leptin and Hirsutism

Whatever the origin of severe insulin resistance (primary insulin receptors defects or lipodystrophies), in vivo hyperinsulinemia has been clearly shown to promote ovarian growth and androgen synthesis independently of gonadotropins. In lipodystrophic syndromes, the endocrine deficiency of adipose tissue has been shown to play important pathophysiological roles in metabolic alterations. In particular leptin is decreased, contributing to the ectopic lipid storage in non-adipose cells, which inhibits insulin signalling (lipotoxicity). Finally, polycystic ovary syndrome (PCOS) features are not always present in insulin resistance syndromes with lipodystrophy. This is in favour of an aggravating, but not a primary role of post-receptor insulin resistance on ovary dysfunctions.

Topics: Adipose Tissue; Female; Hirsutism; Humans; Insulin Resistance; Leptin; Lipodystrophy; Phenotype; Polycystic Ovary Syndrome; Receptor, Insulin

Hyperandrogenism in postmenopausal women is due to ovarian hyperthecosis or an androgen-secreting ovarian/adrenal tumor. Making the correct diagnosis might be complicated due to the possible existence of an adrenal neoplasm secreting testosterone only, ectopic ovarian tissue or ectopic luteinizing hormone/human chorionic gonadotropin receptors in the adrenals, as well as the relatively low sensitivity of imaging techniques (computed tomography, magnetic resonance imaging) and vein catheterization for this type of pathology. We present the case of an obese postmenopausal woman with metabolic syndrome, hyperandrogenism (high testosterone levels, suppressed gonadotropins), adrenal macronodular hyperplasia and Leydig-cell ovarian tumor. At presentation she had low leptin levels despite high body fat content. After a catheter study left adrenalectomy was carried out but hyperandrogenism persisted. Then, bilateral oophorectomy with hysterectomy was performed and a small Leydig-cell tumor was found in the left ovary. Postoperatively, testosterone and gonadotropin levels were normal (postmenopausal) and leptin level became elevated without change in body mass index or body fat content. In conclusion, we speculate that low leptin levels in obese hyperandrogenic women might be a marker for androgen-secreting tumors.

Topics: Adrenal Glands; Alopecia; Biomarkers; Female; Hirsutism; Humans; Hyperandrogenism; Hyperplasia; Leptin; Leydig Cell Tumor; Metabolic Syndrome; Middle Aged; Obesity; Ovarian Neoplasms

Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels.. Adiponectin and ghrelin levels were evaluated in 51 hirsute PCOS patients referred to the outpatient clinic of an academic, tertiary care medical centre and in 63 weight-matched female controls. Relationships between adiponectin, ghrelin, leptin, body composition, testosterone and insulin were examined.. Measurements of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase.. Adiponectin levels were significantly decreased in obese PCOS patients compared with weight-matched controls (geometric mean (-2 to 2 s.d.) 5.3 (2.5-11.1) vs 7.3 (3.0-17.4) mg/l, P<0.05). Mean ghrelin was significantly lower in hirsute PCOS patients than in controls (0.6 (0.3 to 1.4) vs 0.8 (0.4 to 1.7) microg/l, P<0.001) and this remained significant after subdividing subjects according to waist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass.. Obese hirsute PCOS patients demonstrated significantly lower adiponectin levels than weight-matched controls suggesting a very high risk for the metabolic syndrome. Furthermore, ghrelin levels were decreased in hirsute PCOS patients and showed a significant, negative correlation with testosterone independent of body composition.

Topics: Absorptiometry, Photon; Adiponectin; Biomarkers; Body Constitution; Body Mass Index; Female; Ghrelin; Hirsutism; Homeostasis; Humans; Insulin; Leptin; Metabolic Syndrome; Peptide Hormones; Polycystic Ovary Syndrome; Regression Analysis; Risk Factors; Testosterone; Waist-Hip Ratio

Topics: 1-Acylglycerol-3-Phosphate O-Acyltransferase; Acanthosis Nigricans; Acyltransferases; Adipose Tissue; Adult; Diabetes Mellitus, Type 2; Fatty Liver; Female; Hirsutism; Humans; Hyperphagia; Hypertriglyceridemia; Insulin Resistance; Leptin; Lipodystrophy; Menstruation Disturbances

Our aim was to investigate whether insulin sensitivity, leptin, androgen or estradiol levels are associated with disturbed GH response to clonidine in lean patients with polycystic ovary syndrome. Fourteen lean polycystic ovary syndrome patients, 11 ovulatory patients presenting idiopathic hirsutism and 10 non-hirsute, normal women with regular cycles paired for age and BMI were included in a cross-sectional study. Baseline hormonal and metabolic variables were assessed and analyzed in association with GH response to oral administration of 0.3 mg of clonidine. Delta GH was significantly higher in the PCOS group than in the IH and control groups (p = 0.014). The groups were similar in terms of body mass index, insulin, glucose, total and HDL cholesterol, triglycerides and estradiol levels. Free androgen index (r = 0. 454, p = 0.015) and leptin (r = 0.419, p = 0.023) were positively correlated with the homeostasis model assessment. The homeostasis model assessment was the only variable that significantly correlated with GH response to clonidine (r = 0.375, p = 0.029) (vs. estradiol, free androgen index, leptin and LH). Nonetheless, when the analysis was adjusted for leptin levels and free androgen index, the statistical significance of this correlation was lost. The increased GH secretion observed in our lean PCOS patients may be associated with slight changes in insulin sensitivity, even in the absence of clinical evidence of insulin resistance. This association seems to be modulated by leptin and androgen levels.

