leptin and Polycystic-Ovary-Syndrome

Polycystic ovarian syndrome (PCOS) affects 5-20% of females and is the most common cause of anovulatory infertility. Leptin seems to have an important role in reproduction. Many reproductive pathologies such as preeclampsia, PCOS, and endometriosis are associated to plasma adiponectin levels. Kisspeptin levels are increased in PCOS women.. A review of the literature was completed through the PubMed database aiming to find articles regarding leptin, adiponectin and kisspeptin and if they are related to PCOS pathogenesis.. Even today it is not clear what is the role of leptin in women with PCOS, although most of the researchers found increased levels of leptin as well as leptin resistance in PCOS (both obese and lean individuals). Many more longitudinal studies should be done to discover the usefulness of measuring adiponectin in prepubertal women who apparently have a possibility to develop PCOS to find out if they finally develop PCOS. Most of the researchers found that PCOS women have decreased levels of adiponectin unrelated to BMI levels. Nevertheless, not all studies had the same result. Moreover, it is necessary more studies to be made to investigate the connection between kisspeptin and other metabolic factors such as LH and insulin resistance.. In general, it remains inconclusive whether leptin, adiponectin, and kisspeptin can be used as clinical and/or biochemical markers of PCOS. Therefore, it is essential to review the current data with regards to the association between PCOS and circulating leptin, adiponectin, and kisspeptin in women with PCOS.

Topics: Adiponectin; Female; Humans; Kisspeptins; Leptin; Obesity; Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common cause of female endocrine infertility. Insulin resistanсе is supposed to be one of the essential factors of this disease pathways. At the same time, the mechanisms of PCOS development in insulin-resistant patients have not been completely established. Leptin and Peroxisome Proliferator-Activated Receptor γ(PPARγ) are involved in carbohydrate metabolism and reproduction function regulation. It indicates that leptin and PPARγ possibly play a role in the pathways of PCOS. This article is a review of publications on this issue. The purpose of this review was to systematize the available information on the molecular mechanisms that determine the role of leptin and PPARγ in the development of PCOS. The literature search was carried out from 04/05/2020 to 05/17/2020 using the scientific literature databases: NCBI PubMed (foreign sources) and Cyberleninka (domestic sources). We analyzed publications for the period 1990-2020.The review presents the current understanding of the possible role of leptin and PPARγ in the regulation of endocrine, immune systems, and reproductive function, as well as in the development of PCOS. Currently, no studies cover the mechanisms of interaction between leptin and PPARγ in the pathways of this syndrome. The available studies indicating the individual contribution and association of leptin and PPARγ with PCOS are conflicting and have many limitations. Therefore, more studies of direct and indirect interaction of leptin and PPARγ, as well as their role in PCOS pathways, are needed.

Topics: Female; Humans; Infertility, Female; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; PPAR gamma

Several peripheral and central signals are involved in the sophisticated regulation of food intake. Women with polycystic ovary syndrome (PCOS) are prone to consume a diet higher in saturated fat and foods with high glycemic index and show impaired appetite regulation and measures of satiety. As a consequence, obesity, mostly of the central type, is prevalent in the syndrome and worsens the endocrine and metabolic profile of the affected patients. This review article briefly analyzes the current knowledge about the neuroendocrine mechanisms underlying the interplay between feeding behavior, obesity, and reproductive abnormalities in PCOS.

Topics: Animals; Appetite Regulation; Female; Ghrelin; Humans; Insulin; Leptin; Neurosecretory Systems; Obesity; Polycystic Ovary Syndrome

This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents re

Topics: Adolescent; Blood Glucose; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Metabolic Diseases; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

Conflicting results regarding leptin levels in women with polycystic ovary syndrome (PCOS) have been reported. We summarize all available evidence from human participant studies to evaluate leptin levels in PCOS.. PubMed, ClinicalTrials.gov , and Web of Science databases were searched with English-language restriction for only human beings from the inception to December 31, 2015. Search terms included PCOS (polycystic ovary syndrome or PCOS) and leptin.. A total of 238 studies were reviewed, and a total of 19 studies, involving 991 women with PCOS and 898 controls, were eligible for our meta-analysis. Studies were eligible if provided leptin means and standard deviation in women with PCOS and healthy women controls.. Parameters, such as body mass index, insulin resistance (IR), and total testosterone, which may influence leptin levels were extracted. Data were collected and analyzed by RevMan 5.3 and Stata/SE14.0. The pooling analysis of all relevant studies revealed that leptin levels were significantly higher in patients with PCOS than in controls, with standardized mean difference of 1.62 (95% confidence interval: 1.01-2.23). However, the heterogeneity across studies was considerable and not eliminated in subgroup analyses. Meta-regression analysis further suggested that the heterogeneity might be relevant to variability in IR and study location.. Elevated leptin levels are detected in women with PCOS compared with non-PCOS controls. Higher leptin levels may be correlated with IR, metabolic disorder, infertility, and even cardiovascular disease risk in PCOS, which may contribute to the etiology and development of PCOS.

Topics: Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Risk Factors; Testosterone

As an essential function for perpetuation of species, reproduction, including puberty onset, is sensitive to the size of body energy stores and the metabolic state of the organism. Accordingly, impaired energy homeostasis, ranging from extreme leanness, such as in anorexia or cachexia, to morbid obesity has an impact on the timing of puberty and is often associated to fertility problems. The neuroendocrine basis for such phenomenon is the close connection between numerous metabolic hormones and nutritional cues with the various elements of the so-called hypothalamic-pituitary-gonadal (HPG) axis. Yet, despite previous fragmentary knowledge, it was only the discovery of the adipose-hormone, leptin, in 1994 what revolutionized our understanding on how metabolic and reproductive systems closely interplay and allowed the definition of the neurohormonal causes of perturbations of puberty and fertility in conditions of impaired body energy homeostasis. In this article, we aim to provide a synoptic view of the mechanisms whereby leptin engages in the regulation of different elements of the HPG axis, with special attention to its effects and mechanisms of action on the different elements of the reproductive brain and its proven direct effects in the gonads. In addition, we will summarize the state-of-the-art regarding the putative roles of leptin during gestation, including its potential function as placental hormone. Finally, comments will be made on the eventual leptin alterations in reproductive disorders, with special attention to the polycystic ovary syndrome (PCOS), a disease in which reproductive, metabolic and neuroendocrine alterations are commonly observed. All in all, we intend to provide an updated account of our knowledge on the physiological roles of leptin in the metabolic regulation of the reproductive axis and its eventual pathophysiological implications in prevalent reproductive disorders, such as PCOS.

Topics: Animals; Female; Humans; Leptin; Neurosecretory Systems; Polycystic Ovary Syndrome; Pregnancy; Reproduction

Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported. To provide high-quality evidence about the effect of metformin treatment on adipocytokines in patients with polycystic ovary syndrome, relevant studies that assessed the levels of adipocytokines (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving treatment with metformin administration were reviewed and analyzed.. A literature search was conducted in the SCI, PUBMED, EMBASE, and Elsevier databases, and personal contact was made with the authors. Standard mean differences and 95% confidence intervals were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed.. A total of 34 data sets were included in 4 different outcomes, involving 744 women with polycystic ovary syndrome and adipocytokine levels measured both before and after metformin administration. Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], -0.43 [-0.75 to -0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (-0.01 [-0.49 to 0.45]) or visfatin level (-0.04 [-1.55 to 1.46]) was found.. Metformin administration was associated with increased serum adiponectin concentrations and decreased serum leptin levels. Further study is needed to elucidate whether this apparent effect decreases the incidence of type 2 diabetes and other metabolic diseases in patients with polycystic ovary syndrome later in life.

Topics: Adiponectin; Cytokines; Female; Gene Expression Regulation; Humans; Leptin; Metformin; Nicotinamide Phosphoribosyltransferase; Polycystic Ovary Syndrome; Resistin; Treatment Outcome

Follicle wall rupture and ovum release, i.e., ovulation, has been described as a controlled inflammatory event. The process involves tissue remodeling achieved through leukocyte-mediated proteolysis. In birds, ovulation is the first step in the energy-intensive process of egg formation, yet hens that consume energy in excess of productive requirements experience impaired egg-laying ability. Broiler chickens, selected for rapid lean muscle gain, and coincidentally hyperphagia, develop adult obesity when given free access to feed. Obese broiler hens experience elevated circulating concentrations of insulin and leptin, changes in lipid and lipoprotein metabolism similar to those of human metabolic syndrome, as well as increased systemic inflammation. Overall, the manifestations in poultry are similar to those of women with polycystic ovary syndrome. It was shown recently that, in hens, as in mammals, changes in lipid synthesis and metabolism cause granulosa cell apoptosis and altered immune function and hormone production, further compromising ovarian function. To date, there is insufficient information on the means used by the ovary to direct leukocyte function toward successful ovulation. More information is needed regarding the control of proteolytic actions by leukocytes with regards to the roles of specific enzymes in both ovulation and atresia. The broiler hen has provided unique insight into the interrelations of energy intake, obesity, leukocyte function, and reproduction. Additional work with this model can serve the dual purposes of improving avian reproduction and providing novel insights into polycystic ovary syndrome in women.

