多囊卵巢综合征患者血清抗苗勒管激素与肥胖、胰岛素抵抗程度的相关性分析

目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者血清抗苗勒管激素(anti-Müllerian hormone,AMH)水平与肥胖、胰岛素抵抗(insulin resistance,IR)程度的相关性。方法:选择在我院生殖中心就诊的139名PCOS患者为研究组,并以月经周期正常、因输卵管因素或男性因素导致不孕者48名作为对照组。检测和比较PCOS患者的血清AMH、性激素水平及代谢指标,分析血清AMH水平与PCOS患者肥胖、胰岛素抵抗程度的关系。结果:PCOS组患者体质量指数(body mass index,BMI)、黄体生成素(luteinizing hormone,LH)、睾酮(testosterone,T)、垂体泌乳素(pituitary prolactin PRL)、空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素(fasting insulin,FINS)、稳态模型胰岛素抵抗指数(homenostasis models assessment-insulin resistance index,HOMA-IR)的水平均显著高于对照组(P0.05),PCOS组和对照组年龄、卵泡刺激素(follicle stimulating hormone,FSH)比较差异无统计学意义(P0.05)。PCOS各表型组的血清AMH浓度、LH/FSH比值均明显高于对照组(P0.05)。肥胖组患者的AMH浓度低于正常体重组,BMI、FPG、FINS、HOMA-IR、甘油三脂(triglycerides,TG)水平均高于正常体重组,LH、LH/FSH、高密度脂蛋白(high density lipoprotein,HDL-C)水平均低于正常体重组(P0.05)。高HOMA-IR组患者的血清AMH浓度、LH、LH/FSH水平均明显低于低HOMA-IR组,BMI、T、FPG、FINS、TG、低密度脂蛋白(low density lipoprotein,LDL-C)水平均高于低HOMA-IR组(P0.05)。PCOS患者血清AMH浓度和BMI及HOMA-IR均存在显著负相关。结论:PCOS患者血清的AMH水平较对照组明显升高,与其肥胖、胰岛素抵抗(IR)程度呈显著负相关。     

Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels

The objective of the study was the comparison of anti-Müllerian hormone (AMH) levels among obese or overweight and normal-weight women with the four different polycystic ovary syndrome (PCOS) phenotypes and healthy control subjects. AMH levels were evaluated in four age- and body mass index (BMI)-matched groups of 25 normal-weight and 25 obese or overweight women each, belonging to the four main subsets of the syndrome resulting from combinations of the three diagnostic criteria [group 1: oligo- and/or anovulation (ANOV), hyperandrogenemia (HA), and polycystic ovaries (PCO) on ultrasonographic evaluation; group 2: ANOV and HA; group 3: HA and PCO, group 4: ANOV and PCO], and in 50 (25 obese or overweight and 25 normal weight) age- and BMI-matched healthy control subjects. Age, BMI, waist circumference, FSH, LH, prolactin, testosterone, Delta(4)-androstenedione, dehydroepiandrosterone-sulfate, 17alpha-OH-progesterone, fasting insulin, glucose, AMH, free androgen index, and homeostasis model assessment for insulin resistance index were analyzed. AMH levels were significantly higher in PCOS groups 1 and 2 compared with groups 3 and 4 and the control group and higher in PCOS groups 3 and 4 compared with the control group. AMH levels were significantly increased in normal-weight compared with obese and overweight women. AMH concentrations were independently predicted, in order of significance, by LH and testosterone levels, BMI (negatively), and the total number of follicles 2-9 mm in diameter. The differences in circulating AMH levels between the main phenotypic groups of PCOS women appear to reflect the severity of the syndrome, but are negatively affected by obesity. Increased LH levels might be the most significant independent link between PCOS-associated disorders of ovulation and the observed increase in circulating AMH concentration.     

