Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study

The metabolic cardiovascular disease (CVD) risk factors of women with self-reported oligomenorrhea and/or hirsutism, which are symptoms of polycystic ovary syndrome (PCOS), were investigated in a general population-based Northern Finland Birth Cohort 1966 Study to determine whether women with PCOS symptoms at 31 yr would be distinguishable from asymptomatic controls in terms of CVD risk factors. A total of 518 cases with oligomenorrhea and/or hirsutism and 1036 randomly selected controls were analyzed. C-Reactive protein (CRP; median, 0.70 vs. 0.60 mg/liter; P = 0.026), triglycerides (mean, 0.97 vs. 0.91 mmol/liter; P = 0.039), body mass index (BMI; mean, 25.1 vs. 24.2 kg/m(2); P < 0.001), and waist/hip ratio (mean, 0.82 vs. 0.81; P = 0.001) were significantly higher, and high-density lipoprotein cholesterol levels were lower (mean, 1.60 vs. 1.66 mmol/liter; P = 0.002) in the cases compared with the controls. Total cholesterol, low-density lipoprotein cholesterol, and blood pressure showed no statistically significant differences between the cases and the controls. In terms of metabolic CVD risk factors, women reporting hirsutism alone were indistinguishable from the control group, and those who reported both oligomenorrhea and hirsutism had the most severe changes in risk factor profiles. Because obesity is strongly related to PCOS symptoms, the analyses were stratified by BMI. After stratification into normal weight (BMI, <25 kg/m(2)), overweight (25 kg/m(2) or=30 kg/m(2)) groups, the waist/hip ratio was significantly higher among the overweight cases (mean, 0.84 vs. 0.83; P = 0.04). Among the obese women, high-density lipoprotein cholesterol was significantly lower (mean, 1.32 vs. 1.48 mmol/liter; P = 0.002) among the cases, and triglycerides tended to be higher (mean, 1.43 vs. 1.27 mmol/liter; P = 0.068) than in controls. In conclusion, these results indicate that self-reported symptoms of oligomenorrhea and/or hirsutism, particularly in the presence of both symptoms, may be helpful to identify women with metabolic cardiovascular risk factor accumulation associated with PCOS.     

The effect of metformin on hirsutism in polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterised by insulin resistance and often associated with hirsutism. Insulin sensitising agents, such as metformin, improve both the biochemical and reproductive parameters; however, no study has been designed to specifically assess the effect of metformin on hair growth. DESIGN AND PATIENTS: Sixteen women with PCOS and hirsutism were enrolled into a 14 month (two 6 month phases with a 2 month washout) double-blind placebo-controlled cross over study. MEASUREMENTS: Hirsutism was assessed using the Ferriman and Gallwey (F-G) score, patient self-assessment and growth velocity. Weight, height and waist-hip ratio were recorded. Gonadotrophins, androgens, plasma glucose and lipids were also measured. RESULTS: Ten women completed the full 14 month study. There was a significant improvement in hirsutism at the end of the metformin phase compared with placebo: F-G score 15.8+/-1.4 vs 17.5+/-1.2 (P=0.025) and patient self-assessment 2.4+/-0.1 vs 3.3+/-0.3 (P=0.014). Growth velocity, in millimetres per day at the end of each phase also improved (0.67+/-0.17 vs 0.77+/-0.11; P=0.03). There was a non-significant improvement in both sex hormone binding globulin (SHBG) and free androgen index (FAI), although there was a significant difference between baseline and metformin treatment for SHBG (P=0.023) and FAI (P=0.036). Metformin treatment also reduced weight significantly (91.5+/-7.6 vs 94.0+/-9.8 kg; P=0.009) and led to a significant improvement in cycle frequency (0.53+/-0.12 vs 0.35+/-0.08 cycles per month; P=0.008). CONCLUSION: We have demonstrated that metformin treatment in a group of women with PCOS results in a clinically and statistically significant improvement in hair growth compared with placebo.     

