Dyslipidemia and metabolic syndrome in the sisters of women with polycystic ovary syndrome

CONTEXT: Dyslipidemia is a feature of polycystic ovary syndrome (PCOS), but its pathogenesis remains controversial. OBJECTIVE: The objective of this study was to test the hypothesis that dyslipidemia is a heritable trait in sisters of women with PCOS. DESIGN: A case-control design was used. SETTING: The study took place at General Clinical Research Centers in four academic medical centers in the United States. PATIENTS: The subjects included 385 sisters of women with PCOS with the following reproductive phenotypes: sisters with PCOS (n = 51), sisters with hyperandrogenemia and regular menses (HA) (n = 38), unaffected sisters (n = 143), and unknown phenotypes (n = 153). One hundred twenty-five control women of comparable age, body mass index, and ethnicity to women with PCOS were included. INTERVENTIONS: Fasting blood was obtained for measurements of lipid profile, reproductive hormones, glucose, and insulin levels. MAIN OUTCOME MEASURES: The main outcome measures included lipid and lipoprotein levels and prevalence of metabolic syndrome. RESULTS: Sisters with PCOS and HA phenotypes had higher total (P < or = 0.001) and low-density lipoprotein cholesterol levels (P < or = 0.01) compared with unaffected sisters and control women. Triglyceride levels were elevated only in sisters with the PCOS phenotype (P < 0.05). The prevalence of metabolic syndrome was increased in sisters with the PCOS (n = 29) and HA (n = 17) phenotypes compared with unaffected sisters (n = 85) (P < 0.001 and P < 0.05, respectively). CONCLUSIONS: Low-density lipoprotein levels are increased in affected sisters of women with PCOS consistent with a heritable trait. The prevalence of metabolic syndrome is increased in affected sisters.     

Circulating ghrelin levels in patients with polycystic ovary syndrome

The syndrome of polycystic ovaries (PCOS) is associated with adiposity and metabolic changes predisposing to insulin resistance and diabetes mellitus. Because the recently discovered GH secretagogue, ghrelin, is intimately involved in the control of appetite and weight regulation, we studied ghrelin levels in a group of 26 otherwise healthy women with PCOS. They were compared with 61 healthy female control subjects and 5 gastrectomized women. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and continuous infusion of glucose with model assessment (CIGMA) in all patients. In PCOS women, serum ghrelin levels were significantly lower than in healthy lean or obese controls (P < 0.001). In insulin-sensitive PCOS women, ghrelin concentrations compared well with the healthy controls, whereas in insulin-resistant PCOS ghrelin levels were significantly lower and indistinguishable from the low levels found in the gastrectomized women. There was a close correlation of ghrelin to insulin sensitivity (HOMA, r(2) = 0.330, P < 0.002; CIGMA, r(2) = 0.568, P < 0.0001). Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations (P < 0.02). Ghrelin levels did not correlate to any of the parameters of hyperandrogenemia, to the LH/FSH ratio, to body mass index, or to fasting insulin and glucose concentrations. In summary, ghrelin levels are decreased in PCOS women and are highly correlated to the degree of insulin resistance. This suggests that ghrelin could be linked to insulin resistance in PCOS women. However, whether low ghrelin in PCOS is a cause or the consequence of insulin resistance awaits further investigations.     

Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Dyslipidemia is a feature of polycystic ovary syndrome (PCOS), but its pathogenesis remains controversial. We performed this study of mothers of women with PCOS to test the hypothesis that dyslipidemia is a heritable trait in families of women with PCOS and to investigate the impact of age on reproductive and metabolic phenotypes. Fasting blood was obtained in 215 non-Hispanic white mothers of women with PCOS and 62 control women. The prevalence of metabolic syndrome was compared with that in non-Hispanic white women of comparable age from the National Health and Nutrition Examination Survey III. Mothers had higher total (P < 0.001) and low-density lipoprotein (LDL) cholesterol levels (P = 0.007), whereas high-density lipoprotein and triglyceride levels did not differ compared with control women. The only predictors of LDL levels in mothers were their daughters' LDL levels (r2 = 0.11, P < 0.001) and their own unbound testosterone levels (r2 = 0.04, P = 0.03). The prevalence of metabolic syndrome was increased in obese (body mass index > or = 30 kg/m2) mothers compared with obese non-Hispanic white women from the National Health and Nutrition Examination Survey III (P = 0.04). Thirty-one percent of mothers reported a history of menstrual irregularity. These mothers had higher androgen levels, markers of insulin resistance, and LDL levels than mothers with regular menses. LDL levels are increased in mothers of women with PCOS, suggestive of a heritable trait. A history of menstrual irregularity identifies mothers with features of PCOS. Obese mothers have a very high prevalence of metabolic syndrome. These findings suggest that both the reproductive and metabolic abnormalities persist with age in PCOS.     

Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is characterized by insulin resistance with compensatory hyperinsulinemia. Insulin resistance also plays a role in the metabolic syndrome (MBS). We hypothesized that the MBS is prevalent in PCOS and that women with both conditions would present with more hyperandrogenism and menstrual cycle irregularity than women with PCOS only. We conducted a retrospective chart review of all women with PCOS seen over a 3-yr period at an endocrinology clinic. Of the 161 PCOS cases reviewed, 106 met the inclusion criteria. The women were divided into two groups: 1) women with PCOS and the MBS (n = 46); and 2) women with PCOS lacking the MBS (n = 60). Prevalence of the MBS was 43%, nearly 2-fold higher than that reported for age-matched women in the general population. Women with PCOS had persistently higher prevalence rates of the MBS than women in the general population, regardless of matched age and body mass index ranges. Acanthosis nigricans was more frequent in women with PCOS and the MBS. Women with PCOS and the MBS had significantly higher levels of serum free testosterone (P = 0.002) and lower levels of serum SHBG (P = 0.001) than women with PCOS without the MBS. No differences in total testosterone were observed between the groups. We conclude that the MBS and its components are common in women with PCOS, placing them at increased risk for cardiovascular disease. Women with PCOS and the MBS differ from their counterparts lacking the MBS in terms of increased hyperandrogenemia, lower serum SHBG, and higher prevalence of acanthosis nigricans, all features that may reflect more severe insulin resistance.     

Altered multihormone synchrony in obese patients with polycystic ovary syndrome

Luteinizing hormone (LH) concentrations and pulsatility are increased in obese women with polycystic ovary syndrome (PCOS). In addition, patients have hyperandrogenemia and insulin resistance. The mechanisms involved in aberrant hormone regulation in PCOS are still unclear. We investigated 15 obese PCOS women with a body mass index between 30 and 54 kg/m² and 9 healthy obese controls (body mass index, 31-60 kg/m²) with regular menstrual cycles. Subjects underwent 24-hour blood sampling at 10-minute intervals for later measurements of LH, leptin, testosterone, and insulin concentrations. Data were analyzed with a new deconvolution program, approximate entropy (and bivariate approximate entropy), and a cross-correlation network. Patients had increased LH pulse frequency and more than 2-fold greater daily LH secretion, with diminished pattern regularity. Testosterone secretion was increased 2-fold, but pattern regularity was similar to that in controls. In the network construct, insulin was correlated positively with LH, whereas leptin and testosterone were correlated negatively with LH. Bivariate synchrony of LH with insulin was decreased. Short-term caloric restriction paradoxically increased LH secretion by 1.5-fold and pattern irregularity, and reduced interpulse variability. Testosterone secretion and fasting concentrations of estradiol and sex hormone-binding globulin levels remained unchanged. Correlations between LH and insulin, leptin, and calculated free testosterone decreased. This study demonstrates marked alterations in the control of LH secretion in PCOS in the fed and calorie-restricted states. The ensemble results point to abnormal feedback control of not only the GnRH-gonadotrope complex, but also LH's relationships with leptin, insulin, and testosterone.     

Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment

CONTEXT: Insulin resistance plays a significant role in the pathogenesis of the polycystic ovary syndrome (PCOS) and represents a link to the unfavorable cardiovascular risk profile frequently found in affected patients. The endogenous nitric oxide synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality. OBJECTIVE: We investigated ADMA levels among other cardiovascular, metabolic, and hormonal parameters in women with PCOS and the effects of metformin treatment on these parameters. DESIGN: A cross-sectional study and clinical trial were performed. PATIENTS AND PARTICIPANTS: Women with PCOS (n = 83) compared with a control group of healthy women (n = 39) were studied. INTERVENTIONS: In a subgroup of patients with PCOS (n = 21), the effect of metformin was assessed after 6 months of treatment. MAIN OUTCOME MEASURES: ADMA, intima media thickness (IMT), metabolic and hormonal parameters, and markers of inflammation were investigated. RESULTS: ADMA levels were significantly higher in the PCOS group compared with controls (0.57 +/- 0.15 vs. 0.50 +/- 0.11; P = 0.024). Androgens, C-reactive protein, fasting C-peptide, area under the curve (AUC) insulin, AUC glucose, homeostatic assessment of insulin resistance, fasting insulin, glycosylated hemoglobin, cholesterol, low-density lipoprotein cholesterol, triglycerides, and IMT were significantly higher in women with PCOS compared with controls. In PCOS patients ADMA was found to be positively correlated with body mass index (BMI), waist to hip ratio, parameters of insulin sensitivity, hyperandrogenemia (free testosterone, free androgen index), and IMT. Treatment with metformin ameliorated hyperandrogenemia and decreased ADMA levels (0.53 +/- 0.06 vs. 0.46 +/- 0.09, P = 0.013). Decrease in ADMA levels subsequent to metformin treatment did not correlate with change in BMI or metabolic parameters. CONCLUSIONS: ADMA amd parameters of insulin sensitivity are elevated in women with PCOS and the degree of insulin resistance confers the greatest influence on ADMA level. Metformin treatment led to improvement of hormonal and metabolic parameters and decreased ADMA levels possibly independent of BMI and metabolic changes.     

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome

Our preliminary family studies have suggested that some female first-degree relatives of women with polycystic ovary syndrome (PCOS) have hyperandrogenemia per se. It was our hypothesis that this may be a genetic trait and thus could represent a phenotype suitable for linkage analysis. To investigate this hypothesis, we examined 115 sisters of 80 probands with PCOS from unrelated families. PCOS was diagnosed by the combination of elevated serum androgen levels and ≤6 menses per year with the exclusion of secondary causes. The sisters were compared with 70 healthy age- and weight-comparable control women with regular menses, no clinical evidence of hyperandrogenemia, and normal glucose tolerance. Twenty-two percent of the sisters fulfilled diagnostic criteria for PCOS. In addition, 24% of the sisters had hyperandrogenemia and regular menstrual cycles. Circulating testosterone (T) and nonsex hormone-binding globulin-bound testosterone (uT) levels in both of these groups of sisters were significantly increased compared with unaffected sisters and control women (P < 0.0001 for both T and uT). Probands, sisters with PCOS, and hyperandrogenemic sisters had elevated serum luteinizing hormone levels compared with control women. We conclude that there is familial aggregation of hyperandrogenemia (with or without oligomenorrhea) in PCOS kindreds. In affected sisters, only one-half have oligomenorrhea and hyperandrogenemia characteristic of PCOS, whereas the remaining one-half have hyperandrogenemia per se. This familial aggregation of hyperandrogenemia in PCOS kindreds suggests that it is a genetic trait. We propose that hyperandrogenemia be used to assign affected status in linkage studies designed to identify PCOS genes.     

