Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy

OBJECTIVE: To investigate the effects of combined rosiglitazone and clomiphene citrate versus clomiphene citrate monotherapy on serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in polycystic ovary syndrome (PCOS) and to evaluate these therapeutic interventions in the link between hyperinsulinemia and hormonal perturbations in PCOS. METHODS: We performed a randomized clinical study at the King Abul-Aziz and Cairo University Hospitals. We studied 50 women with PCOS. Clinical diagnosis was based on hyperandrogenism; hyperinsulinism; oligomenorrhea; or amenorrhea, anovulatory cycles, and ultrasonographic findings. They were randomly assigned to two groups of 25 women each. One group was treated with rosiglitazone and clomiphene citrate; the other was treated only with clomiphene citrate. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), free testosterone, IGF-1, and IFGBP-3 were measured by specific radioimmunoassays before and after treatment. RESULTS: Combined rosiglitazone and clomiphene treatment led to a significant reduction in area under the insulin curve (AUC insulin), whereas clomiphene monotherapy did not lead to this reduction. Both types of treatment induced a significant decrease in LH, LH:FSH ratio, free testosterone, and IGF1:IGBP-3 ratio and were associated with a significant increase in IGFBP-3 levels. These changes were more pronounced in PCOS patients treated with combined rosiglitazone and clomiphene than in those treated with clomiphene monotherapy. Regular menstrual cycles occurred in 72% of the former group and 48% of the latter. CONCLUSION: Combined rosiglitazone and clomiphene was an effective therapeutic regimen for correcting insulin resistance in patients with PCOS, possibly by reducing IGF1 bioavailability to the ovaries, thus modifying the hyperandrogenic intrafollicular milieu that occurs in PCOS. In addition, the clinical and hormonal responses were better than with clomiphene alone.     

Androgen excess contributes to altered growth hormone/insulin-like growth factor-1 axis in nonobese women with polycystic ovary syndrome

OBJECTIVE: To investigate the relationship between ovarian androgen excess and impaired growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: A prospective, controlled clinical study.Setting: Reproductive Endocrine Unit, Department of Obstetrics and Gynecology, Jinling Hospital, Nanjing University School of Clinical Medicine. PATIENT(s): Six patients with PCOS with both clomiphene resistance and gonadotropin hyperreponsiveness and six controls with regular cycles, matched for age and body mass index (BMI). INTERVENTION(s): Bilateral ovarian wedge resection (OWR) was performed to induce ovulation surgically for these refractory women with PCOS. A GH stimulation test with oral L-dopa was arranged for controls and for patients with PCOS before and again 6 months later after OWR. MAIN OUTCOME MEASURE(s): Plasma GH, IGF-1, FSH, LH, testosterone, androstenedione, estradiol, progesterone, prolactin, insulin, and glucose. RESULT(s): Basal levels and areas under the response curve of GH and GH-IGF-1 ratio to L-dopa were significantly lower in patients with PCOS before surgery than those of controls. The OWR in patients with PCOS obviously reduced their androstenedione and testosterone levels and insulin-glucose ratios, and increased the GH and GH-IGF-1 responses to L-dopa. CONCLUSION(s): Impaired somatotrophic axis caused by a defect in central dopaminergic activity may be responsible for severe anovulation in these women with PCOS, which could be reversed by removing excessive androgens with OWR.     

Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome

OBJECTIVES: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance, compensatory hyperinsulinemia, and increased levels of free insulin-like growth factor-I (IGF-I), presumably due to a decline in IGF binding protein 1 (IGFBP-1). This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I. STUDY DESIGN: Twenty-seven obese, hyperandrogenic PCOS women with elevated fasting insulin were treated for 12 weeks with metformin (500 mg p.o., t.i.d.). Serum levels of insulin, testosterone, sex hormone binding globulin (SHBG), IGF-I, and IGFBP-1 were measured before and after treatment. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy. RESULTS: Metformin therapy significantly increased IGFBP-1 concentration by 38% (P = 0.05) but had no demonstrable effect on the total IGF-I levels. Fasting insulin levels declined by 38% (P = 0.0001) while the glucose/insulin ratio increased by 72% (P = 0.0001) and quantitative insulin sensitivity check index (QUICKI) increased by 8% (P = 0.0001). Metformin treatment also significantly decreased testosterone (by 37%, P = 0.0001) and increased SHBG concentration (by 16%, P = 0.04). Multiple linear regression analysis revealed that baseline IGFBP-1 levels correlated inversely and independently with two baseline parameters: WHR (P = 0.003) and free testosterone index (P = 0.04). CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1. We provide further arguments in favor of metformin therapy in hyperinsulinemic women with PCOS.     

