Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study

OBJECTIVE: Hyperandrogenia and insulin resistance are heritable family traits, likely to cluster in children of polycystic ovary syndrome (PCOS) mothers. DESIGN: We performed a case control study of PCOS children (n = 32) compared with children from control women (n = 38) for reproductive and metabolic abnormalities, stratifying results by three Tanner stage groupings. The children underwent history and physical examinations, a 3-h timed urine collection, a 2-h oral glucose tolerance test, and abdominal ultrasound examination (females only). Serum was obtained in older children (age > 8 yr) who consented. RESULTS: Urine LH levels were significantly lower in the Tanner IV-V PCOS girls compared with controls (P = 0.04). Urine testosterone levels were significantly elevated in Tanner II-III PCOS boys compared with controls (P = 0.007). There were no significant differences in dehydroepiandrosterone levels. We validated the correlation between salivary and serum levels of insulin (insulin areas under the curve) in an adult population [n =30, Pearson correlation coefficient (r) = 0.67; P < 0.0001], which also replicated in the children (2-h insulin r = 0.57; P = 0.0004). Mean area under the curve salivary insulin levels were significantly higher in the Tanner IV-V PCOS girls in the later stages of puberty when compared with controls (3625 +/- 1372 vs. 1766 +/- 621 min x muU/ml, 95% confidence interval 475-3242; P < 0.02). CONCLUSIONS: Hyperinsulinism may be a familial characteristic of PCOS children (or at least girls) but does not appear until the later stages of puberty. Other reproductive abnormalities that characterize PCOS may develop later.     

Risk of atherosclerosis in women with polycystic ovary syndrome: a study from South India

Women with polycystic ovary syndrome (PCOS) often present for cosmetic and or reproductive symptoms; attention is generally not paid to the future risk of atherosclerosis for these women. Given that Asian Indians are insulin resistant and prone to metabolic syndrome at an earlier age, we assessed glucose/insulin ratio and intimal medial thickness (IMT) in young women with PCOS from south India. In this cross-sectional case control study, we assessed insulin resistance and carotid IMT in 40 women presenting with hyperandrogenic features of PCOS. Insulin resistance was assessed by fasting glucose/insulin ratio and IMT by the Doppler system with electrical linear transducer midfrequency of 12 MHz. Women with PCOS had higher fasting insulin levels (36.58 +/- 17.81 muU/mL, vs. 16.60 +/- 3.22 muU/mL in controls; p < 0.001), higher insulin resistance (glucose/insulin ratio 2.81 +/- 1.47 vs. 5.47 +/- 1.46 in controls; p < 0.001), and greater IMT (0.53 +/- 0.14 mm vs. 0.39 +/- 0.06 mm in controls; p < 0.001). Women with PCOS had a higher body mass index (BMI) (26.46 +/- 5.24 vs. 23.24 +/- 3.05 in controls; p < 0.001), and the differences between PCOS and controls persisted, even among those who had a BMI of less than 25. We concluded that South Indian women with the reproductive abnormalities of PCOS have greater insulin resistance and IMT, and therefore they must be advised about lowering the risk of future vascular disease.     

Cardiovascular risk in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that has received an immense amount of attention in the recent years due to the possible associated risk of cardiovascular disease. Women with PCOS demonstrate an adverse cardiovascular profile characteristic of the cardiometabolic syndrome and an established risk of progression to type 2 diabetes. Despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease, it is unclear if they develop accelerated atherosclerosis. This article summarized the recent development and findings of cardiovascular risk in women with PCOS, and finally the therapeutic options will be discussed.     

Insulin sensitivity in women with polycystic ovary syndrome

The aim of our study was to compare insulin sensitivity in lean and obese European polycystic ovary syndrome (PCOS) women with lean healthy women. We performed the euglycemic hyperinsulinemic clamp in 83 women with PCOS [53 lean with body mass index (BMI) of 21.5 +/- 1.8 kg/m2 and 30 obese with BMI of 29.6 +/- 3.7 kg/m2] and in 15 healthy women with BMI of 21.6 +/- 1.8 kg/m2 to determine glucose disposal (M) and the insulin sensitivity index (ISI). Statistical evaluation was done using Kruskal-Wallis ANOVA followed by Kruskal-Wallis multiple-comparison z-value test. The basal blood glucose was significantly higher in lean and obese PCOS women than in controls (P < 0.02). Fasting insulin was significantly higher in both lean and obese PCOS women than in controls (P < 0.000001). Obese PCOS women were more insulin resistant than controls (P < 0.02 for M and P < 0.0008 for ISI); lean PCOS women did not differ from controls in M or ISI. Posthepatic insulin delivery was significantly higher in both lean and obese PCOS women compared with controls (P < 0.000008). We conclude that lean PCOS women are not more insulin resistant than healthy controls. Insulin hypersecretion, on the other hand, is present even in lean PCOS women.     

