Impaired glucose tolerance is associated with changes in clinical and biochemical parameters in women with polycystic ovary syndrome

BACKGROUND: To characterize the phenotype of women with polycystic ovary syndrome with and without impaired glucose tolerance by determining various polycystic ovary syndrome-associated clinical and laboratory parameters. METHODS: In a prospective clinical study, we evaluated a series of 102 Caucasian women with polycystic ovary syndrome. Women completed a detailed questionnaire and underwent a standardized oral glucose tolerance test. Various polycystic ovary syndrome-associated laboratory values such as hormonal and metabolic parameters were determined in these women and correlated to clinical data and the presence/absence of impaired glucose tolerance. Furthermore, the insulin resistance was calculated using the homeostasis model assessment index and correlated with clinical and biochemical parameters. RESULTS: Eighty-eight (86.3%) and 14 (13.7%) women were diagnosed as having non-impaired glucose tolerance and impaired glucose tolerance, respectively. Presence of impaired glucose tolerance was associated with an increased body mass index, increased body weight, elevated serum levels of bioavailable testosterone, insulin like growth factor-1, insulin, HbA1c, leucocytes, uric acid, alkaline phosphatase, hepatic C-reactive protein, and decreased serum levels of sex-hormone binding globulin. No association was ascertained with subfertility, hirsutism, and menstrual irregularities. We ascertained a positive correlation between the homeostasis model assessment index and body mass index, body weight, alkaline phosphatase, and hepatic C-reactive protein. CONCLUSIONS: Impaired glucose tolerance seems to be associated with a specific phenotype within polycystic ovary syndrome. This phenotype is more likely to present with biochemical parameters similar to an inflammatory reaction and a metabolic disorder.     

Abnormal glucose tolerance in polycystic ovary syndrome

AIM: To investigate the incidence of abnormal glucose tolerance (AGT) in women with polycystic ovary syndrome (PCOS), and the reliability of fasting plasma glucose level (FPG) as a screening test for this metabolic abnormality. METHODS: Two hundred and three women (62 adolescents and 141 adults) diagnosed with PCOS underwent estimation of FPG and 2-h plasma glucose after ingestion of 75 g of glucose on an empty stomach. In each case, body mass index (BMI) was calculated from height and weight measurements. Results: AGT was found in 16.3% of cases (33/203). AGT was found in 9.7% of adolescent cases (6/62) and 19.1% of adults (27/141) (P=0.03). Women with abnormal glucose tolerance had higher BMI than those with normal glucose tolerance in the two subgroups (not statistically significant). Difference in BMI between adults and adolescents with normal glucose tolerance was statistically significant, but not in cases with AGT. CONCLUSION: AGT was found in 16.3% of women with PCOS (19.1% of adults and 9.7% of adolescents). BMI alone is not a significant contributory factor causing deterioration of glucose tolerance as a woman with PCOS matures. Other clinical parameters of obesity such as upper body obesity need to be studied. All women with PCOS should undergo periodic screening for abnormal glucose tolerance. Fasting plasma glucose is a poor screening test to detect abnormal glucose tolerance.     

Placental steroidogenesis in pregnant women with polycystic ovary syndrome

Objective

To evaluate the placental activity of steroid sulfatase (STS), 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD-1) and P450 aromatase (P450arom) in polycystic ovarian syndrome (PCOS) compared to normal pregnant women.

Design

Twenty pregnant women with PCOS and 30 control pregnant women who delivered at term were studied. Samples of placental tissue and cord blood were obtained after delivery. A maternal blood sample was obtained during the 34th week of gestation. In placental tissue, the activities of STS, 3β-HSD-1 and P450arom were evaluated. In the blood samples, progesterone, DHEAS, DHEA, androstenedione, testosterone, estrone, estradiol and total estriol were determined.

Result

In placental tissue from women with PCOS, higher 3β-HSD-1 and lower P450 aromatase activities were observed compared to control women. Moreover, women with PCOS showed higher androstenedione and testosterone concentrations compared to normal pregnant women (p = 0.016 and p = 0.025, respectively). In cord blood, female newborns of women with PCOS exhibited lower androstenedione and higher estriol concentrations compared to daughters of control women (p = 0.038; p = 0.031, respectively).

Conclusion

These data suggest that placental tissue from women with PCOS shows changes in the activities of two important enzymes for steroid synthesis, higher 3β-HSD-1 and lower P450, which could increase androgen production during pregnancy.     

Metformin reduces abortion in pregnant women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin - owing to its metabolic, endocrine, vascular and anti-inflammatory effects - may reduce the incidence of first-trimester abortion in PCOS women. MATERIALS AND METHODS: A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000-2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group. RESULTS: Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11-0.42). CONCLUSIONS: Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.     