The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance

This study was designed to assess the biological variability of total testosterone and SHBG in polycystic ovarian syndrome (PCOS) and to determine the use of SHBG as a surrogate marker of insulin resistance in PCOS. Fasting blood samples were collected at 4-d intervals on 10 consecutive occasions from 12 PCOS patients and 11 age- and weight-matched controls. Duplicate samples were analyzed for SHBG, testosterone, and insulin in a single batch, and insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR). The PCOS group had higher testosterone (mean +/- SD, 3.9 +/- 0.8 vs. 3.2 +/- 1.3 nmol/liter; P = 0.001), lower SHBG (28.6 +/- 17.1 vs. 57.6 +/- 30.2 nmol/liter; P = 0.001), and greater HOMA-IR (5.85 +/- 5.3 vs. 1.67 +/- 0.63 U; P = 0.001) than the controls. In contrast to HOMA-IR (1.09 vs. 0.48 U; P = 0.001), the intraindividual variation in SHBG was lower in the PCOS group (mean, 3.4 vs. 6.3 nmol/liter; P = 0.041). The index of individuality for SHBG and testosterone in PCOS was 0.49 and 0.69, respectively. This study shows that for patients with PCOS, SHBG is an integrated marker of insulin resistance that may be of use to identify insulin-resistant individuals for targeted treatment with insulin-sensitizing agents. However, SHBG and testosterone concentrations measured in isolation are inherently unsuitable for use as tests to detect hyperandrogenemia.     

Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents

Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.     

Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile

This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women.     

多囊卵巢综合征患者性激素结合球蛋白和总睾酮与胰岛素抵抗的相关性

目的 了解性激素结合球蛋白(SHBG)和总睾酮在预测多囊卵巢综合征(PCOS)患者胰岛素抵抗和生殖内分泌以及糖脂代谢紊乱中的作用.方法 选择2004年6月至2006年5月在复旦大学附属妇产科医院就诊的344例PCOS患者为病例组,年龄12～35岁,平均年龄(23±5)岁.选择同期月经规律、基础体温双相的100名妇女作为对照组,比较PCOS患者SHBG和总睾酮与对照组的差异,并用Spearman相关分析法分别分析SHBG和总睾酮与其他指标的相关性,Logistic回归分析胰岛素抵抗的风险因子并做SHBG对胰岛素抵抗的受试者操作特征(ROC)曲线,获得预测胰岛素抵抗的风险值,比较不同水平SHBG患者的糖脂代谢紊乱的程度.结果 PCOS患者SHBG为(114±88)mmol/L,与对照组[(201±106)mmol/L]比较差异有统计学意义(t=-5.60,P<0.01),总睾酮为(2.8±1.0)nmol/L,与对照组[(1.7±0.6)nmol/L]比较差异有统计学意义(t=7.73,P<0.01);SHBG与空腹胰岛素、胰岛素释放试验曲线下面积、口服葡萄糖耐量试验(OGTT)的葡萄糖曲线下面积、胰岛素抵抗指数、甘油三酯和腰围/臀围比呈负相关(r值分别为:-0.30、-0.26、-0.29、-0.19、-0.20、-0.29、-0.22,均P<0.01);总睾酮与空腹胰岛素(r=0.14,P<0.01)、胰岛素释放试验(1、2、3 h的r值分别为0.15、0.12、0.11,均P<0.05)以及相应的曲线下面积(r=0.15,P<0.05)、胰岛素抵抗指数(r=0.11,P<0.05)呈正相关.Logistic回归分析发现SHBG是PCOS患者胰岛素抵抗的独立危险因素(OR=3.741).由ROC曲线得到SHBG预测胰岛素抵抗的大致风险值为88 mmol/L(95%CI为0.668～0.774).在低SHBG(<88 mmol/L)患者中,空腹胰岛素、胰岛素释放试验相应的曲线下面积、胰岛素抵抗指数、空腹血糖、OGTT的葡萄糖曲线下面积与高SHBG(≥88 mmoL/L)患者比较差异有统计学意义(t值分别为-6.45、-5.08、-6.19、-3.16、-3.66,均P<0.01),甘油三酯也高于高SHBG患者(t=-2.06,P<0.05).结论 PCOS患者总睾酮水平高于对照组,SHBG低?     