Topics: Animals; Body Weight; Chickens; Disease Models, Animal; Energy Intake; Female; Humans; Insulin; Leptin; Mammals; Obesity; Ovary; Oviposition; Polycystic Ovary Syndrome; Reproduction

The complex mechanisms linking fat excess to metabolic syndrome are not well understood, but several experimental studies have shown that altered production of adipokines plays a main role in development and progression of this disorder. In particular, reduced secretion of adiponectin has a crucial role in inducing insulin resistance but also in determining the clustering of elevated triglycerides and small, dense LDL particles. Increased leptin secretion may be responsible for sympathetic nervous system overactivity and hypertension, while reduced omentin may have an important permissive role in the development of atherogenic processes. Finally, cytokines and other adipokines (resistin, visfatin) determine and modulate the inflammatory process that is an essential component of this condition of cardiovascular risk. Because obesity is prevalent in polycystic ovary syndrome (PCOS), it is not surprising that patients with PCOS present altered adipokine levels and increased prevalence of metabolic syndrome. However, because of the presence of other CV risk factors (androgen excess), in PCOS adipokine dysfunction is particularly severe. Understanding and treating adipokine dysfunction in young women with PCOS is an essential component of any politics of prevention of CV diseases in the general population.

Topics: Abdominal Fat; Adipokines; Adiponectin; Androgens; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Risk Factors

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Dysfunction of adipose tissue has been implicated in the pathophysiology of PCOS. Increasing evidence shows that the dysregulated expression of adipokines, the secreted products of adipose tissue, plays an important role in the pathology of PCOS. Here, we review the role of several identified adipokines that may act as a link between obesity and PCOS. PCOS also reciprocally influences the profile of adipokines. Insight into the underlying mechanisms will help better understand the pathology of PCOS and identify new therapeutic targets of this syndrome.

Topics: Acute-Phase Proteins; Adipokines; Chemokines; Cytokines; Female; GPI-Linked Proteins; Humans; Intercellular Signaling Peptides and Proteins; Lectins; Leptin; Lipocalin-2; Lipocalins; Nicotinamide Phosphoribosyltransferase; Obesity; Polycystic Ovary Syndrome; Proto-Oncogene Proteins; Resistin; Retinol-Binding Proteins, Plasma

Polycystic ovary syndrome (PCOS) is the most frequent female endocrine disorder, affecting 5%-10% of women, causing infertility due to dysfunctional follicular maturation and ovulation, distinctive multicystic ovaries and hyperandrogenism, together with metabolic abnormalities including obesity, hyperinsulinism, an increased risk of type 2 diabetes, and cardiovascular disease. The etiology of PCOS is unclear, and decisive clinical studies are limited by ethical and logistic constraints. Consequently treatment is palliative rather than curative and focuses on symptomatic approaches. Hence, a suitable animal model could provide a valuable means with which to study the pathogenesis of the characteristic reproductive and metabolic abnormalities and thereby identify novel and more effective treatments. So far there is no consensus on the best experimental animal model, which should ideally reproduce the key features associated with human PCOS. The prenatally androgenized rhesus monkey displays many characteristics of the human condition, including hyperandrogenism, anovulation, polycystic ovaries, increased adiposity, and insulin insensitivity. However, the high cost of nonhuman primate studies limits the practical utility of these large-animal models. Rodent models, on the other hand, are inexpensive, provide well-characterized and stable genetic backgrounds readily accessible for targeted genetic manipulation, and shorter reproductive life spans and generation times. Recent rodent models display both reproductive and metabolic disturbances associated with human PCOS. This review aimed to evaluate the rodent models reported to identify the advantages and disadvantages of the distinct rodent models used to investigate this complex endocrine disorder.

Topics: Androgens; Animals; Aromatase Inhibitors; Disease Models, Animal; Estrogens; Female; Humans; Leptin; Luteinizing Hormone; Mice; Mutation; Obesity; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Progestins; Rats; Receptors, Leptin

Women with mood disorders, especially bipolar disorder (BD), have been shown to have high rates of reproductive and metabolic dysfunction. The available data on the functional, anatomic, and clinical neuroendocrine abnormalities in women with BD suggest a two-tiered relationship with mood pathology. First, many of the medications commonly used in the treatment of BD can have deleterious effects on blood levels of reproductive hormones and consequently on the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. Studies that have specifically addressed the association between psychotropic medications and menstrual abnormalities, polycystic ovary syndrome, and overall reproductive endocrine function in women with BD have found high rates of HPG irregularities in women with BD. Second, there is evidence of reproductive dysfunction in women with BD prior to treatment. In addition, many of the psychotropic medications used in the treatment of BD are associated with weight gain, insulin resistance, and dyslipidemia. These metabolic side effects further compound the neuroendocrine system dysregulation in women with BD. Current understanding of the reproductive and metabolic function in women with BD points to vulnerability, which in turn increases the risk of later-life cardiovascular disease and diabetes, among other morbidities, for women with BD.

Topics: Bipolar Disorder; Dyslipidemias; Endocrine System Diseases; Female; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Lithium Carbonate; Menstruation; Obesity; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Psychotropic Drugs; Valproic Acid

Obesity is the most serious long-term health risk currently facing America's adolescents. Weight gain during adolescence carries a higher risk for adult obesity and the metabolic syndrome. This review highlights early adolescence as a particularly high-risk time for weight gain due to the synergy of naturally occurring metabolic changes along with increasing behavioral risk factors. One of the first potential health effects of abnormal weight gain during this period is earlier puberty, usually manifested as thelarche. The obesity epidemic is clearly implicated in the national trend toward earlier thelarche, although the data are not as strong in relation to menarche. Leptin activation of the hypothalamic-pituitary axis, combined with insulin resistance, and increased adiposity may result in the higher estrogen levels that are linked to breast development. Young adolescents also experience a sharp decline in their level of physical activity, worsening nutritional habits, and other important psychosocial and developmental risk factors that may contribute to obesity and estrogen-dependent disease in later life, including polycystic ovary syndrome and breast cancer. Unfortunately, the very psychosocial factors that contribute to abnormal weight gain during early adolescence make prevention and treatment in this population particularly challenging. Therefore, intervening prior to pubertal onset becomes even more important given the risk factors present once puberty begins.

Topics: Adolescent; Adult; Breast Neoplasms; Estrogens; Female; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Puberty; Risk Factors; Weight Gain

Despite the early recognition of the strong association between obstructive sleep apnoea (OSA) and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a "local abnormality" of the respiratory track rather than as a "systemic illness". In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. In subsequent studies, it was shown that IL-6, TNFalpha, and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat was the primary parameter linked with sleep apnoea. Further studies showed that women with the polycystic ovary syndrome (PCOS) were much more likely than controls to have sleep-disordered breathing (SDB) and daytime sleepiness, suggesting a pathogenetic role of insulin resistance in OSA. Additional accumulated evidence that supports the role of obesity and the associated metabolic aberrations in the pathogenesis of sleep apnoea and related symptoms include: obesity without sleep apnoea is associated with daytime sleepiness; the protective role of gonadal hormones as suggested by the increased prevalence of sleep apnoea in post-menopausal women and the significantly reduced risk for OSA in women on hormonal therapy; partial effects of continuous positive airway pressure (CPAP) in obese patients with apnoea on hypercytokinemia, insulin resistance indices, and visceral fat; and that the prevalence of the metabolic syndrome in the U.S. population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnoea in general random samples. Furthermore, the beneficial effect of a cytokine antagonist on EDS and apnoea in obese, male apnoeics and that of exercise and weight loss on SDB and EDS in general random or clinical samples, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnoea in humans. Finally, our recent finding that in obese, hypothalamic CRH neuron is hypoactive, provides additional evidence on the potential central neural mechanisms for depressed ventilation and consequent development of sleep apnoea in obese individuals. In conclusion, accumulating evidence provides support to our thesis that obesity via inflammation, insulin resistance, visceral adiposity, and

Topics: Adiposity; Female; Humans; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Models, Biological; Obesity; Polycystic Ovary Syndrome; Sleep Apnea Syndromes

Polycystic ovarian syndrome (PCOS) is the most common cause of functional infertility. It concerns 5-10% women of reproductive age. PCOS is connected with many clinical symptoms, mostly menstrual disorders like oligomenorrhoea with chronic anovulation. In laboratory assays hyperandrogenism is found. In some patients also metabolic disturbances like insulin resistance, hyperinsulinemia, dyslipidemy, and hyperleptinemia are found. Ultrasound characteristic features polycystic ovaries. In 2003 on Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Meeting new PCOS criteria were defined. Recent studies revealed that increased leptin concentration is characteristic for PCOS patients. It can be connected with coexistence of impaired glucose tolerance and obesity, nevertheless still more studies concerning role of leptin in PCOS pathogenesis are needed.