Polycystic ovary syndrome and endothelial dysfunction: A potential role for soluble lectin-like oxidized low density lipoprotein receptor-1

The aims of this study were to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), oxidized LDL (oxLDL), paraoxonase-1(PON-1) and hydroperoxide (LOOH) levels are altered in women with polycystic ovary syndrome (PCOS) and also to determine if hyperandrogenism, insulin resistance (IR) and Anti-Müllerian Hormone (AMH) are associated with endothelial dysfunction in PCOS. A total of 46 women with PCOS and 46 non-PCOS healthy controls were recruited. Women with PCOS had significantly higher sLOX-1, oxLDL and LOOH concentrations than non-PCOS women [6.16 (3.92−13.95) vs 1.37 (0.63−4.43) ng/mL, p < 0.001; 6.48 ± 1.03 vs 3.16 ± 1.02 μU/L, p < 0.001; 2.45 (1.45−3.45) vs 1.06 (0.64−1.56) μmol/L, p < 0.001]. The mean PON-1 level of PCOS group was lower than non-PCOS group (69.47 ± 10.75 vs 104.08 ± 21.43 U/mL, p < 0.001). There was no significant difference in terms of the sLOX-1, oxLDL, LOOH and PON-1 levels between normal weight and overweight PCOS women. On univariate logistic regression analysis, Ferriman-Gallwey scale (FGS), HOMA-IR and AMH were an independent predictors of high risk group of endothelial dysfunction markers (HR-EDm). Age and BMI were not associated with HR-EDm. When incorporated into the multivariate model, endotelial dysfunction markers independently correlated with clinical hyperandrogenism (FGS) but not with AMH. In conclusion, our results indicated that an increased concentration of sLOX-1 might be an early predictor of endothelial damage in patients with PCOS. Women with PCOS have elevated sLOX-1, oxLDL, LOOH and decreased PON-1 levels, independent of BMI. Endothelial dysfunction in women with PCOS is associated with hyperandrogenism. Further studies are required to confirm our findings.     

Anti-Müllerian hormone in women with polycystic ovary syndrome before and after therapy with metformin

Anti-Müllerian hormone (AMH) is largely expressed throughout folliculogenesis and its levels may represent both the quantity and quality of ovarian follicle pool. We conducted this study to evaluate the levels of AMH in women with polycystic ovarian syndrome (PCOS) before and after metformin therapy. 22 consecutive patients with PCOS and 20 healthy age-matched controls were investigated. The patients received 2?550?mg/day metformin for 6 months. Serum levels of AMH, sex hormones, insulin, blood glucose, and lipids were measured before and after metformin therapy. The basal AMH levels in patients with PCOS (42.34±6.42?pmol/l) were significantly elevated in comparison with the controls (21.58±3.41?pmol/l), p=0.008. 17 patients completed 6 months therapy with metformin. Of them, 13 responded clinically by restoration of regular menstrual cycles. The AMH levels of these 13 women decreased from 45.67±9.30?pmol/l to 38.25±6.89?pmol/l (16.27%). In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30±16.52 to 80.77±12.73 (p=0.021). The patients who responded to metformin were significantly overweight, had higher BMI, waist circumference, body fat, and blood pressure as compared to nonresponders. AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin. Furthermore, obese PCOS patients are more likely to respond to metformin therapy with maximal doses as compared to the ones with low body mass index.     

Effects of metformin on the expression of GLUT4 in endometrium of obese women with polycystic ovary syndrome

The objective was to explore the effects of metformin on the expression of endometrial glucose transporter 4 (GLUT4) and analyze the related factors of GLUT4 in patients with polycystic ovary syndrome (PCOS). This study included 20 obese patients with PCOS (PCOS group) and 20 obese patients who had infertility caused by oviducal or pelvic factors but had no PCOS (control group). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol-2 (E(2)), testosterone (T), fasting serum glucose (FSG), fasting insulin serum (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and endometrial GLUT4 expression were determined in the two groups. In PCOS group, patients were given 500 mg of metformin three times per day for 3 mo, and then the parameters above were determined again and compared with that before metformin treatment. The parameters above also were compared between PCOS and control groups. The correlation of GLUT4 with its related factors was analyzed. The levels of T, FINS, and HOMA-IR were higher in PCOS group than in the control group (P < 0.01). The levels of protein and mRNA of endometrial GLUT4 were lower in the PCOS group than in the control group (P < 0.001). The expression of protein and mRNA of endometrial GLUT4 increased after metformin treatment (P < 0.001). HOMA-IR was negatively correlated with GLUT4 expression (P = 0.027). In patients with PCOS, the levels of protein and mRNA of endometrial GLUT4 were lower compared with that in non-PCOS women, and HOMA-IR was strongly associated with endometrial GLUT4 expression. Metformin may up-regulate endometrial GLUT4 expression to improve endometrial IR.     