Regulation of insulin-like growth factor binding protein secretion by human granulosa luteal cells in a polycystic ovary-like environment

OBJECTIVE: To determine the effect of androstenedione (A), insulin, and LH on secretion of insulin-like growth factor binding proteins (IGFBPs) from human granulosa luteal cells. DESIGN: Human granulosa cells were cultured for a total of 4 days in serum-free medium containing A (10(-6) mol/L), with or without insulin (100 microU/mL-800 microU/mL), LH (1 microU/mL-10 microg/L), and A (10(-5) mol/L). SETTING: Granulosa cells were obtained from IVF procedures. PATIENT(S): Women undergoing IVF for tubal disease. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Immunoassay and autoradiographs of Western ligand blotting detected IGFBP accumulations in the medium. RESULT(S): Cultured granulosa cells secreted IGFBP-1 through IGFBP-4. Insulin (100 microU/mL-800 microU/mL), LH (1 microg/L-10 microg/L), and A (10(-5) mol/L) caused a significant decrease in IGFBP-1 accumulation in the medium both alone and when added in combination. The release of IGFBP-2 and IGFBP-4 was significantly stimulated by insulin, whereas LH had no effect. Elevated levels of androgen (10(-5) mol/L) significantly stimulated the secretion of IGFBP-2, whereas the release of IGFBP-4 was reduced. CONCLUSION(S): These results demonstrate that androgen and insulin are important regulators of IGFBP release and that elevated levels of the two hormones may contribute to the altered IGFBP profile found in PCOS follicles, compared with the case of estrogen-dominant follicles.     

Serum levels of insulin, IGF-1, and IGFBP-1 in pre-eclampsia and eclampsia.

OBJECTIVES: To investigate whether the serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women with mild pre-eclampsia, severe pre-eclampsia, and eclampsia. METHODS: In this prospective study, we investigated 20 mild pre-eclamptic, 20 severe pre-eclamptic, and 20 eclamptic patients in the third trimester. The control group consisted of 20 healthy pregnant women. Serum levels of insulin, IGF-1, and IGFBP-1 were measured. RESULTS: In patients with eclampsia, serum levels of IGF-1 were lower, and IGFBP-1 were higher, respectively, than control and other study groups (P<0.001) The values of IGF-1 in mild pre-eclampsia and severe pre-eclampsia were lower compared with control groups (both P<0.01), but there were no differences between mild and severe pre-eclampsia. The serum levels of IGFBP-1 in severe pre-eclampsia were higher compared with control groups (P<0.01), but there was no statistical difference between mild pre-eclampsia and other groups. CONCLUSIONS: IGF-1 was lower, and IGFBP-1 was higher in pre-eclamptic and eclamptic patients than controls, these alterations were related to the severity of pre-eclampsia.     

IGF-1 and IGFBP-1 in peripheral blood and decidua of early miscarriages with euploid embryos: comparison between women with and without PCOS

This study aims to demonstrate the possible relationship between the insulin-like growth factor (IGF) system and early miscarriage in polycystic ovarian syndrome (PCOS) patients with euploid embryos. 40 pregnant women included. 9 had PCOS and miscarried; 20 had PCOS and a successful ongoing pregnancy; the remaining 11 women did not have PCOS and miscarried. An ultrasound scan was performed to prove clinical pregnancy and a blood sample was taken on day 55?±?4 of gestation. Serum samples of IGF-1, insulin-like growth factor binding protein-1 (IGFBP-1), total testosterone, serum hormone binding protein (SHBG), leptin and soluble leptin receptor (sOb-R) were obtained. In miscarriages, samples of decidua were obtained during vaccum curettage. Embryonic chromosomes in all miscarriages were proven to be normal. The expression of IGF-1, IGFBP-1, leptin, long-form leptin receptor and androge sOb-R n receptor (AR) were examined in the decidua. We found that miscarried PCOS patients showed significantly increased free androgen index and free IGF index, as well as decreased SHBG and IGFBP-1 than other two groups in peripheral blood. In the decidua, miscarried PCOS patients showed significantly increased expression of IGF-1 and decreased IGFBP-1 when compared with non-PCOS. AR was not expressed in the decidua of either group. Our results suggest that early miscarriage is associated with increased IGF-1 and decreased IGFBP-1 in PCOS patients.     