多囊卵巢综合征患者糖耐量异常及相关因素分析

目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者糖耐量受损(IGT)和2型糖尿病(NIDDM)的发生率及其高危因素。方法:回顾分析101例PCOS患者口服葡萄糖耐量(OGTT)实验后的临床资料,多因素logistic回归分析探讨PCOS患者糖耐量异常的危险因素。结果:(1)根据葡萄糖耐量实验结果分成糖耐量正常组(NGT)77例与糖耐量异常组(AGT)24例(IGT22例、NIDDM2例),IGT发生率21.8%,NIDDM发生率1.98%;(2)AGT组的年龄、腰臀比(WHR)、体重指数(BMI)、睾酮(T)、空腹血糖(FPG)、2h血糖增高,与NGT组的差异有统计学意义(P<0.05),空腹胰岛素(FINS)、2h胰岛素、稳态模式胰岛素抵抗指数(HOMA-IR)升高,差异有统计学意义(P<0.01)。初潮年龄、黄体生成素/卵泡刺激素(LH/FSH)两组差异无统计学意义(P>0.05);(3)AGT组糖尿病家族史发生率高于NGT组,差异有统计学意义(P<0.01);(4)多因素logistic回归分析显示,年龄、BMI、2型糖尿病家族史、空腹胰岛素升高为PCOS糖耐量异常的高危因素。结论:多囊卵巢综合征发生糖耐量受损、糖尿病的危险性增加,葡萄糖耐量2h血糖水平是监测PCOS糖耐量异常的较好指标。年龄、BMI、2型糖尿病家族史、空腹胰岛素升高是PCOS糖耐量异常发生的危险因素。     

Metformin reduces abortion in pregnant women with polycystic ovary syndrome

Background.?Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin – owing to its metabolic, endocrine, vascular and anti-inflammatory effects – may reduce the incidence of first-trimester abortion in PCOS women.

Materials and methods.?A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000–2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group.

Results.?Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11–0.42).

Conclusions.?Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.     

Acanthosis nigricans: clinical predictor of abnormal glucose tolerance in Asian women with polycystic ovary syndrome.

The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS). Data from the record forms and electronic form of 121 PCOS women who consecutively attended the Reproductive Endocrinology and Infertility Unit were reviewed. In accordance with the unit's guidelines, all women received a physical examination, had anthropometric measurements taken and underwent as a 75-g oral glucose tolerance test after diagnosis. Their age, body mass index (BMI) and waist/hip ratio (WHR) was 29.1+/-6.1 years, 27.4+/-6.8 kg/m2 and 0.84+/-0.6 (mean+/-standard deviation), respectively. The prevalence of AGT was 42.9%, with 1.6% having impaired fasting glucose, 32.3% having impaired glucose tolerance and 9.1% having type 2 diabetes mellitus. The PCOS women with acanthosis nigricans had significantly higher BMI, WHR, fasting glucose, 2-h post-load glucose, fasting insulin, 2-h post-load insulin and prevalence of AGT compared with those without acanthosis nigricans. By logistic regression analysis, acanthosis nigricans and WHR were independent predictors for AGT, with an odds ratio (95% confidence interval) of 2.7 (1.1-7.1) and 10.1 (1.8-20.7), respectively. In conclusion, acanthosis nigricans was demonstrated as a predictive factor for AGT in Asian women with PCOS.     

Decrease in adiponectin levels in women with polycystic ovary syndrome after an oral glucose tolerance test

Adiponectin levels are decreased after an oral glucose tolerance test. At t = 2 hours, they are increased in obese and overweight women with polycystic ovary syndrome, compared with controls matched for body mass index.     

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in Asian women with polycystic ovary syndrome.

OBJECTIVES: To determine the prevalence of abnormalities of glucose metabolism in Asian women with polycystic ovary syndrome (PCOS) and to assess the different impacts of the 1985 and 1999 WHO consultations and the ADA criteria for the diagnosis of type 2 diabetes mellitus (DM). METHODS: Eighty-five women with PCOS were consecutively included in the study at the Reproductive Endocrinology Unit, Department of Ob-Gyn, Ramathibodi Hospital, Mahidol University. All women underwent a standard oral glucose tolerance test (OGTT). Fasting insulin and testosterone levels were also measured. RESULTS: Seventy-nine women consented to the OGTT. The prevalence of impaired glucose tolerance (IGT) and type 2 DM was 22.8 and 15.2% with the 1985 WHO criteria, and 20.3 and 17.7% according to the 1999 WHO consultation criteria, respectively. The recommendation of the ADA using the fasting glucose levels could only determine a prevalence of 6.3% for type 2 DM. The fasting insulin and testosterone levels were significantly higher in DM than IGT and normal glucose tolerance (NGT) subgroups. The PCOS women with abnormalities of glucose metabolism had a greater body mass index (BMI), higher fasting glucose and 2-h post-load glucose levels than those with NGT. The prevalence of glucose intolerance significantly increased with BMI. CONCLUSIONS: Similar to other ethnic populations, Asian women with PCOS are at risk of developing IGT and type 2 DM especially if obese. The recommendation of the ADA is not appropriate for the diagnosis of type 2 DM in PCOS women.     