Insulin resistance in nonobese patients with polycystic ovary syndrome

OBJECTIVES: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. METHOD: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. RESULTS: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 +/- 1.32 vs. 1.18 +/- 0.53 pg/ml, p < 0.001, and 11.63 +/- 5.37 vs. 4.98 +/- 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 +/- 14.94 vs. 73.98 +/- 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 +/- 4.98 vs. 19.56 +/- 2.21 microU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 +/- 27.8 vs. 427.8 +/- 88.9 micromol x kg(-1) x min(-1), p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = -0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = -0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. CONCLUSIONS: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.     

黄连素对PCOS模型大鼠LPS /NF-κB、MAPK信号通路的影响*

目的: 探讨黄连素对多囊卵巢综合征(PCOS)模型大鼠糖脂代谢、性激素结合蛋白和脂联素(LPS)以及NF-κB、MAPK信号通路的影响。方法: 将SD雌性大鼠随机分成空白组、PCOS模型组、黄连素组(0.216 g/kg)、二甲双胍组(0.135 g/kg)和达英-35(0.18 mg/kg)组,每组10只。PCOS模型组用来曲唑(1 mg/(kg·d))连续灌胃3周,随后药物干预28 d,检测大鼠体重、卵巢和子宫指数,HE染色观察大鼠卵巢卵泡数量变化,用ELISA法检测血清性激素水平、空腹葡萄糖和胰岛素、甘油三酯和胆固醇、性激素结合蛋白和脂联素水平以及用蛋白印迹法检测卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达。结果: 与空白组比较,模型组大鼠体重显著增加(P＜0.05),子宫指数显著降低(P＜0.05),囊状卵泡数量显著增加(P＜0.05),血清黄体生成素(LH)、睾酮(T)水平和LH/FSH比值显著升高(P＜0.05),卵泡刺激素(FSH)水平显著下降(P＜0.05),总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素和胰岛素指数(HOMA)显著增加(P＜0.05),性激素结合蛋白(SHBG)含量显著减少以及脂联素(LPS)含量显著增加(P＜0.05),卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达上调(P＜0.05)。与模型组比较,黄连素能显著增加子宫指数(P＜0.05)、次级卵泡数量(P＜0.05),显著降低血清促黄体生成素(LH)水平、睾酮(T)水平和LH/FSH比值(P＜ 0.05),显著下调卵巢组织p38-MAPK和NF-κB蛋白表达(P＜0.05),作用类似达英-35;黄连素能明显降低血清甘油三酯(TG)、胰岛素水平和胰岛素指数(P＜0.05),升高血清SHBG水平,降低LPS水平(P＜0.05),作用类似二甲双胍。结论: 黄连素通过下调卵巢组织p38-MAPK和NF-κB蛋白表达,降低血清LPS含量,起到调控PCOS大鼠性激素紊乱和胰岛素抵抗(IR)的作用。     

Gender-specific differences of serum leptin in obese and normal-weight adolescents: studies in type-I diabetes and Turner syndrome

The influence of exogenous insulin and estrogen substitution on serum leptin-like immunoreactivity was studied longitudinally in patients with type-I diabetes and Turner syndrome using a specific radioimmunoassay. Prepubertal, pubertal and postpubertal samples of 17 patients (9 girls, 8 boys) with type-I diabetes mellitus developing obesity were compared to those of 17 normal-weight controls matched for gender, age and diabetes duration. Six obese and six normal-weight girls with Turner syndrome were studied without hormone substitution, with ethinylestradiol alone, and with cyclic estradiol/gestagen substitution. The mean leptin levels of the girls with diabetes were two times higher than boys at all times, while insulin doses and glycemic control had no influence. In Turner syndrome estrogen substitution led to increased leptin levels only in the obese group. This study revealed that both body weight above normal and female sex steroids seem to be necessary to elevate leptin concentrations, while exogenous insulin has no effect.     

