Serum levels of insulin-like growth factor-1, IGF binding protein-1 and insulin and the response to human menopausal gonadotrophins in women with polycystic ovary syndrome

In order to determine which factors influence the large variationsin sensitivity to gonadotrophins witnessed in women with polycysticovary syndrome (PCOS), a prospective study was conducted ofthe correlation between basal clinical and endocrinologicalfeatures and gonadotrophin requirements of 20 women with clomiphene-resistantPCOS undergoing ovulation induction. Baseline evaluation ofserum concentrations of luteinizing hormone (LH), follicle stimulatinghormone (FSH), testosterone, fasting insulin, insulin-like growthfactor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-bindingglobulin (SHBG) were performed before administering gonadotrophin-releasinghormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin(HMG) was given in a standard individualized protocol accordingto ovarian response, until human chorionic gonadotrophin (HCG)was given. Serum concentrations of insulin, IGF-1, and IGFBP-1were unaffected by GnRHa. The BMI correlated positively withinsulin and inversely with IGFBP-1 serum concentrations andinsulin and IGFBP-1 were inversely correlated. The amount ofHMG required correlated positively with BMI and insulin concentrationsand inversely with IGFBP-1 in the whole group and these correlationswere maintained in the sub-group of lean women. No correlationwas observed between HMG requirements and IGF-1 or other hormones.Womenwith hyperinsulinaemia and low IGFBP-1 concentrations requiredsignificantly more HMG. Multiple regression analysis revealedthat insulin concentration is the most significant determinantof HMG requirement even when dissociated from BMI. We concludedthat requirement of HMG in PCOS is not merely determined byobesity but by a cardinal role of insulin concentrations which,when high, induce, hypothetically, a hyperandrogenic intrafollicularmilieu.     

多囊卵巢综合征IGF-Ⅰ、IGFBP-1相关因素探讨

目的探讨多囊卵巢综合征(PCOS)患者胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合球蛋白-1(IGFBP-1)水平与肥胖、性激素、糖代谢各项指标之间的关系。方法测定31例PCOS研究组和29例健康对照组IGF-Ⅰ、IGFBP-1水平及肥胖、性激素、糖代谢各项指标,比较两组间差异;分析研究组IGF-Ⅰ、IGFBP-1水平与其他各项指标之间相关性。结果研究组IGFBP-1,性激素结合球蛋白(SHBG)低于对照组,体重指数(BMI),臀围比值(WHR),多毛评分(F-G评分),黄体生成素(LH),黄体生成素/卵泡刺激素(LH/FSH),总睾酮(T),游离睾酮(FT),雄烯二酮(A2),硫酸脱氢表雄酮(DHEAS),空腹胰岛素(FINS),胰岛素抵抗指数(HomaIR)高于对照组,差异均有显著性(P0.001～0.05),IGF-Ⅰ,FSH,雌二醇(E2),17羟孕酮(17-OHP),泌乳素(PRL),空腹血糖(FBG)差别无显著性(P0.05)。研究组中IGFBP-1与BMI呈负相关(r=-0.372,P0.05),与FINS呈负相关(r=-0.481,P0.01),与SHBG呈正相关(r=0.504,P0.01),IGF-Ⅰ与各指标之间无明显相关性。结论 IGFBP-1与PCOS患者肥胖、空腹胰岛素水平密切相关。     

Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance

BACKGROUND: The aim of this study was to investigate the relationship between resistin and insulin resistance in patients with polycystic ovary syndrome (PCOS). METHODS: We compared serum resistin levels in 17 PCOS women and 10 lean, healthy, age-matched non-PCOS women and also compared levels of insulin receptor (IR), phosphatidylinositol-3 kinase (PI3-kinase), glucose transporter 4 (GLUT4) protein and resistin mRNA in adipocytes isolated from the omental adipose tissue of five of the PCOS patients and five age- and weight-matched, non-PCOS controls, to look for local defects in insulin action in PCOS. RESULTS: The PCOS group was hyperinsulinaemic and displayed an impaired insulin response in a 75 g oral glucose tolerance test and an abnormal homeostasis model insulin resistance index. Serum resistin levels were similar in PCOS patients and controls; however, resistin mRNA levels were 2-fold higher in adipocytes from PCOS patients. No correlation was found between serum resistin levels and either the BMI or testosterone levels. Western blot analysis showed that adipocyte levels of insulin receptor, PI3-kinase, and GLUT4 were respectively decreased by 56, 39.4 and 54% in PCOS patients compared with controls. CONCLUSIONS: These results suggest that overexpression of the resistin gene in adipocytes may be a local determinant factor in the pathogenesis of PCOS.     

Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries

BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS.     

Clomiphene citrate increases insulin-like growth factor binding protein-1 and reduces insulin-like growth factor-I without correcting insulin resistance associated with polycystic ovarian syndrome

The induction of ovulation by clomiphene could be the result of interaction of the drug at various levels: hypothalamus, pituitary and ovary. It was demonstrated that administration of clomiphene to women with polycystic ovarian syndrome (PCOS) is accompanied by a reduction in plasma concentrations of insulin-like growth factor-I (IGF-I). IGF-I seems to have an overall negative effect on normal folliculogenesis and ovulation. The aim of the present study was to evaluate the effect of clomiphene on plasma concentrations of IGF-I and IGF binding protein (IGFBP)-1 and on insulin resistance associated with PCOS. Fifteen patients diagnosed with PCOS were recruited. Clinical diagnosis was based on chronic oligomenorrhoea or amenorrhoea and hyperandrogenaemia. Clomiphene citrate was administered at a dose of 100mg/day to all women from day 5 to day 9 of the spontaneous or medroxyprogesterone acetate (MAP)-induced menstrual cycle. Blood sampling and a 2 h oral glucose loading test (75 g) were performed the day before and after the course of clomiphene. Ovulation was confirmed in 13/15 PCOS patients. Plasma concentrations of IGF-I decreased by 31.5% (434 +/- 84 versus 297 +/- 71 ng/ml; P: < 0.05) after 5 days of clomiphene therapy, whereas plasma concentrations of IGFBP-1 increased by approximately 28.1% (26.3 +/- 4 versus 36.6 +/- 7 ng/ml; P: < 0.05). This gave a 56.5% reduction in the IGF-I:IGFBP-1 ratio (21.9 versus 9.53). No significant changes in basal plasma concentrations of fasting insulin or area under the insulin curve were observed in response to oral loading. The present results show that clomiphene does not cause changes in insulin resistance associated with PCOS but reduces plasma concentrations of IGF-I and increases those of IGFBP-1, with a consequent marked reduction in the IGF-I:IGFBP-1 ratio.     

Serum and follicular resistin levels in women with polycystic ovarian syndrome during IVF-stimulated cycles

BACKGROUND: Resistin is a hormone linking obesity and insulin resistance. The aim of this study was to compare resistin levels in serum or follicular fluid from women with polycystic ovarian syndrome (PCOS) and controls, both of whom were undergoing IVF. METHODS: We compared serum and follicular resistin levels in 21 PCOS women and in 18 healthy, normal ovulation, age- and body mass index (BMI)-matched non-PCOS women undergoing IVF. Correlations between serum or follicular fluid resistin levels and reproductive outcome were evaluated. RESULTS: There was no significant difference in either serum or follicular resistin levels between the control group and the PCOS group as a whole or those with insulin resistance [homeostasis model assessment of insulin resistance index applied to oral glucose tolerance test (HOMA(OGTT)) <4.7]. However, resistin levels in follicular fluid were unexpectedly significantly lower than serum levels (P<0.0001) in both the PCOS and control groups. No significant correlation was found between resistin levels and BMI, estradiol, LH, or fasting or 2 h glucose or insulin levels or between follicular resistin levels and fertilization rate, implantation rate, clinical pregnancy rate, or early miscarriage rate in PCOS. CONCLUSION: Resistin is unlikely to be a major determining factor in the growth and maturation of oocytes during IVF-stimulated cycles in PCOS.     

