Effect of orlistat or metformin in overweight and obese polycystic ovary syndrome patients with insulin resistance

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin?>?10?mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p?=?.015), MD (p?=?.001) and OMD (p?=?.004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p?相似文献   

Effects of low-dose metformin in Japanese women with clomiphene-resistant polycystic ovary syndrome

Background and Aims  The aim of the present prospective observational study was to evaluate the effects of low-dose, short-term metformin, in combination with domiphene (CC), in CC-resistant infertile Japanese women with polycystic ovary syndrome (PCOS). Methods  Metformin therapy was administered orally (one 250 mg tablet, twice daily) to 15 CC-resistant infertile patients with PCOS, beginning on the third day of progestin-induced withdrawal bleeding, and was continued for 14 days in the first cycle. In the event of anovulation, 100 mg/day of CC was given during subsequent cycles on days 5–9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast. Results  None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2 months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin Alc and total cholesterol was seen, while serum LH/follide-stimulating hormone ratio and serum level of low-density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n = 11) and non-responder (n = 2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non-responder group compared with the responder group after three cycles. Conclusion  Low-dose, short-term metformin, combined with CC, can improve ovulation rates in CC-resistant infertile Japanese women with PCOS.     

A pilot trial of metformin for insulin resistance and mood disturbances in adolescent and adult women with polycystic ovary syndrome

We examine the effects of metformin on insulin resistance (IR) and mood including in adolescent and adult women with polycystic ovary syndrome (PCOS). This trial was conducted in 19 adolescents (age ≤18 years) and 25 adult (age >18 years) women with PCOS. Anthropometric and measurements including, serum glucose, endocrine panel, and lipid profile were performed at baseline. IR was measured by Homeostasis Model Assessment IR (HOMA-IR). Anxiety and depression were measured by Beck’s Anxiety (BAI) and Depression Inventories (BDI-II). All tests were repeated after a 90-day treatment with metformin (1,500?mg/day). The severity of depression and anxiety decreased after 90-day treatment with metformin in women diagnosed with PCOS. The BAI scores were higher in adolescent group while BDI-II scores were higher in the adult group (p?=?.016). After 90-day metformin treatment, both BDI-II and BAI scores were decreased by 3.3 and 3.4, respectively (p?<?.001). Indicators of IR and obesity were improved with this therapy. Although the adolescents weighed lower than the adults, baseline HOMA-IR 5.5?±?1.7 was higher in this group than 4.4?±?1.2 in the adult women (p?=.022). The findings suggest that metformin decrease IR and improve mood both in adolescent and adult women with PCOS.     

Metformin in normal-weight hirsute women with polycystic ovary syndrome with normal insulin sensitivity

Fifteen normal-weight (body mass index (BMI) 21.50 ± 1.65 kg/m²) hirsute women with polycystic ovary syndrome and normal insulin sensitivity were treated with 850 mg metformin orally, three times daily, for 4 months. Before and at the end of the treatment, clinical data as well as serum concentrations of sex steroid hormones, gonadotropins, fasting plasma glucose and insulin, insulin resistance – homeostasis model assessment (HOMA-IR), carbohydrate tolerance and the area under the curve for insulin (AUC_insulin) were analyzed. Three patients withdrew from the study. Seven of the remaining 12 patients presented menstrual pattern improvement, followed by ovulatory cycles at the end of the treatment period. There were no changes in BMI and hirsutism score. A significant (p < 0.05) decrease in luteinizing hormone (LH) (from 8.18 ± 4.34 to 5.05 ± 1.53 IU/ml), testosterone (from 104.66 ± 27.54 to 82.00 ± 23.05 ng/dl), fasting insulin (from 9.66 ± 4.79 to 7.83 ± 3.06 µIU/ml), AUC_insulin (from 9239 ± 3285 to 7660 ± 2565 µUI/ml × min) and HOMA-IR (from 2.15 ± 1.2 to 1.67 ± 0.74), and a significant increase in follicle-stimulating hormone (FSH) (from 4.05 ± 1.53 to 5.96 ± 2.13 IU/ml), were observed at the end of the treatment period. A higher LH and a lower FSH predicted clinical improvement, while basal insulin and AUC_insulin showed lower predictive value.     

Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin

OBJECTIVE: To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Gynecology of Federal University of S?o Paulo, S?o Paulo, Brazil. PATIENT(S): Twenty-nine patients with PCOS. INTERVENTION(S): Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months. MAIN OUTCOME MEASURE(S): Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment. RESULT(S): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2). CONCLUSION(S): Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen.     

Relationship between insulin resistance and gonadotropin dissociation in obese and nonobese women with polycystic ovary syndrome

OBJECTIVE: To test the interdependence between insulin resistance (IR) and gonadotropin dissociation (GD) in polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional prospective study. SETTING: Clinical research center. PATIENT(S): Thirty-two PCOS patients aged 19-34 years; 16 obese (BMI > or = 27) and 16 nonobese (BMI < 27). INTERVENTION(S): A 75-g oral glucose tolerance test (OGTT) and a 100-microg i.v. GnRH test were performed on different days. Blood was taken at 0, 30, 60, 90, 120, and 180 minutes in each test. Serum glucose, insulin, LH, and FSH were measured. MAIN OUTCOME MEASURE(S): Area under the curve was calculated for glucose, insulin, and glucose-to-insulin ratio (GIR), and for LH, FSH, and LH-FSH ratio. RESULT(S): Glucose, insulin, and GIR were not modified significantly during the GnRH test, nor LH, FSH and LH-FSH ratio throughout the OGTT. There were no significant differences in GIR response of patients with and without GD, nor in LH-FSH ratio of patients with and without IR, after OGTT and GnRH test. However, obese patients with IR had a significantly larger (P<.04) area under the curve for LH-FSH ratio than those without IR after GnRH test, but not after OGTT test. CONCLUSION(S): Insulin resistance and GD do not appear to be related events in PCOS, suggesting that each one might be determined by different genetic disorders. However, IR can affect GD after chronic stimulation in obese patients.     

吡格列酮对多囊卵巢综合征伴胰岛素抵抗患者的疗效观察

目的了解吡格列酮对多囊卵巢综合征伴胰岛素抵抗的疗效。方法选择2003年1月～2005年10月于我院就诊的多囊卵巢综合征伴胰岛素抵抗的患者为研究对象，予吡格列酮口服12周。检测治疗前后BMI、血脂、外周胰岛素敏感度（SI）、FSH、LH、游离睾酮、硫酸脱氢表雄酮（DHEAs）、雄烯二酮、性激素结合球蛋白（sHBG）等指标。结果①BMI治疗前后差异无显著性（P〉0．05），血胆固醇、甘油三酯、低密度脂蛋白于治疗后均降低（P〈0．05），SI于治疗后升高（P〈0．05）；②FSH治疗前后差异无显著性（P〉0．05），LH、游离睾酮、DHEAS、雄烯二酮于治疗后均下降（P〈0．05），SHBG于治疗后升高（P〈0．05）。结论吡格列酮可改善多囊卵巢综合征患者的胰岛素抵抗，进而改善高雄激素症，恢复排卵月经。     

Effects of metformin treatment in women with polycystic ovary syndrome depends on insulin resistance

Polycystic ovary syndrome (PCOS) affects 5–10% of women at reproductive age, and is the most common reason for hyperandrogenism and chronic anovulation. Some patients with PCOS are insulin-resistant. Also, lowered sex hormone-binding globulin (SHBG) concentration is usually observed. As a consequence, the amount of free and biologically active androgens increases. This implies that, by improving insulin and carbohydrate metabolism, metformin administration in PCOS patients could indirectly contribute to increase SHBG concentration. The aim of the present study was to assess the effects of metformin treatment in PCOS patients both with and without insulin resistance. Thirty-six patients completed treatment. Body mass index (BMI) was considerably reduced after therapy. Statistically significant decreases were noted in luteinizing hormone (LH) and fasting insulin concentrations and the free androgen index (FAI), and significant increases in follicle-stimulating hormone (FSH)/LH ratio and SHBG concentration. In the insulin-resistant group, BMI and fasting insulin concentrations were reduced considerably after treatment, and SHBG increased slightly. In the group of patients without insulin resistance, BMI, LH and FAI showed significant reductions, and FSH/LH and SHBG considerable increases. Considering the favorable effects of metformin treatment in PCOS patients both with insulin resistance and without it, it is purposeful to use this drug in both groups of women.     

