Effect of the opioid blockade on the feeding-induced growth hormone response to growth hormone-releasing hormone in women with polycystic ovary syndrome

OBJECTIVE: To investigate the effect of naloxone, an opioid receptor antagonist, on the release of growth hormone (GH) induced by the growth hormone-releasing hormone (GHRH) in normal-weight and obese women with PCOS in relation to feeding. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Seventeen women with PCOS (10 who were normal weight and 7 who were obese) and 14 control women (7 who were normal weight and 7 who were obese). INTERVENTION(S): A GHRH test (50 microg i.v.) and, on a different day, a GHRH test during a naloxone infusion (1.6 mg/h) during fasting. The same tests were repeated after a standard meal. MAIN OUTCOME MEASURE(S): GH response to GHRH (expressed as the area under the curve [AUC]) in different experimental conditions. RESULT(S): All normal-weight women showed a significantly higher AUC-GH compared with obese women in the fasting state. Normal-weight controls had a decrease in GH response to GHRH after feeding, and naloxone did not reverse the decrease. In obese controls, feeding increased the GH response but naloxone induced a decrease in the AUC. In fasting, normal-weight women with PCOS, naloxone significantly decreased the AUC-GH; in these patients, food intake induced an inhibition of GH response to GHRH, reversed by naloxone infusion. In obese PCOS patients, GH levels did not increase significantly after GHRH stimulation, either in the fasting state or after a meal, and naloxone did not affect these responses. CONCLUSION(S): Factors other than obesity and insulin may be involved in disruption of GH secretion in women with PCOS.     

Serum resistin and adiponectin levels in women with polycystic ovary syndrome

Aim.?This study was performed to compare the serum levels of resistin and adiponectin in women with polycystic ovary syndrome (PCOS) and normal controls.

Materials and methods.?Seventy-six patients (36 obese, 40 non-obese) with PCOS and 42 healthy subjects were included in the study. Serum levels of resistin, adiponectin, follicle-stimulating hormone, luteinising hormone, dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxy progesterone, free testosterone, androstenedione, glucose, insulin and lipid parameters were measured. Insulin resistance and carbohydrate metabolism were evaluated by using the homeostasis model (HOMA) and the area under the insulin curve (AUCI).

Results.?Plasma resistin levels, HOMA-IR and AUCI were significantly higher and adiponectin level was lower in women with PCOS than those in healthy women. Plasma resistin levels were similar among obese and non-obese women with PCOS. No correlation was observed between resistin, body mass index (BMI), HOMA-IR, AUCI, insulin, lipid parameters and serum androgen levels. In obese PCOS patients, adiponectin levels were lower than in the lean PCOS patients. A negative correlation was observed among adiponectin, HOMA-IR, AUCI, BMI, testosterone, DHEAS, total-cholesterol, LDL-cholesterol and lipoprotein (a) levels.

Conclusion.?These results suggest that the serum adiponectin level may be involved in the pathogenesis of PCOS. But resistin levels were independently associated with insulin resistance and BMI in PCOS patients. Nevertheless, wider-scale trials are required to be performed on this subject.     

Increased plasma metastin levels in adolescent women with polycystic ovary syndrome

Objective

This study was designed to:

(1)

measure metastin levels in women with polycystic ovary syndrome (PCOS) and in adolescent controls;

(2)

investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances.

Study design

The study was a clinical study. Nineteen adolescent women with PCOS, twenty-three adult women with the syndrome, and twenty adolescent controls were selected. Blood samples were collected between day 1 and day 5 of a spontaneous bleeding episode in the PCOS groups and of a menstrual cycle of the controls at 9 a.m. after an overnight fast. Circulating levels of LH, FSH, prolactin, testosterone (T), free testosterone, DHEAS, sex hormone-binding globulin, insulin, glucose and metastin were measured.

Result(s)

Plasma metastin levels are increased in adolescent women with PCOS compared to adolescent controls. Plasma metastin levels were positively correlated with LH levels, 2-h glucose levels and T levels.

Conclusion(s)

These results indicate that metastin is increased in adolescent PCOS women. The increased metastin levels were positively correlated with LH and T levels, and may affect the development of PCOS in adolescents.     