青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化

目的观察青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化。方法选取4周龄SPF级雌性SD大鼠10只,随机分为观察组和对照组各5只。观察组大鼠经尾静脉注射阿霉素6.5mg/kg制备肾病模型,对照组大鼠经尾静脉注射等量生理盐水。观察阿霉素注射后1、2、3、4周SD大鼠体质量、子宫湿重、头尾长、胫骨长度变化及测定24h尿蛋白;透射电镜下观察足细胞超微结构变化;放射免疫法分析血清雌二醇(E_2)、促黄体生成素(LH)、促卵泡生成素(FSH)、胰岛素样生长因子1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)的变化。结果阿霉素注射后4周青春早期SD雌性大鼠尿蛋白显著高于对照组,差异有统计学意义(P0.05)。青春期雌性SD大鼠在阿霉素注射后足细胞足突融合逐渐加剧,在阿霉素注射后4周雌性SD大鼠肾小球足细胞足突出现广泛融合。观察组体质量在阿霉素注射后2、3、4周减轻逐渐加剧,与对照组比较差异有统计学意义(P0.05)。观察组头尾长在阿霉素注射后4周较对照组明显减少,差异有统计学意义(P0.05)。观察组胫骨长度和子宫湿重在阿霉素注射后2、3、4周后与对照组比较无明显减少,差异无统计学意义(P0.05)。观察组血清LH、FSH、E_2、IGF-1和IGFBP-3在阿霉素注射后2、3、4周与对照组比较无明显改变,差异无统计学意义(P0.05)。结论青春早期雌性SD大鼠在阿霉素肾病模型过程中未出现明显的生长发育迟滞,血清生长相关激素和性激素分泌未出现明显降低。     

Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome

OBJECTIVE: To evaluate the effects of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: Women with PCOS attending as outpatients of the Endocrine Division, Hospital Durand, Buenos Aires. PATIENT(S): Twenty-four insulin-resistant women with PCOS. INTERVENTION(S): Hormonal evaluations and a standardized oral glucose tolerance test before and after a 3-month trial of 4 mg of rosiglitazone daily. MAIN OUTCOME MEASURE(S): Serum LH, FSH, T, IGF-1, IGFBP-1, IGFBP-3, leptin, 17alpha-hydroxyprogesterone, insulin, and glucose concentrations. The area under insulin curve (AUC-insulin), the HOMA index (insulin resistance), the QUICKI index (insulin sensitivity), and the beta-cell function were calculated. Body mass index (BMI) and the waist/hip ratio were evaluated. RESULT(S): A significant decrease was observed in serum fasting insulin, AUC insulin, HOMA index, beta-cell function, IGF-1, LH, and waist/hip ratio. The QUICKI index and IGFBP-1 increased significantly. Serum sex hormone-binding globulin, androgens, leptin, IGFBP-3, and BMI remained unchanged. Twenty-two of 23 females had their menses restored, and three patients became pregnant. One patient was excluded because she became pregnant at the second month. CONCLUSION(S): Associated with the decrease in LH, rosiglitazone improved insulin-resistance parameters and normalized the menstrual cycle, which suggests that this drug could improve the endocrine-reproductive condition in insulin-resistant women with PCOS.     

Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in women with premenstrual syndrome

Objective: To determine whether women with premenstrual syndrome (PMS) have aberrations of the GH axis as has been demonstrated in individuals with depression.

Design: Prospective trial.

Setting: Department of Obstetrics and Gynecology, University of California, Los Angeles.

Patient(s): After prospective screening, 32 healthy women with PMS and 32 asymptomatic controls completed the study.

Intervention(s): Subjects completed a daily PMS symptom diary and a Beck Depression Inventory. They underwent phlebotomy 5 days and 12 days after the LH midcycle surge, which was identified with the use of a urinary LH detection kit.

Main Outcome Measure(s): Serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), E₂, and progesterone.