The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis

While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone‐binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment‐insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total‐cholesterol and low‐density lipoprotein‐cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.     

The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome

Context: In overweight women with polycystic ovary syndrome (PCOS), the benefits of the addition of exercise to an energy-restricted diet in further improving cardiometabolic risk factors and reproductive function has not been extensively studied. Objective: The objective was to evaluate the effects of aerobic and aerobic-resistance exercise when combined with an energy-restricted high protein diet (5000-6000 kJ/d) on metabolic risk factors and reproductive function in women with PCOS. Design and Setting: A 20-wk outpatient, randomized, parallel study was conducted in a metropolitan research clinic. Patients and Intervention: Ninety-four overweight and obese women with PCOS (age 29.3 +/- 0.7 yr; body mass index 36.1 +/- 0.5 kg/m(2)) were randomized to diet only (DO; n = 30), diet and aerobic exercise (DA; n = 31), or diet and combined aerobic-resistance exercise (DC; n = 33). Main Outcome Measures: Weight, body composition, cardiometabolic risk factors, hormonal status, menstrual cyclicity, and ovulatory function were assessed. Results: All interventions reduced weight (DO 8.9 +/- 1.6%, DA 10.6 +/- 1.7%, and DC 8.7 +/- 1.7%; P < 0.001) with no difference between treatments (P = 0.7, time x treatment). Fat mass decreased more (3 kg) and fat-free mass decreased less (2 kg) in DA and DC compared with DO (P 相似文献   

多囊卵巢综合征患者胰岛素抵抗与糖脂代谢及性激素的研究

目的通过高胰岛素正葡萄糖钳夹试验评估多囊卵巢综合征(PCOS)患者的胰岛素抵抗,探讨伴胰岛素抵抗PCOS患者糖脂代谢及性激素水平特点。方法将2017年7月至2019年2月就诊于遵义医科大学附属医院内分泌科住院及门诊的73例PCOS患者和体重指数及年龄匹配的27名健康女性行高胰岛素正葡萄糖钳夹试验,根据葡萄糖代谢率、体重指数和稳态模型评估的胰岛素抵抗指数(HOMA-IR)分组,分析PCOS患者糖脂代谢及性激素指标的变化及差异。结果在PCOS组中,糖调节受损者占3.23%(1/31),血脂代谢异常者占9.68%(3/31);而在PCOS合并胰岛素抵抗组中,糖调节受损者占7.14%(3/42),血脂代谢异常者达47.62%(20/42),5例患者被诊断为代谢综合征,占11.90%。相关分析显示,葡萄糖代谢率与体重指数、腰臀比、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、皮质醇、三酰甘油、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、游离雄激素指数(FAI)和谷氨酰转肽酶(GGT)呈负相关(P<0.05),与高密度脂蛋白胆固醇(HDL-C)呈正相关(P=0.028);HOMA-IR与体重指数、腰臀比、收缩压、空腹血糖、空腹胰岛素、HbA1C、LDL-C呈正相关(P<0.05),与葡萄糖代谢率和HDL-C呈负相关(P<0.05);体重指数与腰臀比、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、三酰甘油和LDL-C呈正相关(P<0.05),与葡萄糖代谢率、HDL-C和性激素结合球蛋白(SHBG)呈负相关(P<0.01)。多元线性逐步回归分析表明,体重指数、总胆固醇、三酰甘油和皮质醇是影响葡萄糖代谢率的重要因素,空腹血糖、空腹胰岛素和收缩压是HOMA-IR的重要影响因素,葡萄糖代谢率、HOMA-IR、HDL-C和SHBG仍然是影响体重指数的重要影响因素。结论FAI、SHBG和皮质醇可能参与到PCOS患者的胰岛素抵抗发生中,存在胰岛素抵抗的PCOS患者更容易发生代谢紊乱。     

A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17-45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score > or = 6) and O/M: group N (n = 108), regular menses and absence of hirsutism; group 1 (n = 56), regular menses and hirsutism; group 2 (n = 10), O/M and absence of hirsutism; and group 3 (n = 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT > or = 95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P < 0.00001) and 1 (P < 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P < 0.0001 and P < 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P < 0.002, P < 0.02, and P < 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P < 0.005 and P < 0.002, respectively) and the hirsute (P < 0.05 and P < 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P < 0.05). Finally, a high incidence of family history of diabetes mellitus (P = 0.001) and menstrual disorders (P = 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity.     