多囊卵巢综合征患者妊娠可能性的预测

最近我们见证了临床医学从一种疗法用于所有患者到较为个体化的"量身定制"方式的转变.这种方式也逐渐应用到不育症的治疗中,特别是与卵巢刺激有关的无排卵性不育及卵巢强刺激辅助生殖技术等.由于目前仍不能控制卵巢刺激的强度,必需加强对卵巢反应的监测以取得疗效与安全性的适当平衡,因而这一领域仍亟待改进.     

Adiponectin levels in women with polycystic ovary syndrome

Serum adiponectin levels were evaluated in 60 women with polycystic ovary syndrome (PCOS), 30 normal-weighted and 30 obese women, and 60 healthy women age and body mass index (BMI) matched with the patients. The homeostasis model assessment (HOMA) score was also calculated. Both in PCOS and controls, serum adiponectin levels were significantly (P < 0.05) lower in obese than normal-weight women, without any difference between PCOS and controls. The HOMA score was significantly (P < 0.05) higher in obese than normal-weight women both in PCOS and controls; additionally, the HOMA score was significantly (P < 0.05) higher in normal-weight PCOS than normal-weight controls. Both in PCOS and controls, adiponectin levels were significantly correlated with BMI (r = -0.51, P < 0.01 in PCOS; r = -0.45, P < 0.01 in controls) and HOMA values (r = -0.39, P < 0.05 in PCOS; r = -0.35, P < 0.05 in controls); HOMA was correlated with BMI (r = 0.51, P < 0.01 in PCOS, r = 0.61, P < 0.001 in controls). In conclusion, our results confirm that adiponectin concentrations change according to variations of fat mass. They further suggest that insulin sensitivity per se probably does not play any pivotal role in the control of adiponectin levels in PCOS women.     

未发现多囊样卵巢的多囊卵巢综合征的临床特征

选择2004年9月至2006年10月在本中心就诊的多囊卵巢综合征(PCOS)患者876例,根据B超检查分为两组:多囊样卵巢组800例,无多囊样卵巢组76例.结果 发现无多囊样卵巢组多毛评分、睾酬、胆固醇和低密度脂蛋白明显高于多囊样卵巢组,差异有统计学意义.无多囊样卵巢组一级亲属中糖尿病、高血压病史的患病率明显增高.     

Adenovirus-36 infection and obesity: A case control study of Turkish women with polycystic ovary syndrome

Background and aimsAdenovirus-36 (Ad-36) seropositivity has been shown to be involved in the aetiology of obesity. The aim of this study was to examine Ad-36 positivity in obese and normal-weight patients with polycystic ovary syndrome (PCOS).MethodsThere were two groups including 92 and 110 subjects. This study was a prospective case-control study. The enzyme-immunoassay method was used to quantitatively determine antibodies (Abs) specific to human Ad-36 in the serum samples. Age, body mass index (BMI), fasting glucose levels and insulin levels of the participants were recorded. The PCOS and control group patients were divided into two groups: the overweight group with BMI ≥25 kg/m² and non-obese group with BMI <25 kg/m².ResultsAd-36 Ab positivity in the PCOS group was found to be significantly higher than that in the control group (p < 0.001). Ad-36 Ab positivity was significantly higher in the PCOS obese group than in the control obese group (p < 0.001). Ad-36 Ab positivity and BMI ≥25 kg/m² were identified as independent predictors of PCOS in logistic regression analysis.ConclusionAd-36 Ab positivity was significantly higher in the obese/overweight PCOS patients. Obesity can be prevented in patients with PCOS by treating Ad-36.     

Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study

We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome (PCOS) (n = 71) and control women (n = 23) with regular menstrual cycles and baseline normal glucose tolerance. Mean follow-up was between 2 and 3 yr for both groups (PCOS 2.5 +/- 1.7 yr; controls 2.9 +/- 2.1 yr). Based on World Health Organization glucose tolerance categories, there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group. In the PCOS group, 25 (37%) had impaired glucose tolerance (IGT) and seven (10%) had type 2 diabetes mellitus at baseline, compared with 30 (45%) and 10 (15%), respectively, at follow-up. There were also no differences within groups (PCOS or control) or between groups (PCOS vs. control) in the oral glucose tolerance test-derived measure of insulin sensitivity, but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus, there was a significant decrease (P < 0.0001). At the follow-up visit, the mean glycohemoglobin level was 6.1 +/- 0.9% in women with PCOS vs. 5.3 +/- 0.7% in the control women (P < 0.001). Women with PCOS and baseline IGT had a low conversion risk of 6% to type 2 diabetes over approximately 3 yr, or 2% per year. The effect of PCOS, given normal glucose tolerance (NGT) at baseline, is more pronounced with 16% conversion to IGT per year. Our study supports that women with PCOS (especially with NGT) should be periodically rescreened for diabetes due to worsening glucose intolerance over time, but this interval may be over several years and not annually.     

