Serum levels of leptin and homocysteine in women with polycystic ovary syndrome and its relationship to endocrine, clinical and metabolic parameters

We examined the relationship between endocrine, clinical and metabolic parameters in 35 women (mean age 27.3 years) with polycystic ovary syndrome (PCOS) and 30 age- and body mass index-matched normal ovulatory women. In PCOS women, serum leptin, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3 levels and the insulin resistance index (HOMA-IR) were significantly higher, while sex hormone-binding globulin and high-density lipoprotein cholesterol levels were lower compared with healthy women. Serum luteinizing hormone (LH), estradiol (E(2)), androstenedione, testosterone and dehydroepiandrosterone sulphate levels were found to be significantly higher in PCOS women compared with healthy women. The levels of E(2), LH and testosterone were positively correlated with leptin levels in PCOS women. Similarly, androstenedione levels and HOMA-IR were positively correlated with homocysteine levels and insulin levels were positively correlated with LH. We conclude that increased homocysteine levels, hyperandrogenaemia, insulin resistance and impaired lipid metabolism contribute to the risk of premature atherosclerosis in PCOS women.     

Basal glucose level as an independent predictor of fertilization rate in patients without polycystic ovary syndrome included in an in-vitro fertilization program

Insulin resistance is a common characteristic of women with polycystic ovary syndrome (PCOS) who are known to differ in their in-vitro fertilization outcomes compared to non-PCOS patients. As insulin resistance can be found in a considerable proportion of normal individuals, we assessed its contribution to ovarian responsiveness and fertilization rate. 26 non-PCOS patients undergoing IVF for the first time were investigated. Insulin resistance was evaluated by using a euglycemic hyperinsulinemic clamp technique. According to multiple regression analysis insulin sensitivity, expressed as insulin stimulated glucose disposal rate, during euglycemic clamp (r = -0.81, p < 0.05 and r = -0.89; p < 0.01) and basal estradiol level (r = -0.54; p < 0.05 and r = -0.56; p < 0.05) appeared significant negative predictors of the number of fertilized oocytes and embryos, respectively. Furthermore, basal glucose level appeared independently as a significant positive predictor of the number of fertilized oocytes and the number of embryos. (r = 0.90; p < 0.01 and r = 0.96; p < 0.01 respectively). We conclude that blood glucose concentration and insulin resistance respectively are independent predictors of IVF outcome.     

Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease

OBJECTIVES: To determine oxidant and antioxidant status in women with polycystic ovary syndrome (PCOS) and its contribution to the risk of cardiovascular disease. DESIGN AND METHODS: 27 women with PCOS were compared with regard to oxidant and antioxidant status with 18 age- and body mass index (BMI)-matched healthy. Oxidant status was evaluated by determination of erythrocyte malondialdehyde (MDA) concentration, while antioxidant status was evaluated by determination of erythrocyte reduced glutathione (GSH) concentration, and glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Area under curve (AUC) for glucose, AUC for insulin and the insulin sensitivity index (ISI) were calculated from two-hour OGTT. RESULTS: Women with PCOS were found to have higher AUC for glucose (p = 0.01), AUC for insulin (p < 0.001), MDA level (p = 0.009) and SOD activity (p = 0.04), and lower ISI (p < 0.001) and GSH level (p = 0.03) than the controls. In correlation analysis, a significant relationship was found between MDA levels and age (p < 0.01), BMI (p < 0.001), waist-to-hip ratio (p < 0.01), systolic and diastolic blood pressures (both p < 0.05), AUCs for glucose and insulin (both p < 0.05), ISI (r = -0.42, p < 0.05) and triglyceride (p < 0.01). CONCLUSIONS: An increase in oxidant status was found in women with PCOS, and this increase was related to central obesity, age, blood pressure, serum glucose, insulin and triglyceride levels and insulin resistance. In contrast, antioxidant status was observed to be insufficient. These findings suggest that increased oxidative stress may contribute to the increased risk of cardiovascular disease in women with PCOS.     

