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.     

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。     

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。     

Testosterone is associated with insulin resistance index independently of adiposity in women with polycystic ovary syndrome

Objective: To study the associations between androgens, glucose homeostasis, inflammation and statin treatment in women with polycystic ovary syndrome (PCOS).

Design and methods: Oral glucose tolerance tests, androgens, hs-CRP and interleukin-1 receptor antagonist (IL-1Ra) were analyzed at baseline and after 6?months of atorvastatin (20?mg/d) or placebo treatment in 27 women with PCOS.

Results: Testosterone associated with insulin resistance measured with ISI_Matsuda independently of BMI, age and SHBG concentrations and the full model, including IL-1Ra, hs-CRP and HDL-C, also showed independency of BMI and waist circumference (p?≤?.042). Free androgen index (FAI) associated with ISI_Matsuda independently of adiposity (p?≤?.025) but in the full model with waist circumference the association was insignificant. ISI_Matsuda decreased with testosterone >1.2?nmol/l compared with lower levels at baseline (p?=?.043) and at six months (p?=?.003). Accordingly, 30-minute insulin levels were increased with moderately elevated testosterone independently of adiposity (p?≤?.046). Increased fasting glucose and AUC insulin associated with statin treatment independently of adiposity and the associations attenuated after adjusting for testosterone.

Conclusions: Moderately elevated testosterone concentrations together with obesity-related inflammatory factors modify glucose homeostasis by increasing insulin resistance and early insulin secretion.     

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。     

Galectin-3 is a potential biomarker to insulin resistance and obesity in women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder that affects women in reproductive age. This study aimed to evaluate Gal-3 levels and its role on metabolic parameters in women with PCOS. Gal-3 was measured in 44 PCOS and 25 women recruited as control group for the case-control study. Gal-3 levels were similar between PCOS and control groups (p?>?0.05), but showed a positive correlation with glucose levels in the oral glucose tolerance test (OGTT) (r?=?0.403, p?=?0.037), body mass index (BMI) (r?=?0.469, p?=?0.027), insulin levels (r?=?0.453, p?=?0.030) and HOMA-IR (r?=?0.738, p?=?0.037) in PCOS group. The data suggest that Gal-3 plays a role in the pathophysiology of the insulin resistance and obesity in PCOS group.     

Morning plasma cortisol is low among obese women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in women. It is associated with wide variety of metabolic disorders. The present study assessed morning plasma cortisol in women with PCOS. One hundred and ninety seven cases and 55 controls were enrolled for this study. The mean age of patients and controls were 23?±?5.6 years and 25?±?4.3 years. One hundred twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were significantly higher in lean PCOS women compared to controls (13.4?±?5.1 versus 11.3?±?4.5, p?<?0.01) and over-weight PCOS women group (13.4?±?5.1 versus 9.3?±?3.2, p?<?0.01). There was a trend for less acne and hirsutism with increase in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning plasma cortisol correlated negatively with BMI in PCOS women with normal glucose tolerance.     

Obesity and insulin resistance increase plasma viscosity in young women with polycystic ovary syndrome

Objective.?To investigate the plasma viscosity in young women with polycystic ovary syndrome (PCOS).

Design.?Patients with PCOS and healthy controls were assessed for plasma viscosity. The acquired data were tested for association with hyperandrogenemia, obesity and insulin resistance (IR) in patients with PCOS. Plasma viscosity was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C.

Patients.?The study included 96 young women with PCOS and 72 healthy controls.

Main outcome measures.?Plasma viscosity and IR.

Results.?Plasma viscosity was 1.243 ± 0.67 mm²/s in the control group and 1.252 ± 0.82 in women with PCOS (p = 0.416). Using multiple regression analysis, total protein (B = 0.348, p = 0.005), area under curve for insulin (B = 0.320, p = 0.011) and BMI (B = 0.315, p = 0.013) were proven to be significantly correlated to plasma viscosity. Plasma viscosity was significantly increased in women with PCOS with IR compared to matched for age and BMI PCOS women without IR (1.300 ± 0.055 vs. 1.231 ± 0.049 mm²/s) (p = 0.004).