Increased micronucleus frequencies in peripheral blood lymphocytes in women with polycystic ovary syndrome

OBJECTIVE: We aimed to assess possible genomic instability in women with polycystic ovary syndrome (PCOS). DESIGN: The frequency of micronuclei in cultured peripheral lymphocytes was used as a biomarker of genomic instability in somatic cells. METHODS: Nineteen women, diagnosed with PCOS and 19 healthy female volunteers of corresponding ages and body-mass index (BMI) were included in the study. Micronuclei frequencies were assessed in cytokinesis-blocked lymphocytes. RESULTS: The frequency of micronucleated cells (per thousand) was 9.00 (5.00) (interquartile range in parentheses) for patient group and 3.0 (3.0) for the control group (P < 0.0001, Mann-Whitney U-test). The serum levels of follicle-stimulating hormone (FSH), estradiol, prolactin, glucose and dehydroepiandrosterone sulfate (DHEAS) and the homeostasis model of assessment of insulin resistance (HOMA-IR) were not different between the two groups (P > 0.05). Serum total testosterone, luteinizing hormone (LH) and insulin levels and hirsutism score in the PCOS group were significantly (P = 0.007, P < 0.0001, P = 0.009 and P < 0.0001 respectively) higher than those of the control group (2.3 (2.1) nmol/l vs 1.7 (0.4) nmol/l; 8.5 (5.88) mU/ml vs 4.8 (4.4) mU/ml; 6.8 (5.1) microU/ml vs 9.7 (4.2) microU/ml; 19.5 (6.5) vs 4.0 (2.5) respectively). However, the mean level of sex hormone-binding globulin (SHBG) in PCOS group was significantly (P = 0.004) lower than in control group (36.4(22.6) nmol/l vs 48.6(25.2) nmol/l respectively). CONCLUSION: These findings suggest that women with PCOS have a high incidence of genomic instability, and this condition is positively correlated with the hirsutism score, BMI, LH and serum total testosterone and insulin levels, and is negatively correlated with SHBG.     

The combination of increased ovarian volume and follicle number is associated with more severe hyperandrogenism in German women with polycystic ovary syndrome.

The prevalence and relevance of polycystic ovaries (PCO) in German women with polycystic ovary syndrome has not been evaluated. This retrospective study included 212 PCOS patients (mean age 28 years) diagnosed by the NIH-criteria and consecutively recruited since 2003. Clinical features including anthropometric variables and the degree of hirsutism, family history, menstrual cyclicity as well as endocrine biochemical parameters were recorded. In addition, 3-h oral glucose tolerance testing for indices of insulin resistance and glucose metabolism was performed in each patient. Transvaginal ultrasound was used to detect polcystic ovaries, defined as the presence of at least one ovary > 10 ml or with at least 12 follicles of 2-9 mm diameter. In this German PCOS cohort, PCO were identified in 166 women (78%). Women with PCO (PXO+) had significantly higher LH/FSH ratios (median 2.1 vs. 1.7) and IGF-1 levels (median 182.5 vs. 160.5 ng/ml) compared to patients without PCO (PCO-). In addition, a significantly higher prevalence of acne (50% vs. 33%) and higher hirsutism scores (median 9 vs. 7) were found in PCO+ patients. Testosterone levels and the free androgen index (FAI) correlated significantly with ovarian volume and the number of ovarian follicles. Also, a subgroup of PCO+ women with a combination of increased ovarian volume and follicle number had higher testosterone levels (median 3.1 vs. 2.1 nmol/l) and FAI (median 7.6 vs. 4.5) compared to women with increased follicle count but normal volume. No differences were found in metabolic parameters or insulin resistance indices. PCO are common finding in German PCOS women. PCO appear to be associated with a more pronounced hyperandrogenemia, especially when both ovarian volume and follicle number are increased.     

Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference?

OBJECTIVE: Polycystic ovary syndrome (PCOS) is more prevalent in South Asian women residing in the UK than in Caucasians. Insulin resistance (IR) is central to the pathogenesis of PCOS, while type 2 diabetes is commoner in South Asians. We aimed to determine a possible ethnic difference in the clinical and biochemical characteristics of South Asian vs. Caucasian women with PCOS. PATIENTS AND DESIGN: A case-control cross-sectional observational study of consecutive women with anovular PCOS (47 South Asians, 40 Caucasians) and their age-matched controls (11 South Asians and 22 Caucasians). MEASUREMENTS: Index subjects: a questionnaire-based interview on clinical symptoms and family history; anthropometric measurements, clinical observations of the presence and degree of acne, hirsutism and acanthosis nigricans; transvaginal pelvic ultrasound; biochemical analyses of fasting blood sugar, fasting plasma insulin, fasting lipids, testosterone, and SHBG concentrations. Control group: age- and weight-matched unrelated women from the same ethnic backgrounds without PCOS seeking treatment for male infertility were studied by similar methods to those used with the index subjects. RESULTS: South Asians with PCOS presented at a younger age (age 26 +/- 4 vs. 30.1 +/- 5 years, P = 0.005). Body mass index (BMI) and waist : hip ratios were similar in the two affected cohorts. More South Asians had oligomenorrhoea commencing at a younger age. Hirsutism (Ferriman Gallwey score 18 vs. 7.5, P = 0.0001), acne, acanthosis nigricans and secondary infertility were significantly more prevalent in South Asians. The fasting glucose was similar (4.52 +/- 0.08 vs. 4.62 +/- 0.09 mmol/l, P = 0.25), the fasting insulin higher (89.4 +/- 8.9 vs. 48.6 +/- 4.8 pmol/l, P = 0.0001) and insulin sensitivity (IS) lower (0.335 +/- 0.005 vs. 0.357 +/- 0.002, P = 0.0001) among South Asians. Serum SHBG was significantly less in South Asians (35 +/- 3.3 vs. 55 +/- 9.4 nmol/l, P = 0.02), while serum testosterone was similar (2.69 +/- 0.11 vs. 2.64 +/- 0.13 nmol/l, P = 0.37). CONCLUSIONS: We conclude that South Asians with anovular PCOS seek treatment at a younger age, have more severe symptoms, and have higher fasting insulin concentrations and lower insulin sensitivity than Caucasians.     

Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance

Functional adrenal hyperandrogenism occurs in women with polycystic ovary syndrome (PCOS). Insulin, similar to its ovarian effect, may impact the regulation of adrenal steroidogenesis by modulating the activity of P450c17alpha, the rate-limiting enzyme in androgen biosynthesis. We previously demonstrated that obese adolescents with PCOS are severely insulin resistant and are at heightened risk for impaired glucose tolerance and type 2 diabetes. In the present study we tested the hypothesis that metformin therapy in obese adolescents with PCOS will attenuate the adrenal steroidogenic response to ACTH, with reduction of insulin resistance/insulinemia. Fifteen adolescents with PCOS and impaired glucose tolerance received 3 months of metformin (850 mg, twice daily) therapy. Pre- and posttherapy they had oral glucose tolerance testing, ACTH stimulation test, a 3-h hyperinsulinemic (80 mU/m(2).min)-euglycemic clamp to assess insulin sensitivity and a hyperglycemic clamp to assess insulin secretion. After 3 months of metformin treatment, glucose intolerance improved, with eight subjects having normal glucose tolerance. Total and free T decreased [1.5 +/- 0.2 vs. 1.0 +/- 0.1 nmol/liter (P = 0.022) and 41.3 +/- 8.3 vs. 22.2 +/- 2.1 pmol/liter (P = 0.028), respectively]. Insulin-stimulated glucose disposal increased (21.5 +/- 2.2 vs. 25.0 +/- 2.2 micromol/kg.min; P = 0.041). Fasting insulin and oral glucose tolerance test insulin and glucose area under the curve decreased significantly. ACTH-stimulated increases in androstenedione, 17-hydroxyprogesterone, and 17-hydroxypregnenelone were lower after metformin treatment [2.8 +/- 0.4 vs. 1.7 +/- 0.3 nmol/liter (P = 0.014), 7.0 +/- 0.6 vs. 5.3 +/- 0.5 nmol/liter (P = 0.011), and 30.4 +/- 3.7 vs. 25.7 +/- 4.2 nmol/liter (P = 0.054)]. Fasting insulin correlated with the 17-hydroxypregnenelone response to ACTH stimulation (r = 0.52; P = 0.008). In summary, metformin treatment of obese adolescents with PCOS and impaired glucose tolerance is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels. Moreover, metformin therapy is associated with attenuation of the adrenal steroidogenic response to ACTH. Metformin therapy was well tolerated. In conclusion, double blind, placebo-controlled studies will determine whether insulin-sensitizing therapy corrects not only ovarian hyperandrogenism but also functional adrenal hyperandrogenism in adolescents with PCOS.     

Oxidised low-density lipoprotein concentration - early marker of an altered lipid metabolism in young women with PCOS

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk for cardiovascular diseases. This study examined the variations in oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin levels in young women with PCOS. DESIGN: Cross-sectional clinical study in tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight) and 56 age- and body mass index-matched controls were examined. METHODS: Blood samples were collected in follicular phase of the cycle for the basal glucose, total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL, triglycerides, apolipoprotein-A1 (Apo-A1) and B (Apo-B), lipoprotein (a), insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model index (HOMA) and free androgen index (FAI) were determined. RESULTS: Overweight and normal weight women with PCOS had higher concentrations of OxLDL than their control counterparts (P = 0.007 and 0.003 respectively). Both the basal insulin (P = 0.003) and HOMA values (P < 0.001) were significantly higher in overweight than normal weight patients. Testosterone and FAI were higher in patients than in the respective controls (P < 0.001). The only independent predictor of increased OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P < 0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3-16.4), while in obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol ratio (P < 0.001, OR 2.8; 95% CI 1.6-4.9). CONCLUSION: Young normal weight and overweight PCOS women have similarly increased OxLDL levels. Our results may indicate the presence of primary alteration in lipid metabolism in patients with PCOS. To answer the question whether the alteration in LDL particle size can by itself pose a higher cardiovascular risk, a careful follow-up of these women is needed.     

Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen transport and metabolism in women with PCOS. DESIGN: Within-group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women. PATIENTS: Forty-seven women who presented with hirsutism, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6 +/- 0.7 years (mean +/- SEM), BMI 27.3 +/- 1.2 kg/m2. MEASUREMENTS: Plasma insulin levels were measured at 30-minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (fT), sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS: Neither basal insulin nor the sum of insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with irregular cycles or amenorrhoea than in those with regular ovulatory menses (8.0 +/- 1.1 vs 3.1 +/- 1.5 mU/l, P less than 0.01) despite similarly raised androgen levels. Both basal insulin and sumINS correlated with BMI in women with PCO (r = 0.37, P less than 0.05 and r = 0.64, P less than 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF-I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an inverse correlation and fT correlated positively with sumINS (r = -0.51, P less than 0.01; r = 0.39, P less than 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens. CONCLUSIONS: These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes in SHBG rather than by direct stimulation of ovarian androgen production. Higher insulin concentrations in anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that insulin resistance in the ovary contributes to the mechanism of anovulation in PCOS.     