二甲双胍对多囊卵巢综合征患者内分泌功能的影响

目的探讨二甲双胍对多囊卵巢综合征(PCOS)合并胰岛素抵抗(IR)患者内分泌的影响。方法 P-COS合并IR患者50例于自然月经或撤退性出血第2天开始服用二甲双胍12周,观察治疗前后血清促卵泡生成素(FSH)、黄体生成素(LH)、睾酮、雌二醇、雄烯二酮、性激素结合蛋白(SHBG)浓度、胰岛素(INS)水平以及血糖的变化。结果治疗后患者各时相INS水平显著下降,差异有统计学意义(P<0.01);患者血清LH、LH/FSH比值、睾酮和雄烯二酮水平均显著下降,差异有统计学意义(P<0.01);SHBG水平显著升高,差异也有统计学意义(P<0.01)。结论二甲双胍通过改善IR降低INS水平,改善患者临床症状和内分泌指标,使PCOS患者异常的血激素相得到明显改善。     

卵巢超声特征联合内分泌指标在不同类型多囊卵巢综合征应用价值分析

目的研究卵巢超声特征联合内分泌指标在胰岛素抵抗型与非胰岛素抵抗型多囊卵巢综合征中的应用价值。方法选取2013年2月—2015年3月于本院就诊的共218例多囊卵巢综合征患者作为研究对象。采用HOMA-IR标准进行分组,HOMA-IR≥2.69的115例为胰岛素抵抗组;HOMA-IR2.69的103例者为非胰岛素抵抗组。同时选取同期进行健康体检者69例作为对照组。检测卵巢超声特征,包括卵巢包膜厚度、卵巢直径、卵泡最大直径、OV、卵泡体积、卵泡数、血流指数。检测内分泌指标,包括FSH、LH、LH/FSH、E2、T、PRL、FINs、FPG、SHBG。结果胰岛素抵抗组和非胰岛素抵抗组卵巢包膜厚度、OV、卵巢直径、卵泡体积、卵泡数、血流指数大于对照组,卵泡最大直径小于对照组,且差异均有统计学意义(P0.05);胰岛素抵抗组的OV、卵巢直径、卵泡体积、卵泡数目、血流指数大于非胰岛素抵抗组,卵泡最大直径小于非胰岛素抵抗组,且差异均有统计学意义(P0.05);胰岛素抵抗组和非胰岛素抵抗组LH、LH/FSH、FSH、FINs及T大于对照组,SHBG、E2小于对照组,且差异均有统计学意义(P0.05);胰岛素抵抗组的FPG大于对照组,且差异具有统计学意义(P0.05);胰岛素抵抗组的T、FINs大于非胰岛素抵抗组,胰岛素抵抗组SHBG小于非胰岛素抵抗组,且差异有统计学意义(P0.05)。单因素相关性分析显示,OV与LH/FSH、T、BMI、HOMA-IR呈正相关(r=0.255,0.267,0.534,0.427,P0.05),卵泡最大直径约T、HOMA-IR、BMI呈负相关(r=-0.426,-0.433,-0.317,P0.05)。卵泡刺激素与卵泡数呈正相关(r=0.817,P0.05)。结论胰岛素抵抗型多囊卵巢综合征患者卵泡最大直径减小,OV增大。OV与LH/FSH、T、BMI、HOMA-IR呈正相关,卵泡最大直径约T、HOMA-IR、BMI呈负相关。卵泡刺激素与卵泡数呈正相关。     

Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome.