Serum resistin levels in women with polycystic ovary syndrome

OBJECTIVE: To measure serum resistin levels in women with polycystic ovary syndrome (PCOS) and assess possible correlations of resistin to the hormonal and metabolic parameters of the syndrome. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): Ninety selected women were classified as follows: group I: 35 anovulatory women with PCOS (body mass index [BMI] >25 kg/m(2)); group II: 35 anovulatory women with PCOS (BMI <25 kg/m(2)); group III: 20 ovulating women (controls) without hyperandrogenemia (BMI <25 kg/m(2)); women of group III were volunteers. INTERVENTION(S): Blood samples were collected between the 3rd and the 6th day of the menstrual cycle of the ovulating women, and between the 3rd and the 6th day of a spontaneous bleeding of the anovulatory women, at 9 a.m., after an overnight fast. MAIN OUTCOME MEASURE(S): Serum levels of FSH, LH, PRL, 17alpha-hydroxyprogesterone, sex hormone-binding globulin, androgens, insulin, resistin, and glucose. RESULT(S): Resistin levels were found to be significantly increased in group I compared with those of group II and those of group III. No significant difference in resistin levels was found between groups II and III, despite significant differences in insulin levels and the glucose-to-insulin ratio. Multiple regression analysis showed that resistin levels do not correlate with any parameter independent of BMI. CONCLUSION(S): Based on the above findings, we presume that resistin is unlikely to be a major determining factor of PCOS-associated insulin resistance and is not actively involved in the pathogenesis of the syndrome.     

Plasma selenium levels in Turkish women with polycystic ovary syndrome

Objective(s)

To evaluate selenium (Se) levels in serum and their relation with hyperandrogenism and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) and in control subjects.

Study design

Women with any gynecological problem who presented to the Kahramanmaras Sutcuimam University Medical Faculty Gynecology and Obstetric Outpatient Clinic were invited to participate. Group 1 consisted of 36 cases with a diagnosis of PCOS according to the 2003 Rotterdam Consensus Criteria, and Group 2 (control group) consisted of 33 age- and BMI-matched healthy women. In all cases, serum total testosterone (tT), dihydroepiandrostenedione-sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), insulin, glucose (mg/dL), total cholesterol (TC) (mg/dL), high density lipoprotein-cholesterol (HDL-C) (mg/dL), low density lipoprotein-cholesterol (LDL-C) (mg/dL), triglyceride (TG) (mg/dL) and Se levels were measured.

Results

The level of FSH was significantly lower, and the levels of LH, E2, tT, and DHEAS were significantly higher in group 1 than in group 2 (p < 0.05). The hirsutism score was significantly higher among PCOS women compared to the control group (p < 0.05). Although insulin levels and HOMA-IR were markedly increased in the PCOS group compared to the control group, the differences were not significant (p > 0.05). The plasma Se level was significantly lower in PCOS women compared to the control group (p < 0.05). When we combined the all women in two groups, regarding them as one group (combined group, n = 69), a negative correlation between Se and LH and tT was present (p < 0.05).

Conclusion(s)

Our results show decreased plasma concentrations of Se and a negative correlation between Se and LH, tT in women with PCOS. These results indicate that Se may play a role in the pathogenesis of PCOS related with hyperandrogenism.     

Serum vaspin and C-reactive protein levels in women with polycystic ovaries and polycystic ovary syndrome

Objective.?Our aim was to evaluate C-reactive protein (CRP) and serum vaspin levels in women with polycystic ovary syndrome (PCOS) or polycystic ovaries (PCO).

Design.?Twenty-four women with PCOS and 23 women with PCO constituted the study groups. The control group comprised 24 healthy women.

Methods.?Homeostatic model assessment for insulin resistance (HOMA-IR), CRP and serum vaspin levels were measured. The receiver–operating characteristic curve (ROC) of vaspin for prediction of women with increased diabetogenic risk was constructed.

Results.?The three groups did not significantly differ in age and body mass index. HOMA-IR was significantly higher in the PCOS and PCO groups than in control group. Median CRP levels in the control, PCO and PCOS groups were 0.66, 1.28 and 3.2?mg/l, respectively (p?=?0.0001). Women with PCOS had significantly higher serum vaspin levels than the healthy controls [3.52?±?1.38 vs. 0.36?±?0.19?ng/ml, p?=?0.0001]. Serum vaspin could differentiate between women with and without increased diabetogenic risk at a cut-off value of 1.82?ng/ml with a sensitivity of 83.3% and a specificity of 66.1%.

Conclusion.?The results of our study showed that the presence of the increased vaspin, CRP and higher HOMA-IR levels in women with PCOS and PCO could contribute to increased diabetogenic and atherogenic risk in these patients.     

