Decreased soluble leptin receptor levels in women with polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level. DESIGN: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 +/- 5.7 years) and 81 healthy controls (aged 25 +/- 4.0 years). METHODS: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism. RESULTS: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 +/- 20.7 vs 45.4 +/- 25.0 vs 67.7 +/- 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 +/- 3.4 vs 6.4 +/- 2.5 vs 5.7 +/- 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 +/- 3.4 vs 12.7 +/- 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 +/- 3.9 vs 2.8 +/- 2.2, P = 0.0285). CONCLUSION: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.     

Androgen receptor gene CAG(n) trinucleotide repeats polymorphism in Chinese women with polycystic ovary syndrome

Trinucleotide repeats CAG(n) in androgen receptor gene is thought to be a potential site of genetic susceptibility to polycystic ovary syndrome (PCOS). However, previous studies of PCOS have shown variable association of CAG(n )polymorphism with PCOS. In order to evaluate CAG(n )polymorphism in Chinese women with PCOS, we have genotyped CAG(n) repeat numbers in female Chinese subjects (148 PCOS patients and 104 control subjects). The mean CAG(n) repeat lengths of PCOS patients and control subjects were similar (22.88 +/- 1.76 vs. 22.85 +/- 1.60; P = NS). No difference in the mean CAG(n) repeat lengths of hyperandrogenic and nonhyperandrogenic subgroups of PCOS patients was found (22.86 +/- 1.68 vs. 22.91 +/- 1.84; P = NS). Moreover, no difference was found in the term of mean CAG(n) repeat lengths in the nonhyperandrogenic subgroup and the control subjects (22.86 +/- 1.68 vs. 22.85 +/- 1.60; P = NS). However, mean CAG(n) repeat lengths were negatively correlated with serum total cholesterol and low-density lipoprotein-cholesterol concentration in PCOS patients (r = -0.182, P < 0.05 and r = -0.210, P < 0.05, respectively), but not with total testosterone, body mass index, waist and hip circumferences. The CAG(n) repeat length polymorphism may not be a major determinant of PCOS, but it may influence the lipid metabolism of PCOS patients.     

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.     

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.     

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.     

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.     

Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome

CONTEXT: Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS. OBJECTIVE: We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls. DESIGN: Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. PARTICIPANTS: Participants included 330 women with PCOS and 289 controls (77% white, 23% black). MAIN MEASUREMENTS: Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured. RESULTS: A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women. CONCLUSIONS: Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.     

GH release after GHRH plus arginine administration in obese and overweight women with polycystic ovary syndrome

Few and unclear data are available in the literature about the relationship between impairment of GH/IGF-I axis and polycystic ovary syndrome (PCOS). This study was aimed to evaluate the basal GH and IGF- levels, and GH release after challenge test in obese and overweight women with PCOS. Thirty patients with PCOS and other 30 healthy women matched for age, body mass index (BMI) and waist-hip ratio (WHR) were studied. Serum follicle-stimulating hormone (FSH), LH, PRL, E2, P, 17OH-progesterone (17OH-P), total T, delta4, DHEA-S, SHBG, GH and IGF-I levels were evaluated in each subject. A GHRH plus arginine challenge test was performed in all subjects. After provocative test, in PCOS and control women the GH levels were significantly (p<0.05) higher in comparison to basal values from 30 min to 120 min. At the same times, a significant (p<0.05) difference was observed between women with PCOS in comparison to healthy women. The mean peak value of GH resulted significantly (p<0.05) lower in PCOS women in comparison to healthy women. The total GH response (area under curve, AUC) to GHRH plus arginine test resulted significantly (p<0.05) lower in PCOS than in healthy women. These findings were statistically significant (p<0.05) also considering the distinction in obese and overweight women. The AUC for GH secretion was significantly lower (p<0.05) in obese in comparison to overweight subjects in the control group, whereas no significant difference was detected between obese and overweight women in the PCOS group. In conclusion, in PCOS women there is a BMI-independent alteration of the GH levels. Further investigations will be necessary to establish the real cause of these data.     

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.     

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     

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.     

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.     

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.     

Vascular compliance in women with polycystic ovary syndrome and healthy women

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, has been associated with the cardiometabolic syndrome and increased risk for cardiovascular diseases. Large (C1) and small (C2) vessel compliance and fasting lipids were measured in 45 healthy women and 36 women with PCOS. There were no differences in vacular compliance (C1, C2) between the 2 groups. Systolic blood pressure (116.8 vs 124.3 mm Hg; P=.01), mean arterial pressure (82.5 vs 87 mm Hg; P=.03), and low-density lipoprotein cholesterol (98.1 vs 119 mg/dL; P=.001) were significantly higher in the PCOS group. This difference was not significant after adjusting for age and body mass index. High-density lipoprotein levels in subjects with PCOS were significantly lower than in healthy women (60.2 vs 48.9 mg/dL, P=.02) even after adjusting for age and body mass index. The study indicates that obesity and low high-density lipoprotein are the major contributing factors to cardiovascular changes in PCOS.     

The metabolic syndrome in young Korean women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and consequent hyperinsulinemia. Insulin resistance also plays an important role in the metabolic syndrome (MS). We conducted a cross-sectional study to determine the prevalence of the MS in young Korean women with PCOS and whether it is associated insulin resistance. One hundred and seventeen young women with PCOS (age: 26+/-5, 16-39 years) were evaluated for the frequency of MS according to the modified Adult Treatment Panel III. Total testosterone (T), free T, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured, and insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp technique. The prevalence of MS in women with PCOS was 14.5%, nearly 3.5-fold higher than in age-matched women in Korean urban population (4.3%) [J.-Y. Oh, Y.-A. Sung, Y.S. Hong, E. Barrett-Conner, Prevalence and factor analysis of metabolic syndrome in an urban Korean population, Diabetes Care 27 (2004) 2027-2032]. The most frequently occurring component of MS was low HDL cholesterol (45%), and the least frequent was high fasting serum glucose level (0.9%). PCOS women with MS had significantly higher free T, and lower SHBG compared with those without MS. And women with MS showed significantly lower M-value and higher fasting/post-glucose load insulin levels. M-value was still significantly lower in women with MS even after the adjustment for BMI. MS is frequent in young Korean women with PCOS and it reflects more severe insulin resistance. These results suggest the importance of early and regular screening of metabolic disturbance in even young women with PCOS.