We have investigated the hypothesis that hyperinsulinemia may cause the polycystic ovary syndrome (PCO) by directly stimulating gonadal steroidogenesis and/or gonadotropin secretion. 10 insulin-resistant women with PCO and 5 age- and weight-matched ovulatory normal women had pulsatile gonadotropin release, gonadotrope sensitivity to gonadotropin-releasing hormone, and sex hormone levels studied on two consecutive study days, basally and during the infusion of insulin (mean +/- SEM steady state insulin levels, 1,254 +/- 63 microU/ml PCO vs. 907 +/- 92 microU/ml normal, P less than or equal to 0.01). Insulin acutely increased mean delta (6 h minus prestudy) levels of androstenedione (A) (P less than or equal to 0.001) and estradiol (E2) (P less than or equal to 0.05) and decreased mean plasma pool (0-6 h) levels of testosterone (T) (P less than 0.05), nonsex hormone binding globulin-bound T (P less than 0.05), and dihydrotestosterone (P less than or equal to 0.01) in the PCO women. Insulin also decreased mean plasma 6 h A to estrone (E1) ratios and increased 6 h E1 levels (both P less than or equal to 0.05) in the PCO women. There were significant sequence effects (insulin + day) in the PCO women on T/E2 ratios, indicating a carryover action of insulin. Insulin had no effects on gonadotropin release in the PCO women. In the normal women, the only significant change was an insulin or study day effect that increased mean 6 h E2 levels (P less than or equal to 0.01). There were significant spontaneous decreases in mean luteinizing hormone (p less than 0.05) and follicle-stimulating hormone levels (p less than or equal to 0.01) in the PCO but not the normal women on the second day of study. This study indicates that insulin can directly alter peripheral sex hormone levels independent of changes in gonadotropin release in insulin-resistent PCO women. Insulin decreased the levels of potent androgens in PCO women and did not increase androgen levels in normal women, arguing against a simple, direct causal relationship between hyperinsulinemia and hyperandrogenism in PCO.     

Precocious signs of polycystic ovaries in obese girls.

As several studies have reported that 35% of patients with polycystic ovary syndrome are obese and that this syndrome seems to originate during the early phase of sexual maturation, we undertook a study of such subjects. We studied ultrasound and hormonal findings in 49 obese girls aged from 7.9 to 19.10 years, with a mean excess weight of 44%; 23 premenarcheal girls and 26 postmenarcheal girls with mean gynecological age of 2.5 years. As controls, we studied 18 girls in the pubertal phase and 17 healthy girls with regular menses, matched for age and gynecological age.Pelvic ultrasonography was carried out in all girls and estrone, estradiol, progesterone, prolactin, follicle stimulating hormone, luteinizing hormone, sex hormone binding globulin (SHBG), testosterone, free testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione and 17-hydroxyprogesterone (17-OHP) were measured by radioimmunoassay in 11 of the 18 postmenarcheal girls. Five girls (10.2%) with excess weight of > 40% presented with mild or severe hirsutism based on Ferriman and Gallway scores; six (12.2%) presented with acne and 14 (28.5%) presented with acanthosis nigricans.Hormonal evaluation showed elevated levels of estrone (p < 0.005) and testosterone (p < 0.01) but lower than normal levels of SHBG (p < 0.05) and estradiol (p <0.05). On the basis of our results, 23%) of the postmenarcheal obese subjects showed clinical, hormonal and ultrasonographic signs of polycystic ovaries, and 23% of postmenarcheal obese girls showed multifollicular ovaries. Six of these, at 1 year after menarche, showed a uterine cross-sectional area larger than normal for gynecological age (21.92 +/- 5.64 cm(2) vs. 16.36 +/- 2.34 cm(2)). Further serial echographic studies and a careful follow-up will demonstrate if both multifollicular ovaries and increased uterine cross-sectional area in obese girls are precocious signs of polycystic ovaries.     

Reduction in hematocrit level after pioglitazone treatment is correlated with decreased plasma free testosterone level, not hemodilution, in women with polycystic ovary syndrome