多囊卵巢综合征肥胖患者血清维生素D、铁蛋白水平、sICAM-1与胰岛素抵抗、糖脂代谢指标的相关性

摘要 目的：探讨多囊卵巢综合征（PCOS）肥胖患者血清维生素D、铁蛋白、可溶性细胞间粘附分子-1（sICAM-1）水平与胰岛素抵抗、糖脂代谢指标的相关性。方法：2018年8月到2021年11月,选择在本院妇科诊治的PCOS患者65例作为研究对象,分为PCOS肥胖组（n=30,体重指数＜28 kg/m²）和PCOS非肥胖组（n=35,体重指数<28 kg/m²）。检测与计算两组清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标并进行相关性分析。结果：两组的血清甲状腺素（T4）、促甲状腺激素（TSH）与泌乳素（PRL）对比差异无统计学意义（P>0.05）,肥胖组的血清促黄体生成素（LH）、促卵泡生成素（FSH）、睾酮（T）水平高于非肥胖组（P<0.05）。肥胖组的血清铁蛋白、sICAM-1水平高于非肥胖组,血清维生素D水平低于非肥胖组（P<0.05）。肥胖组的胰岛素抵抗指数（HOMA-IR）、胰岛素水平（FINS）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）较非肥胖组,高密度脂蛋白胆固醇（HDL-C）低于非肥胖组（P<0.05）。在PCOS肥胖患者中,Pearson分析显示血清维生素D、铁蛋白、sICAM-1与胰岛素抵抗、糖脂代谢指标都存在相关性（P<0.05）。结论：PCOS肥胖患者与非肥胖患者的血清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标水平存在差异,血清维生素D、铁蛋白、sICAM-1水平与胰岛素抵抗、糖脂代谢指标存在相关性。     

Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects,before and after 45 min of a Turkish bath or running

The purpose of this study was to ascertain (1) whether human saliva contains irisin and whether its level correlates with serum irisin concentration, (2) whether salivary glands, eccrine glands and sebaceous glands in human skin produce irisin, (3) how the changes in saliva and serum irisin concentrations after the Turkish bath at 47 ± 3 °C compare with the changes caused by moderate exercise in obese and normal weight subjects. Seven obese male subjects and seven normal weight subjects were enrolled for Turkish bath. Seven obese male subjects and seven normal weight subjects were also enrolled for moderate outdoor exercise, and thirteen male normal weight subjects neither exercised nor showered at the Turkish bath. From each participant, 1.5 ml of saliva and 5 ml blood were collected simultaneously before and after the moderate exercise and Turkish bath. Salivary glands and eccrine and sebaceous glands in the skin were screened immunohistochemically for irisin while serum and saliva irisin were measured with an ELISA. Submandibular glands, eccrine glands and sebaceous glands in the human skin showed strong irisin immunoreactivity. Human saliva contained irisin and its level was significantly higher than the serum levels in both obese and normal weight subjects. However, irisin concentrations were more markedly increased in both saliva and serum samples from subjects who had showered at a Turkish bath than in obese subjects who had exercised or in normal weight subjects. Human submandibular glands, eccrine sweat glands and sebaceous glands synthesize irisin.     

