scholarly journals Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide

1998 ◽  
pp. 184-189 ◽  
Author(s):  
GE Krassas ◽  
TT Kaltsas ◽  
N Pontikides ◽  
H Jacobs ◽  
W Blum ◽  
...  

Leptin, a product of the ob gene, is a 16 kDa protein which is produced by adipocytes. In humans, obesity is a common finding in women with polycystic ovary syndrome (PCOS). The role, however, of leptin in PCOS is not clear. Some studies have reported increased levels of leptin in PCOS, while others report that they are normal. Also, insulin resistance is a common finding in PCOS. The aim of this study was to investigate further the role of insulin in leptin secretion in patients with PCOS by treating them for 10 days with diazoxide, an insulin-reducing compound. Eight women with PCOS, mean age 22.1 +/- 2.7 years, with mean body mass index (BMI) 28.4 +/- 5.7kg/m2, were studied. An oral glucose tolerance test (OGTT) was performed in all women and blood samples were taken before and at 30, 60, 90, 120 and 150 min after the administration of glucose. Glucose, insulin, leptin, free testosterone, delta4 androstenedione, sex hormone binding globulin (SHBG), LH, FSH, IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were measured in the sera taken before the administration of glucose, while glucose and insulin levels were measured in all samples which were collected after the administration of glucose. Diazoxide 300 mg daily was given to all women starting after the end of the OGTT for 10 days. A second OGTT was performed the day after the discontinuation of the diazoxide treatment. The same hormonal and biochemical parameters were also measured in all patients during the second OGTT. After the administration of diazoxide a reduction in sum insulin (262 +/- 147 vs 679 +/- 341 microU/ml. P<().01), leptin (18.5 +/- 10.6 vs 24.2 +/- 10.2 ng/ml, P<0.01), free testosterone (3.0 +/- 1.9 vs 5.1 +/- 1.9 pg/ml, P<0.01), delta4 androstenedione (3.8 +/- 1.9 vs 5.7 +/- 2.0 ng/ml, P<0.01) and IGF-I (219.5 +/- 69.2 vs 314.5 +/- 82.3 ng/ml, P<0.01) levels was observed. Serum SHBG (38.8 +/- 16.8 vs 27.8 +/- 12.1 nmol/l, P<0.01) and sum glucose levels (994.1 +/- 252.7 vs 711.1 +/- 166.1 mg/dl, P<0.05) were increased while IGFBP-3 (3.96 +/- 2.49 vs 3.75 +/- 2.24mg/l), FSH (6.2 +/- 1.8 vs 6.0 +/- 2.5 mU/l) and LH (18.9 +/- 6.7 vs 21.4 +/- 6.7 mU/l) concentrations did not change significantly. A significant positive correlation was found between serum leptin and BMI values before and after administration of diazoxide as well as between leptin, insulin and IGFBP-3 values. Also, sum insulin values correlated significantly with BMI. However, when multiple regression analysis was used this correlation was eliminated except that between leptin and BMI. This was most probably due to the small number of cases. The mechanism of the reduction of leptin levels is unclear. However, it is suggested that the concomitant decrease of insulin levels may play a role.

2012 ◽  
Vol 166 (4) ◽  
pp. 703-710 ◽  
Author(s):  
Gabriella Donà ◽  
Chiara Sabbadin ◽  
Cristina Fiore ◽  
Marcantonio Bragadin ◽  
Francesco L Giorgino ◽  
...  

ObjectivePossibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations in erythrocytes and anti-inflammatory effects of inositol in women with PCOS before and after treatment with myo-inositol (MYO).MethodsTwenty-six normal-weight PCOS patients were investigated before and after MYO administration (1200 mg/day for 12 weeks;n=18) or placebo (n=8) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, insulin area under the curve (AUC), and glucose AUC after oral glucose tolerance test and homeostasis model of assessment–IR. In erythrocytes, band 3 tyrosine phosphorylation (Tyr-P) level, glutathione (GSH) content, and glutathionylated proteins (GSSP) were also assessed.ResultsData show that PCOS patients' erythrocytes underwent oxidative stress as indicated by band 3 Tyr-P values, reduced cytosolic GSH content, and increased membrane protein glutathionylation. MYO treatment significantly improved metabolic and biochemical parameters. Significant reductions were found in IR and serum values of androstenedione and testosterone. A significant association between band 3 Tyr-P levels and insulin AUC was found at baseline but disappeared after MYO treatment, while a correlation between band 3 Tyr-P and testosterone levels was detected both before and after MYO treatment.ConclusionsPCOS patients suffer from a systemic inflammatory status that induces erythrocyte membrane alterations. Treatment with MYO is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR.