First trimester insulin resistance and subsequent preeclampsia: a prospective study

Insulin resistance is implicated in the pathogenesis of preeclampsia, but prospective data are limited. SHBG, a marker of insulin resistance among nonpregnant individuals, has not been studied in detail during pregnancy. We conducted a prospective, nested, case-control study to test the hypothesis that increased insulin resistance, marked by reduced first trimester SHBG levels, is associated with increased risk of subsequent preeclampsia. First trimester SHBG levels were measured in 45 nulliparous women who subsequently developed preeclampsia (blood pressure, > or =140/90 mm Hg; proteinuria, either > or =2+ by dipstick or > or =300 mg/24 h, after 20 wk gestation) and in 90 randomly selected normotensive nulliparous controls. Compared with controls, women who developed preeclampsia had significantly reduced first trimester SHBG levels (302 +/- 130 vs. 396 +/- 186 nmol/liter; P < 0.01). Every 100 nmol/liter increase in SHBG was associated with a 31% reduced risk of preeclampsia [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.55, 0.88; P < 0.01]. After adjusting for covariates in a multiple logistic regression model, the association between first trimester SHBG and preeclampsia remained significant (per 100 nmol/liter increase; OR, 0.66; 95% CI, 0.47, 0.92; P = 0.01). When subjects were stratified by body mass index (lean: body mass index, < 25 kg/m(2); overweight: body mass index, > or =25 kg/m(2)), overweight women had lower SHBG levels than lean women (286 +/- 156 vs. 410 +/- 166 nmol/liter; P < 0.01), and within each stratum, women with preeclampsia had lower SHBG levels than their respective controls. In a multivariable analysis, the association between SHBG and preeclampsia strengthened among lean women, such that every 100 nmol/liter increase in serum SHBG was associated with a 55% reduction in the risk of preeclampsia (OR, 0.45; 95% CI, 0.27, 0.77; P < 0.01), whereas in overweight women, the association was mitigated (OR, 1.02; 95% CI, 0.62, 1.69; P = 0.9). We conclude that increased early pregnancy insulin resistance is independently associated with subsequent preeclampsia. First trimester SHBG levels may be a useful biomarker for preeclampsia, especially among lean women who otherwise would be perceived to be at low risk.     

Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome

The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.     

Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end-products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes. DESIGN/PATIENTS: We investigated serum AGE levels in 29 young women with PCOS as well as the expression of their receptor, RAGE, in circulating monocytes and compared them levels with 22 healthy control women. MEASUREMENTS/RESULTS: Women with PCOS had higher levels of serum AGE proteins compared to healthy individuals (9.81 +/- 0.16 vs. 5.11 +/- 0.16, P < 0.0001), and increased RAGE expression was observed in monocytes of PCOS women compared to controls (30.91 +/- 10.11 vs. 7.97 +/- 2.61, P < 0.02). A positive correlation was observed between AGE proteins and testosterone (T) levels (r = 0.73, P < 0.0001). The correlation between AGE proteins and T levels remained high (partial correlation coefficient = 0.61, P = 0.0001) after controlling for body mass index (BMI), insulin levels and the area under the curve for glucose (AUCGLU) during an oral glucose tolerance test (OGTT). A positive correlation was also observed between AGE proteins and the free androgen index (FAI) (r = 0.58, P < 0.0001), waist-to-hip ratio (WHR) (r = 0.31, P < 0.02), insulin (r = 0.46, P < 0.001), homeostasis model assessment (HOMA) (r = 0.47, P < 0.0001), AUCGLU (r = 0.52, P < 0.002) and RAGE (r = 0.59, P < 0.01). A negative correlation was observed between AGE proteins and glucose/insulin ratio (GLU/INS) (r = -0.35, P < 0.01), and the quantitative insulin sensitivity check index (QUICKI) (r =-0.50, P < 0.01). In multiple regression analysis T was the only independent predictor of AGE levels (P < 0.0001, b = 0.044) between BMI, insulin, SHBG and AUCGLU (adjusted R2 = 0.59, F = 44.41, P < 0.0001). CONCLUSION: These data clearly demonstrate, for the first time, that PCOS women without overt hyperglycaemia have increased AGE levels and elevated RAGE expression when compared with controls.