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: metabolic aspects

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic disorder in women, a high percentage of whom exhibit peripheral insulin resistance. After delivery, in normal women, lactation imposes a metabolic adaptation, the impact of which on the insulin resistance of PCOS patients is not known. The aim of this study was to evaluate the effect of lactation on insulin resistance, glucose and insulin metabolism, and sex hormone-binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP)-1 concentrations in fully breast-feeding normal and PCOS women during the postpartum period (lactational amenorrhoea) and also after weaning. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age and body mass index (BMI) were selected for the study. At the 4th and the 8th week postpartum (pp), and 8 weeks after weaning, a 2 h, 75 g oral glucose tolerance test (oGGT) was performed, followed by an insulin tolerance test 2 days later. For the oGGT, glucose and insulin were measured in each sample and SHBG and IGFBP-1 were determined in the fasting sample. RESULTS: During lactation, fasting insulin levels were similar in both groups. In LPCOS women 2 h insulin concentrations were significantly higher, and SHBG and IGFBP-1 concentrations were significantly lower, than those observed in NL women. In both groups, insulin sensitivity evaluated by the insulin tolerance test was not modified. After weaning, in LPCOS women, SHBG and IGFBP-1 concentrations remained lower and insulin concentrations remained higher than those observed in NL women ( P < 0.05 ). CONCLUSIONS: In PCOS women, insulin resistance is not modified during lactation. Lactation has a transitory beneficial effect on insulin levels and biological markers of insulin resistance.     

多囊卵巢综合征患者血清IGF-1水平与胰岛素抵抗

目的探讨血清胰岛素样生长因子1(IGF-1)、胰岛素敏感指数(ISI)与多囊卵巢综合征(PCOS)的关系。方法采集90例PCOS患者和41例正常对照组血清,应用电化学发光法检测胰岛素水平,葡萄糖氧化酶终点法检测空腹葡萄糖(FPG)水平,酶联免疫吸附试验(ELISA)检测IGF-1水平。结果 1.PCOS患者FPG、血清胰岛素、IGF-1水平明显高于正常对照组(t=16.72,2.24,4.51;P<0.01),且均与患者是否肥胖高度相关(t=5.08,2.07,3.30;P<0.01);2.PCOS患者胰岛素敏感性明显低于对照组,差别有显著性意义(t=3.12,P<0.05);3.PCOS患者血清IGF-1的含量与胰岛素敏感指数呈显著负相关,差别有显著性意义(r=-0.57,P<0.05);对照组血清IGF-1含量与胰岛素敏感指数无明显相关性(r=0.14,P>0.05)。结论多囊卵巢综合征患者存在不同程度的胰岛素抵抗(IR),IGF-1水平增高与PCOS患者发生IR有关,IGF-1可能与PCOS发生、发展有一定的内在联系并起协同作用。     

Supplementary growth hormone treatment of women with poor ovarian response to exogenous gonadotrophins: changes in serum and follicular fluid insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3)

The effects of supplementary growth hormone (GH) treatment uponinsulin-like growth factor-1 (IGF-1), IGF binding protein-3(IGFBP-3) concentrations in serum and ovarian follicular fluidwere investigated in women undergoing buserelin human menopausalgonadotrophin (HMG) ovulation induction for in-vitro fertilization.Women (n = 40), aged 24–39 (mean 35 years), who showedpoor ovarian responses to HMG, were recruited and randomly dividedinto two groups. Each patient received two cycles of ovulationinduction, one with GH (12 IU/day x 12 days/HMG/buserelin) andanother with placebo/HMG. Serum IGF-1 increased substantiallyduring the GH treatment and remained significantly higher thanthe control 2 days after the last GH injection. Serum IGFBP-3fell steadily during the placebo/HMG treatment and to a nadiron the day of oocyte retrieval (P <0.05 compared to serumbefore any treatment). In contrast, IGFBP-3 was increased (P<0.01) during the GH administration and returned to the controllevel 2 days after GH injection. Serum oestradiol concentrationson the eighth day of HMG and the day of human chorionic gonadotrophin(HCG) were not significantly different between the two groups.Serum IGF-1 was highly correlated with IGFBP-3 before any treatment(r = 0.433, P < 0.001). This correlation disappeared afterbuserelin, placebo/HMG treatment in the control group, but itwas maintained during GH/HMG treatment (r = 0.343, P = 0.04).Follicular fluid concentrations of GH and IGF-1, not IGFBP-3or oestradiol, were significantly elevated in the GH-treatedwomen. Serum IGF-1 on the day of oocyte retrieval was highlycorrelated to the follicular fluid IGF-1 in both groups. Therelationships between the follicular fluid GH and IGF-1 werecompletely opposite in the two groups, being positive in thecontrol group and negative in the GH-treated group. In the controlgroup, significant correlations were found between follicularfluid concentrations of IGF-1 and IGFBP-3, and GH and IGFBP-3which were not found in the GH-treated group. There were nocorrelations found between follicular fluid concentrations ofGH or IGF-1 or IGFBP-3 and oestradiol. The results clearly demonstratethat the normal GH, IGF-1, IGFBP-3 relationships can be alteredby treatments which influence the ovarian—pituitary axis;the significance of such changes to ovulation remains to bediscovered.     