Topics: Female; Humans; Leptin; Polycystic Ovary Syndrome

Obesity is associated with several endocrine diseases, including common ones such as hypothyroidism and polycystic ovarian syndrome to rare ones such as Cushing's syndrome, central hypothyroidism and hypothalamic disorders. The mechanisms for the development of obesity vary in according to the endocrine condition. Hypothyroidism is associated with accumulation of hyaluronic acid within various tissues, additional fluid retention due to reduced cardiac output and reduced thermogenesis. The pathophysiology of obesity associated with polycystic ovarian syndrome remains complex as obesity itself may simultaneously be the cause and the effect of the syndrome. Net excess of androgen appears to be pivotal in the development of central obesity. In Cushing's syndrome, an interaction with thyroid and growth hormones plays an important role in addition to an increased adipocyte differentiation and adipogenesis. This review also describes remaining rare cases: hypothalamic obesity due to central hypothyroidism and combined hormone deficiencies.

Topics: Catecholamines; Cushing Syndrome; Endocrine System Diseases; Female; Glucocorticoids; Humans; Hypothalamic Diseases; Hypothyroidism; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Thyroid Function Tests; Triiodothyronine

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

Abdominal adiposity, overweightness and obesity are frequently present in patients with polycystic ovary syndrome (PCOS). A large body of evidence suggests that abdominal adiposity and the resulting insulin resistance contribute to ovarian and, possibly, adrenal hyperandrogenism. However, androgen excess itself might also contribute to abdominal fat deposition in hyperandrogenic women. Recent genomic and proteomic analyses of visceral fat from PCOS patients have detected differences in gene expression and protein content compared with those of non-hyperandrogenic women. Here we review the existing evidence for a vicious circle whereby androgen excess favoring the abdominal deposition of fat further facilitates androgen secretion by the ovaries and adrenals in PCOS patients.

Topics: Abdominal Fat; Adiposity; Female; Humans; Hyperandrogenism; Hyperinsulinism; Insulin Resistance; Leptin; Models, Biological; Polycystic Ovary Syndrome

Leptin, a key hormone in energy homeostasis and neuroendocrine function, has a permissive role in initiating puberty and is crucial in the pathogenesis of reproductive dysfunction in several disease states of energy imbalance. KiSS1 neurons have recently been suggested to mediate leptin's effect on the reproductive system. New insights from recent animal studies and clinical trials are discussed.. Alterations in the expression profile of the KiSS1 gene and the kisspeptin receptor have been linked to reproductive dysfunction in leptin-deficient states. Neuroendocrine, including reproductive, dysfunction can be restored in humans and animals by leptin-replacement therapy. These insights have significantly advanced our understanding of hormonal systems needed to maintain normal reproduction. These data, if confirmed, also suggest a role for leptin as a novel therapeutic approach in several disease states.. Recent proof-of-concept studies involving leptin administration to humans underline the critical role of leptin not only in regulating energy homeostasis, but also in maintaining normal reproductive function. Leptin-replacement therapy is currently under intensive investigation as a potential novel therapeutic option for several conditions associated with reproductive dysfunction due to hypoleptinemia.

Topics: Amenorrhea; Animals; Anorexia Nervosa; Energy Metabolism; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Infertility; Kisspeptins; Leptin; Male; Menarche; Obesity; Polycystic Ovary Syndrome; Puberty; Reproduction; Sex Characteristics; Tumor Suppressor Proteins

Obese women are characterized by similar comorbidities to men, particularly type 2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some specific problems, including fertility-related disorders and some hormone-dependent forms of cancer. The relationship between excess body fat and reproductive disturbances appears to be stronger for early-onset obesity. Early onset of obesity, particularly during adolescence, favours the development of menses irregularities, chronic oligo-anovulation and infertility in adulthood. Moreover, obesity in women can increase the risk of miscarriage and impair the outcome of assisted reproductive technologies. The main factor implicated in the association between obesity and fertility-related disorders is insulin excess, which accompanies insulin resistance. Hyperinsulinaemia may be directly responsible for the development of androgen excess, through its effects in reducing sex hormone-binding globulin synthesis and circulating concentrations, and in stimulating ovarian androgen production rates. Androgen excess, in turn, represents one of the major factors leading to altered ovarian physiology and associated ovulatory disturbances. Obesity-associated hyperleptinaemia may represent an additional factor involved in anovulation, not only through the induction of insulin resistance, but also through a direct impairment of ovarian function.

Topics: Androgens; Animals; Female; Humans; Hyperinsulinism; Infertility, Female; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Reproduction

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.

Topics: Adipose Tissue; Adult; Cannabinoid Receptor Modulators; Female; Humans; Hyperandrogenism; Infertility, Female; Insulin Resistance; Leptin; Male; Menstruation Disturbances; Obesity; Phenotype; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects

Leptin is a protein hormone synthesized and secreted by adipose tissue and also probably in other organs and systems in human body. It has multiple functions such as to regulate feed intake and energy balance, gonadal regulation, action in the hypothalamo-pituitary-gonadal axis, regulates the metabolism of the fetal-placental unit in the pregnancy, fertility and reproductive systems, actions in the endometrium, mammary gland with corresponding influences on important physiologic processes such as menstruation, pregnancy and lactation. In the gynecologic surgery the serum leptin concentration is also modified. The knowledge of serum leptin concentration in the oncological diseases is going-up. Leptin is modified in the choriocarcinoma, Meigs' syndrome and other tumors. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with abnormalities of fetal maturity and development, general concept growth, trophoblast endocrinology, and placental sufficiency. Further investigations in this area will be necessary to improve new knowledge and a better understanding of the actions about this hormone.

Topics: Energy Metabolism; Female; Fertility; Fetal Diseases; Fetal Organ Maturity; Genital Diseases, Female; Humans; Hydatidiform Mole; Hypothalamo-Hypophyseal System; Leptin; Meigs Syndrome; Placenta; Polycystic Ovary Syndrome; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Receptors, Leptin; Reproduction; Uterine Neoplasms

The metabolic syndrome, an emerging public health problem, represents a constellation of cardiovascular risk factors. It has been suggested that the presence of obstructive sleep apnea (OSA) may increase the risk of developing some of the features of the metabolic syndrome, including hypertension, insulin resistance, and type 2 diabetes. In this article, we discuss the parallels between the metabolic syndrome and obstructive sleep apnea and describe possible OSA-related factors that may contribute to the metabolic syndrome, specifically the roles of obesity, hypertension, dyslipidemia, sex hormones, inflammation, vascular dysfunction, leptin, insulin resistance, and sleep deprivation.

Topics: Female; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Risk Factors; Sleep Apnea, Obstructive

Topics: Adrenal Glands; Adult; Androgens; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hydrocortisone; Insulin Resistance; Leptin; Luteinizing Hormone; Ovary; Pituitary Gland; Polycystic Ovary Syndrome

The relationship between metabolism and reproduction remains a mystery in female endocrinology. Such substances as insulin, amino acids and IGFBP-I have been proposed as signals of body mass fat on the genital axis. Today this role is claimed by leptin, a protein hormone decoded from the obesity gene and is secreted exclusively from adipose tissue. This hormone acts on the central nervous system (CNS) to result in the suppression of food intake and increase in energy consumption. What is more, it also influences the capacity for reproduction. This paper reports findings with regard to the factors influencing the secretion of leptin and identification of the leptin's hormonal receptors. Particular emphasis was placed on the relationship between secretion of leptin and disturbances in menstruation, the anticipated role of this hormone in the pathogenesis of the polycystic ovarian syndrome (PCOS) and its effects on the reproductive capacity.

Topics: Adipose Tissue; Animals; Female; Fertility; Humans; Leptin; Male; Menstrual Cycle; Mice; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Receptors, Cell Surface; Receptors, Leptin

The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity. Here we will summarize the data supporting the effect of metformin on improving hyperandrogenaemia and hyperinsulinaemia in PCOS patients. We propose that metformin benefits PCOS patients undergoing gonadotrophin therapy and IVF as well as ovulation induction. We also advocate the use of insulin sensitizing drugs to reduce miscarriage rates, and risks associated with coronary artery disease, gestational diabetes and obesity.