Impaired uterine perfusion associated with metabolic disorders in women with polycystic ovary syndrome

BACKGROUND: Risk factors for cardiovascular disease, including chronic anovulation, obesity, hyperandrogenism, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS). We evaluated uterine perfusion and its correlation with clinical and biochemical parameters in women with PCOS. METHODS: We performed a pulsed Doppler study on uterine arterial blood flow in 25 women with PCOS and 45 control women with regular menstrual cycles. PCOS was diagnosed based on oligomenorrhea, polycystic ovaries determined by means of ultrasonography, and elevated luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio. RESULTS: Women with PCOS had a significantly higher body mass index (BMI) and serum testosterone, and showed insulin resistance and dyslipidemia, including increased total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C). The uterine arterial pulsatility index (PI) in women with PCOS was significantly higher than that in the control women during the follicular phase. The PI was correlated with BMI, LH/FSH ratio, or LDL-C/HDL-C ratio, whereas it was inversely correlated with the HDL-C level. Women with PCOS had reduced endometrial thickness and elevated uterine arterial PI in the luteal phase, in which implantation occurs. CONCLUSIONS: Elevation of uterine arterial blood flow resistance is associated with risk factors for cardiovascular events. Furthermore, the impaired uterine perfusion in the luteal phase may cause endometrial dysfunction in women with PCOS.     

Impaired cholecystokinin secretion and disturbed appetite regulation in women with polycystic ovary syndrome

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the ‘satiety peptide’ cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p <?0.05) with no association with satiety, as in the controls (r?=?0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p?=?0.07) but no correlation with insulin, as in the controls (r?=?0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r?=??0.60) and the CCK response was positively correlated with levels of free testosterone (r?=?0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.     

Risk factors for glucose intolerance in Danish women with polycystic ovary syndrome

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are reported to be at risk for glucose intolerance. The aim of the study was to describe these risk factors in a population of Danish PCOS women attending a gynecologic clinic and to identify the parameters with the strongest correlation to the fasting blood glucose levels. In addition, we studied whether the oral glucose tolerance test (OGTT) diagnosed more cases of glucose intolerance in this PCOS population than the fasting plasma glucose value (FPG) alone. METHODS: Cross-sectional study of 91 women with oligomenorrhea or amenorrhea and elevated serum testosterone, followed by an OGTT in 27 of the women. RESULTS: Women with a FPG above normal were older and had a higher body mass index (BMI), cholesterol, and triglycerides and a lower sexual hormone binding globulin (SHBG). Of the 21 women older than 34, eight (38%) had a FPG above normal. The OGTT study showed that one of five with abnormal glucose tolerance would not have been diagnosed, if the FPG alone had been performed. CONCLUSIONS: In this study, 38% of women with symptoms of PCOS over the age of 34 had abnormal blood glucose values. These women should receive blood glucose testing regardless of BMI, testosterone levels and family history of type 2 diabetes mellitus. An OGTT may be necessary to find all cases of impaired glucose intolerance.     

Metabolic syndrome in women with polycystic ovary syndrome

The prevalence of the metabolic syndrome in polycystic ovary syndrome (PCOS) is high across all age groups. Dyslipidemia, particularly a decreased high-density lipoprotein cholesterol level, also is common in women with PCOS.     

Metformin therapy in women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. METHOD: 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. RESULT: In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. CONCLUSION: A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.     

Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance.

We studied the in vitro response to insulin of granulosa-lutein cells derived from patients with polycystic ovary syndrome (PCOS) and clinically defined insulin resistance. Insulin sensitivity was assessed by continuous infusion of glucose with model assessment test (CIGMA). Insulin resistant (PCOS-IR; n = 8), noninsulin resistant (PCOS-NIR; n = 9) patients with PCOS, and women with tubal factor infertility (TF; n = 8) underwent controlled ovarian stimulation with long-term gonadotropin-releasing hormone (GnRH) agonist, recombinant follicle stimulating hormone (FSH), and in vitro fertilization. Primary cultures of granulosa-lutein cells were incubated with insulin (10, 100, 500 ng/ml) and/or luteinizing hormone (LH) (10, 100 ng/ml) in the presence of low density lipoprotein (100 micrograms/ml). The progesterone and lactate accumulation were measured in the culture medium. LH potently stimulated the progesterone secretion in all groups. Insulin alone had no effect on progesterone release in any of the groups, but stimulated lactate formation in the PCOS-NIR and TF groups. Insulin augmented the effect of LH on progesterone secretion selectively in the PCOS-NIR group. The expression of the insulin receptor was determined by Western blotting in separate cultures of granulosa-lutein cells, and showed receptor down-regulation in the PCOS-IR patients. We infer that the in vitro effect of insulin on progesterone and lactate release by granulosa-lutein cells is impaired in insulin resistant PCOS patients.     