Long-term follow-up of patients with polycystic ovary syndrome after laparoscopic ovarian drilling: endocrine and ultrasonographic outcomes

BACKGROUND: There is considerable controversy as to how long the beneficial effects of laparoscopic ovarian drilling (LOD) last. This follow-up study was undertaken to investigate the long-term effects of LOD. METHODS: The study included 116 anovulatory women with polycystic ovary syndrome (PCOS) who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period, who had not undergone LOD (comparison group). The hospital records were reviewed and most patients attended for a transvaginal ultrasound scan and blood sampling to measure the serum concentrations of LH, FSH, testosterone, androstenedione and sex hormone-binding globulin. The results before and at different intervals, short- (<1 year), medium- (1-3 years) and long-term (4-9 years), after LOD were compared. RESULTS: The LH:FSH ratio, mean serum concentrations of LH and testosterone and free androgen index decreased significantly after LOD and remained low during the medium- and long-term follow-up periods. The mean ovarian volume decreased significantly (P < 0.05) from 11 ml before LOD to 8.5 ml at medium-term and remained low (8.4 ml) at long-term follow-up. CONCLUSION: The beneficial endocrinological and morphological effects of LOD appear to be sustained for up to 9 years in most patients with PCOS.     

Leptin concentrations in hirsute women with polycystic ovary syndrome or idiopathic hirsutism: influence on LH and relationship with hormonal, metabolic, and anthropometric measurements.

BACKGROUND: The known association between leptin, obesity and insulin action suggests that leptin may have a role in polycystic ovarian syndrome (PCOS) but this has only been addressed peripherally. METHODS: We assessed the influence of leptin on LH and investigated the relationship between leptin and body mass index (BMI), waist:hip ratio (WHR), androgen concentrations, fasting insulin and insulin:glucose ratio (IGR) in 27 women with PCOS and in 20 age- and weight-matched women with regular, ovulatory menstrual cycles and idiopathic hirsutism (IH). RESULTS: Leptin concentrations were significantly higher in obese PCOS women than in normal weight women with either PCOS or IH (P = 0.0028), but did not differ between obese women with PCOS and IH. WHR, insulin concentrations and IGR were significantly higher in obese PCOS patients in comparison with the three other groups. In IH patients, the association between leptin concentrations and WHR was lost after adjustment for BMI. In PCOS patients, a significant correlation was observed between leptin and fasting insulin concentrations, IGR, WHR and LH. After adjustment for BMI, only the correlation with LH remained significant. A stepwise regression model was set up with LH as the dependent variable to test the hypothesis that the concentrations of leptin might be modulating the concentrations of LH in PCOS patients. The relationship of LH concentrations with IGR was found to be BMI dependent. In contrast, leptin concentrations contributed negatively and significantly to LH concentrations, independently of either BMI or IGR. CONCLUSIONS: We speculate that the known attenuation in basal or stimulated response of LH in obese PCOS patients might be related to leptin resistance, which could influence LH hypersecretion. In IH ovulatory patients, normal LH concentrations suggest the presence of preserved regulatory mechanisms of GnRH pulsatility. Further studies are needed to specifically investigate the proposed correlation between leptin and GnRH modulation in PCOS.     

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

BACKGROUND: The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). METHODS: A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. RESULTS: Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). CONCLUSION: Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.     