Thiazolidinediones have gained widespread use for the treatment of type 2 diabetes mellitus and other insulin resistance states, including polycystic ovary syndrome (PCOS). In thiazolidinedione-treated patients a small reduction in hemoglobin and hematocrit levels often is observed, and this generally has been attributed to fluid retention. Because testosterone is a hematopoietic hormone, we investigated whether a reduction in plasma free testosterone concentration was associated with the decrease in hemoglobin and hematocrit levels in 22 nondiabetic women (9 with normal glucose tolerance and 13 with impaired glucose tolerance; mean age, 29 +/- 5 years; mean body mass index, 35.6 +/- 5.8 kg/m2) with PCOS who were treated with pioglitazone, 45 mg/d. Before treatment and after 4 months, subjects underwent an oral glucose tolerance test and measurement of total body water content with bioimpedance. Plasma testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin, and hematocrit levels were evaluated at baseline and every month for 4 months. The fasting plasma glucose concentration (98 +/- 9 mg/dL) was unchanged after pioglitazone treatment, whereas the 2-hour plasma glucose concentration declined from 146 +/- 41 to 119 +/- 20 mg/dL (P = .002). Both the free androgen index and the free testosterone levels calculated according to Vermeulen et al decreased significantly (from 14.4 +/- 7.1 to 10.6 +/- 7.8 [P = .02] and from 59.4 +/- 23.4 to 46.6 +/- 23.3 [P = .03], respectively). The plasma androstenedione level declined from 259 +/- 134 to 190 +/- 109 ng/dL (P = .01), whereas the dehydroepiandrosterone sulfate level did not change significantly (from 139 +/- 90 to 127 +/- 84 mug/dL, P = .2 [not significant]). The levels of both hemoglobin (from 13.6 +/- 1.0 to 12.8 +/- 1.1 g/dL, P = .0002) and hematocrit (from 39.7% +/- 2.2% to 37.9% +/- 2.7%, P = .002) fell slightly after 4 months of pioglitazone administration. Collectively, before and after pioglitazone administration, the plasma free testosterone level according to Vermeulen et al correlated positively with the levels of hemoglobin (r = 0.49, P < .0001) and hematocrit (r = 0.40, P < .0001), as well as the free androgen index (r = 0.38 [P < .0003] with hemoglobin and r = 0.29 [P < .006] with hematocrit); the decrement in plasma free testosterone level and free androgen index also correlated with the decrements in the levels of both hemoglobin (r = 0.51 [P = .01] and r = 0.54 [P = .01], respectively) and hematocrit (r = 0.42 [P = .05] and r = 0.50 [P = .02], respectively). Body weight increased from 90.5 +/- 17.3 to 92.4 +/- 18.8 kg after pioglitazone administration (P = .05), as did body fat content (from 42.7 +/- 15.3 to 44.8 +/- 17.1 kg, P = .03), which could explain the increase in weight, because edema did not develop in any of the subjects. Total body water content did not change significantly after pioglitazone administration (from 37.7 +/- 5.0 to 37.8 +/- 4.9 L, P = .68 [not significant]). In summary, pioglitazone treatment is associated with a mild decline in hematocrit or hemoglobin level, which is correlated with the reduction in plasma testosterone level. These results suggest that increased body water content cannot explain the reduction in hematocrit or hemoglobin level in women with PCOS. Further studies are necessary to evaluate whether the same scenario is applicable to normoandrogenic women and individuals with type 2 diabetes mellitus.     

Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyl oestradiol/cyproterone acetate

Polycystic ovary syndrome (PCOS) is associated with abnormalities of insulin action and insulin secretion. Ethinyl oestradiol/cyproterone acetate is a common agent used to treat the symptoms of PCOS, but its effects on insulin action and insulin pulsatility have not been examined. We investigated the relationship between insulin action and insulin secretion in 11 patients with PCOS, at diagnosis and after 3 months of treatment with ethinyl oestradiol/cyproterone acetate, and in 13 controls. Insulin action was assessed using the euglycaemic hyperinsulinaemic clamp (2 mU/kg/min for 2 h). Insulin pulsatility was examined over 90 min by 2 min sampling. Short-term insulin pulses were identified using PULSAR. Treatment with ethinyl oestradiol/cyproterone acetate resulted in significant reductions in testosterone (3.3+/-0.7 vs. 1.9+/-0.2 nmol/l, p<0.05), free androgen index (10.2+/-0.7 vs. 1.2+/-0.2, p<0.05) and LH/FSH ratio (2.6+/-0.5 vs. 1.0+/-0.2, p<0.05). During hyperinsulinaemic clamps, the glucose infusion rate (GIR) required to maintain euglycaemia was lower in PCOS compared to controls (33.6+/-2.7 vs. 45.1+/-3.5 micromol/kg/min, p<0.05) but similar in PCOS before and after treatment (33.6+/-2.8 vs. 33.6+/-2.7 micromol/kg/min, p=0.9). Numbers of pulses identified in PCOS and controls were similar and unaltered by ethinyl oestradiol/cyproterone acetate. There was no correlation between GIR and frequency of insulin pulses in PCOS before or after treatment (r=0.2, p=0.6; post r=-0.5, p=0.1) unlike controls (r=-0.6, p=0.04). Despite considerable improvement in androgen profile, treatment with ethinyl oestradiol/cyproterone acetate did not alter insulin action in PCOS, and this insulin resistance does not appear to be determined by insulin pulse frequency.     