多囊卵巢综合征患者肥胖和高雄激素血症与胰岛素抵抗的相关性

收集多囊卵巢综合征(PCOS)患者101例,招募30名正常健康志愿者。根据血清雄激素水平及稳态模型评估的胰岛素抵抗指数(HOMA-IR)水平分层分析肥胖、高雄激素和胰岛素抵抗的关系。结果显示,101例PCOS患者中39.8％患者体重正常,24.5％超重,35.7％肥胖。将PCOS患者分为正常雄激素组(睾酮＜0.51 μg/L)和高雄激素组(睾酮≥0.51 μg/L),两组体重指数(BMI)、空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及HOMA-IR均无统计学差异。将PCOS患者分为非胰岛素抵抗组(HOMA-IR＜2.29)和胰岛素抵抗组(HOMA-IR≥2.29),两组血清睾酮水平无统计学差异,胰岛素抵抗组的BMI、FPG、TG、TC、LDL-C明显高于非胰岛素抵抗组(P＜0.05或P＜0.01),HDL-C明显低于非胰岛素抵抗组(P＜0.01)。HOMA-IR与BMI显著相关(P＜0.01),而与血清睾酮水平无显著相关性,提示PCOS患者体重增加与HOMA-IR的相关性独立于血清睾酮水平。     

Neck circumference a good predictor of raised insulin and free androgen index in obese premenopausal women: changes with weight loss

OBJECTIVE: Severe obesity can be associated with evidence of androgen excess and insulin resistance, which are features of the metabolic and polycystic ovary syndromes (PCOS). In this study, we examined the association between clinical and biochemical features of these syndromes and assess changes with weight loss. DESIGN: A consecutive series of 107 severely obese premenopausal women presenting for obesity surgery. MEASUREMENTS: Pre-operative assessment included details of clinical comorbidity, anthropometric measures and biochemical measures, including fasting insulin, glucose, lipid profile and sex hormone analysis. Changes in these measures for 42 of 52 (81%) patients at 1 year post surgery are reported. RESULTS: Neck circumference and younger age were independent predictors of higher free androgen index (FAI) (combined r2 = 0.36). If neck circumference is not included, then younger age, higher body mass index and raised fasting insulin levels were all independent predictors of FAI (r2 = 0.29). Waist to hip ratio showed no predictive value (r = 0.14). Neck circumference was also a good clinical predictor of menstrual irregularity, hirsutism, infertility, insulin resistance and the PCOS. Neck circumference of less than 39, 39-42 and greater than 42 cm reflect a low, intermediate and high risk of the metabolic and PCOS syndromes in obese premenopausal women. For 42 patients who were followed for 1 year after surgery, the weight loss was associated with reduction of FAI, less insulin resistance and improved menstrual regularity and resolution of the PCOS in 11 of 12 cases. CONCLUSIONS: Neck circumference is a good predictive measure of hyperinsulinaemia and raised androgens in obese premenopausal women. Weight loss following surgery improves ovarian function and vasculopathic risk.     

The use of anti-mullerian hormone in predicting menstrual response after weight loss in overweight women with polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities, specifically menstrual dysfunction and anovulation in conjunction with elevated pre-antral follicle number and arrested follicular maturation. Although anti-müllerian hormone (AMH), an inhibitor of follicle recruitment and maturation, is increased in women with PCOS, the usefulness of circulating AMH levels as a clinical predictor of menstrual response to weight loss in PCOS is not known. METHODS: Overweight women with PCOS (n = 26, age 32.9 +/- 5.8 yr, weight 98.9 +/- 20.8 kg, body mass index 36.1 +/- 7.0 kg/m(2), mean +/- sd) followed an 8-wk weight loss and 6-month weight maintenance program. RESULTS: Net reductions in weight (4.6 +/- 4.8 kg), waist circumference (6.0 +/- 5.3 cm), testosterone (0.3 +/- 0.6 nmol/liter), fasting insulin (3.7 +/- 7.6 mU/liter), and the homeostasis model assessment of insulin sensitivity (0.7 +/- 1.3) occurred for all subjects over the entire study duration. Of 26 subjects, 15 (57.7%) responded to the intervention with improvements in menstrual cyclicity (responders). Compared to nonresponders, responders had lower AMH levels at baseline (23.6 +/- 12.0 vs. 37.9 +/- 17.8 pmol/liter; P = 0.021). Only responders had reductions in fasting insulin (6.1 +/- 5.9 mU/liter; P = 0.001) and homeostasis model assessment (1.3 +/- 5.9; P = 0.002) with acute weight loss (wk 0-8). Baseline AMH was most strongly predicted by baseline ghrelin, free testosterone, and insulin (r(2) = 0.528; P = 0.002). CONCLUSIONS: Overweight women with PCOS who respond to weight loss with menstrual improvements have significantly reduced preweight loss AMH and demonstrate improvements in surrogate measures of insulin resistance with weight loss. Pretreatment AMH is a potential clinical predictor of menstrual improvements with weight loss in PCOS.     

Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study

Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. Metformin did not have any effect on glucose tolerance or insulin sensitivity, but fasting insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic insulin clearance increased during the treatment. Furthermore, metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on glucose tolerance, serum insulin levels, or insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum leptin concentrations (P < 0.001) and decreased serum testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.     

Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome

Since an increase in tumor necrosis factor alpha (TNFalpha) expression has been associated with insulin resistance, this study was undertaken to determine the status of circulating TNFalpha and the relationship of TNFalpha with insulin levels, body weight, or both in women with polycystic ovary syndrome (PCOS). Fasting serum samples were analyzed in 34 subjects with PCOS, of whom 22 were obese (body mass index [BMI]>27 kg/m2), and in 40 normal control women, of whom 20 were obese. Women with PCOS exhibited a significantly (P<.02) higher mean serum TNFalpha concentration compared with the controls. The serum TNFalpha level and BMI were directly correlated in women with PCOS (r=.48, P<.005) and highly correlated in controls (r=.78, P<.001). When subjects were classified by body weight, the mean serum TNFalpha concentration was significantly (P<.001) elevated in normal-weight women with PCOS compared with normal-weight controls. On the other hand, mean serum TNFalpha concentrations in obese women with PCOS and obese controls were similar and significantly (P<.02) higher than in normal-weight women with PCOS. A direct correlation between serum fasting insulin and TNFalpha was evident in controls (r=.35, P<.03), but not in women with PCOS. However, in the subgroup of obese women with PCOS, fasting insulin directly correlated (r=.49, P<.03) with TNFalpha and the median fasting serum insulin concentration was significantly (P<.05) higher compared with the level in normal-weight women with PCOS and all controls. Fasting insulin and TNFalpha were no longer correlated in controls as a group and in obese women with PCOS when controlling for body weight. Serum TNFalpha did not correlate with luteinizing hormone (LH), testosterone (T), or dehydroepiandrosterone sulfate (DHEAS) in women with PCOS. However, serum insulin was significantly correlated (r=.49, P<.0004) with T and the BMI exhibited a trend for correlation with serum T (r=.33, P=.05) in women with PCOS. Finally, the mean serum LH concentration was significantly (P<.02) higher in normal-weight women with PCOS versus obese women with PCOS, and serum LH levels exhibited a trend for an inverse correlation with the BMI (r=.31, P=.09) in women with PCOS. We conclude that (1) serum TNFalpha is increased in normal-weight women with PCOS and is even higher in obese individuals regardless of whether they have PCOS; (2) factors other than obesity are the cause of elevated serum TNFalpha in normal-weight women with PCOS; and (3) whereas increased circulating TNFalpha may mediate insulin resistance in obesity, which may in turn promote hyperandrogenism in obese women with PCOS, it remains to be demonstrated whether this is also the case in normal-weight women with PCOS.     

Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome

CONTEXT: Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). OBJECTIVE: The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. DESIGN: A single-blind, placebo-controlled study was performed, lasting for 7 months. SETTING: The patients were ambulatory throughout the study. PATIENTS: Twenty PCOS subjects were enrolled. Eighteen completed the study. INTERVENTIONS: A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). MAIN OUTCOME MEASURES: The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. RESULTS: Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). CONCLUSIONS: Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.     

Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome

OBJECTIVE: The polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis. Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and putative antiatherosclerotic properties. The aim of the study was to elucidate determinants of circulating adiponectin levels and to investigate the potential role of adiponectin in insulin resistance in PCOS women. PATIENTS AND MEASUREMENTS: Plasma adiponectin and parameters of obesity, insulin resistance and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female controls. RESULTS: Both in PCOS and controls, adiponectin levels were lower in overweight or obese women than in normal-weight women, without any difference between PCOS and controls after adjustment for body mass index (BMI). In PCOS and in controls there was a significant correlation of adiponectin with BMI (r = -0.516, P < 0.001), fasting insulin (r = -0.404, P < 0.001), homeostasis model sensitivity (HOMA %S) (r = -0.424, P < 0.001) and testosterone (r = -0.279, P < 0.01), but no correlation with androstenedione (r = -0.112, P = 0.325), 17-OH-progesterone (r =-0.031, P = 0.784) or the LH/FSH ratio (r =-0.033, P = 0.753). Multiple linear regression analysis revealed that BMI and HOMA %S but not testosterone were independently associated with adiponectin plasma levels, explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin, respectively. In PCOS patients insulin sensitivity, as indicated by continuous infusion of glucose with model assessment (CIGMA %S) was significantly correlated with adiponectin (r = 0.55; P < 0.001), BMI (r =-0.575; P < 0.001), waist-to-hip ratio (WHR) (r =-0.48; P = 0.001), body fat mass assessed by dual-energy X-ray-absorptiometry (DEXA) [Dexa-fat (total) (r = -0.61; P < 0.001) and Dexa-fat (trunk) (r = -0.59; P < 0.001)] and with testosterone (r = -0.42; P = 0.001). Multiple linear regression analysis demonstrated that markers of obesity such as BMI, total or truncal fat mass, age and adiponectin were independently associated with CIGMA %S, and that circulating adiponectin accounted for about 18% of the degree of insulin resistance in PCOS. By contrast, testosterone was not a significant factor, suggesting that PCOS per se did not affect insulin sensitivity independent from obesity, age and adiponectin. Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0.59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia. CONCLUSIONS: PCOS per se is not associated with decreased levels of plasma adiponectin. However, circulating adiponectin is independently associated with the degree of insulin resistance in PCOS women and may contribute to the development and/or maintenance of insulin resistance independent from adiposity.     

多囊卵巢综合征患者血清对氧磷酯酶1活性、氧化应激与胰岛素抵抗的关系

目的探讨对氧磷酯酶1（PON-1）活性、氧化应激在多囊卵巢综合征（PCOS）患者发生胰岛素抵抗（IR）中的作用。方法41例PCOS患者分为肥胖组17例和非肥胖组24例,另有20名健康女性纳入正常对照组。所有研究对象均行口服糖耐量试验（OGTT）和胰岛素释放试验,使用稳态模型评价IR及胰岛B细胞分泌功能,空腹静脉取血检测丙二醛（MDA）、超氧化物歧化酶（SOD）活性及PON-1活性。结果（1）PCOS非肥胖组和PCOS肥胖组的空腹胰岛素、餐后2小时血糖及胰岛素、HOMA—IR及HOMA-β均高于正常组（P〈0．05）,且PCOS肥胖组的空腹胰岛素、餐后2小时血糖及胰岛素、HOMA—IR均高于PCOS非肥胖组（P％0．05）。（2）PCOS非肥胖组和PCOS肥胖组的MDA、SOD及PON-1与正常组比较差异有统计学意义（P〈0．05）;PCOS肥胖组的SOD显著低于PCOS非肥胖组（P％0．01）,而MDA及PON-1两组之间差异无统计学意义（P〉0．05）。（3）相关分析显示：在PCOS非肥胖组,SOD与PON—1正相关（r=0．417,P〈0．05）,SOD与IR负相关（r=0．492,P〈0．05）。结论PCOS患者无论肥胖与否,均存在餐后血糖升高、PON-1活性降低、氧化应激、IR,且肥胖患者更为严重;PCOS患者的氧化应激与IR相关。     

Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance

Our objective was to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone in obese women with polycystic ovary syndrome (PCOS) and severe insulin resistance. Twelve obese women with PCOS were recruited. All were hirsute and anovulatory with acanthosis nigricans indicating severe insulin resistance. All women were treated with 4 mg of rosiglitazone daily for 6 months. A standard 75-g oral glucose tolerance test with insulin levels was performed before and after the women were treated with rosiglitazone. Glucose and insulin areas under the curve (AUC) were calculated. Serum levels of total and free testosterone, dehydroepiandrosterone sulfate, LH, and 17-hydroxyprogesterone were also measured before and after treatment. The body mass index was determined before and after treatment. There was a highly significant (r = 0.881, P < 0.0001) positive correlation between insulin response during oral glucose tolerance test and basal total testosterone levels. After treatment with rosiglitazone, there were significant decreases in fasting insulin levels (46.0 +/- 6.5 vs. 16.9 +/- 2.0 microU/ml; P < 0.001), insulin AUC (749.3 +/- 136.3 vs. 225.0 +/- 15.7 microU/ml; P = 0.003), fasting glucose levels (90.8 +/- 3.0 vs. 81.8 +/- 1.9 mg/dl; P = 0.003), and glucose AUC (437.9 +/- 25.0 vs. 322.5 +/- 14.7 mg/dl; P < 0.001). Both total testosterone (96.3 +/- 17.3 vs. 56.1 +/- 5.8 ng/dl; P = 0.01) and free testosterone (5.8 +/- 0.6 vs. 3.4 +/- 0.5 pg/ml; P < 0.001) decreased significantly after treatment, although there was no significant change in LH levels. Levels of SHBG increased significantly (18.3 +/- 3.4 vs. 25.8 +/- 6.6 nmol/liter; P = 0.009) after treatment, and dehydroepiandrosterone sulfate levels decreased significantly (P = 0.04). There was no significant change in body mass index (40.4 +/- 2.4 vs. 41.1 +/- 2.7 kg/m(2)). Eleven of the women reverted to regular ovulatory cycles during the treatment period. We conclude that 1) rosiglitazone therapy improves insulin resistance and glucose tolerance in obese women with PCOS; 2) rosiglitazone decreases ovarian androgen production, which appears to be independent of any changes in LH levels; 3) hyperinsulinemia appears to play a key role in the overproduction of ovarian androgens in these women because attenuation of insulin levels is associated with decreased testosterone levels; and 4) short-term rosiglitazone therapy helps restore spontaneous ovulation.     

Lower insulin sensitivity differentiates hirsute from non-hirsute Sicilian women with polycystic ovary syndrome

OBJECTIVE: It is well known that hyperandrogenism and insulin-resistance with or without compensatory hyperinsulinism are closely associated, but the Rotterdam Consensus has concluded that principally obese women with polycystic ovary syndrome (PCOS) should be evaluated for the metabolic syndrome. Our aim was to study insulin sensitivity in PCOS women with hirsutism regardless of obesity. METHODS: Clinical characteristics, sex hormones and fasting- and after OGTT-glycemia and insulinemia, homeostatic model of insulin resistance (HOMA IR), and Matsuda index of insulin sensitivity were analyzed in 130 women with PCOS. Hirsutism has been evaluated through the Ferriman-Gallwey (FG) map scoring system. RESULTS: PCOS women with hirsutism (57.7% of participants) showed significant higher values of total testosterone levels (P = 0.016), free testosterone (P = 0.027), DHEA sulfate (P = 0.017), and Delta4androstenedione (P = 0.018). They had similar body mass index (BMI) (P = 0.073) and were significantly less insulin sensitive (P = 0.002) than those without hirsutism (42.3% of participants). In women with PCOS and hirsutism, there was a significant correlation between FG score and insulin-sensitivity indexes (HOMA IR, rho = 0.33, P = 0.005; Matsuda index, rho = -0.34, P = 0.003) but not with the androgen levels. Moreover, women with hirsutism showed a significantly greater insulin (P = 0.019), C-peptide (P = 0.002), and glucose (P = 0.024) areas under the curve (auc2h). CONCLUSIONS: Our study suggests that the increased responsiveness of the pilo-sebaceous unit to androgens seems to be influenced by insulin sensitivity and that insulin resistance should be assessed in all hirsute women with PCOS regardless of their BMI, as insulin resistance was found in hirsute women irrespective of whether they were overweight or obese.     