多囊卵巢综合征卵泡颗粒细胞提前对黄体生成素反应

目的： 探讨多囊卵巢综合征（PCOS）卵泡液中激素和颗粒细胞黄体生成素（LH）受体mRNA表达的关系。方法: 对PCOS组12例和对照组15例患者于月经周期的第7-10 d手术获取卵泡和卵泡液，采用微粒子化学发光法检测卵泡液中卵泡刺激素（FSH）、LH、孕酮（P）、雌二醇（E2）和胰岛素（insulin）的水平，采用ELISA检测卵泡液中雄烯二酮（A）的水平，对颗粒细胞和卵泡膜细胞LH受体mRNA进行RT-PCR半定量检测。结果: PCOS组卵泡液中LH［（3.8±2.1 vs 1.7±0.8)U/L, P<0.01］、A［(600.0±373.4 vs 212.4±205.4)μg/L, P<0.05］和颗粒细胞LH受体mRNA的表达(0.29±0.16 vs 0.12±0.13, P<0.01)显著高于对照组， PCOS组卵泡的颗粒细胞提前表达LH受体mRNA; 对照组卵泡直径小于 7 mm 时，RT-PCR检测不到颗粒细胞LH受体mRNA表达，而PCOS组卵泡直径达到 4 mm 时，发现颗粒细胞LH受体mRNA已提前表达。颗粒细胞LH受体mRNA的表达与卵泡液中LH(r=0.67,P<0.01)、胰岛素(r=0.51,P<0.05)及卵泡膜细胞LH受体mRNA表达的水平(r=0.6,P<0.01)呈正相关。结论: PCOS的卵泡液中存在高水平的LH，PCOS卵泡颗粒细胞提前对LH反应，颗粒细胞和卵泡膜细胞合成A和P增强，这可能是PCOS卵泡发育停滞的原因之一。     

The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome

BACKGROUND: Oxidative stress and hyperhomocysteinaemia are risk factors for cardiovascular diseases. The aim of this study was to assess the effects of rosiglitazone and metformin on cardiovascular disease risk factors such as insulin resistance, oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome (PCOS). METHODS: Fifty lean patients (BMI <25 kg/m2) with PCOS and 35 healthy subjects were included this study. Serum homocysteine, sex steroids, fasting insulin, fasting glucose and lipid levels were measured. Total antioxidant status (TAS; combines concentrations of individual antioxidants) and malonyldialdehyde concentration (MDA) were determined. Insulin resistance was evaluated by using the homeostasis model insulin resistance index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Area under the curve insulin (AUCI) and the insulin sensitivity index (ISI). Patients were divided into two groups. One group was treated with metformin (n = 25) and the other received rosiglitazone (n = 25) for 12 weeks. All measurements were repeated at the end of 12 weeks. RESULTS: Compared with healthy women, those with PCOS had significantly elevated serum MDA, homocysteine, HOMA-IR, AUCI and lipoprotein a levels, and significantly decreased serum TAS, QUICKI and ISI. Serum free testosterone levels showed a significant positive correlation with MDA, AUCI and HOMA-IR, and a negative correlation with TAS, ISI and QUICKI in PCOS patients. HOMA-IR and AUCI significantly decreased, while QUICKI and ISI significantly increased after treatment in both groups. Serum TAS level increased and serum MDA level decreased after the rosiglitazone treatment, but these parameters did not change after the metformin treatment. Serum homocysteine and lipid levels did not change in either group, while serum androgen levels and LH/FSH ratio significantly decreased after the treatment period in only the rosiglitazone-treated group. CONCLUSION: Elevated insulin resistance, oxidative stress and plasma homocysteine levels and changes in serum lipid profile (risk factors for cardiovascular disease) were observed in lean PCOS patients. Rosiglitazone seemed to decrease elevated oxidative stress when compared with metformin treatment in lean PCOS patients.     

Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound

Polycystic-appearing ovaries (PAO) on ultrasound have been described in a variety of endocrinopathies and also occur in ovulatory women. By some investigators this is merely referred to as 'PCO' (polycystic ovaries). Although there is controversy in this regard, we do not consider women with PAO/PCO who have no known endocrine disturbance to have polycystic ovary syndrome (PCOS) and therefore prefer not to use the term 'PCO' which is often equated with PCOS. We studied 15 ovulatory women with normal-appearing (NAO) ovaries on ultrasound and 15 matched ovulatory women with PAO/PCO. Compared to ovulatory women, 25 other women were studied who were considered to have PCOS. Of these, 15 were overweight and 10 were of normal weight. All the PCOS women had serum concentrations of luteinizing hormone (LH), testosterone, unbound testosterone, androstenedione and dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P < 0.01) than values in the normal women, regardless of ovarian morphology. These values were similar in the two groups of ovulatory women with NAO and PAO/PCO. Fasting insulin was elevated in women with PCOS with increased body weight (P < 0.01) and was higher than in ovulatory women with NAO and PAO/PCO and than in women of normal weight with PCOS. Serum insulin- like growth factor (IGF)-I and binding protein (BP)-3 were similar in all groups but serum IGFBP-1 was significantly (P < 0.01) lower in those women with PCOS with increased body weight, compared to all other groups. Compared to values in ovulatory women with NAO, serum IGFBP-1 was also significantly (P < 0.05) lower in women with PAO/PCO and those women with PCOS of normal weight. These lower values were similar in women with PAO/PCO and in normal weight women with PCOS. On an individual basis, an elevation of at least one serum androgen value was found in 33% of women with PAO/PCO. These data confirm that increased body weight accentuates the metabolic alterations in PCOS, but suggest that subtle endocrine disturbances, similar to those that are found in PCOS, may be uncovered in up to a third of ovulatory women with PAO/PCO. It appears that a disturbance of the IGF/IGFBP-1 axis is common and apparently closely associated with alterations in ovarian morphology.      