Topics: Androgens; Cardiovascular Diseases; Female; Fertilization in Vitro; Gonadotropins; Humans; Hypoglycemic Agents; Infertility, Female; Insulin; Insulin Resistance; Leptin; Menstrual Cycle; Metformin; Ovulation Induction; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome

Leptin participates in regulation of ovarian folliculogenesis indirectly via control of luteinizing hormone and follicle-stimulating hormone secretion. More recent evidence suggests that leptin also has direct regulatory actions on the developing follicle. The presence of leptin receptors on follicular cells, including oocytes, and early preimplantation embryos suggests that leptin may play a direct physiologic role in follicular maturation, oocyte development, and early cleavage. Because circulating leptin levels are directly related to body adiposity, elevated leptin concentrations associated with obesity may partly explain the negative impact of obesity on fertility. The influence of leptin on follicular development and oocyte maturation has important implications for ovulation induction and assisted reproductive technologies. Moreover, polycystic ovarian syndrome may be associated with altered leptin phsyiology.

Topics: Female; Gonadotropins; Humans; Leptin; Menstrual Cycle; Ovarian Follicle; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Reproductive Techniques, Assisted; Treatment Outcome

The reproductive activity is closely related to the nutritional status of the organism. A new hormone--leptin has been discovered a few years ago, which informs the brain about fat supplies in the body. Leptin participates in the regulation of the reproductive system at both, peripheral and central, levels. There are discussions about leptin as a possible trigger of puberty. The prepubertal leptin levels are low in both sexes; they increase with the onset of puberty. It has been suggested that leptin resistance might exist in the childhood, allowing the onset of the puberty only at the moment, when the adipose stores are adequate for the strongly demanding period of the adolescence. The role of leptin in pathogenesis of polycystic ovary syndrome (PCOS) is studied. The significance of leptin during pregnancy and after birth remains still unclear.

Topics: Body Weight; Female; Humans; Leptin; Male; Polycystic Ovary Syndrome; Puberty; Reproduction

An established fact in the polycystic ovarian syndrome (POS) is an abnormal ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the syndrome could also be influenced by factors outside the ovaries. Although of unknown etiology, the POS is one of the most frequent endocrine disorders in the gynecologic practice. The disorder is characterized by ultrasound findings of enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and including the appearance of infertility. There are a series of mechanisms involved in the extraovarian androgen increase in patients with POS. Among these mechanisms are implicated those of central and peripheral origin, genetic factors and adrenocortical dysfunction. In the same way, the alterations produced could imply genetic, molecular biological, biochemical, physiological and endocrinological factors. Sometimes all these factors could interact at the same time. The high serum androgen level could stop the pituitary gonadotropin production, either as a direct mechanism or as a result of its peripheral conversion. The increased androgens also explain the manifestations of clinical acne, hirsutism, and the detention in follicular ovarian maturation. All these manifestations are related with the menstrual disorders, anovulation, and infertility that these patients develop. The characteristics of the extraovarian POS include the 17-hydroxyprogesterone elevation in response to the ACTH test and the dexamethasone suppression of adrenal androgens. It is possible to improve the ovarian function in some patients with POS. This could be achieved with clomiphene citrate associated with glucocorticoids to induce ovulation.

Topics: 11-beta-Hydroxysteroid Dehydrogenases; 17-alpha-Hydroxyprogesterone; 3-Hydroxysteroid Dehydrogenases; Adrenal Cortex; Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Androgens; Catecholamines; Clomiphene; Corticotropin-Releasing Hormone; Cortisone; Dexamethasone; Female; Glucocorticoids; Gonadal Steroid Hormones; Humans; Hydroxysteroid Dehydrogenases; Hyperinsulinism; Hyperprolactinemia; Hypothalamo-Hypophyseal System; Infant, Newborn; Infertility, Female; Insulin Resistance; Leptin; Mineralocorticoids; Obesity; Ovary; Ovulation Induction; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Pseudopregnancy; Steroid 11-beta-Hydroxylase; Steroid 17-alpha-Hydroxylase; Steroids; Sterol Esterase; Stress, Psychological

This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate.

Topics: Adipose Tissue; Animals; Anorexia Nervosa; Body Weight; Carrier Proteins; Female; Humans; Infant, Newborn; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Puberty; Receptors, Cell Surface; Receptors, Leptin; Sex Characteristics; Thyroid Gland

Topics: Endocrine System Diseases; Female; Humans; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Thyroid Diseases

Leptin is mainly synthesized by adipocytes and might represent the connecting link between fatty tissue and brain. In reference to reproduction, leptin resistance could play a role particularly in the pathogenesis of the PCO syndrome. However, there exists at present contradictory data on this, so that further clarification is necessary. Leptin interacts with the steroid synthesis to a degree not yet precisely clarified and possesses receptors in numerous tissues, which suggests extensive local and endocrine effects. Its exact significance for the initiation of puberty still remains unknown. The same is true for first data regarding leptin and endometriosis and the interpretation of hyperleptinemia during pregnancy. It is clear that this protein mediates between fatty tissue and the reproductive function. However, the detailed physiologic and pathophysiologic role of leptin in reproduction can only be clarified through further extensive studies. To date there is not yet a practical importance for the measurement of leptin in routine work in reproductive medicine.

Topics: Adipose Tissue; Adolescent; Adult; Child; Endometriosis; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Pregnancy; Sexual Maturation

Obesity gains increasing prevalence world-wide. Multifactorially caused it presents itself in numerous heterogeneous phenotypes with a wide spectrum of clinical symptoms. The full-blown female obesity syndrome is initiated already in childhood, associated with ovarian hyperandrogenaemia (polycystic ovary syndrome) in the reproductive phase, and characterised by increasing co-morbidity (cancer; metabolic syndrome; arteriosclerosis) in the postmenopausal state leading to shortened longevity. Due to the complexity of psychic, somatic and endocrine-metabolic disturbances a causal break-through in the treatment of the disease could not be achieved yet, but the enhanced basal understanding and recently investigated pharmaceutical principles might enable to improve the therapeutical approaches.

Topics: Adolescent; Adult; Aged; Arteriosclerosis; Child; Combined Modality Therapy; Female; Gene Expression; Humans; Insulin Resistance; Leptin; Middle Aged; Neoplasms; Obesity; Polycystic Ovary Syndrome; Pregnancy; Proteins; Risk Factors

What is the signal between the metabolic state and reproductive function--it is one of the scientific puzzles in gynecological endocrinology. Previously it was suggested that such substances as insulin, amino acids, IGFBP-I may play a role as a metabolic signal. Leptin a newly discovered hormonal product of obesity (ob) gene is expressed by adipocytes and thought to play a role in the regulation of food intake, metabolism and reproduction. In this article some informations about leptin secretion, its regulation and localization of leptin receptors have been presented. Particular attention to leptin influence on GnRH secretion have been paid. Probably on the base of this mechanism leptin acts as a link between metabolic state and reproductive system. Some data about leptin secretion in obesity, weight loss related amenorrhoea and anorexia nervosa have been discussed. The putative role of leptin in the pathophysiology of polycystic ovary syndrome and initiation of puberty also have been analyzed.

Topics: Adipocytes; Amenorrhea; Anorexia Nervosa; Carrier Proteins; Eating; Female; Gonadotropin-Releasing Hormone; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins; Receptors, Cell Surface; Receptors, Leptin; Reproduction

The aim of this study was to investigate the effects of sitagliptin/metformin (sitaformin), metformin and sitagliptin in PCOS patients. PCOS is a hormonal disorder and therefore the use of treatments that modulate hormone levels Like AMH, testosterone, insulin, leptin and especially FAI and HOMA-IR can reclaim the symptoms of PCOS. PCOS also increases oxidative stress and lipid peroxidation. Therefore, in clinical and research trials, the level of these factors is usually examined to reduce patients' symptoms. Participants were randomly assigned to receive metformin, sitagliptin, sitaformin or placebo Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of ovum pick up. The serum levels of HOMA-IR and FAI decreased significantly in the treated groups compared to the placebo. The serum and the FF levels of leptin also decreased significantly in the sitaformin group when compared to the metformin and sitagliptin groups. Moreover, the serum and FF levels of AMH and MDA had a significant decrease in the sitaformin and sitagliptin group compared to the placebo. The mRNA expression and protein levels of GDF9 and BMP15 in the cumulus cells increased significantly in the sitaformin compared to metformin and sitagliptin groups. The expression level of GDF9 and BMP15 mRNA were positively correlated with the fertilization rate and grade I embryos. Sitaformin improves levels of GDF9 and BMP15 in PCOS compared to metformin and sitagliptin, which can increase the rate of fertilization and grade I embryos.