血清OC、TSP-1、ANGPTL2与多囊卵巢综合征患者胰岛素抵抗、性激素和卵巢间质血流的关系研究

摘要 目的：分析血清骨钙素（OC）、血小板反应蛋白-1（TSP-1）、血管生成素样蛋白2（ANGPTL2）与多囊卵巢综合征（PCOS）患者胰岛素抵抗（IR）、性激素和卵巢间质血流的关系。方法：选取2020年1月～2022年4月内蒙古自治区人民医院收治的125例PCOS患者（PCOS组）,根据稳态模型评估（HOMA）-IR分为IR组68例和非IR组57例,另选取同期67例体检健康成年女性（对照组）。收集研究对象HOMA-IR和性激素、卵巢间质血流指标,采用酶联免疫吸附法检测血清OC、TSP-1、ANGPTL2水平。比较PCOS组与对照组、IR组与非IR组之间性激素、卵巢间质血流指标、血清OC、TSP-1、ANGPTL2水平的差异。采用Pearson/Spearman相关性分析法分析PCOS患者血清OC、TSP-1、ANGPTL2水平与HOMA-IR、性激素和卵巢间质血流指标的相关性。结果：PCOS组HOMA-IR、黄体生成素（LH）、LH/促卵泡生成素（FSH）、睾酮（T）、收缩期峰值速度（PSV）、ANGPTL2水平高于对照组,搏动指数（PI）和阻力指数（RI）、OC、TSP-1水平低于对照组（P＜0.05）。IR组LH、LH/FSH、T、PSV、ANGPTL2水平高于非IR组,PI、RI、OC、TSP-1水平低于非IR组（P＜0.05）。Pearson/Spearman相关性分析显示,PCOS患者血清OC、TSP-1水平与HOMA-IR、LH、LH/FSH、T、PSV呈负相关,与PI、RI呈正相关（P＜0.05）;血清ANGPTL2水平与PCOS患者HOMA-IR、LH、LH/FSH、T、PSV呈正相关,与PI、RI呈负相关（P＜0.05）。结论：血清OC、TSP-1在PCOS患者血清中低表达,ANGPTL2在PCOS患者血清中高表达,三者与PCOS患者IR、性激素和卵巢间质血流密切相关。     

Exercise decreases anti-müllerian hormone in anovulatory overweight women with polycystic ovary syndrome: a pilot study

Polycystic ovary syndrome (PCOS) is a common condition in women associated with menstrual irregularity and anovulation. While obesity worsens and weight loss or exercise improves reproduction function in PCOS, the mechanism for this is unclear. The aim of this study was to examine the effect of exercise on ovarian hormones [anti-Müllerian hormone (AMH)] and menstrual and ovulatory function in women with and without PCOS. Overweight women with (n=7) and without (n=8) PCOS of comparable age, weight and BMI undertook a 12-week intensified endurance exercise training program (1?h 3 times/week) with no structured energy restriction. Primary outcomes were AMH, ovulation (weekly urinary pregnanediol) and menstrual regularity. Secondary outcomes were insulin resistance (euglycemic hyperinsulinemic clamp) and body composition (computed tomography and dual X-ray absorptiometry). Exercise decreased BMI, total and android fat mass and improved insulin sensitivity for all women. AMH was significantly higher in women with PCOS compared to controls before (p<0.001) and after exercise (p=0.001). There was a significant interaction between AMH changes with exercise and PCOS status (p=0.007) such that women without PCOS had no change in AMH (+1.4±5.2?pmol/l, p=0.48) while women with PCOS had a decrease in AMH (-?13.2±11.7?pmol/l, p=0.025). Exercise is associated with improvements in ovarian hormones in women with abnormal ovarian function. This suggests that mechanisms associated with ovarian dysfunction can be improved by exercise in PCOS.     