部分卵母细胞浆内单精子注射的临床结局及影响受精率的相关因素分析 #br#

目的分析中国南方多囊卵巢综合征（polycystic ovary syndrome,PCOS）患者中胰岛素抵抗的发生情况及其与代谢综合征（metabolic syndrome,MetS）发生的相关性。方法回顾性分析中山大学孙逸仙纪念医院2004年1月至2008年10月初诊的578例PCOS患者各表征胰岛素抵抗指标的发生率,及其与代谢综合征发生的关系。结果 PCOS患者中,332例（57.4%）稳态模型测定（HOMA-IR）〉75th,133例（23.0%）空腹胰岛素（FIN）〉95th,73例（12.6%）胰岛素释放实验2h胰岛素（2h-INS）〉150mU/L,49例（8.5%）FIN和2h-INS同时超标,157例（27.2%）发生高胰岛素血症（HIN）,FIN和/或2h-INS超标。FIN升高、2h-INS升高、HIN和HOMA-IR超标者,代谢综合征发生率分别为40.6%、41.1%、39.5%和26.8%。与指标正常者比较,其发生代谢综合征的风险明显增加（P〈0.001）。结论应用不同表征胰岛素抵抗的指标得到的PCOS患者胰岛素抵抗的发生率存在差异,但是存在任一胰岛素抵抗指标异常的患者合并代谢综合征的风险显著高于无高胰岛素血症及HOMA-IR正常者。因此,判断和纠正PCOS患者的胰岛素抵抗对于预防代谢综合征的发生有临床意义。     

Comparison of two insulin sensitizers,metformin and myo-inositol,in women with polycystic ovary syndrome (PCOS)

Insulin resistance (IR) plays a pivotal role in PCOS. Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS. The purpose of this study is to compare their effects on the clinical and metabolic features of the women with PCOS. Fifty PCOS women with IR and/or hyperinsulinemia were randomized to treatment with metformin (1500?mg/day) or myo-inositol (4?g/day). IR was defined as HOMA-IR >2.5, while hyperinsulinemia was defined as a value of AUC for insulin after a glucose load over the cutoff of our laboratory obtained in normal women. The Matsusa Index has been calculated. The women have been evaluated for insulin secretion, BMI, menstrual cycle length, acne and hirsutism, at baseline and after 6 months of therapy. The results obtained in both groups were similar. The insulin sensitivity improved in both treatment groups. The BMI significantly decreased and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne and hirsutism were observed. The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.     

盐酸吡咯列酮治疗多囊卵巢综合征临床疗效分析

目的探讨盐酸吡咯列酮对多囊卵巢综合征（PCOS）患者血清睾酮、血脂、空腹胰岛素、血糖的影响，为其临床应用提供依据。方法应用自身对照研究，对30例PCOS患者给予盐酸毗咯列酮每日30mg口服，3个月。进行服药前后的血清睾酮、血脂、空腹胰岛素、血糖及服糖后2h胰岛素和血糖的测定，同时于服药后记录月经周期、体重变化，服药后不适感及B超监测排卵。结果服药前后体重无明显变化（P〉0．05）。服药后空腹胰岛素、服糖后2h胰岛素和血糖、HOMA指数均有下降（P〈0.05）。服药后血清睾酮明显下降，特别是肥胖组下降明显（P〈0.05），而非肥胖组无变化（P〉0.05）。服药后高密度脂蛋白（HDL）升高，甘油三脂（TG）降低（P〈0.05）。23例无排卵患者服药后观察69个周期，21个周期有排卵，排卵率为30．43％。26例月经异常者中20例得到改善，改善率为76．92％。不良反应中，乳房胀痛1例，胃痛1例，疲劳感1例，其余患者无不适主诉，未发现肝、肾功能异常。结论吡咯列酮可以改善PCOS患者胰岛素抵抗，降低血清睾酮水平，调节脂代谢、诱发排卵，短期应用未出现严重的不良反应。     