育龄期多囊卵巢综合征患者的糖代谢异常和胰岛素抵抗

目的探讨育龄期多囊卵巢综合征（PCOS）患者的糖代谢异常和胰岛素抵抗。方法选择育龄期PCOS患者168例,分为肥胖PCOS组78例和非肥胖PCOS组90例,正常对照组100例,对比临床表现及检测内分泌激素、空腹血糖、空腹胰岛素、服糖后2h血糖及2h胰岛素。结果育龄期PCOS患者的月经周期、多毛、痤疮、B超提示卵巢增大、卵巢多囊性改变、有不孕史与对照组比较,差异均有显著性（P〈0．05）,育龄期PCOS组的血清LH、T与对照组比较,差异有显著性（P〈0．05）。育龄期肥胖P-COS组的空腹血糖、服糖后2h血糖、空腹胰岛素、服糖后2h胰岛素与对照组比较,差异均有显著性（P〈0．05）。结论早期出现月经稀发、BMI升高的患者是否存在PCOS,值得重视。育龄期PCOS患者尤其肥胖型要高度重视糖代谢异常及胰岛素抵抗,以决定是否采取干预措施,避免出现远期并发症而对PCOS患者造成健康威胁。     

Testosterone and Androstenedione Blood Production Rates in Normal Women and Women with Idiopathic Hirsutism or Polycystic Ovaries

The average plasma testosterone concentration of women with either hirsutism or polycystic ovaries and hirsutism was higher (p < 0.01) than that of normal women although the ranges overlapped. Testosterone blood production rates averaged 830 +/- 120 SE and 1,180 +/- 310 SE mug per day in the two groups of hirsute women and 230 +/- 33 SE mug per day in normal women. The ranges did not overlap.The testosterone metabolic clearance rates of hirsute women (1,090 +/- 140 SE L per day) and of men (1,240 +/- 136 SE L per day) were significantly higher than those of normal women (590 +/- 44 SE L per day). These differences persisted when the metabolic clearance rates were corrected for surface area. We suggest that testosterone metabolic clearance rates vary directly with some function of testosterone production.The mean plasma androstenedione levels (2.8 +/- 0.35 SE and 2.8 +/- 0.30 SE mug per L) and production rates (6,060 +/- 450 SE and 7,360 +/- 345 SE mug per day) of the women with hirsutism or polycystic ovaries, respectively, were significantly higher than those of normal women (1.5 +/- 0.22 SE mug per L; 3,300 +/- 830 SE mug per day). The androstenedione metabolic clearance rates were the same in each group. Plasma androstenedione was the precursor of 49% of plasma testosterone in normal women and of 26% of plasma testosterone in hirsute women. Thus, 74% of the plasma testosterone in these subjects must have been either secreted or derived from a precursor that did not enter the plasma androstenedione pool.     