Treatment of infertility in women with polycystic ovary syndrome

The treatment of infertility in polycystic ovary syndrome (PCOS) associates lifestyle measures, and the use of drugs to induce ovulation. In this endeavour, clomifene citrate (CC) should be used as the first line of treatment, followed eventually by low dose gonadotrophin stimulation, as a second line. In rare cases, in case of failure of the CC treatment, ovarian drilling i.e. laparoscopic ovarian surgery (LOS), and finally assisted reproduction techniques can be used, if needed. Overall, ovulation induction (representing the CC-gonadotrophin paradigm) is highly effective with a cumulative singleton live birth rate of 72%. The use of insulin sensitizers i.e. metformin in PCOS should be restricted to women with glucose intolerance and/or insulin resistance. Based on recent data available, the routine use of this drug, alone, in ovulation induction is not recommended.     

Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case–control study

Aims To compare maternal and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with either metformin or insulin. Methods One hundred and twenty‐seven women with GDM not adequately controlled by dietary measures received metformin 500 mg twice daily initially. The dose was titrated to achieve target blood glucose values. Pregnancy outcomes in the 100 women who remained exclusively on metformin were compared with 100 women with GDM treated with insulin matched for age, weight and ethnicity. Results There were no significant differences in baseline maternal risk factors. Women treated with insulin had significantly greater mean (sem ) weight gain from enrolment to term (2.72 ± 0.4 vs. 0.94 ± 0.3 kg; P < 0.001). There was no difference between the metformin and insulin groups, respectively, comparing gestational hypertension (6 vs. 7%, P = 0.9), pre‐eclampsia (9 vs. 2%, P = 0.06) induction of labour (26 vs. 24%, P = 0.87) or rate of Caesarean section (48 vs. 52%, P = 0.67). No perinatal loss occurred in either group. Neonatal morbidity was improved in the metformin group; prematurity (0 vs. 10%, P < 0.01), neonatal jaundice (8 vs. 30%, P < 0.01) and admission to neonatal unit (6 vs. 19%, P < 0.01). The incidence of macrosomia (birthweight centile > 90) was not significantly different [metformin (14%) vs. insulin (25%); P = 0.07]. Conclusions Women with GDM treated with metformin and with similar baseline risk factors for adverse pregnancy outcomes had less weight gain and improved neonatal outcomes compared with those treated with insulin.     

Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with higher prevalence of cardiovascular risk factors but the relative prevalence of cardiovascular disease in women with PCOS has not previously been reported. We have compared cardiovascular mortality and morbidity in middle-aged women previously diagnosed with PCOS and age-matched control women. DESIGN: A retrospective cohort study of women diagnosed with PCOS in the United Kingdom before 1979. PATIENTS: Seventy cohort members died before 31 March 1999. Morbidity data were collected from 319 women with PCOS and 1060 age-matched control women. Sixty-one women with PCOS and 63 control women attended a clinical examination. MEASUREMENTS: Data were collected from death certificates, general practitioners' records and questionnaires with measurement of cardiovascular risk factors in a subsample of questionnaire respondents. RESULTS: All-cause and cardiovascular mortality in the cohort were similar to women in the general population (standardized mortality ratios (95% CI): 93 (72-117) and 78 (45-124), respectively). Women with PCOS had higher levels of several cardiovascular risk factors: diabetes (P = 0.002) hypertension (P = 0.04), hypercholesterolaemia (P < 0.001), hypertriglyceridaemia (P = 0.02) and increased waist:hip ratio (P = 0.004). After adjustment for BMI, odds ratios (OR) were 2.2 (0.9-5. 2) for diabetes, 1.4 (0.9-2.0) for hypertension and 3.2 (1.7-6.0) for hypercholesterolaemia. A history of coronary heart disease (CHD) was not significantly more common in women with PCOS (crude OR (95%CI) 1.5 (0.7-2.9)) but the crude OR for cerebrovascular disease was 2.8 (1.1-7.1). CONCLUSION: At long-term follow-up, a history of nonfatal cerebrovascular disease and cardiovascular risk factors including diabetes are more prevalent among women with polycystic ovary syndrome. Morbidity and mortality from of coronary heart disease among women with polycystic ovary syndrome is not as high as previously predicted. This finding challenges our understanding of the aetiology of coronary heart disease in women.     