Conclusion.?Young women with PCOS presented a plasma viscosity that was increased by obesity and IR. Therefore, clinical management of young overweight women with PCOS with IR should always include a serious reduction in body weight and the use of oral contraceptive treatment with cautious.     

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.     

Association between anti-Mullerian hormone and insulin resistance in non-obese adolescent females with polycystic ovary syndrome

Objective: The present study was designed to evaluate the association between anti-Mullerian hormone (AMH) and insulin resistance (IR) in non-obese adolescent females with polycystic ovary syndrome (PCOS) with and without IR.

Methods: Seventy-seven consecutive non-obese patients were recruited and distributed into three groups according to diagnoses of PCOS and IR. Group I included 27 females diagnosed with PCOS and IR, group II included 18 females diagnosed with PCOS but without IR, and group III included 32 controls without PCOS.

Results: Group I had significantly higher AMH levels compared to group II and group III (p?p?p?=?0.004). There was a significant positive correlation between serum AMH and HOMA-IR levels in adolescent females with PCOS (p?=?0.003).

Conclusion: We found that serum AMH levels were higher in non-obese adolescent females with PCOS and IR than in PCOS patients without IR and the healthy controls. There was a significant positive correlation between AMH levels and IR in non-obese adolescent females with PCOS.     

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.     

多囊卵巢综合征子宫内膜局部胰岛素抵抗的研究

目的探讨多囊卵巢综合征(PCOS)患者子宫内膜是否存在局部胰岛素抵抗(IR)。方法分离28例PCOS患者(PCOS组)和32例不孕症患者(对照组)的子宫内膜上皮和间质细胞并体外培养;采用葡萄糖氧化酶法测定PCOS子宫内膜细胞对葡萄糖的摄取量;应用免疫组化法检测胰岛素(Ins)、胰岛素受体(InsR)和葡萄糖转运蛋白4(GLUT4)在PCOS患者子宫内膜的表达。结果 PCOS组子宫内膜细胞葡萄糖摄取量与对照组比较,差异无统计学意义(P0.05);加入1×10-7mmol/L胰岛素后,PCOS组葡萄糖摄取量低于对照组(P0.05);PCOS肥胖及IR组葡萄糖摄取量低于非肥胖及非IR组(P0.05)。PCOS组子宫内膜Ins表达与对照组比较,差异无统计学意义(P0.05),但InsR及GLUT4表达低于对照组(P0.05);PCOS肥胖和IR组子宫内膜InsR及GLUT4表达低于非肥胖和非IR组,但差异无统计学意义(P0.05)。结论 P-COS患者子宫内膜存在局部IR,肥胖及全身IR加重子宫内膜局部IR。     

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.     

多囊卵巢综合征患者妊娠期胰岛素抵抗及妊娠结局观察分析

目的探讨多囊卵巢综合征(PCOS)患者妊娠期胰岛素抵抗的变化及与妊娠结局的关系。方法选择2007年9月至2009年2月在中山大学孙逸仙纪念医院妇产科确诊为PCOS并妊娠成功的102例孕妇为PCOS组,同期在本院早孕检查、产检及分娩的普通孕产妇701例为对照组,比较两组孕妇的妊娠并发症及妊娠结局。对PCOS组中的38例及对照组中的50例孕妇于24～28周进行75g葡萄糖耐量检查及胰岛素释放试验,计算胰岛素抵抗指数(HOMA-IR)、胰岛β细胞分泌功能指数(HOMA-β)、血糖和胰岛素曲线下面积。结果 PCOS组血糖曲线下面积及胰岛素曲线下面积大于对照组(22.22±4.48、19.29±3.19,228.93±130.05、155.62±69.54,P<0.05);PCOS组空腹血糖、空腹胰岛素、HOMA-IR、HOMA-β大于对照组,分别为4.61±0.57、4.56±0.39,7.81±4.65、6.35±4.45,1.65±1.08、1.31±0.95,169.47±119.4、126.94±85.81,但差异无统计学意义。PCOS组与对照组妊娠并发症发生率分别为自然流产23.53%、8.27%,妊娠期糖...     

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.     

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