The correlation of plasma homocysteine with insulin resistance in polycystic ovary syndrome

AIM: This study aims to investigate the existence of any relationship between homocysteine levels and insulin resistance in Turkish women with polycystic ovary syndrome. METHODS: A case-controlled, cross-sectional, observational study was undertaken in a total of 94 infertile Turkish women who required professional help in the Department of Infertility of Dr Zekai Tahir Burak Women's Health Research and Education Hospital. The correlation between serum homocysteine with age, body mass index, hormone profile, fasting insulin and glucose concentrations and insulin resistance were examined in patients with polycystic ovary syndrome and the results were compared to those of women with normal ovaries, who served as a control group. RESULTS: The mean serum fasting glucose and insulin levels, thus insulin resistance index of women with polycystic ovary syndrome, were significantly higher than those of the control subjects. The mean serum homocysteine levels were significantly higher in women with polycystic ovary syndrome than those in the control group. A positive correlation was detected between the mean homocysteine, the insulin resistance index determined by homeostasis model assessment and the fasting insulin levels in polycystic ovary syndrome patients. CONCLUSIONS: Serum homocysteine levels are elevated in women with polycystic ovary syndrome, and this elevation is associated with the serum insulin level rather than androgen excess. The intense treatment of hyperhomocysteinemia in women with polycystic ovary syndrome might improve reproductive outcome and contribute to protection from cardiovascular risks.     

Anti-Mullerian hormone and insulin resistance in polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent disease affecting women of reproductive age. It may be associated with metabolic disorders such as insulin resistance (IR) and obesity. The anti-Mullerian hormone (AMH) levels seem to be higher in patients with PCOS.

Objective: The present study was designed to evaluate the association between AMH and insulin in women with PCOS with and without IR.

Methods: Cross-sectional study, including 86 patients, selected and divided into three groups: Group A: 26 women with PCOS and IR; Group B: 30 women with PCOS and without IR; and Group C: 30 controls without PCOS.

Results: We found significant difference between serum AMH levels in the group of women with PCOS and without IR when compared to the control group, thus showing that PCOS and IR play an important role in elevating the levels of this hormone. When the groups were compared with each other following adjustment for BMI, serum AMH levels were significantly higher in the group of women with PCOS and IR.

Conclusion: AMH levels are significantly higher in patients with PCOS, particularly in those women with PCOS and IR. Nevertheless, larger samples are required to confirm these findings.     

Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling

AIM: To evaluate the effects of metformin on insulin resistance, androgen concentration, ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS). METHODS: Forty-two infertile women with PCOS were selected in this randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were randomly divided into group 1 (n = 21) and group 2 (n = 21). Group 1 patients were treated with laparoscopic ovarian drilling (LOD). Group 2 patients underwent laparoscopic ovarian drilling (LOD) and received 1700 mg per day of metformin for 6 months. LOD was performed in women with PCOS using a unipolar electrode. Serum progesterone (P) level > 5 ng/mL was considered as a confirmation of ovulation. Ovulation and pregnancy rates were determined after six cycles. RESULTS: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD (34.6 +/- 25.4 ng/mL, 8.4 +/- 1.1 mm) than in those treated with LOD alone (26.2 +/- 24.7 ng/mL, 7.9 +/- 2.8 mm) (P < 0.05). The ovulation (56 of 65 cycles, 86.1% vs 29 of 65 cycles, 44.6%) and pregnancy rates (nine of 21 women, 47.6% vs four of 21 women, 19.1%) were significantly higher in group 2 than in group I. CONCLUSIONS: Metformin improves insulin resistance, reduces androgen levels and significantly increases the ovulation and pregnancy rates in infertile women, following LOD.     

High plasma level of long Pentraxin 3 is associated with insulin resistance in women with polycystic ovary syndrome

Objectives: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS. Materials and Methods: Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Results: Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p?=?0.021, p?=?0.002 and p?=?0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p?<?0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p?<?0.05, for all). Conclusion: PTX3 level is increased in patients with PCOS in concordance with insulin resistance.