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome

BACKGROUND: Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. METHODS: The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. RESULTS: The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. CONCLUSIONS: Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.     

Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls

BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.     

儿童青少年血清IGF-1及IGFBP-3的 正常参考值研究

目的 探讨儿童青少年血清胰岛素生长因子-1（IGF-1）及胰岛素因子结合蛋白-3（IGFBP-3）的正常参考值。方法 选取2018年1月~2019年1月在我院体检的312例健康的儿童、青少年为研究对象,分别测定其IGF-1、IGFBP-3水平,并分析IGF-1、IGFBP-3与年龄、性别、发育阶段的关系。结果 男孩血清IGF-1峰值为13岁,女孩为11岁;男孩血清IGFBP-3峰值为14岁,女孩为11岁;高峰值出现后,IGF-1、IGFBP-3水平随年龄增长缓慢下降或维持高峰值;同年龄比较男孩血清IGF-1水平高于女孩、IGFBP-3水平低于女孩,差异有统计学意义（P＜0.05）;年龄、发育阶段与血清IGF-1值呈正相关（r=0.241,P＜0.01）,IGFBP-3与年龄呈正相关（r=0.323,P＜0.01）。结论 建立儿童青少年IGF-1、IGFBP-3水平正常参考值,可与监测其生长、临床症状以及生长激素治疗后随访具有重要的参考价值。     

检测血清IGF-1和IGFBP-3对儿童生长激素缺乏症的诊断价值

目的：探讨血清胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)浓度在诊断生长激素缺乏症(GHD)患儿中的应用价值。方法：用免疫放射分析检测38例GHD患儿和42例对照儿童的血清IGF-1和IGFBP-3,同时进行生长激素(GH)激发试验,用化学发光法检测GH,对两组结果进行比较。结果：GHD组患儿IGF-1和IGFBP-3均显著低于对照组儿童,且在GH激发试验中,GH的增加值也明显低于对照组。结论：检测血清中的IGF-1和IGFBP-3,对诊断GHD儿童具有重要价值。     

Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome?

Animal and human studies suggest that leptin modulates hypothalamic-pituitary-gonadal axis functions. Leptin may stimulate gonadotrophin-releasing hormone (GnRH) release from the hypothalamus and luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women, suggesting that leptin probably also regulates the episodic secretion of LH. In some pathological conditions, such as polycystic ovarian syndrome (PCOS), LH-leptin interactions are not known. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin in PCOS patients compared to regularly menstruating women. Six PCOS patients and six normal cycling (NC) women of similar age and body mass index (BMI) were studied. To assess episodic hormone secretion, blood samples were collected at 10-min intervals for 6 h. LH and leptin concentrations were measured in all samples. For pulse analysis the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of copulsatility was employed. LH concentrations were significantly higher in the PCOS group in comparison to NC women, however serum leptin concentrations and leptin pulse characteristics for PCOS patients did not differ from NC women. A strong synchronicity between LH and leptin pulses was observed in NC women; 11 coincident leptin pulses were counted with a phase shift of 0 min (P = 0.027), 18 pulses with a phase shift of -1 (P = 0.025) and 24 pulses with a phase shift of -2 (P = 0.028). PCOS patients also exhibited a synchronicity between LH and leptin pulses but weaker (only 20 of 39 pulses) and with a phase shift greater than in normal women, leptin pulses preceding LH pulses by 20 min (P = 0.0163). These results demonstrate that circulating leptin and LH are synchronized in normal women and patients with PCOS. The real significance of the apparent copulsatility between LH and leptin must be elucidated, as well as the mechanisms that account for the ultradian leptin release.