Metabolic profile in sons of women with polycystic ovary syndrome

CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder with strong familial aggregation. It has been demonstrated that parents and brothers of PCOS women exhibit insulin resistance and related metabolic defects. However, metabolic phenotypes in sons of PCOS women have not been described. OBJECTIVE: Our objective was to assess the metabolic profiles in sons of women with PCOS during different stages of life: early infancy, childhood, and adulthood. DESIGN: Eighty sons of women with PCOS (PCOS(S)) and 56 sons of control women without hyperandrogenism (C(S)), matched for age, were studied. In early infancy, glucose and insulin were determined in the basal sample. In children and adults, a 2-h oral glucose tolerance test was performed with measurements of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, and serum lipids were determined in the basal sample during the three periods. RESULTS: During early infancy, PCOS(S) showed higher weight (P = 0.038) and weight sd score (P = 0.031) than C(S). During childhood, weight (P = 0.003), body mass index (BMI) (P < 0.001), BMI sd score (P < 0.001), waist circumference (P = 0.001), total cholesterol (P = 0.007), and low-density lipoprotein cholesterol (P = 0.022) were higher in PCOS(S) compared with C(S), but after adjusting for BMI, these differences were nonsignificant. During adulthood, PCOS(S) exhibited higher weight (P = 0.022), BMI (P = 0.046), and waist circumference (P = 0.028) than C(S). Fasting insulin (P = 0.030), homeostasis model assessment for insulin resistance (P = 0.034), total cholesterol (P = 0.043), low-density lipoprotein cholesterol (P = 0.034), and 2-h insulin (P = 0.006) were also significantly higher and insulin sensitivity index composite significantly lower in PCOS(S) than in C(S) (P = 0.003). After adjusting for BMI, only 2-h insulin and insulin sensitivity index composite remained significantly different. CONCLUSIONS: This study indicates that sons of PCOS women exhibit higher body weight from early infancy. In addition, insulin resistance became evident as the subjects got older, which may place them at risk for the development of type 2 diabetes and cardiovascular disease.     

多囊卵巢综合征(PCOS)患者子嗣的代谢特征

多囊卵巢综合征(PCOS)是一种家族性内分泌代谢疾病,在育龄妇女中的比例约为5%-8%,特征为月经不规则、长期无排卵、不育及高雄激素血症.约50%的PCOS患者超重或肥胖,大多数人腹部脂肪过多.此外,PCOS患者也可有其它方面的代谢异常,如胰岛素抵抗、糖耐量受损、2型糖尿病以及与脂代谢相关的异常发生率增高.     

Altered vascular function in young women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinemic insulin resistance, a metabolic disorder that in other circumstances is associated with increased cardiovascular risk. We compared macrovascular and microvascular function in 19 women with PCOS with 12 control subjects matched as a group for body mass index. Macrovascular function was assessed by recording pulse wave velocity (PWV) across the aorta and brachial artery. Microvascular function was studied by wire myography, by measuring the concentration response curve to norepinephrine (NE) before and after incubation with insulin (100 and 1,000 pM). PWV at the level of the brachial artery was found to be significantly elevated in the PCOS group [9.08 (range, 8.34-11.15) m/sec(-1) vs. 8.27 (range, 7.5-9.01) m/sec(-1); P = 0.03]. In contrast, PWV measured in the aorta did not differ between the two groups [7.49 +/- 1.21 vs. 7.84 +/- 1.44 m/sec(-1); P = 0.8]. In vessels from control subjects, insulin reduced the contraction response to NE. At an insulin concentration of 100 pM, NE negative log EC50 (pD(2)) was 6.2 +/- 0.24 vs. 6.7 +/- 0.15 (P = 0.02). At a concentration of 1,000 pM, NE pD(2) was 6.4 +/- 0.14 vs. 6.9 +/- 0.19 (P = 0.0006). Both concentrations also caused attenuation in maximal tension developed in response to NE (insulin 100 pM, 12 +/- 3%, P = 0.002; insulin 1,000 pM, 17 +/- 5%, P = 0.009). In contrast, there was no change in the PCOS group with insulin at 100 pM for either pD(2) (6.7 +/- 0.24 vs. 6.8 +/- 0.27; P = 0.3) or maximum contraction (-0.4 +/- 2%; P = 0.8). At 1,000 pM, there was a change in pD(2) (6.4 +/- 0.2 vs. 6.8 +/- 0.2; P = 0.003) but not maximum contraction (4 +/- 3%; P = 0.2). In conclusion, this study is the first to demonstrate increased vascular stiffness and a functional defect in the vascular action of insulin ex vivo in patients with PCOS. We suggest that these findings are indicative of insulin resistance at a vascular level in women without overt cardiovascular disease.     

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.     

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.     

Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome

Obese women with polycystic ovary syndrome (PCOS) exhibit impaired endothelial function, which is strongly and directly correlated with both testosterone levels and insulin resistance. Endothelial dysfunction is considered a potent risk factor for macrovascular disease. Because troglitazone (Tgz) improves both hormonal profiles and insulin sensitivity, we tested whether Tgz treatment ameliorates endothelial function in these patients. We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m(2) x min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d). A group of 13 obese women (OBW) matched for age, weight, body fat (>40% in both groups), blood pressure, and total cholesterol served as controls. PCOS patients exhibited elevated free testosterone (fT) and triglycerides (TG) and lower high density lipoprotein cholesterol levels compared with OBW [14.0 +/- 1.0 vs. 3.7 +/- 0.6 pmol/liter (P < 0.0001), 1.60 +/- 0.28 vs. 0.94 +/- 0.09 mmol/liter (P < 0.02), and 0.91 +/- 0.04 vs. 1.1 +/- 0.04 mmol/liter (P < 0.005), respectively]. Tgz treatment reduced fT levels, but did not improve the TG and high density lipoprotein profile [to 9.7 +/- 2.8 pmol/liter (P < 0.007), 1.49 +/- 0.34 mmol/liter (P = NS), and 0.93 +/- 0.07 mmol/liter (P = NS), respectively]. Basal LBF was unchanged after Tgz. In PCOS compared with OBW, insulin stimulated glucose disposal (52.7 +/- 6.6 vs. 85.5 +/- 4.4 micromol/kg fat-free mass x min; P < 0.0005) and vasodilation (increase in LBF, 22 +/- 14% vs. 59 +/- 15%; P < 0.05) were significantly improved after Tgz treatment to 68.8 +/- 7.2 micromol/kg fat-free mass x min (P < 0.0001) and 101 +/- 48% (P < 0.03), respectively. The increase in LBF in response to MCh in PCOS was markedly more pronounced after treatment (P < 0.01, by ANOVA) and was similar to that observed in OBW. Before Tgz treatment, maximal LBF increments in response to MCh were 130 +/- 25% and 233 +/- 29% in PCOS and OBW, respectively (P < 0.01). After Tgz treatment, PCOS values improved, achieving increments similar to those in OBW (245 +/- 45%; P < 0.04). Tgz treatment in PCOS improves both hormonal and metabolic features. These modifications are associated with improvement of endothelial function, suggesting that Tgz could be a useful tool to reduce the risk of macrovascular disease in women with PCOS and perhaps in other insulin-resistant syndromes.     

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.     

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.     

Exaggerated glucagon responses to hypoglycemia in women with polycystic ovary syndrome

ContextPremenopausal women have blunted counter-regulatory hormone responses (CRR) to hypoglycemia compared to men. Postmenopausal women have CRR similar to men; the premenopausal pattern can be restored by estrogen. However, glucagon and pancreatic polypeptide (PP) responses remain lower in postmenopausal women than in men. Since hyperandrogenemia contributes to the metabolic phenotype of polycystic ovary syndrome (PCOS), we hypothesize that CRR to hypoglycemia especially of glucagon and PP is exaggerated in premenopausal women with PCOS compared to premenopausal control women.Study Subjects and MethodsTen obese women with PCOS and 9 control women of similar ethnicity, age and BMI underwent determination of CRR in response to hypoglycemia during 180-min 60 mU/m²/min insulin dose hypoglycemic clamp with isotopic assessment of endogenous glucose production (EGP). To assess CRR to hypoglycemia, glucagon, cortisol, growth hormone (GH), epinephrine, norepinephrine, PP, lactate, free fatty acid (FFA), β-hydroxybutyrate, and glycerol levels were sampled at 15-min intervals throughout the clamp.Main FindingsIncremental glucagon levels were ~ 3-fold higher during hypoglycemia (P = 0.03) in PCOS. Postabsorptive, steady-state and incremental GH, cortisol, epinephrine, norepinephrine, PP, FFA, glycerol and β-hydroxybutyrate did not differ. At target glucose levels of ~ 52 mg/dL, insulin mediated glucose disposal (IMGD) was decreased by ~ 40% (P = 0.02) in PCOS, compared to control women, despite ~ 20% higher steady-state insulin levels (P = 0.03). Neither postabsorptive nor steady-state EGP differed. However, postabsorptive lactate levels were ~ 50% higher (P = 0.02). PCOS status (P = 0.04) and IMGD (P = 0.02) predicted the differential glucagon response to hypoglycemia in separate regression models, however, neither parameter remained an independent predictor in a combined model.Principal ConclusionsGlucagon responses were increased in PCOS, whereas other CRR did not differ. Women with PCOS were insulin resistant under hypoglycemic conditions and higher postabsorptive lactate levels in PCOS were consistent with this finding. Insulin resistance may have contributed to exaggerated glucagon response to hypoglycemia in PCOS.     

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