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.     

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.     

Serum ghrelin level in women with polycystic ovary syndrome and its relationship with endocrine and metabolic parameters

Aims. To compare ghrelin levels in women with polycystic ovary syndrome (PCOS) and healthy subjects and to evaluate the relationships between circulating ghrelin and the heterogeneity of clinical and biochemical manifestations of PCOS women.

Methods. Forty-five women with PCOS and 20 controls were included in the study. Serum levels of ghrelin, leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, luteinizing hormone and follicle-stimulating hormone were measured. Free androgen index and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.

Results. Serum ghrelin levels in PCOS patients were lower than in the control group (mean±standard error of the mean: 21.78±2.12 vs. 34.67±3.57 ng/ml; p = 0.04). In women with PCOS, a strong negative correlation was observed between ghrelin values and the clinical (BMI, WHR, waist circumference) and hormonal indices of insulin resistance (IRI and HOMA-IR). The negative correlative relationship between ghrelin and HOMA-IR disappeared after partial correlation analysis when controlling for WHR and BMI. Negative correlation existed between ghrelin and testosterone (r = ?0.315; p<0.05) and between ghrelin and leptin levels (r = ?0.306; p<0.05). The latter correlation disappeared after partial correlation analysis controlling for BMI, WHR and HOMA-IR.

Conclusion. The ghrelin level in women with PCOS reflects the metabolic and hormonal changes which are characteristics of the syndrome. The inverse correlation between ghrelin and leptin in these women is mediated through metabolic factors.     

The relationship between thyroid function and metabolic changes in Chinese women with polycystic ovary syndrome

Objectives: Aim was to evaluate endocrine, metabolic and thyroid parameters which could help to explore the relationship between thyroid function and metabolic changes in Chinese polycystic ovary syndrome (PCOS) patients.

Methods: Within a prospective study in PCOS patients compared with healthy women, thyroid parameters were assessed, as well as changes of endocrine, metabolic and clinical characteristics.

Results: 144 PCOS patients and 48 normo-ovulatory women matched by age as controls were included. There were significant increases of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) in the PCOS patients. Body mass index (BMI), waist and hip ratio (WHR), luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) and total testosterone (T) were significantly higher in PCOS compared with the controls. Total cholesterol (CHO), triglycerides (TG) and apolipoprotein B (ApoB) levels in PCOS were higher, whereas high-density lipoprotein (HDL) and apolipoprotein A (ApoA) were lower compared with the controls. Insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in patients with PCOS.

Conclusions: Our study confirms the well-known negative metabolic changes in PCOS patients. The small increases of TSH, TT3 and TT4 level may be related with these metabolic changes in PCOS patients. Further studies may improve the understanding of the relationship between thyroid function and metabolic changes.     

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。     

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   

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.     

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.     

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.     

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。     

The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome--a randomised, double-blind, placebo-controlled trial

OBJECTIVE: To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Reproductive medicine clinic. POPULATION: Forty women with anovulatory PCOS. METHODS: Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months. MAIN OUTCOME MEASURES: Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation. RESULTS: We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy. CONCLUSIONS: Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it.     

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99?±?5.38 versus 24.77?±?4.32?kg/m²; P?=?0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20?±?3.39 versus 3.01?±?2.6; P?=?0.006) and QUICKI (0.140?±?0.013 versus 0.147?±?0.015; P?=?0.03) while PCOS from Srinagar had higher FG score (12.12?±?3.91 versus 10.32?±?2.22; P?=?0.01) and serum total testosterone levels (0.65?±?0.69 versus 0.86?±?0.41?ng/ml; P?=?0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.     

Effects of metformin and ethinyl estradiol-cyproterone acetate on clinical,endocrine and metabolic factors in women with polycystic ovary syndrome

Background. Polycystic ovary syndrome (PCOS) is a major endocrine abnormality that affects women of reproductive age. Oral contraceptive pills are usually the first choice of treatment for PCOS when fertility is not desired. Metformin, an insulin-sensitizing drug, has been shown to improve such metabolic abnormality.

Aim. To compare the effects of a contraceptive pill in combination with metformin on the clinical, endocrine and metabolic parameters in obese and non-obese patients with PCOS.

Methods. Sixty PCOS patients (25 obese, 35 non-obese) were enrolled in this prospective clinical study. PCOS was defined according to the Rotterdam criteria. Patients were randomized to oral treatment with Diane35® (35 μg ethinyl estradiol plus 2 mg cyproterone acetate), metformin or a combination of Diane35/metformin for 3 months. Body mass index (BMI), waist-to-hip ratio (WHR), Ferriman–Gallwey (FG) score, leuteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, fasting insulin and glucose/insulin ratio were measured at baseline and at the end of treatment.

Results. Diane35 resulted in a higher reduction of FG score in both obese and non-obese PCOS patients compared with metformin. Menstrual regularity was restored in all PCOS patients treated with Diane35 compared with only 28% of those receiving metformin. Metformin significantly decreased BMI and WHR in obese patients (p < 0.05). Testosterone levels decreased in all three groups. LH levels and LH/FSH ratio decreased with Diane35 and Diane35/metformin in both obese and non-obese patients. Metformin significantly decreased fasting insulin concentrations (p < 0.05 and p < 0.01) and increased the insulin sensitivity (p < 0.05) in both obese and non-obese PCOS patients, while no significant changes were observed in the Diane35 group. In addition, insulin levels also decreased (p < 0.05) in the Diane35/metformin group.

Conclusions. Our data show that a combination of metformin and contraceptive pill may be more effective in suppressing the hyperandrogenemia of obese and non-obese PCOS patients than metformin alone and may reduce insulin levels more than contraceptive pill alone. Hence, combined treatment may become a more effective therapeutic option for PCOS.     

Serological markers of autoimmunity in pregnant women with polycystic ovary syndrome: a pilot study

Background.?Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes.

Aim.?To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by auto-antibodies.

Methods.?Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22–28, a 2-h, 75?g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies.

Results.?A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCOS women.

Conclusion.?A highly prevalence of anti-GAD65 was observed in women with GDM which is in agreement with previous studies. Nevertheless, the frequency of these auto-antibodies was very low in NP and PPCOS women.     

Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome

Objective

To evaluate the clinical, endocrine and metabolic effects of metformin and N-acetyl-cysteine (NAC) in patients with polycystic ovary syndrome (PCOS).

Study design

In this prospective trial, 100 women with PCOS were randomly divided to receive metformin (500 mg p.o. three times daily) or NAC (600 mg p.o. three times daily) for 24 weeks. Hyperandrogenism, lipid profiles, hirsutism scores, menstrual irregularity, insulin sensitivity and tumour necrosis factor-α (TNF-α) levels were measured at baseline and after the treatment period.

Results

Both treatments resulted in a significant decrease in body mass index, hirsutism score, fasting insulin, HOMA index, free testosterone and menstrual irregularity compared with baseline values, and both treatments had equal efficacy. NAC led to a significant decrease in both total cholesterol and low-density lipoprotein levels, whereas metformin only led to a decrease in total cholesterol level. Although TNF-α levels increased following treatment for both groups, the difference from baseline was not significant.

Conclusions

Metformin and NAC appear to have comparable effects on hyperandrogenism, hyperinsulinaemia and menstrual irregularity in women with PCOS. The effects of metformin and NAC on insulin sensitivity are not associated with TNF-α.