Topics: Bone Morphogenetic Protein 15; Female; Fertilization; Growth Differentiation Factor 9; Humans; Leptin; Metformin; Polycystic Ovary Syndrome; RNA, Messenger; Sitagliptin Phosphate

Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. With the increasing prevalence of PCOS in different countries, the use of herbal medicine as an alternative treatment is growing in these patients. This study aimed to evaluate the effects of flaxseed powder supplementation on metabolic biomarkers of patients with PCOS.. This randomized open-labeled controlled clinical trial was conducted on 41 patients with PCOS. The participants were randomized to take either flaxseed powder (30 g/day) plus lifestyle modification or only lifestyle modification for 12 weeks. Anthropometric and biochemical evaluations were performed for all patients at the beginning and end of the study.. The flaxseed group showed a significant reduction in body weight, insulin concentration, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), high-sensitivity C-Reactive Protein (hs-CRP), and leptin and an increase in Quantitative Insulin-Sensitivity Check Index (QUICKI), High Density Lipoprotein (HDL), and adiponectin compared to the baseline (p < 0.05). Flaxseed supplementation also led to a significant reduction in insulin concentration, HOMA-IR, TG, hs-CRP, Interleukin 6 (IL- 6), and leptin and an increase in QUICKI, HDL, and adiponectin compared to the control group (p < 0.05). No significant changes were observed in other parameters.. Flaxseed supplementation plus lifestyle modification was more effective compared to lifestyle modification alone in biochemical and anthropometric variables in patients with PCOS.. The trial protocol was approved by the Ethics Board at Ahvaz Jundishapur University of Medical Sciences and was registered at Iranian Registry of Clinical Trials (code: IRCT20120704010181N11).

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Body Weight; C-Reactive Protein; Dietary Supplements; Female; Flax; Humans; Insulin; Iran; Leptin; Lipoproteins, HDL; Male; Middle Aged; Polycystic Ovary Syndrome; Triglycerides; Young Adult

Women with PCOS are linked to insulin resistance, inflammation, and vitamin D (VD) deficiency. The study endeavors to comprehend the differential impact of insulin sensitizers vs. anti-androgen on serum leptin levels among women with PCOS rendered vitamin D replete with high VD oral supplement. This was open-labeled randomized study that screened 180 eligible women presenting to Endocrine clinic with oligomenorrhea or features of hyperandrogenism. Ninety-nine women who furnished written informed consent and fulfilled the Rotterdam 2003 criteria for diagnosis of PCOS were randomized into 3 drug treatment arms to receive either spironolactone (50 mg/d; n=30), metformin (1000 mg/d; n=30) or pioglitazone (30 mg/d; n=30). These women were also administered oral VD (4000 IU/day) in addition to the allocated drug for a period of 6 months. Detailed history, clinical examination, and laboratory evaluation was carried out at baseline and 6 months after intervention. Number of menstrual cycles/year increased while as Ferriman-Gallwey score, blood glucose, HOMA-IR, and plasma insulin levels significantly decreased in all the three arms with better outcomes in spironolactone and pioglitazone arms (p<0.05). Similarly, serum leptin levels superiorly improved in spironolactone and pioglitazone group. Pioglitazone group showed better efficacy in lowering serum total testosterone (p<0.05). Co-supplementation of high dosage VD with spironolactone or pioglitazone are more effective in reducing plasma leptin levels than metformin, and thus might prove to be better therapeutic strategies for women with PCOS.

Topics: Adult; Blood Glucose; Female; Humans; Insulin; Insulin Resistance; Leptin; Metformin; Pioglitazone; Polycystic Ovary Syndrome; Spironolactone; Testosterone; Vitamin D; Young Adult

To observe the effect of Qingre Yangyin Recipe (QRYYR) on sex hormones and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients.. Totally 90 PCOS patients were randomly assigned to the Chinese herbs group,the Western medicine group, the combined group, 30 in each group. Patients in the Chinese herbs group took QRYYR, one dose per day in two portions, once in the morning and once in the evening. Patients in the Western medicine group took Metformin 500 mg, twice per day for 3 consecutive months. Patients in the combined group took QRYYR and Metformin (the same as the former said two groups) in the 1st month, and took QRYYR for the following two months. Fasting blood glucose (FPG) and postprandial 2 h blood glucose (2 h GLU) were determined using hexokinase method before and after treatment. Fasting insulin (FINS), postprandial 2 h insulin (2 h INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), and testosterone (T) were detected using chemiluminescent method. Leptin and adiponectin (APN) were determined using ELISA. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Body weight and height were measured once before treatment and once after treatment to calculate body mass index (BMI). The total two-phase basal body temperature (BBT) actually obtained within 3 months was statistically collected to calculate the two-phase BBT rate. Scores for Chinese medical syndromes were compared between the two groups before and after treatment.. Compared with before treatment in the same group, BMI, FINS, 2 h INS, HOMA-IR, leptin, LH, PRL, T, and scores for Chinese medical syndromes obviously decreased, and APN levels increased (P < 0.05). FPG and 2 h FPG obviously decreased in the Western medicine group and the combined group (P < 0.05). E2 levels obviously decreased in the combined group with statistical difference (P < 0.05). Compared with the Chinese herbs group, the difference of BMI between pre-treatment and post-treatment was more in the combined group (P < 0.05). The difference of FPG,2 h GLU, 2 h INS, HOMA-IR, and APN between pre-treatment and post-treatment was more in the Chinese herbs group and the combined group (P < 0.05). Compared with the Western medicine group, the difference of PRL, T, and scores for Chinese medical syndromes was more in the Western medicine group and the combined group (P < 0.05); the difference of E2 and LH was even more in the combined group (P < 0.05). Compared with the combined group, the biphasic rate was obviously lowered in the Western medicine group (P < 0.05).. QRYYR could improve IR but with weaker power to that of Metformin. It also could decrease serum levels of LH, T, PRL, and scores for Chinese medical syndromes, with superior effect to that of Metformin. The effect in the combined group was better.

Topics: Adiponectin; Blood Glucose; Body Mass Index; Drugs, Chinese Herbal; Estradiol; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Insulin; Insulin Resistance; Leptin; Luteinizing Hormone; Metformin; Polycystic Ovary Syndrome; Progesterone; Prolactin; Testosterone

To explore the effect of electroacupuncture and Chinese kidney-nourishing medicine on insulin (INS), adiponectin (APN), leptin (LEP), and glucolipid metabolism of obese patients with polycystic ovary syndrome (PCOS).. Sixty-seven obese PCOS patients were randomly divided into two groups. Thirty-three patients in the acupuncture-medicine group were treated three times a week with electroacupuncture at the Tianshu (ST 25), Zhongwan (CV 12), Qi-hai (CV 6), Sanyinjiao (SP 6), Geshu (BL 17), and Ciliao (BL 32) acupoints. They also took the Chinese drug, Tiankui capsule, for 3 months as a course of treatment. Point-taking and treatment in the electroacupuncture group of 34 patients was the same as those in the acupuncture-medicine group. We observed and compared the changes in the obesity-related indexes of body weight (BW), body mass index (BMI), and waist-hip ratio (WHR), as well as fasting plasma glucose (FPG), fasting insulin (FINS), APN, and LEP.. BW, BMI, WHR, and FINS decreased and insulin sensitivity index (ISI) and APN were higher in the acupuncture-medicine group than in the electroacupuncture group (P < 0.01). There was no obvious difference in LEP between the two groups (P > 0.05).. Acupuncture combined with medicine is better than just electroacupuncture for obese PCOS patients by improving obesity-related indexes, insulin sensitivity, and APN level. This indicates that acupuncture-medicine therapy is worth clinical popularization.

Topics: Adiponectin; Adolescent; Adult; Body Weight; Combined Modality Therapy; Drugs, Chinese Herbal; Electroacupuncture; Female; Glucose; Humans; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Waist-Hip Ratio; Young Adult

Polycystic ovary syndrome (PCOS) is considered as the most common endocrinopathy among women of reproductive age. Oral contraceptives (OCs) and metformin are one of the main drug groups in the long-term treatment of PCOS. This study was undertaken to investigate the effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ultrasonographic markers, body fat mass (BFM) index, leptin-ghrelin.. This was a prospective clinical study conducted at Kocaeli University Department of Obstetrics and Gynecology on 42 PCOS patients. Patients were randomly allocated into two groups [Group I (n = 22): drospirenone-ethinyl estradiol (DEE); Group II (n = 20): drospirenone-ethinyl estradiol + metformin (M)] according to Body Mass Index (BMI) findings. Patients were evaluated in terms of leptin-ghrelin, ultrasound, and body fat distribution before and 6 months after therapy. Main outcome measures were to investigate the effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ovarian ultrasonographic markers, BFM index, leptin, and ghrelin.. In patients with higher BMI, ovarian volume, numbers of follicles, stromal area, and echogenicity have been reported to be larger. In group II, a negative correlation between ghrelin and abdominal fat mass after treatment has been noted, whereas in group I a positive correlation between leptin and abdominal fat mass after treatment has been observed.. Addition of metformin could have beneficial effects on abdominal fat mass. Stromal area measurement and assessment of fat mass with Dual X-ray Absorptiometry could be helpful as a quantitative way of measurement.