经阴道超声诊断多囊性卵巢综合征与激素水平测定对比研究

本文对６１例多囊卵巢综合征（ＰＣＯＳ）患者和４１例正常妇女进行经阴道超声检查与生殖内分泌激素水平测定。结果显示：经阴道超声下的卵巢多囊性改变是ＰＣＯＳ患者相对恒定特征。ＰＣＯＳ患者平均血清总睾酮、游离睾酮、硫酸脱氢表雄酮及雄烯二酮比正常组显著增高，ＰＣＯＳ患者卵巢卵泡个数与睾酮水平显著相关。     

多囊卵巢综合征大鼠骨骼肌细胞胰岛素受体底物1及其丝氨酸307位点磷酸化的表达

背景:胰岛素受体底物1的丝氨酸307位点磷酸化程度的增加参与了骨骼肌胰岛素抵抗的发生。目的:观察多囊卵巢综合征大鼠骨骼肌细胞胰岛素受体底物1的含量及其丝氨酸307位点磷酸化程度的变化。方法:将大鼠随机分为模型组和对照组,模型组给予人绒毛膜促性腺激素联合胰岛素皮下注射,并配以高脂饮食,构建大鼠多囊卵巢综合征模型;对照组皮下注射生理盐水,正常饲料喂养。结果与结论:干预6周后,Western blot检测结果显示,与对照组相比,模型组大鼠骨骼肌细胞胰岛素受体底物1表达量显著下降(P<0.05),而其丝氨酸307位点磷酸化蛋白表达明显升高(P<0.05)。结果提示,多囊卵巢综合征大鼠骨骼肌细胞中胰岛素受体底物1蛋白表达下调及其丝氨酸307位点磷酸化蛋白表达上调与多囊卵巢综合征大鼠骨骼肌胰岛素抵抗的发生密切相关。     

Increased Total Renin Levels but Not Angiotensin-Converting Enzyme Activity in Obese Patients with Polycystic Ovary Syndrome

Objective

To investigate the renin-angiotensin-aldosterone system and angiotensin-converting enzyme (ACE) activity in patients with polycystic ovarian syndrome (PCOS).

Subjects and Methods

In this case-control study, 41 obese (PCOS) women and 29 healthy controls, matched for age and body mass index, were enrolled. Anthropometric, metabolic, and hormonal patterns, including plasma aldosterone, plasma renin, and ACE activity, were measured in each subject.

Results

Plasma renin levels were significantly higher in PCOS patients (19.7 ± 14.5 µg/ml) compared with controls (12.9 ± 9.0 µg/ml, p < 0.05). ACE activity and aldosterone levels did not significantly differ between both groups (p = 0.15 and p = 0.18, respectively). Analysis of PCOS patients showed a significant correlation of fasting insulin levels with levels of renin (r = 0.305, p < 0.01) and free testosterone (r = 0.384, p = 0.001). Similarly, homeostasis model assessment index was positively correlated with total renin concentrations (r = 0.366, p < 0.01) and free testosterone (r = 0.352, p < 0.01).

Conclusion

Obese PCOS women had higher total renin levels, but not ACE activity and aldosterone levels, related to insulin resistance compared with controls.Key Words: Polycystic ovary syndrome, Angiotensin-converting enzyme, Renin     

Benefits of short-term structured exercise in non-overweight women with polycystic ovary syndrome: a prospective randomized controlled study

[Purpose] The short-term effects of structured exercise on the anthropometric, cardiovascular, and metabolic parameters of non-overweight women diagnosed with polycystic ovary syndrome were evaluated. [Subjects and Methods] Thirty women with a diagnosis of polycystic ovary syndrome were prospectively randomized to either a control group (n=16) or a training group (n=14) for a period of 8 weeks. Anthropometric, cardiovascular, and metabolic parameters and hormone levels were measured and compared before and after the intervention. [Results] Waist and hip measurements (anthropometric parameters); diastolic blood pressure; respiratory rate (cardiovascular parameters); levels of low-density lipoprotein cholesterol, total cholesterol, fasting glucose, and fasting insulin; and the homeostasis model assessment of insulin resistance index (metabolic parameters) were significantly lower in the training group after 8 weeks of exercise compared to the baseline values. After exercise, the training group had significantly higher oxygen consumption and high-density lipoprotein levels and significantly shorter menstrual cycle intervals. The corresponding values for controls did not significantly differ between the start and end of the 8-week experiment. [Conclusion] Short-term regular exercise programs can lead to improvements in anthropometric, cardiovascular, and metabolic parameters of non-overweight women with polycystic ovary syndrome.Key words: Exercise, Non-overweight, Polycystic ovary syndrome     

Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome

OBJECTIVE: Evidence suggests that some actions of insulin are effected by inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D-chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to insulin resistance in humans. RESEARCH DESIGN AND METHODS: To assess this possibility in polycystic ovary syndrome (PCOS), we determined insulin sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/mass spectrometry), and the release of insulin and DCI-IPG during the oral glucose tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal women. RESULTS: Women with PCOS were heavier than control subjects (P = 0.002 for BMI), but also had decreased Si (P < 0.001) and increased AUC(insulin) (P < 0.001) compared with normal women, even when corrected for BMI. The urinary clearance of DCI (uCl(DCI)) was increased almost sixfold in PCOS compared with normal women (P = 0.001), but not MYO clearance (P = 0.10). uCl(DCI) correlated inversely with Si when all women were analyzed together (n = 49, r = -0.50, P < 0.001) and was one of the three best independent parameters predicting Si. Finally, the ratio of AUC(DCI-IPG) to AUC(insulin) was decreased threefold in women with PCOS (P < 0.001). CONCLUSIONS: uCl(DCI) is inversely correlated with insulin sensitivity in women and is a strong independent predictor of insulin resistance in multivariate models. PCOS, which is characterized by insulin resistance, is associated with a selective increase in uCl(DCI) and impaired DCI-IPG release in response to insulin. These findings are consistent with a defect in tissue availability or utilization of DCI in PCOS that may contribute to the insulin resistance of the syndrome.     

Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors

OBJECTIVES: Recent epidemiologic studies have shown that obesity is associated with elevated blood concentrations of prothrombotic-proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), von Willebrand factor (vWF), and homocysteine. We have assessed whether these markers are associated with percentage of body fat (BF), insulin sensitivity as well as with leptin concentrations. DESIGN AND METHODS: Twenty-five men aged 49.6 +/- 12.7 yr (mean +/- SD) underwent whole-body air displacement plethysmography (Bod-Pod(R)) for estimating BF. Blood analyses for leptin and several other metabolic and cardiovascular markers were carried out. RESULTS: Obese subjects had higher levels as compared to controls of BF (37.5 +/- 5.1 vs. 26.0 +/- 6.6, p < 0.01), fibrinogen (3.30 +/- 0.43 vs. 2.67 +/- 0.11, p < 0.01), vWF (136.4 +/- 50.4% vs. 81.6 +/- 12.6%, p < 0.05), and leptin (17.6 +/- 8.7 vs. 6.2 +/- 3.3, p < 0.01), lower concentrations of HDL-cholesterol (1.09 +/- 0.20 vs. 1.51 +/- 0.10, p < 0.001) and lower QUICKI (1/[log(Ins(0)) + log(Glu(0))]) (0.31 +/- 0.03 vs. 0.34 +/- 0.02, p < 0.05). No significant changes were observed in CRP (5.7 +/- 3.4 vs. 3.8 +/- 1.6, p = 0.327) and homocysteine (9.4 +/- 4.2 vs. 8.3 +/- 0.9, p = 0.749). A positive correlation was observed between BF and fibrinogen (r = 0.67, p = 0.0003). Plasma leptin concentrations were correlated with fibrinogen (r = 0.71, p = 0.0001) and CRP (r = 0.43, p = 0.044). After adjustment for BF leptin emerged as a significant predictor of fibrinogen (beta = 0.47, p = 0.023; R(2) = 0.59, p < 0.001). QUICKI was positively correlated with HDL-cholesterol (r = 0.59, p = 0.010) and negatively with fibrinogen (r = -0.53, p = 0.025), CRP (r = -0.52, p = 0.028) and vWF (r = -0.56, p = 0.013). CONCLUSIONS: Increased BF and impaired insulin sensitivity are associated with increased concentrations of cardiovascular risk factors. Leptin seems to be involved in this elevation and emerges as a predictor of circulating fibrinogen concentrations.     