Do polycystic ovaries on ultrasound scan indicate decreased insulin sensitivity in sisters of women with polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenemia, insulin resistance, altered lipid profile, and therefore with subsequently increased risk for metabolic complications such as type 2 diabetes and cardiovascular diseases. It has been reported that sisters of probands with PCOS, who themselves had PCOS or hyperandrogenemia with normal menses, were more insulin resistant than unaffected sisters. We have previously reported that 60% of first-degree relatives (premenopausal mothers and sisters) of PCOS probands had polycystic ovaries (PCO) on ultrascan. Sisters with PCO were more likely to have oligomenorrhea and increased androgen levels than sisters without PCO. The aims of this study were to assess insulin sensitivity status [homeostasis model of assessment, quantitative insulin sensitivity check index, glucose to insulin ratio (G/I)] and lipid profiles in probands with PCOS and their sisters with PCO and without PCO on ultrascan. Mixed model hierarchical regression analysis, to accommodate the nonindependent nature of the subjects (family relationships), with the three groups together did not show significant differences in insulin sensitivity, calculated as quantitative insulin sensitivity check index, homeostasis model of assessment, and G/I for PCOS probands, through sisters with PCO on ultrascan, to sisters without PCO on ultrascan. There was a significant association of measures of insulin sensitivity with body mass index. Lipid parameters did not differ between the groups. These data suggest that presence of PCO on ultrasound scan per se does not predispose to reduced insulin sensitivity in sisters of women with PCOS. Because about 20% of premenopausal women in the general population have PCO on ultrascan, and obesity/overweight is becoming more prevalent, it is important that future studies take full account of the contribution made by obesity to risk factors for metabolic/vascular complications.     

Cardiovascular disease risk characteristics of the main polycystic ovary syndrome phenotypes

The aim of this article was to evaluate the clinical, endocrine, and cardiovascular disease risk profile differences among main polycystic ovary syndrome (PCOS) phenotypes. One hundred and thirty-nine consecutive women were included in the study. Body mass index (BMI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate, fasting glucose, low density lipoprotein (LDL-C), total cholesterol, high density lipoprotein (HDL-C) high sensitive CRP, c-peptide, insulin, insulin sensitivity and carotid intima thickness were compared among different phenotype groups of PCOS: Group 1-PCO (polycystic ovaries)-anovulation (n = 34), Group 2-Hyperandrogenemia (HA)-anovulation (n = 30), Group 3-HA-PCO (n = 32), and Group 4-HA-PCO-anovulation (n = 43). Statistically significant differences among the different phenotype groups in terms of waist hip ratio, total cholesterol, LH, estradiol, fasting glucose, progesterone, free testosterone, and carotid intima media thickness were observed. The lowest mean CIMT was observed in Group 3, and the highest fasting glucose levels were in Group 4, while the lowest mean free testesterone was measured in Group 1. BMI, LDL-C, and total cholesterol showed significant positive correlations with CIMT (r = 0.411, P = 0.001; r = 0.258, P = 0.006; r = 0.199, P = 0.033). The lowest LDL-C, total cholesterol, and BMI were found in Group 3, but differences were not statistically significant. High-sensitive CRP levels were similar among the groups (P = 0.103). Group 3 PCOS with PCO and hyperandrogenemia phenotype has lower cardiovascular disease risk compared to other phenotypes.     

Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P 相似文献