Topics: Abdominal Fat; Adiposity; Adolescent; Adult; Androstenes; Body Mass Index; Drug Therapy, Combination; Ethinyl Estradiol; Female; Ghrelin; Humans; Leptin; Metformin; Organ Size; Ovarian Follicle; Ovary; Polycystic Ovary Syndrome; Reproductive Control Agents; Ultrasonography; Young Adult

The lipodystrophies (LD) are characterized by metabolic abnormalities (insulin resistance, hypertriglyceridemia, and diabetes) and a polycystic ovarian syndrome (PCOS) phenotype. Therapeutic administration of leptin improves insulin sensitivity and the metabolic features.. The objective of the study was to investigate whether the PCOS features are corrected by increasing insulin sensitivity as a function of leptin treatment.. This was a prospective, open-label trial using leptin replacement in various forms of lipodystrophy.. The study was performed at the Clinical Center at the National Institutes of Health.. Twenty-three female patients with LD were enrolled in a leptin replacement trial from 2000 to the present. Different parameters were assessed at baseline and after 1 yr of therapy.. Patients were treated with leptin for at least 1 yr.. We evaluated free testosterone, SHBG, and IGF-I at baseline and after 1 yr of leptin.. Testosterone levels decreased from 3.05 ±0.6 ng/ml at baseline to 1.7 ±0.3 ng/ml (P = 0.02). SHBG increased from 14.5 ±2 to 25 ±3.5 nmol/liter after 1 yr of leptin therapy. There were no significant changes in the levels of gonadotropins and ovarian size as a result of leptin replacement therapy. IGF-I increased significantly after leptin therapy from 150 ±14 to 195 ±17. There was a significant decrease in triglycerides and glycosylated hemoglobin in the context of reduced insulin requirements.. In the present study, we show that LD may be a model for the common forms of PCOS and that the endocrine features are corrected by leptin therapy, which reduces insulin resistance.

Topics: Adolescent; Adult; Child; Female; Follow-Up Studies; Hormone Replacement Therapy; Humans; Hyperandrogenism; Insulin Resistance; Leptin; Lipodystrophy; Polycystic Ovary Syndrome; Time Factors; Young Adult

To evaluate retinol-binding protein 4 (RBP4), leptin, and asymmetric dimethylarginine (ADMA) levels in young women with polycystic ovary syndrome (PCOS) and to investigate their relationship with each other and with clinical, metabolic, and hormonal parameters.. Clinical study.. University hospital.. Fifty-seven young women with PCOS (obese [n = 27] and nonobese [n = 30]) and 27 age-matched healthy controls.. History and physical examination, peripheral venous blood sampling.. Asymmetric dimethylarginine, RBP4, leptin, LH, FSH, DHEAS, total T, E(2), total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride (TG), and homeostasis model assessment insulin resistance index (HOMA-IR).. Obese women with PCOS had significantly higher HOMA-IR, DHEAS, leptin, RBP4, and ADMA levels. Leptin levels were significantly increased in nonobese subjects with PCOS. Leptin and ADMA levels were positively correlated with HOMA-IR in PCOS. There was no correlation between RBP4 and HOMA-IR. Leptin, RBP4, and ADMA levels are positively correlated in PCOS.. [1] Young obese women with PCOS have increased ADMA, RBP4, and leptin levels, and they are positively correlated with each other. [2] The increased levels of leptin are independent of obesity, and leptin seems to have an association with IR. [3] Levels of RBP4 may not reflect IR in PCOS.

Topics: Adult; Arginine; Biomarkers; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Retinol-Binding Proteins, Plasma; Young Adult

To detect the levels of visfatin and leptin in the serum as well as in the follicular fluid (FF) of polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian stimulation and to compare them with the levels found in age- and weight-matched normally ovulating women under IVF treatment.. Prospective study.. Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece.. Forty patients with diagnosed PCOS and 40 age- and weight-matched non-PCOS control women enrolled in the IVF program.. Blood and FF samples were collected from all subjects at oocyte retrieval.. Visfatin and leptin levels were measured in serum and FF using ELISA.. Serum visfatin levels were significantly increased in women with PCOS, whereas FF visfatin levels, which were lower than serum levels, did not differ between groups. Serum leptin levels did not differ between groups and were lower than FF levels.. Women with polycystic ovaries exhibit significantly increased serum visfatin and decreased FF leptin levels compared with control subjects of similar age and body mass index, indicating a probable role for visfatin in the general state of insulin resistance and a local contribution in the follicle for leptin in patients undergoing IVF treatment.

Topics: Adult; Age Factors; Body Mass Index; Cytokines; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility, Female; Insulin; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities.. The aim of this study was to assess novel inflammatory markers [adipokines leptin, adiponectin, and leptinadiponectin ratio (L/A)] in overweight women with and without PCOS and to examine alterations in these markers [aldosterone, leptin, adiponectin, and L/A] with pharmacological interventions modulating insulin resistance (IR) in PCOS.. Overweight age, and body mass index (BMI)-matched women with (no.=80) or without PCOS (no.=27) were assessed cross-sectionally. Subjects with PCOS were then randomised to 6 months metformin (1 g b.d, no.=26) or oral contraceptive pill (OCP) (35 g ethinyl estradiol/2 mg cytoproterone acetate, no.=30). Outcome measures were leptin, adiponectin, L/A, aldosterone, highly sensitive C-reactive protein, lipid profile, IR, and androgen levels.. Leptin levels were lower (156.4+/-85.9 vs 208.5+/-105.2 ng/ml, p=0.015) while adiponectin and L/A were not different between women with and without PCOS. Following intervention, IR increased for the OCP and decreased for metformin, however leptin and aldosterone decreased equivalently with the OCP and metformin with no difference between each treatment (p=0.583 and p=0.801, respectively). There was no change in adiponectin or L/A with the OCP or metformin. On multiple regression, the only baseline predictor of leptin was BMI (r(2)=0.485, p<0.001) and the strongest predictor of change in leptin was change in weight (r(2)=0.402, p<0.001).. Alterations in leptin between women with and without PCOS and following pharmacological interventions are primarily related to adiposity and not IR. Aldosterone was reduced equivalently with metformin and the OCP despite differential effects on IR.

Topics: Adiponectin; Adiposity; Aldosterone; Biomarkers; Body Mass Index; Cross-Sectional Studies; Female; Humans; Hypoglycemic Agents; Leptin; Metformin; Overweight; Polycystic Ovary Syndrome; Pregnancy

To compare the effects of protein vs. simple sugars on weight loss, body composition, and metabolic and endocrine parameters in polycystic ovary syndrome (PCOS).. A 2-month, free-living, randomized, single-blinded study.. University PCOS clinic.. Thirty-three patients with PCOS.. To achieve a final energy reduction of 450 kcal/day, first the daily energy intake was reduced by 700 kcal; then a 240-kcal supplement containing either whey protein or simple sugars was added.. Changes in weight, fat mass, fasting glucose and insulin, plasma lipoproteins, and sex steroids.. Twenty-four subjects (13 in the simple sugars group and 11 in the protein group) completed the study. The protein group lost more weight (-3.3 +/- 0.8 kg vs. -1.1 +/- 0.6 kg) and more fat mass (-3.1 +/- 0.9 kg vs. -0.5 +/- 0.6 kg) and had larger decreases in serum cholesterol (-33.0 +/- 8.4 mg/dL vs. -2.3 +/- 6.8 mg/dL), high-density lipoprotein cholesterol (-4.5 +/- 1.3 mg/dL vs. -0.4 +/- 1.3 mg/dL), and apoprotein B (-20 +/- 5 mg/dL vs. 3 +/- 5 mg/dL).. In patients with PCOS, a hypocaloric diet supplemented with protein reduced body weight, fat mass, serum cholesterol, and apoprotein B more than the diet supplemented with simple sugars.

Topics: Adolescent; Adult; Body Composition; Body Mass Index; Calorimetry; Diet, Reducing; Dietary Carbohydrates; Dietary Proteins; Dietary Sucrose; Energy Intake; Female; Humans; Leptin; Middle Aged; National Institutes of Health (U.S.); Polycystic Ovary Syndrome; Single-Blind Method; United States; Weight Loss; Young Adult

To evaluate short-term leptin and ghrelin concentrations in women with polycystic ovary syndrome (PCOS) who use low-dose oral contraceptives containing drospirenone.. Prospective study.. Department of obstetrics and gynaecology in a university hospital.. Twenty women with PCOS were enrolled in the study.. A low-dose oral contraceptive containing ethinyl estradiol and drospirenone was given for three cycles.. Serum androstenedione, free T, T, dehydroepiandrosterone sulphate, sex hormone-binding globulin, FSH, LH, E(2), lipid profiles, leptin, and ghrelin levels were measured in each subject. Insulin resistance was estimated by the homeostasis model assessment-insulin resistance (HOMA-IR).. While leptin concentrations did not change with therapy, ghrelin levels increased statistically. Baseline leptin concentrations were correlated positively with body mass index, waist-to-hip ratio, insulin, and HOMA-IR and negatively with ghrelin. After controlling for body mass index and waist-to-hip ratio in a partial correlation analysis, leptin levels were not correlated with these parameters. Ghrelin was inversely correlated with body mass index, waist-to-hip ratio, insulin, HOMA-IR, and free T.. In patients with PCOS, an oral contraceptive containing ethinyl estradiol and drospirenone increases ghrelin levels but not leptin levels in a 3-month period. Ghrelin might be related to the metabolic and androgenic changes in patients with PCOS.