不同表型多囊卵巢综合征患者的代谢特征

目的 通过比较不同表型多囊卵巢综合征患者的代谢特征,寻找多囊卵巢综合征(PCOS)患者临床特点与代谢综合征及心血管疾病风险独立预测因子血脂、C-反应蛋白(CRP)之间的关系.方法 依据2003年鹿特丹会议制定的诊断标准选择PCOS 患者48例,依据患者的不同表型分为三组:高雄激素无排卵型、高雄激素有排卵型、非高雄激素无排卵型.比较不同表型多囊卵巢综合征患者胰岛素抵抗指数、肥胖发生率及血脂、CRP的差异.结果 高雄激素无排卵型多囊卵巢综合征患者胰岛素抵抗率及肥胖发生率明显高于高雄激素有排卵型及非高雄激素无排卵型,差异均有统计学意义(χ2分别=4.49、3.88、5.34、6.44,P 均＜0.05);高雄激素无排卵型多囊卵巢综合征患者血清甘油三脂水平、低密度脂蛋白水平明显高于高雄激素有排卵型及非高雄激素无排卵型,差异均有统计学意义(t分别=2.17、2.39、2.23、2.13,P均＜0.05).高雄激素无排卵型多囊卵巢综合征患者血清C-反应蛋白水平明显高于高雄激素有排卵型,差异有统计学意义(t=2.30,P＜0.05).结论高雄激素无排卵型的PCOS患者将来更易发生代谢综合征,可能更易患心血管疾病.     

Color Doppler sonographic analysis of uterine and ovarian artery blood flow in women with polycystic ovary syndrome

PURPOSE: To study the blood flow patterns of utero-ovarian circulation in polycystic ovary syndrome (PCOS) and to assess their relationship with clinical, metabolic, and hormonal data. METHODS: Forty-three women with PCOS and 43 age-matched healthy controls underwent Doppler examination of the utero-ovarian circulation in the follicular phase. Demographic, hormonal, and metabolic parameters were determined. Student's t-test, chi(2)-test, and Spearman correlation test were used for statistical analysis. RESULTS: The ovarian artery pulsatility index (PI), resistance index (RI), and SD ratios were significantly lower in PCOS than in controls on the right side (p < 0.001, p = 0.02, p = 0.001, respectively) as well as on the left side (p < 0.001, p < 0.001, p < 0.001, respectively). The uterine artery systolic/diastolic (S/D) ratio was higher on both sides (p = 0.01) and the PI was higher on the left side (p = 0.02) in PCOS than in controls. The right uterine artery PI was positively correlated with luteinizing hormone and hemoglobin (r = 0.417, p = 0.043; r = 0.427, p = 0.033, respectively), the right uterine artery S/D was positively correlated with body mass index (r = 0.479, p = 0.015), and the left uterine artery PI was positively correlated with insulin (r = 0.458, p = 0.021). CONCLUSION: Doppler sonography of the utero-ovarian circulation may contribute to the evaluation of PCOS patients and a better understanding of the pathophysiology of this syndrome.     

Haemoglobin,C‐reactive protein and androgen levels in uncomplicated and complicated pregnancies of women with polycystic ovary syndrome

Objective. We studied a possible association between pregnancy complications and blood/serum levels of haemoglobin, C‐reactive protein, sex hormones and lipids in women with polycystic ovary syndrome. Material and methods. Twenty‐one women with polycystic ovary syndrome were followed prospectively from the first trimester to delivery. Women with pregnancy complications (n = 10) were compared to women without complications (n = 11). Outcome measures were blood/serum levels of haemoglobin, C‐reactive protein, dehydroepiandrosterone sulphate, androstenedione, testosterone, sex hormone binding globulin, free testosterone index, oestrogens and lipids. Results. Haemoglobin levels were higher in complicated pregnancies compared to uncomplicated pregnancies throughout the complete pregnancy, while C‐reactive protein levels were higher for complicated pregnancies at gestational weeks 19 and 32. Serum levels of lipids, androgens and oestrogens did not differ throughout pregnancy. Conclusion. In women suffering from polycystic ovary syndrome, pregnancy complications were associated with elevated blood/serum levels of haemoglobin and C‐reactive protein. Androgen, oestrogen and lipid levels did not differ between groups.