Infertility and pregnancy in women with polycystic ovary syndrome

Management of polycystic ovary syndrome (PCOS) usually spans a woman's reproductive years. While treatment of androgenic symptoms is often a primary concern, periodically, the regimen has to be modified because of a desire for pregnancy. At this time the couple should be evaluated for factors that may contribute to infertility and this should include semen analysis. However, for many, anovulation is likely to be the cause of infertility and ovulation induction is generally required. The premise on which ovulation induction in PCOS is based is two-fold: increasing ovarian exposure to follicle stimulating hormone (FSH) and/or correcting hormonal derangements. Potential differences in pathogenesis, evidenced clinically by phenotypic diversity, would suggest that treatment should be individualized. After a brief overview of factors relating to infertility, this paper outlines treatments available for ovulation induction in women with PCOS and provides a critical appraisal of management options. These options include the use of clomiphene citrate, insulin sensitizers, and the combination. Protocols for ovulation induction with FSH injections are outlined and the relative risks of multiple gestation and severe ovarian hyperstimulation syndrome of these various protocols discussed. The use of aromatase inhibitors and the occasional use of glucocorticoids are briefly reviewed, and indications for in vitro fertilization and laparoscopic ovarian diathermy outlined. Pregnancy outcome in this patient population is also discussed.     

多囊卵巢综合征患者血清瘦素水平测定的意义

为了探讨多囊卵巢综合征(PCOS)患者血清瘦素(Leptin)水平测定的临床意义,选择47例PCOS患者与34例体重相匹配的对照妇女,于卵泡期测定Leptin、体重指数(BMI)、腰围(WC)、腰臀比(WHR)、胰岛素(INS)、内分泌激素,并对其进行相关与回归分析。结果:PCOS组血清Leptin浓度(18.69±8.05)ng/ml,对照组(17.09±10.35)ng/ml,差异无显著性(P>0.05);PCOS组血清INS浓度(12.45±8.07)mU/L,对照组(5.95±1.19)mU/L,差异有显著性(P<0.01)。Leptin与BMI、WC、WHR、INS成正相关。认为PCOS患者血清Leptin水平并不高于对照组,Leptin水平与体脂分布、INS有关,可能间接参与PCOS的病变形成。     

Cardiopulmonary impairment in young women with polycystic ovary syndrome

CONTEXT: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related to mitochondrial function, particularly with maximal oxygen consumption (VO(2max)). At the moment, no evaluation of cardiopulmonary functional capacity in young patients with PCOS has been performed. OBJECTIVE: Our objective was to assess cardiopulmonary functional capacity in young PCOS overweight patients. DESIGN AND SETTING: We conducted a prospective baseline-controlled clinical study at University Federico II of Naples, School of Medicine (Naples, Italy). PATIENTS: Forty-five PCOS patients were matched with 45 healthy women for age (mean +/- sd, 21.3 +/- 2.0 vs. 21.6 +/- 1.9 yr, respectively) and body mass index (29.4 +/- 3.6 vs. 29.0 +/- 3.4 kg/m(2), respectively). MEAN OUTCOME MEASURES: We assessed hormonal and metabolic pattern and functional capacity by cardiopulmonary exercise testing to evaluate maximal oxygen consumption (VO(2max)), oxygen consumption at anaerobic threshold (VO(2AT)), and the maximal workload at peak exercise. RESULTS: VO(2max) (17.0 +/- 3.7 vs. 26.8 +/- 3.5 ml/kg.min), oxygen consumption at anaerobic threshold (13.9 +/- 3.0 vs. 21.2 +/- 3.8 ml/kg.min), and maximal workload at peak exercise (101.3 +/- 25.2 vs. 135 +/- 22.6 W) were significantly (P < 0.001) reduced in PCOS subjects compared with healthy women. The multiple linear regression analysis showed that only homeostasis model assessment appears to have a strong negative linear relation with VO(2max) in PCOS. No relation was found in controls. CONCLUSIONS: Our data demonstrate a reduced cardiopulmonary functional capacity in young PCOS patients.     

多囊卵巢综合征性激素水平检测

目的：探讨血清性激素各项检测指标与不同年龄段的多囊卵巢综合征（PCOS）患者的关系及其临床意义。方法：以月经周期正常的健康妇女为对照组,采用化学发光法测定30岁以下年龄组和30岁及以上年龄组PCOS患者促黄体生成素（LH）、促卵泡生成素（FSH）、泌乳素（PRL）、雌二醇（E2）、睾酮（TESTO）、孕酮（Prog）水平,通过统计学软件进行比较分析。结果：多囊卵巢综合征患者,30岁以下年龄组和30岁及以上年龄组LH高于对照组（P〈0．01）,E2高于对照组（P〈0．05）,TESTO高于对照组（P〈0．01）。30岁以下PCOS患者组和30岁及以上PCOS患者组各检测指标之间差异无统计学意义（P〉0．05）。结论：血清中LH,E2高水平及TESTO增高可能是多囊卵巢综合征的预示因子,高LH、高E2、高雄激素血症可能是引起PCOS发生的因素之