2011 ◽  
Vol 165 (6) ◽  
pp. 935-943 ◽  
Author(s):  
Elisabeth Lerchbaum ◽  
Hans-Jürgen Gruber ◽  
Verena Schwetz ◽  
Albrecht Giuliani ◽  
Reinhard Möller ◽  
...  

IntroductionWomen with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances and might be affected by hepatic steatosis. The fatty liver index (FLI) was developed as a simple and accurate predictor of hepatic steatosis. We aimed to analyze the association of FLI with endocrine and metabolic parameters in a cohort of PCOS and control women.MethodsFLI was calculated using body mass index (BMI), waist circumference, triglycerides, and gamma-glutamyl transferase in 611 PCOS and 139 BMI-matched control women within the same age range. Elevated FLI was defined as >60. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed.ResultsPCOS women had significantly higher FLI levels than control women in age-adjusted analyses (11.4 (4.3–48.8) and 8.8 (3.9–35.0), respectively,P=0.001), whereas fibrosis indices were similar (aspartate amino transferase-to-platelet ratio index) or lower (FIB-4) respectively. In binary logistic regression analysis adjusted for age, odds ratio (OR) for elevated FLI was 2.52 (1.31–4.85),P=0.006, for PCOS women when compared with controls. PCOS women with high FLI levels had an adverse anthropometric, metabolic, and endocrine risk profile. The prevalence of elevated FLI was 88.7% in PCOS women with metabolic syndrome (MS) and 11.3% in PCOS women without MS (P<0.001). In control women, elevated FLI was present in 66.7% of women with MS and 30.8% of women without MS.ConclusionHigh FLI levels are a common finding in obese PCOS women and are closely linked to MS. FLI calculation might be a useful tool for identifying PCOS patients at high risk for metabolic and hepatic disturbances.


2018 ◽  
Vol 30 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Alon Eliakim

The Pediatric Exercise Science “Year That Was” section aims to highlight the most important (to the author’s opinion) manuscripts that were published in 2017 in the field of endocrinology and pediatric exercise science. This year’s selection includes studies showing that 1) in pubertal swimmers, there is a decrease in insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) during intense training (a catabolic-type hormonal response) with an anabolic “rebound” characterized by a significant increase of these growth factors during training tapering down. Moreover, it was shown that changes of IGF-I and IGFBP-3 paralleled changes in peak and average force but not with endurance properties, showing decreases during intense training and increases during tapering; 2) a meta-analysis showing that growth hormone administration elicits significant changes in body composition and possible limited effect on anaerobic performance but does not increase either muscle strength or aerobic exercise capacity in healthy, young subjects; and 3) short-term exercise intervention can prevent the development of polycystic ovary syndrome in a dose-dependent manner in letrozole-induced polycystic ovary syndrome rat model with high-intensity exercise being most effective. The implication of these studies to the pediatric population, their importance, and the new research avenues that were opened by these studies is emphasized.


2013 ◽  
Vol 20 (2) ◽  
pp. 123-126
Author(s):  
Ana Raluca Memu ◽  
Ioana Zosin ◽  
Gabriela Negrişanu