青少年多囊卵巢综合征的临床、超声和生化特征及其诊断意义

青春期多囊卵巢综合征(PCOS)的诊断具有一定的临床挑战性。迄今未有报道青少年人群PCOS的患病率以及临床、超声和生化特征。为了评估PCOS的临床和生化特征在14~16岁月经初潮女孩中的普遍程度,确定内循环雄激素水平在卵泡期早期的正常范围。本研究进行了一项前瞻性群组研究,研究群组是244名未经选择的月经初潮后的女孩,平均年龄在15.2岁。从一个大的以人口为基础的出生群组(Raine队列)中招募受试者。临床高雄激素血症(HA)使用Ferriman-Gallwey评分进行量化。在卵泡期的初期(第2~第6天),本研究使用免疫法测定循环雄激素和性激素结合球蛋白,并通过经腹部超声检查来评估卵巢形态,得到了青少年女性群体卵泡期初期的雄激素的正常范围。循环游离睾酮水平的前5%和10%分别为45.6 pmol/L和34.5 pmol/L。51%的女孩报告月经不规律。临床HA是罕见的,仅观察到3.5%的女孩罹患此病。平均卵巢体积大于其他报道中成年妇女的卵巢体积,35%的女孩在经腹超声时显示有多囊卵巢形态。按照游离睾酮数值排序,取前5%作为HA。42名女孩(18.5%)符合PCOS的Rotterdam标准,11个女孩(5%)雄激素超出社会标准。本研究表明,月经不规律在青春期是常见的,不涉及临床或生化HA。卵巢体积和形态的PCOS诊断在青春期可能有局限性。     

Insulin Levels,Physical Activity,and Urinary Catecholamine Excretion of Obese and Non-Obese Rhesus Monkeys

The hypothesis that spontaneous obesity in rhesus monkeys is associated with abnormalities in energy expenditure was tested. Obese (n=7) and non-obese (n=5) monkeys were described in terms of body size and composition, food intake, and physical activity. Additionally, the relationships among fasting and stimulated insulin levels in serum, C-peptide levels in serum and urine, and urinary catecholamines were examined. Obese animals had primarily abdominal deposition of excess body fat, as indicated by markedly elevated abdominal circumferences and skin-fold thicknesses. Food intake did not differ between groups. Physical activity was much lower in the obese group. Obese monkeys had markedly higher serum insulin and C-peptide levels in the fasted state and in response to an intravenous glucose challenge. Urinary excretion of C-peptide and catecholamines was measured during successive 2-day periods of ad libitum feeding, food deprivation, and refeeding in order to examine potential differences between groups in sympathoadrenal activity and their relationship to insulin secretion. C-peptide excretion was greater for obese and decreased for both groups during food deprivation. Urinary dopamine (DA), norepinephrine (NE), and epinephrine (E) levels were significantly greater for obese animals in all conditions. DA excretion was lowest during deprivation and E excretion was lowest during refeeding, whereas NE excretion was relatively unaffected by feeding condition. The overall patterns of C-peptide and catecholamine excretion were qualitatively similar for both groups, and there were no reliable differences between obese and non-obese in their responses to the feeding manipulation. The results suggest that hyperinsulinemia associated with obesity in rhesus monkeys is linked to increased catecholamine secretion and a resistance to cate-cholaminergic action.     

Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS

We hypothesized that short-term calorie restriction would blunt luteinizing hormone (LH) hypersecretion in obese women with polycystic ovary syndrome (PCOS) and thereby ameliorate the anovulatory endocrine milieu. To test this hypothesis, 15 obese patients with PCOS and nine age- and body mass index-matched healthy women underwent 24-h blood sampling to quantitate plasma LH, leptin, and insulin levels. PCOS subjects were prescribed a very low caloric liquid diet (4.2 MJ/day) for 7 days and were then resampled. Basal and pulsatile LH secretion was threefold higher in PCOS subjects, but plasma insulin and leptin levels were not different in the calorie-replete state. Contrary to expectation, calorie restriction enhanced basal and pulsatile LH secretion even further. As expected, plasma glucose, insulin, and leptin concentrations decreased by 18, 75, and 50%, respectively. Serum total testosterone concentration fell by 23%, whereas serum estrone, estradiol, sex hormone-binding globulin (SHBG), and androstenedione concentrations remained unchanged. Enhanced LH secretion in the presence of normal metabolic and hormonal adaptations to calorie restriction points to anomalous feedback control of pituitary LH release in PCOS.     