Topics: Adult; Androstenes; Contraceptives, Oral; Dose-Response Relationship, Drug; Estrogens; Female; Ghrelin; Humans; Leptin; Polycystic Ovary Syndrome; Treatment Outcome

Increasing evidence suggests that adipocyte function is altered in the polycystic ovary syndrome (PCOS) as a result of androgen excess, providing an explanation for its frequent association with abdominal adiposity and insulin resistance. We here compared the response of serum adiponectin and leptin levels to the amelioration of androgen excess by means of treatment with an antiandrogenic oral contraceptive pill, as compared with the response to insulin sensitization with metformin. Thirty-four women presenting with PCOS were randomized to treatment with an oral contraceptive containing 35 microg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35) Diario) or with metformin (850 mg twice daily). Serum adiponectin and leptin levels were evaluated at baseline and after 12 and 24 weeks of treatment. In obese PCOS women, treatment with Diane(35) Diario resulted in an increase in serum adiponectin levels and in the adiponectin/leptin ratio, in parallel with a marked decrease in serum androgen concentrations, whereas no statistically significant changes were observed during treatment with metformin. On the contrary, leptin concentrations did not show any statistically significant change during the study with any of the drugs studied here. In summary, our present results might suggest a direct inhibitory effect of androgen excess on adiponectin secretion by adipocytes in obese PCOS women, supporting the hypothesis that androgen excess contributes to adipocyte dysfunction in these women.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Adult; Androgen Antagonists; Area Under Curve; Body Weight; Contraceptives, Oral; Dehydroepiandrosterone Sulfate; Female; Humans; Insulin; Leptin; Metformin; Obesity; Polycystic Ovary Syndrome; Testosterone; Young Adult

Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder which may concern about 3-8% of women. Some PCOS women have the increased leptin concentration in blood serum. Leptin concentration is higher in patients with high body mass index (BMI) and impaired tissue sensitivity to insulin. The aim of this study was to determine leptin concentrations in PCOS patients before and after metformin treatment depending on BMI, insulin resistance calculated on the basis of the Homeostasis Model Assessment (HOMA) index, as well as concentrations of androgens: testosterone and androstendion. Such values as BMI, insulin resistance according to the HOMA index, and concentrations of androstendion, testosterone and leptin were determined in 35 patients with PCOS before and after 3-month metformin treatment administered in daily doses of 2 x 850 mg. Increased leptin levels before the therapy were observed in 91.3% (21 out of 23) of obese patients, in 75% (9 out of 12) non-obese patients, in 100% (8 patients) insulin resistance women, in 81.5% (22 out of 27) insulin sensitive patients, in 94.7% (18 out of 19) women with elevated androstendion concentration and in 75% (12 out of 16) with normal androstendion concentration, in 93.7% (15 out of 16) patients with increased testosterone concentration and in 78.9% (15 out of 19) patients with testosterone concentrations within the normal range. After treatment statistically significant decrease in leptin concentration was obtained in the patients with BMI

Topics: Androgens; Body Mass Index; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Leptin; Metformin; Polycystic Ovary Syndrome

Leptin, particularly in its free form, is deeply involved in the regulation of energy balance. Insulin was suggested to influence plasmatic leptin levels and soluble leptin receptor in humans. However, this study indicates that metformin treatment, although improving insulin levels, does not exert a significant effect on either total leptin level or free leptin index in obese women with hyperinsulinemia and PCOS.

Topics: Adult; Female; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Leptin; Metformin; Obesity; Polycystic Ovary Syndrome

Insulin, ghrelin, neuropeptide Y (NPY) and leptin interact in the regulation of energy homeostasis. Most of these signals are altered in polycystic ovary syndrome (PCOS), which is characterized by a high prevalence of obesity. The present study was conducted to evaluate ghrelin-NPY and ghrelin-leptin interplays in relation to insulin secretion in obese PCOS subjects.. Pilot prospective study.. Seven obese PCOS women and seven age-weight matched controls.. Hormonal measurements, oral glucose tolerance test (OGTT) and a ghrelin test (1 microg/kg i.v. bolus). PCOS patients repeated the clinical work-up after 4 months of metformin treatment (1500 mg/day orally).. At baseline, PCOS women showed a significantly higher insulinaemic response to the OGTT compared to controls (P < 0.05). In basal conditions, PCOS women exhibited lower NPY levels than controls (P < 0.01). Ghrelin injection markedly increased NPY in controls (P < 0.01), whereas PCOS women showed a deeply blunted NPY response to the stimulus (area under the curve--AUC-NPY: P < 0.01 vs. controls.). Metformin treatment induced a significant decrease in insulin levels (P < 0.01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC-NPY: P < 0.05 vs. baseline) in PCOS women. Leptin levels, which were similar in the two groups, were not modified by ghrelin injection; metformin did not affect this pattern.. Hyperinsulinaemia seems to play a pivotal role in the alteration of NPY response to ghrelin in obese PCOS women. This derangement could be implicated in the physiopatology of obesity in these patients.

Topics: Adult; Female; Ghrelin; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Leptin; Metformin; Neuropeptide Y; Obesity; Pilot Projects; Polycystic Ovary Syndrome; Signal Transduction; Young Adult

The novel peptide ghrelin displays multiple endocrine and non-endocrine actions. Its strong GH-releasing activity in humans has long been recognized. However, in obesity, ghrelin administration induces a blunted GH secretion, enhances glucose and reduces insulin levels. The effects of ghrelin administration have not been investigated in polycystic ovary syndrome (PCOS), which can be associated with obesity, hyperinsulinism, and GH hyposecretion. Leptin is a mediator for energy balance opposed to ghrelin; both of them are supposed to act as regulators of reproductive functions.. Evaluate the endocrine and metabolic response to ghrelin administration in PCOS obese patients compared to body mass index (BMI)-matched and normal weight women.. Nine obese PCOS patients (BMI: 35.4+/-1.2 kg/m(2)) (OB PCOS), 6 obese controls (BMI: 38.4+/-1.1 kg/m(2)) (Ob), and 6 normal-weight women (BMI: 23+/-0.6 kg/m(2)) (NW) were enrolled in the study. In all patients we performed: 1) basal hormonal evaluation including FSH, LH, estradiol, testosterone, androstenedione, DHEAS, SHBG, 17-hydroxyprogesterone (17OHP), IGF-I, free T3 (FT3), free T4 (FT4) and ghrelin levels; 2) metabolic evaluation as follows: concentration of non-esterified fatty acid (NEFA) and oral glucose tolerance test (OGTT) (75 g); homeostasis model assessment (HOMA); glucose and insulin response to ghrelin administration (1 microg/kg); 3) measurement of GH, PRL, TSH, and leptin levels after infusion of ghrelin.. Administration of ghrelin increased glucose and reduced insulin levels in both Ob and OB PCOS. Moreover, ghrelin enhanced GH and PRL levels in all groups but it did not modify TSH and leptin levels. GH peak and area under the curve (AUC) in OB PCOS and Ob were lower than controls (p<0.05). Similar PRL peak and AUC values were observed in all groups.. In both obese and PCOS obese patients, leptin levels are not influenced by ghrelin administration. Moreover, the GH response after ghrelin administration is blunted. However, ghrelin exerts glucose- enhancing and insulin-lowering effects, the latter absent in NW.

Topics: Adult; Blood Glucose; Fatty Acids, Nonesterified; Female; Ghrelin; Growth Hormone; Humans; Insulin; Leptin; Obesity; Polycystic Ovary Syndrome; Prolactin; Thyrotropin

To evaluate levels of soluble receptor (sOB-R) and free leptin in women with polycystic ovarian syndrome (PCOS) and note any relationships with insulin resistance, adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound to an sOB-R. Only free leptin is biologically active.. Prospective, case-control study.. University-based reproductive endocrinology practice.. Forty women with PCOS and severe insulin resistance and 15 body mass index (BMI)-matched ovulatory controls.. Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone.. Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were measured to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R.. Total leptin and FLI correlated significantly with BMI in both patients with PCOS and in controls. There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose levels. The sOB-R levels increased significantly 3 hours after oral glucose ingestion, resulting in a significant decline in FLI.. [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. [2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels.