Result(s): Levels of IGF-1, IGFBP-3, E₂, and progesterone did not differ between women with prospectively documented PMS and control subjects.

Conclusion(s): Premenstrual syndrome and affective disorder share common symptoms and possibly a common cause. Biochemical markers such as alterations in the somatotropic system often are associated with major depression. Levels of IGF-1 and IGFBP-3 did not differ between women with PMS and control subjects, supporting the concept that PMS and endogenous depression are biologically distinct entities.     

Leptin,VEGF, IGF-1, and IGFBP-3 concentrations in serum and follicular fluid of women undergoing in vitro fertilization

We studied the influence of recombinant follicle-stimulating hormone (rFSH) stimulation on the concentration of leptin, vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in serum and follicular fluid (FF) in women undergoing assisted reproduction. To test the hypothesis that these hormones could predict successful implantation and that the levels correlate with pregnancy rate. Sequential serum samples were drawn at the beginning of stimulation and on the day of embryo transfer (ET) from 84 women undergoing IVF. The follicular fluid (FF) obtained during oocyte retrieval was collected and the concentration of leptin, VEGF, IGF-1 and IGFBP-3 were measured in all samples. The hormones were measured by commercially available IRMA, RIA or EIA. Patients' characteristics and results of the assisted reproductive cycles were registered. Serum concentrations of VEGF, IGF-1 and IGFBP-3 significantly decreased during rFSH treatment. In contrast, serum leptin significantly increased after rFSH treatment. A strong correlation was found between the FF - levels of IGF-1, IGFBP-3, leptin and respective serum levels. With regard to IVF outcome, higher serum concentrations of IGF-1, IGFBP-3 and VEGF on the day of oocyte retrieval were observed in conception cycles vs. non-conception cycles. No such difference, however, was apparent at the beginning of the stimulation cycle. There was no association between FF levels of any of these hormones and IVF outcome. Our results demonstrate that VEGF, IGF-1, IGFBP-3 and leptin levels are affected by rFSH during controlled ovarian hyperstimulation and that there is a direct association between serum and FF levels, albeit without clinical implications     

Maternal zinc and cord blood zinc, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels in small-for-gestational-age newborns

PURPOSE: To determine the relationship between maternal serum zinc (Zn) levels and birth weight of the offspring and their correlation with cord blood Zn, insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels. METHOD: 22 term small-for-gestational-age (SGA) and 34 term appropriate-for-gestational-age (AGA) infants and their mothers were included. Maternal and cord blood Zn levels and cord blood IGF-1 and IGFBP-3 levels were measured. RESULTS: Eighteen percent of mothers had Zn deficiency (< 75 mcg/dl). No significant difference between IGF-1 and IGFBP-3 levels and birth weight of infants of the mothers with and without Zn deficiency was found. Maternal and neonatal Zn levels correlated (r = 0.38, p < 0.01). Mean IGF-1 and IGFBP-3 levels were significantly lower in the SGA group compared to the AGA group (42.3 +/- 16.8 ng/ml, 1.2 +/- 0.2 mcg/ml, and 62.4 +/- 22.7 ng/ml, 1.5 +/- 0.4 mcg/ml, p < 0.001). A correlation was found between birth weight, IGF-1 and IGFBP-3 levels, and weight gain of the mother during pregnancy (p < 0.01). CONCLUSIONS: Zn deficiency was not observed to be a risk factor for low birth weight. The significant difference between the SGA and AGA babies' IGF-1 and IGFBP-3 levels emphasizes function of the IGF system in intrauterine growth.     

Maternal and fetal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3, and their relationship to fetal acidosis at delivery

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and in fetal cord blood at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, Illinois, USA), with p<0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking and in fetal blood by cord blood analysis at delivery. Cord pH was also recorded. RESULTS: There was no significant correlation between maternal IGF-1, IGF-2, or IGFBP-3 levels and fetal acidosis. However, a significant correlation does exist between cord IGF-1 levels and fetal acidosis. CONCLUSION: Fetal cord IGF-1 has a significant correlation with fetal acidosis at delivery.     

Effect of IGF-I and TNF-α on intensification of steroid pathways in women with PCOS phenotypes are not identical. Enhancement of progesterone pathway in women with PCOS increases the concentration of TNF-α

Objective: The aim of this study was to determine the correlations between the concentration of tumor necrosis factor (TNF-α) and insulin-like growth factor I (IGF-I) in each woman with polycystic ovary syndrome (PCOS) phenotypes based on the levels of androgen.