二甲双胍对多囊卵巢综合征肥胖型患者LH和FSH的影响

目的：探讨二甲双胍对多囊卵巢综合征肥胖型患者血清中胰岛素、LH和FSH水平的影响。方法：将84例PCOS肥胖型患者随机分成44例对照组（克罗米芬）和40例观察组（二甲双胍）,采用放射免疫法测定黄体生成素（LH）和卵泡刺激素（FSH）的水平,分别于服药前（0分钟）和服后60、120分钟经前臂静脉采血,测血糖浓度及血清胰岛素水平。结果：对照组患者治疗前0min、60min及120min的血糖OGTT分别为（4．57±0．25）mmol／L、（8．38±7．05）mmol/L（7.21±0．12）mmol／L。治疗后0min、60min及120min的血糖OGTT无明显变化。观察组患者治疗前0min、60min及120min的血糖OGTT分别为（4．11±0．31）mmol／L、（8．23±6．57）mmol／L及（7．25±0．13）mmol／L,治疗后0min、60min及120min的血糖0GTT明显降低。对照组患者治疗前血清中胰岛素为（47．32±9．52）U／ml,治疗后为（42．25±7．65）U／ml,治疗前后无明显差异。观察组患者治疗前血清中胰岛素为（46．41±6．11）U／ml,治疗后血清胰岛素水平明显降低。对照组患者治疗后血清中LH为（17．22±2．14）mU／ml,FSH为（1．24±0．33）mU／ml,而与对照组相比,观察组患者血清中的LH明显降低,而FSH水平升高。结论：二甲双胍导致多囊卵巢综合征患者血清中胰岛素水平降低,从而减轻了胰岛素对LH的刺激作用,使LH水平下降,FSH升高,进而改善机体的激素紊乱,最终达到治疗PCOS的目的。     

游离睾酮指数联合血清GnSAF、SHBG对多囊卵巢综合征不孕患者IVF-ET治疗妊娠结局的预测价值

摘要 目的：探讨游离睾酮指数（FAI）联合血清促性腺激素平抑因子（GnSAF）、性激素结合球蛋白（SHBG）对多囊卵巢综合征（PCOS）不孕患者体外受精-胚胎移植（IVF-ET）治疗妊娠结局的预测价值。方法：选取2020年1月～2022年6月湖南省妇幼保健院生殖医学中心收治的197例PCOS不孕患者为PCOS组,根据IVF-ET治疗妊娠结局分为妊娠失败组和妊娠成功组,另选取同期68名体检健康妇女为对照组。收集PCOS不孕患者临床资料,计算FAI并检测血清GnSAF、SHBG水平。采用单因素和多因素Logistic回归分析PCOS不孕患者IVF-ET治疗妊娠结局的影响因素,采用受试者工作特征（ROC）曲线分析FAI和血清GnSAF、SHBG对PCOS不孕患者IVF-ET治疗妊娠结局的预测价值。结果：PCOS组FAI和血清GnSAF水平高于对照组,SHBG水平低于对照组（P＜0.05）。197例PCOS不孕患者IVF-ET治疗妊娠成功率为51.27%（101/197）。单因素分析显示,妊娠失败组体质指数、黄体生成素（LH）、LH/促卵泡生成素（FSH）、睾酮、抗苗勒管激素（AMH）、FAI、GnSAF高于妊娠成功组,FSH、受精率、优胚率、SHBG低于妊娠成功组（P＜0.05）。多因素Logistic回归分析显示,体质指数增加和LH、LH/FSH、AMH、FAI、GnSAF升高为PCOS不孕患者IVF-ET治疗妊娠失败的独立危险因素,SHBG升高为其独立保护因素（P＜0.05）。ROC曲线分析显示,FAI和血清GnSAF、SHBG联合预测PCOS不孕患者IVF-ET治疗妊娠结局的曲线下面积大于FAI、GnSAF、SHBG单独预测。结论：FAI和血清GnSAF、SHBG水平联合预测PCOS不孕患者IVF-ET治疗妊娠结局的价值较高。     