Preptin in women with polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) patients, frequently develop metabolic complications, such as insulin resistance (IR), impaired carbohydrate metabolism, dyslipidemia, obesity. Among the new markers responsible for metabolic disorders, preptin seems to be of great significance.

Material: One hundred and thirty-four women aged 17–45 were enrolled. PCOS was diagnosed in 73 women on the basis of ESHRE-ASRM criteria. Non-PCOS group consisted of 61 women with regular menstruation matched for nutritional status.

Methods: All women underwent anamnesis, physical examination, anthropometric measurements, the abdominal ultrasound examination, and dual energy X-ray absorptiometry (DXA). Serum adropin levels were determined by ELISA. Biochemical and hormonal (testosterone, androstenedione, LH, FSH, estradiol) measurements were also performed. Insulin resistance indices (HOMA, QUICKI, Matsuda) and free androgen index (FAI) were calculated with the test results according to the standard formula. For all comparisons, statistical significance was defined by p?≤?.05.

Results: Serum preptin levels were significantly higher in the PCOS group. No significant correlations between preptin level and metabolic and hormonal markers were observed. The logistic regression analysis demonstrated that serum preptin level was an independent factor differentiating the two groups.

Conclusions: Serum preptin levels were significantly higher in women with PCOS compared with controls. This peptide might be an independent predictor of PCOS in the future.     

Associations between maternal BMI as well as glucose tolerance and adverse pregnancy outcomes in women with polycystic ovary syndrome

This retrospective, cohort study examined the association between maternal pre-pregnancy body mass index (BMI), independent of glucose tolerance and adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), for which there are few previous studies. Medical records from 2012 to 2015 at Guangzhou Women and Children’s Medical Center, China were reviewed for women previously diagnosed with PCOS with normal 2-h 75-g oral glucose tolerance test (OGTT) results (n?=?1249). The separate and joint effects of maternal BMI and glucose levels on pregnancy outcomes were assessed. Maternal pre-pregnancy BMI was associated with hypertensive disorders of pregnancy (HDP) (OR: 1.22, 95% CI: 1.02–1.45), preterm birth (OR: 1.49, 95% CI: 1.08–2.17), and large for gestational age (LGA) (OR: 1.69, 95% CI: 1.16–2.20). Elevated fasting glucose and maternal pre-pregnancy BMI were jointly associated with increased risks of HDP, preterm birth, and LGA. Therefore, among women with PCOS and normal glucose tolerance, maternal pre-pregnancy BMI is an independent risk factor of adverse pregnancy outcomes.     

Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance

We studied the in vitro response to insulin of granulosalutein cells derived from patients with polycystic ovary syndrome (PCOS) and clinically defined insulin resistance. Insulin sensitivity was assessed by continuous infusion of glucose with model assessment test (CIGMA). Insulin resistant (PCOS-IR; n = 8), non-insulin resistant (PCOS-NIR; n = 9) patients with PCOS, and women with tubal factor infertility (TF; n = 8) underwent controlled ovarian stimulation with long-term gonadotropin-releasing hormone (GnRH) agonist, recombinant follicle stimulating hormone (FSH), and in vitro fertilization. Primary cultures of granulosa-lutein cells were incubated with insulin (10, 100, 500 ng/ml) and/or luteinzing hormone (LH) (10, 100 ng/ml) in the presence of low density lipoprotein (100 μg/ml). The progesterone and lactate accumulation were measured in the culture medium. LH potently stimulated the progesterone secretion in all groups. Insulin alone had no effect on progesterone release in any of the groups, but stimulated lactate formation in the PCOS-NIR and TF groups. Insulin augmented the effect of LH on progesterone secretion selectively in the PCOS-NIR group. The expression of the insulin receptor was determined by Western blotting in separate cultures of granulosa-lutein cells, and showed receptor down-regulation in the PCOS-IR patients. We infer that the in vitro effect of insulin on progesterone and lactate release by granulosa-lutein cells is impaired in insulin resistant PCOS patients.