AbstractBackground and Aims. Polycystic ovary syndrome (PCOS) is associated with disturbances in carbohydrate and lipid metabolism. Statins appear to have beneficial effects in PCOS, although some meta-analyzes showed an increased risk of developing diabetes mellitus. The aim of this study was to evaluate the effect of treatment with 20 mg of atorvastatin daily for three months on glucose tolerance in a group of 8 normal weight patients with PCOS and dyslipidemia. Material andMethods. We evaluated 8 patients aged between 29 and 40 years, with normal weight, diagnosed with PCOS and dyslipidemia. The carbohydrate metabolism was assessed by oral glucose tolerance test (OGTT) before and after 3 months of therapy with 20 mg of atorvastatin daily. Results. Treatment with atorvastatin resulted in a statistically significant reduction in total cholesterol (p = 0.001), LDL cholesterol (p = 0.001), triglycerides (p = 0.01) and statistically significant increase in HDL cholesterol (p = 0.003). Fasting plasma glucose (p = 0.59) and the 2-hour OGTT glycemia (p = 0.54) were not significantly changed. Total testosterone decreased significantly ( p= 0.04). Conclusions. At baseline, all patients included in our study showed unaffected carbohydrate metabolism. Even after 3 months of therapy with atorvastatin 20 mg daily no changes in glucose homeostasis were noted.


2009 ◽  
Vol 94 (5) ◽  
pp. 1587-1594 ◽  
Author(s):  
Jennifer Hirshfeld-Cytron ◽  
Randall B. Barnes ◽  
David A. Ehrmann ◽  
Anthony Caruso ◽  
Monica M. Mortensen ◽  
...  

Abstract Context: The typical polycystic ovary syndrome (PCOS) phenotype includes 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHag) testing. Functionally atypical PCOS lacks this feature. Objective: The hypothesis was tested that the typical PCOS ovarian dysfunction results from intrinsically increased sensitivity to LH/human chorionic gonadotropin (hCG) due to a flaw in FSH action. Participants/Design/Interventions/Main Outcome Measures: After phenotyping a cohort of 60 women, steroid and inhibin-B responses to gonadotropins were evaluated in representative typical (n = 7) and atypical (n = 5) PCOS and healthy controls (n = 8). Submaximal hCG testing before and after an FSH test dose was performed in random order before and after prolonged ovarian suppression by depot GnRHag. Setting: The study was performed at a Clinical Research Center. Results: Of our PCOS cohort, 68% were the typical type. Typical PCOS had 17OHP hyperresponsiveness and, unlike controls, significant androgen and estradiol responses to hCG. FSH increased inhibin-B and did not inhibit free testosterone or enhance estradiol responsiveness to hCG, all unlike controls. After ovarian suppression, 17OHP, androstenedione, and inhibin-B responsiveness to gonadotropin testing persisted. Atypical PCOS had significantly higher body mass index but lower ovarian volume and plasma free testosterone than typical PCOS. Steroid responses to hCG were insignificant and similar to controls. FSH suppressed free testosterone but stimulated inhibin-B. The estradiol level after combined hCG-FSH was subnormal. Free testosterone was less GnRHag suppressible than in typical PCOS. Conclusions: Typical PCOS is characterized by intrinsic ovarian hypersensitivity to hCG to which excessive paracrine FSH signaling via inhibin-B may contribute. Atypical PCOS is due to a unique type of ovarian dysfunction that is relatively gonadotropin hyposensitive.


2002 ◽  
pp. 207-216 ◽  
Author(s):  
MC Garcia-Rudaz ◽  
MG Ropelato ◽  
ME Escobar ◽  
JD Veldhuis ◽  
M Barontini

OBJECTIVE: The present study evaluated the hypothesis that pulsatile GH secretion is altered in adolescents with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Thirteen adolescent girls with PCOS (ages 13-19 years) and ten eumenorrheic controls (ages 14-19 years) matched for a range of body mass index (BMI) values underwent blood sampling every 20 min for 12 h overnight. METHODS: Serum concentrations of GH and LH were measured by specific immunofluorometric assays (IFMA). Pulsatile secretion was quantitated by deconvolution analysis and pattern orderliness by the approximate entropy (ApEn) statistic. Fasting serum androstenedione, testosterone, 17-hydroxyprogesterone, estrone, estradiol, insulin and IGF-I concentrations were measured by RIA, GH-binding protein (GHBP) by IFMA and IGF-binding protein (IGFBP)-1 and IGFBP-3 by IRMA. RESULTS: Twelve-hour mean and integrated GH concentrations, the mass of GH secreted per burst, and the GH pulse frequency were not distinguishable in patients with PCOS and controls as a whole. Subanalysis of non-obese (BMI<25 kg/m(2)) PCOS and healthy volunteers disclosed elevated 12-h GH production rates (P=0.03) and integrated serum GH concentrations (P=0.04) in (lean) patients with PCOS. ApEn analysis of the orderliness of GH release showed remarkably more regular GH secretion patterns (lower ApEn of GH release) in girls with PCOS compared with controls (P=0.02). Serum GHBP, IGF-I and IGFBP-3 concentrations were similar in both groups, whether lean or obese. However, IGFBP-1 levels were lower in the combined group of PCOS subjects compared with BMI-matched controls (P<0.05). In volunteers with PCOS, mean (12-h) serum GH concentrations correlated positively with mean serum LH levels (P=0.006). Based on deconvolution analysis, the 12-h production rate and the mass of GH secreted per burst also correlated strongly with the cognate LH measure (both predicted) (P=0.004) in PCOS. Androstenedione levels were also related to the 12-h GH secretion rate (P=0.02). CONCLUSIONS: This study shows that non-obese adolescents with PCOS secrete GH at a higher rate and with more orderly patterns, resembling a male profile. Determining whether this pattern reflects an intrinsic hypothalamic abnormality or is secondary to androgen excess in PCOS will require further studies.