The effect of weight loss on inflammation in obese women with polycystic ovary syndrome

INTRODUCTION: The aim of the present study was to evaluate the effect of modest weight reduction on serum concentrations of tumour necrosis factor alpha (TNF-alpha), TNF soluble receptors (sTNFRs) and interleukin-6 (IL-6) in obese women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study group consisted of 15 obese women with PCOS (mean age 28.5 +/- 7.7 years). Serum concentrations of TNF-alpha, sTNFRs and IL-6, insulin, FSH, LH, DHEAS, androstendione, total and free testosterone, cortisol, 17OH-progesterone, oestradiol and sex hormone binding globulin (SHBG), glucose, total cholesterol, HDL cholesterol and triglycerides were measured before treatment and after 10% weight loss. All patients were advised to follow a 1000-1200 kcal diet with a limited intake of simple carbohydrate and animal fats and to exercise regularly (30 min, 3 times a week). Body composition was measured by bioimpedance. Serum concentrations of TNF-alpha, sTNFRs and IL-6 were determined by enzyme linked immunosorbent assay (ELISA). Plasma insulin, FSH, LH, DHEAS, androstendione, total and free testosterone, cortisol, 17OH-progesterone, oestradiol and SHBG were measured by a commercial RIA. Blood glucose, total cholesterol, HDL cholesterol and triglycerides were measured by an enzymatic procedure. RESULTS: We observed no differences in serum concentrations of TNF-alpha, sTNFRs or IL-6 after treatment. CONCLUSIONS: It seems that more than a modest weight reduction is necessary to obtain a decrease in serum concentrations of proinflammatory cytokines and an improvement in ovarian function in obese women with polycystic ovary syndrome.     

Evidence for unimpaired pancreatic secretion and hepatic removal of insulin in healthy offspring of type 2 (noninsulin-dependent) diabetic couples

The aim of the present study was to investigate the secretion and the hepatic removal of insulin in a group of 14 unaffected offspring of 14 type 2 (noninsulin-dependent) diabetic couples compared to 14 healthy subjects without family history of diabetes mellitus. The two groups, each consisting of 5 obese and 9 nonobese subjects, were carefully matched for sex, age, and body weight. We examined glucose, insulin, and C-peptide levels, as well as C-peptide to insulin ratios and relations during the oral glucose tolerance test. Glucose concentrations and incremental areas were similar in the two groups, as well as insulin and C-peptide levels and areas. C-peptide to insulin molar ratios, both in fasting state and after glucose load, as well as relations between C-peptide and insulin incremental areas were not different. Our results suggest that the healthy offspring of type 2 diabetic couples have a normal response of beta-cell to oral glucose as well as a normal removal of insulin by the liver.     

Hyperandrogenemia in Obese Peripubertal Girls: Correlates and Potential Etiological Determinants

Obesity in peripubertal girls is associated with hyperandrogenemia (HA), which can represent a forerunner of polycystic ovary syndrome (PCOS). However, not all obese girls demonstrate HA, and determinants of HA in obese girls remain unclear. We hypothesized that insulin and luteinizing hormone (LH) are independent predictors of free testosterone (T) concentration in obese girls. To assess this further, fasting morning blood samples were collected from 92 obese (BMI‐for‐age percentile ≥95) girls in various stages of puberty. A multivariate regression model was then constructed using free T (dependent variable), LH, insulin, pubertal group (early, mid‐, or late puberty), BMI z‐score, and age. Free testosterone (T) concentrations were highly variable among obese girls in each pubertal group. The regression model accounted for roughly half of the variability of free T in obese girls (adjusted R² = 0.53, P < 0.001). LH was found to have the greatest independent ability to predict free T, followed by insulin, then age and BMI z‐score. Pubertal group was not an independent predictor of free T. We conclude that morning LH and fasting insulin are significant predictors of free T in obese girls, even after adjusting for potential confounders (age, pubertal group, adiposity). We suggest that abnormal LH secretion and hyperinsulinemia can promote HA in some peripubertal girls with obesity.