leptin and Sexual-Dysfunction--Physiological

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.

Topics: Animals; Atherosclerosis; Bone Density; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Hematocrit; Humans; Hypogonadism; Inflammation Mediators; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Models, Biological; Obesity; Prostatic Neoplasms; Sexual Dysfunction, Physiological; Testosterone

To evaluate serum leptin levels (an adipocyte hormone involved in the suppression of appetite) in patients with premature ejaculation before and after treatment with citalopram, a selective serotonin reuptake inhibitor, with the hypothesis that leptin levels might become normal during this treatment.. The inhibitory effect of serotonin on libido, ejaculation and orgasm is well documented. Although there is no direct evidence of an association involving brain pathways which are related to sexual behaviour, there is an interaction between leptinergic and serotonergic systems. In a previous study serum leptin levels were high in patients with premature ejaculation. The present study comprised 30 patients with premature ejaculation according to the Diagnostic and Statistical Manual of Mental Disorders Third Revised Version. Fifteen patients (group I) were randomly assigned to 8 weeks of citalopram treatment and the remainder (15, group II) received no therapy. The patients were asked to determine the average intravaginal ejaculation latency time, and their fasting serum leptin levels were measured at baseline and after 8 weeks.. There was no significant difference in the mean intravaginal ejaculation latency time between the groups at baseline; it increased after 8 weeks of treatment with citalopram in group I, to a mean (sd) of 209 (72.1) s, but not in group II. No difference was detected in leptin levels between the groups at baseline, but at 8 weeks they were lower in group I.. As hypothesized, leptin levels decreased in patients with premature ejaculation after treatment with citalopram, and this decrease seemed to be linked to the therapeutic effect. Further experimental studies are needed.

Topics: Adult; Biomarkers; Body Mass Index; Citalopram; Double-Blind Method; Ejaculation; Humans; Leptin; Male; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological

Proopiomelanocortin (POMC)-derived peptides like α-melanocyte-stimulating hormone (MSH) substantially improve hepatic insulin sensitivity and regulate energy expenditure. Melanocortinergic agents are also powerful inducers of sexual arousal that are being investigated for a possible therapeutic role in erectile dysfunction. It is currently unclear whether reduced melanocortin (MC) activity may contribute to the sexual dysfunction accompanying obesity and type 2 diabetes. Male rodents with leptin and insulin resistance targeted to POMC neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity, hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study, we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic alterations in sexual behavior. Remarkably, these reproductive changes are accompanied by decreased α-MSH production not present when a single receptor type is deleted. Unexpectedly, behavioral sensitivity to α-MSH and MC receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation of the MC system to altered α-MSH production. Together, these results suggest that concurrent insulin and leptin resistance in POMC neurons in individuals with obesity or type 2 diabetes can reduce endogenous α-MSH levels and impair sexual function.

Topics: Aggression; Animals; Insulin; Insulin Resistance; Leptin; Male; Melanocortins; Mice; Mice, Knockout; Neurons; Pro-Opiomelanocortin; Receptor, Insulin; Receptors, Leptin; Sexual Dysfunction, Physiological

Apart from energy homeostasis leptin has been shown to be involved in a number of neuronal networks. The aim of this study was to investigate how the residual variance of leptin levels, after controlling for BMI, is linked to eating-disorder-specific psychopathology and sexual desire in patients with anorexia nervosa (AN) compared to healthy controls. The sample included 57 subjects with acute AN and 77 healthy controls. Psychopathology was determined by EDI-2 and SCL-90-R and sexual problems were rated according to the Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX). Plasma leptin was assessed by ELISA. Patients with a high drive for thinness had lower leptin levels at a given BMI and low leptin levels were associated with sexual problems, i.e. the absence of sexual desire and intimate relationships. Our results are in accordance with recent animal experiments linking low leptin levels with decreased sexual interest irrespective of body weight.

Topics: Adolescent; Adult; Body Mass Index; Child; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Female; Humans; Leptin; Middle Aged; Models, Psychological; Psychopathology; Sexual Dysfunction, Physiological; Statistics, Nonparametric; Young Adult

Premature ejaculation (PE) is regarded as the most common male sexual disorder. To date, there is no accurate and objective diagnostic test for PE.. To determine the diagnostic value of serum leptin level for PE.. In a case-control design, the serum leptin level of 46 PE patients referred to our outpatient clinic were determined and compared with 44 control patients referred to the same clinic with the complaint of nephrolithiasis. PE was defined based on the Diagnostic and Statistical Manual of Mental Disorders IV criteria and an intravaginal ejaculatory latency time of less than a minute.. Serum leptin level and presence of PE.. The PE patients had significantly higher serum leptin levels (8.3+/-3 ng/mL) than the controls (3.3+/-1 ng/mL) (P<0.001). Sensitivity and specificity for the test as a predictive diagnostic tool for PE were 80.4% and 97.7%, respectively, at the cutoff value of 6.3 ng/mL.. According to our results, leptin level in patients with PE was significantly higher than in the control subjects. More studies are necessary to determine the value of serum leptin as a diagnostic tool for PE.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Ejaculation; Humans; Leptin; Male; Predictive Value of Tests; Reference Values; Sexual Dysfunction, Physiological