2021 ◽  
Vol 48 (2) ◽  
pp. 156-162
Author(s):  
Sungwook Chun

Objective: The aim of the present study was to evaluate the predictive capability of fasting-state measurements of glucose and insulin levels alone for abnormal glucose tolerance in women with polycystic ovary syndrome (PCOS).Methods: In total, 153 Korean women with PCOS were included in this study. The correlations between the 2-hour postload glucose (2-hr PG) level during the 75-g oral glucose tolerance test (OGTT) and other parameters were evaluated using Pearson correlation coefficients and linear regression analysis. The predictive accuracy of fasting glucose and insulin levels and other fasting-state indices for assessing insulin sensitivity derived from glucose and insulin levels for abnormal glucose tolerance was evaluated using receiver operating characteristic (ROC) curve analysis.Results: Significant correlations were observed between the 2-hr PG level and most fasting-state parameters in women with PCOS. However, the area under the ROC curve values for each fasting-state parameter for predicting abnormal glucose tolerance were all between 0.5 and 0.7 in the study participants, which falls into the “less accurate” category for prediction.Conclusion: Fasting-state measurements of glucose and insulin alone are not enough to predict abnormal glucose tolerance in women with PCOS. A standard OGTT is needed to screen for impaired glucose tolerance and type 2 diabetes mellitus in women with PCOS.


1998 ◽  
pp. 269-274 ◽  
Author(s):  
E Diamanti-Kandarakis ◽  
C Kouli ◽  
T Tsianateli ◽  
A Bergiele

Evidence suggests that insulin resistance and hyperinsulinaemia are associated with ovarian hyperandrogenism and menstrual irregularities in polycystic ovary syndrome (PCOS). Sixteen obese women with PCOS on a weight-maintaining diet were studied before and after 6 months of therapy with the insulin-sensitizing antidiabetic agent metformin at a dose of 1700 mg per day. Compared with baseline values, glucose utilization was markedly enhanced at 6 months using the two-step euglycaemic-hyperinsulinaemic clamp to measure changes in insulin sensitivity (2.56 +/- 0.32 vs 4.68 +/- 0.49 mg/kg per min, P = 0.0001, when 40 mU insulin/m2 per min was infused, and 6.48 +/- 0.58 vs 9.84 +/- 0.72 mg/kg per min, P = 0.0002, when 400 mU insulin insulin/m2 per min was infused). The improvement in insulin action was accompanied by significant increases in the levels of sex hormone-binding globulin (24.5 +/- 7.2 vs 39.8 +/- 16.2 nmol/l, P = 0.003) and decreases in free testosterone (12.8 +/- 5.8 vs 9.0 +/- 3.0 pmol/l, P = 0.03) and androstenedione (12.9 +/- 5.6 vs 7.3 +/- 1.7 nmol/l, P = 0.003). No significant changes were recorded in body weight. Seven subjects resumed normal menstruation and two cases of spontaneous pregnancy occurred during treatment. Metformin was well tolerated except for one case of flatulence. These results confirm that metformin treatment can lead to improvements in insulin resistance and ovarian hyperandrogenism.


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