Serum Caspase-1 levels in women with polycystic ovary syndrome

ObjectiveCaspase-1 is implicated in several important inflammatory diseases and controls adipocyte differentiation and insulin sensitivity. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and plays an important role in chronic inflammatory conditions. This study was planned to determine if there is any relationship between Caspase-1 and IL-10 levels in women with PCOS.Materials and methodsForty-two women with PCOS and thirty-seven healthy controls were evaluated in this controlled clinical study. Caspase-1 and IL-10 levels, serum lipid sub-fractions, fasting glucose, fasting insulin and other hormones (gonadotropins, androgens), malondialdehyde (MDA) and glutathione (GSH) levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance.ResultsFree androgen index (FAI), HOMA-IR, MDA and Caspase-1 levels were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower GSH concentration levels than healthy subjects. Serum IL-10 levels were higher in study subjects than in controls, though it was statistically insignificant. Caspase-1 was positively associated with IL-10.ConclusionThese outcomes propose that Caspase-1 may have a role in triggering the processes leading to chronic low-grade inflammation in women with PCOS, independent of insulin resistance, androgen excess and oxidative stress. Nevertheless, the precise role of Caspase-1 in the pathogenesis of the disease remains to be elucidated.     

Serum visfatin levels in women with polycystic ovary syndrome

The aim of this study is to determine the serum levels of visfatin in patients with polycystic ovary syndrome (PCOS) and to understand its correlations with other metabolic and hormonal parameters. Thirty-seven patients with PCOS and 30 women without concomitant disease were included in this study. Serum visfatin levels were similar in patients with PCOS and control group. Visfatin levels were higher in normal weight PCOS when compared with obese PCOS, but it did not reach statistical significance. Visfatin levels correlated negatively with fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL) and lipoprotein-a levels in PCOS patients. CRP levels increased both in obese PCOS and in obese controls. Plasma visfatin levels had no correlation with homeostasis model assessment-insulin resistance and fasting insulin levels, but the negative correlation between plasma visfatin levels and lipoprotein-a, fasting plasma glucose, TC and LDL levels may indicate a role for visfatin in cardiovascular disease independent of insulin resistance.     

Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome

Objective: To determine whether the administration of metformin, an insulin-sensitizing agent, is followed by changes in adrenal steroidogenesis in women with polycystic ovary syndrome (PCOS).

Design: Prospective trial.

Setting: Department of Obstetrics and Gynecology, University of Siena, Siena, Italy.

Patient(s): Fourteen women with PCOS.

Intervention(s): Blood samples were obtained before (−15 and 0 minutes) and after (15, 30, 45, and 60 minutes) the administration of ACTH (250 μg). Metformin then was given at a dosage of 500 mg three times a day for 30–32 days, at which time the pretreatment study was repeated.

Main Outcome Measure(s): The adrenal androgen responses to ACTH before and after treatment with metformin.

Result(s): Ovulation occurred in two women (14%) in response to metformin treatment. A significant reduction in basal concentrations of free testosterone and a significant increase in concentrations of sex hormone-binding globulin were observed. The administration of metformin was associated with a significant reduction in the response of 17-hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH. The ratio of 17-hydroxyprogesterone to progesterone, which indicates 17-hydroxylase activity, and the ratio of androstenedione to 17-hydroxyprogesterone, which indicates 17,20-lyase activity, were significantly lower after a month of metformin treatment, indicating a reduction in the activities of these enzymes.

Conclusion(s): The administration of metformin to unselected women with PCOS led to a reduction in the adrenal steroidogenesis response to ACTH. This finding supports the hypothesis that high insulin levels associated with PCOS may cause an increase in plasma levels of adrenal androgens.     

Sleep disturbances in women with polycystic ovary syndrome

Sleep disturbances in women with Polycystic Ovary Syndrome (PCOS) have been reported in recent years. The majority of published studies are related to Obstructive Sleep Apnea (OSA) while not many researches have analyzed any other causes of sleep disturbances. A group of ninety five women with Polycystic Ovary Syndrome were enrolled into the study. Sleep disturbances were assessed using validated questionnaires. On the grounds of Athens Insomnia Scale (AIS) evaluation a clinically significant insomnia was ascertained in 12.6% of women with PCOS, while according to Insomnia Severity Index (ISI) in 10.5%. Clinically significant insomnia according to both AIS and ISI, occurred significantly more often in women with PCOS than in women without PCOS based on the chi-square test. The Mann–Whitney U test revealed statistically significant difference between women with and without PCOS based on total values of ISI. An excessive daytime sleepiness occurred at 7.4% of women with PCOS. Statistically significant dependance between: clinically significant insomnia in both AIS and ISI and excessive daytime sleepiness indicated by Epworth Sleepiness Scale (ESS) was observed. Sleep disorders are common in women with PCOS. Screening assessment of sleep disturbances should be a part of medical diagnostics in women with PCOS.     

