated dilation (FMD) and nitrate-mediated dilation in the brachial artery (diameter change during hand hyperemia and after sublingual glyceryl trinitrate administration, respectively). RESULTS: FMD and nitrate-mediated dilation were significantly lower in PCOS than in control women (reduced by approximately 50 and 25%, respectively; both P < 0.0005). Insulin resistance, total testosterone, and total cholesterol were independent predictors of FMD, accounting for 21, 10, and 9% of the variance, respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to overweight and obese PCOS women was observed, but differences among groups were not statistically significant. CONCLUSIONS: Women with PCOS have significant endothelial dysfunction at an early age (i.e. early 20s), and largely independent of obesity. This suggests that women with PCOS are at increased risk for early onset cardiovascular disease and may gain particular benefit from measures to improve endothelial function.