Topics: Adrenergic alpha-Agonists; Adult; Androgens; Body Mass Index; Clonidine; Dose-Response Relationship, Drug; Female; Growth Hormone; Hirsutism; Humans; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome

Polycystic ovary syndrome is considered to originate during puberty. The aim of this study was to investigate hormonal status in relationship to anthropometric data in girls with premature adrenarche and adolescent girls with hyperandrogenism, as these conditions are related to polycystic ovary syndrome in adulthood.. 20 girls with premature adrenarche (aged 4.9-10.2 years), 21 postmenarcheal girls with hirsutism (aged 13.3-17.8 years), 2 groups (n=13 in each) of healthy volunteers of similar age and body mass index participated in the study.. Serum testosterone and dehydroepiandrosterone sulphate levels were significantly higher in all patients than in controls. Free androgen index and leptin levels were significantly higher, and sex-hormone-binding globulin lower in hirsute adolescents vs. controls. Birth weight standard deviation scores were comparable in all 4 groups. Serum dehydroepiandrosterone sulphate negatively correlated with birth weight standard deviation scores in the group of girls with premature adrenarche (r=-0.57, p<0.001). By linear regression, 76% in variation of serum leptin levels could be explained by subscapular skinfold thickness standard deviation scores, and by serum sex-hormone-binding globulin, insulin, and dehydroepiandrosterone sulphate levels in all participants. Mean age of onset of menarche was younger in hirsute girls vs. controls (12.1+/-1.3 vs. 13.5+/-1.3 years, p=0.004).. Inverse correlation of dehydroepiandrosterone sulphate levels and weight at birth indicates relationship between premature adrenarche in girls and fetal growth. Higher leptin levels in adolescents with hyperandrogenism than in healthy girls show possible involvement of leptin in pathogenesis of hyperandrogenism.

Topics: Adolescent; Age Factors; Birth Weight; Body Height; Body Mass Index; Body Weight; Child; Child, Preschool; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Hyperandrogenism; Insulin; Leptin; Linear Models; Menarche; Polycystic Ovary Syndrome; Puberty, Precocious; Risk Factors; Testosterone

The known association between leptin, obesity and insulin action suggests that leptin may have a role in polycystic ovarian syndrome (PCOS) but this has only been addressed peripherally.. We assessed the influence of leptin on LH and investigated the relationship between leptin and body mass index (BMI), waist:hip ratio (WHR), androgen concentrations, fasting insulin and insulin:glucose ratio (IGR) in 27 women with PCOS and in 20 age- and weight-matched women with regular, ovulatory menstrual cycles and idiopathic hirsutism (IH).. Leptin concentrations were significantly higher in obese PCOS women than in normal weight women with either PCOS or IH (P = 0.0028), but did not differ between obese women with PCOS and IH. WHR, insulin concentrations and IGR were significantly higher in obese PCOS patients in comparison with the three other groups. In IH patients, the association between leptin concentrations and WHR was lost after adjustment for BMI. In PCOS patients, a significant correlation was observed between leptin and fasting insulin concentrations, IGR, WHR and LH. After adjustment for BMI, only the correlation with LH remained significant. A stepwise regression model was set up with LH as the dependent variable to test the hypothesis that the concentrations of leptin might be modulating the concentrations of LH in PCOS patients. The relationship of LH concentrations with IGR was found to be BMI dependent. In contrast, leptin concentrations contributed negatively and significantly to LH concentrations, independently of either BMI or IGR.. We speculate that the known attenuation in basal or stimulated response of LH in obese PCOS patients might be related to leptin resistance, which could influence LH hypersecretion. In IH ovulatory patients, normal LH concentrations suggest the presence of preserved regulatory mechanisms of GnRH pulsatility. Further studies are needed to specifically investigate the proposed correlation between leptin and GnRH modulation in PCOS.

Topics: Adolescent; Adult; Androgens; Blood Glucose; Body Constitution; Body Mass Index; Fasting; Female; Hirsutism; Humans; Insulin; Leptin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Regression Analysis

To evaluate serum leptin concentrations in hirsute women.. Controlled clinical study.. Tertiary institutional hospital.. Thirty-three hirsute women and 11 healthy female controls.. Serum samples were obtained at baseline and on day 1 (gonadal stimulation) and day 21 (gonadal suppression) after the IM injection of a single 3.75-mg dose of triptorelin.. Leptin, T, sex hormone-binding globulin (SHBG), insulin, and glucose levels and free androgen index.. Leptin levels were increased in hirsute women in comparison with control subjects at baseline and on day 1. Leptin levels increased on day 1 compared with baseline and then decreased to baseline by day 21. Leptin levels correlated with body mass index (r = 0.76), SHBG levels (r = -0.52), free androgen index (r = 0.38), insulin levels (r = 0.46), and the glucose/insulin ratio (r = -0.38). When the effect of obesity on these results was removed by analysis of covariance and partial correlation analysis, leptin levels remained elevated only on day 1 and the only correlations that remained significant were those of leptin with insulin (r = 0.24) and the glucose/insulin ratio (r = -0.24).. The increased leptin levels found in hirsute women are related mainly to obesity and also to insulin resistance. Leptin levels increased during gonadal stimulation and returned to baseline during gonadal suppression, suggesting that leptin also is influenced by the gonadal axis.

Topics: Adrenocorticotropic Hormone; Adult; Body Mass Index; Estradiol; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Leptin; Luteinizing Hormone; Obesity; Proteins; Reference Values; Sex Hormone-Binding Globulin; Testosterone; Triptorelin Pamoate