Effects of metformin on serum insulin and anti-mullerian hormone levels and on hyperandrogenism in patients with polycystic ovary syndrome

Objective: To evaluate the relationship between serum anti-mullerian hormone levels (AMH) and insulin resistance (IR) before and after meformin treatment and to compare AMH levels of polycystic ovary syndrome (PCOS) women in the early follicular phase. Methods: Twenty PCOS women with IR, taking metformin 1500?mg/day for 8 weeks, and 16 non-PCOS controls were enrolled in this longitudinal study. Serum levels of AMH, insulin, glucose, testosterone, and quantitative insulin check index (QUICKI), were assessed before and after treatment in PCOS group. Results: AMH levels were higher in untreated PCOS (p < 0.0001), as were luteinizing hormone (LH) (p = 0.0004), testosterone (p = 0.0017) as well as 17-hydroxyprogesterone (p = 0.03). PCOS women show positive correlation between AMH and testosterone (R = 0.83; p < 0.0001) only prior to treatment. Metformin treatment, lead to a significant decrease in serum insulin (p = 0.0132) and testosterone (p = 0.0017) levels. However, no alteration in AMH levels was observed after treatment. Conclusion: Despite the improvement of metabolic parameters and the reduction of androgen levels, AMH levels did not change after metformin treatment. Maybe, the dose, and possibly the time of use, of metformin are factors associated with the reduction of AMH levels.     

Prevalence and predictors of abnormal glucose metabolism in Mediterranean women with polycystic ovary syndrome

Impaired glucose tolerance (IGT) and Type 2 diabetes mellitus (DM) are common in women with polycystic ovary syndrome (PCOS) in American studies. However, whether rates are similar in other countries with a lower frequency of insulin resistance is not clear. Our purpose was to investigate the prevalence of abnormal glucose metabolism (AGM) in women with PCOS and asses the ability of clinical data and biochemical tests to predict these abnormalities within our population. One hundred and three PCOS women undergo a 75-g oral glucose tolerance test. Glucose tolerance was categorised according to World Health Organisation criteria. Glucose tolerance was abnormal in 18.5% of women: 10.7% had IGT and 7.7% had DM. Women with DM were older than those with IGT or normal glucose tolerance. Women with AGM were more obese, had a higher waist/hip ratio and free testosterone levels than normal glucose metabolism patients. QUICKI was the best predictor of AGM. Receiver operating characteristics analysis suggested a threshold value of 0.31 in quantitative insulin-sensitivity check index (QUICKI) (94.1% sensitivity, 86% specificity, 57.1 positive predictive value and 98.6 negative predictive value) for the prediction of AGM. In conclusion, Mediterranean women with PCOS are at lower risk of AGM than that published from other countries; however, the incidence is still high compared with populations of women without PCOS. We recommend that PCOS patients undergo periodic metabolic screening for AGM using QUICKI.     

Increased growth hormone response to clonidine in nonobese normoinsulinemic patients with polycystic ovary syndrome

OBJECTIVE: To assess growth hormone (GH) levels in response to acute clonidine stimulation in nonobese patients with polycystic ovary syndrome (PCOS) in comparison to patients with idiopathic hirsutism (IH) and normal women without hirsutism. DESIGN: Cross-sectional study.Outpatient clinic, Porto Alegre, Brazil. PATIENT(S): Fourteen patients with PCOS, 11 women with IH, and 10 age- and weight-matched normal women without hirsutism were studied. All subjects presented normal body mass index (<25 kg/m(2)) and insulin levels (<25 microIU/mL). INTERVENTION(S): Growth hormone levels were assessed in all patients before and 30, 60, 90, and 120 minutes after oral administration of 0.3 mg of clonidine. MAIN OUTCOME MEASURE(S): Growth hormone levels before and after clonidine administration. RESULT(S): Delta GH and GH levels at 30, 60, and 120 minutes were significantly higher in the PCOS group than in the IH and control groups. CONCLUSION(S): The greater GH response to clonidine in nonobese normoinsulinemic PCOS patients observed in this study suggests a dysregulation in GH secretion in these patients. Further studies are required to elucidate the role of GH in the pathogenesis of PCOS and to investigate the existence of an association between androgens, IGF-I, and GH modulation in PCOS.