Methods: Two groups of women with PCOS differing in their levels of androgens. The test group composed of 39 women with PCOS according to the Rotterdam criteria in their reproductive age. The hormonal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin (PRL), androstenedione, testosterone (T), estradiol (E₂) and sex hormone binding globulin (SHBG) were measured. Correlations analysis were performed calculating Spearman’s rank correlation coefficient of hormones with relation to TNF-α and IGF-I.

Results: There was a medium positive correlation of IGF-1 with LH levels (p?<?0.05) and negative medium correlation of TNF-α with of dehydroepiandrosterone (DHEA)-SO₄ levels (p?<?0.05) only in group of PCOS women with elevated androgens.

Conclusion: Analysis of TNF-α showed that women with high testosterone negative correlation between level of TNF-α and the concentration of DHEA-SO4. Inflammatory state involving TNF-α in women with PCOS and high concentration of androgens is caused by intensified Δ4 (progesterone) pathway and omitted or limited Δ5 (dehydroepiandrosterone) pathway of testosterone biosynthesis.     

Growth hormone and somatomedin-C secretion in patients with polycystic ovarian disease. Their relationships with hyperinsulinism and hyperandrogenism

Nineteen women with polycystic ovarian disease (PCO; 9 obese) and 15 normal ovulatory women (7 obese) were studied at their follicular phase. All patients had an oral glucose tolerance test (OGTT) before and after treatment with gonadotropin-releasing hormone (GnRH) agonist (Buserelin 400 micrograms/die s.c. for 8 weeks) to investigate the relationship between ovarian steroidogenesis and insulin and growth hormone (GH) and insulin-like growth factor (SmC) secretion. Luteinizing hormone, follicle-stimulating, estradiol, androstenedione, testosterone, dehydroepiandrosterone sulfate, cortisol, insulin, GH and SmC were measured basally at the time of OGTT. PCO patients showed higher androgen basal levels than control patients. All subjects showed a normal glycemic response to OGTT. The mean fasting level and area under the curve of plasma insulin were also significantly greater in PCO than in control patients (p less than 0.05), while GH and SmC plasma concentrations did not differ between the groups. Despite a considerable decrease in androgens and the similar levels in both PCO and control women, buserelin treatment did not determine any significant changes of insulin and GH-SmC secretion. GH and SmC did not correlate with ideal body weight (IBW), insulin or androgens, whereas insulin correlated with both testosterone and androstenedione levels (p less than 0.05) and with IBW (p less than 0.01); after the buserelin regimen only IBW remained related to plasma insulin (p less than 0.01). In conclusion results of this study confirm that hyperinsulinism is a characteristic picture of PCO and is related in an unclear way with hyperandrogenism and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations.

OBJECTIVE: To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endocrinologic parameters in PCOS women. SETTING: University Hospital Reproductive Endocrinology Unit. PATIENTS: Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS: Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS: The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.     

Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study.

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary.     

多囊卵巢综合征患者用克罗米酚促排卵结局与相关因素的探讨

目的　探讨在多囊卵巢综合征 (PCOS)患者中影响克罗米酚 (CC)促排卵因素。方法　对 94例因多囊卵巢综合征不孕患者 ,用CC促排卵治疗。采用放射免疫方法测定卵泡刺激素 (FSH)、黄体生成素 (LH)、雌二醇 (E2 )、睾酮 (T)、雄烯二酮 (A)、泌乳素 (PRL)水平及胰岛素释放反应。分析了排卵结局与年龄、基础激素水平、胰岛素抵抗 (IR)、胰岛素反应曲线下面积 (AUCI)及体重指数 (BMI)之间的关系。结果　用克罗米酚促排卵 94个周期中排卵率为 5 5 2 % (5 2 / 94) ,未排卵组的基础血雄激素、LH、AUCI 和BMI均较排卵组高。结论　PCOS患者的高雄激素、高LH血症、IR、高BMI对促排卵的结局产生负影响。     

Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization?–?embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17?mm or an estradiol value of at least 100?pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the Δ-5 steroid synthesis pathway in the adrenals and/or in the ovary.     

Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy.

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.