Topics: Acanthosis Nigricans; Adiposity; Adult; Androgens; Body Mass Index; Case-Control Studies; Comorbidity; Female; Humans; Incidence; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Receptors, Cell Surface; Receptors, Leptin; Risk Assessment; Risk Factors; Texas

Lipodystrophy patients are hypoleptinemic and insulin resistant. Women have enlarged polycystic ovaries, hyperandrogenism, and amenorrhea. We have determined the role of correction of hypoleptinemia on these metabolic and neuroendocrine parameters. Ten females and 4 males with generalized lipodystrophy were treated with recombinant methionyl human leptin (r-metHuLeptin) in physiologic doses in an open-labeled study for a period of 12 and 8 months, respectively. In the female group, serum free testosterone decreased from 39.6 +/- 11 to 18.9 +/- 4.5 ng/dL (P < 0.01) and serum sex hormone binding globulin increased from 14 +/- 2.5 to 25 +/- 4.8 nmol/L (P < 0.02). Luteinizing hormone (LH) responses to LH releasing hormone were more robust after therapy and significantly changed in the youngest group of 3 female patients (P < 0.01). Ovarian ultrasound showed a polycystic ovarian disease pattern in all patients and did not change after therapy. Eight of the 10 patients had amenorrhea prior to therapy and all 8 developed normal menses after therapy. In the male group, serum testosterone tended to increase from 433 +/- 110 to 725 +/- 184 ng/dL (P = 0.1) and sex hormone binding globulin also increased from 18.25 +/- 2.6 to 27 +/- 1.7 nmol/L (P < 0.04) following r-metHuLeptin therapy. Serum LH response to LH releasing hormone did not show significant changes. Five additional hypoleptinemic male subjects with minimal metabolic abnormalities underwent normal pubertal development without receiving r-metHuLeptin therapy. In both genders, insulin-like growth factor increased significantly and there were no differences in growth hormone, thyroid, or adrenal hormone levels following r-metHuLeptin therapy. Glycemic parameters significantly improved after r-metHuLeptin therapy in both groups. Hypoglycemic medications were discontinued in 7 of 12 patients and dramatically reduced in 5 patients. r-metHuLeptin therapy plays an important role in insulin sensitivity. In females, it plays an additional role in normalizing menstrual function. This is likely to occur both from increasing insulin sensitivity and from restoring LH pulsatility. The persistent hypoleptinemic state in these subjects did not inhibit pubertal development.

Topics: Adolescent; Adult; Aged; Amenorrhea; Androgens; Blood Glucose; Child; Female; Human Growth Hormone; Humans; Hyperandrogenism; Insulin-Like Growth Factor I; Leptin; Lipodystrophy; Luteinizing Hormone; Male; Menstruation; Pituitary Function Tests; Pituitary Gland; Polycystic Ovary Syndrome; Puberty; Recombinant Proteins; Sex Hormone-Binding Globulin; Testosterone; Thyroid Gland

To assess changes in serum hormone levels and ovarian stromal blood flow after laparoscopic ovarian drilling (LOD) in young adult women with polycystic ovary syndrome (PCOS).. Prospective, nonrandomized study (Canadian Task Force classification II-1).. Tertiary care, major teaching hospitals.. Anovulatory young women with PCOS who were resistant to clomiphene citrate.. Laparoscopic ovarian drilling.. To evaluate the endocrinological effects of LOD, serum leptin, insulin-like growth factor-1, estrone (E1), and estradiol were measured before and after ovarian drilling in the early follicular phase. Three-dimensional transabdominal power Doppler examinations were performed to determine the effects of LOD. Serum leptin was correlated with body mass index (BMI) before LOD. Levels of BMI, fasting blood sugar, and leptin were higher and LH, LH/FSH, and the sugar/insulin ratio were lower in the obese group. There were significant decreases in the free androgen index, and total testosterone, luteinizing hormone (LH), and LH/follicle-stimulating hormone (FSH) levels, and a significant increase in sex hormonebinding globulin (SHBG) concentration in the 3 months after the operation. The vascularization index and vascularization flow index of the intraovarian stroma significantly decreased after treatment. Reversed correlations between leptin and LH, LH/FSH, E1, thyroid-stimulating hormone, and SHBG were noted 3 months after the operation compared with levels obtained before the operation.. Treatment of young adult women with PCOS using LOD did not influence leptin levels but changed the ovarian stromal blood flow dynamics during short-term follow-up. The surgical procedure may be beneficial both to endocrine profiles and to intraovarian stromal flow in patients with PCOS.

Topics: Adolescent; Adult; Age Factors; Body Mass Index; Body Weight; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Hormones; Humans; Laparoscopy; Leptin; Linear Models; Obesity; Polycystic Ovary Syndrome; Probability; Prospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler, Color

Weight reduction on its own is observed to cause improvement in some of the abnormalities seen in patients with polycystic ovary syndrome (PCOS). With respect to this observation, we studied the possible effects of different serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels that might play a role in the obesity component seen in patients with PCOS. In a random design, sixteen patients were assigned to fluoxetine and sibutramine for a period of 10 days. In both treatment groups, no significant differences were observed between pre-treatment and post-treatment values in insulin levels (p > 0.05). There was no significant difference between pretreatment and post-treatment serum leptin levels in the fluoxetine treatment group (p > 0.05). However, a significant reduction was observed in the serum leptin levels at the end of treatment in the sibutramine group (p < 0.05). The observed difference in the serum leptin response to the treatment effect of sibutramine compared to fluoxetine seems to be due to a mechanism independent of serotonin reuptake inhibition, possibly to the thermogenic effect of the sibutramine itself. Further studies with larger groups are warranted, to examine the mechanism of the weight-reducing effect of sibutramine. Detailed analyses of basal metabolic activity and change in serum leptin levels should be carried out.

Topics: Adult; Appetite Depressants; Body Mass Index; Cyclobutanes; Female; Fluoxetine; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Selective Serotonin Reuptake Inhibitors

Controversial data were reported on GH response to different provocative stimuli in obese patients with polycystic ovary syndrome (PCOS). The objective of our study was to assess the effect of short-term fasting on GH response to combined stimulus with GHRH+GH-releasing peptide-6 (GHRP-6) in obese patients with PCOS and possible relation with leptin and insulin changes during fasting. Twelve obese PCOS women and nine obese control women participated in 3-day fasting. GH response, IGF-I, insulin and leptin were measured after GHRH+ GHRP-6, before and after short-term fasting. Obese PCOS patients had significantly greater GH peak after GHRH+GHRP-6 before fasting. Enhanced response to GH stimulation was found after fasting without substantial differences between obese PCOS and obese controls. Insulin and leptin significantly decreased, while insulin sensitivity significantly improved in both groups during fasting. In conclusion, obese PCOS patients have peculiar type of GH response to GHRH+GHRP-6 before fasting, possibly due to enhanced sensitivity of somatotrophs. Observed changes in insulin and leptin may participate in modulation of enhanced GH response after short-term fasting to GHRH+GHRP-6 in PCOS and obese controls.

Topics: Adult; Fasting; Female; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Obesity; Oligopeptides; Polycystic Ovary Syndrome

Topics: Administration, Oral; Adult; Androgen Antagonists; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Cyproterone Acetate; Desogestrel; Drug Combinations; Estradiol Congeners; Ethinyl Estradiol; Female; Gonadal Steroid Hormones; Humans; Leptin; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Steroids

To evaluate the serum leptin levels and the effects of flutamide treatment on the leptin levels in women with polycystic ovary syndrome (PCOS).. 20 women with PCOS and 20 controls were enrolled in the study. Leptin levels and leptin response to an oral glucose tolerance test were assessed in both groups before and after a 4-week flutamide therapy period.. The leptin levels were similar in both groups at baseline. In the PCOS group, leptin levels and area under curve for leptin levels increased significantly after flutamide treatment.. Women with PCOS had similar leptin levels to those of controls with similar age and body mass index. Flutamide treatment led to increased leptin levels and leptin responses to oral glucose tolerance tests in PCOS patients. Further studies are needed to gain insights into the clinical consequences of these effects of flutamide.

Topics: Adolescent; Adult; Androgen Antagonists; Anthropometry; Area Under Curve; Blood Glucose; Case-Control Studies; Female; Flutamide; Glucose Tolerance Test; Hormones; Humans; Leptin; Polycystic Ovary Syndrome

To evaluate the effect of rosiglitazone on insulin resistance and hyperandrogenism in polycystic ovary syndrome (PCOS).. Rosiglitazone was given 4 mg daily to 30 patients with PCOS for 12 weeks. Before and after treatment, body mass index (BMI), plasma glucose, insulin, levels insulin resistance index (HOMA IR), blood lipid spectrum, leptin, neuropeptide Y, and sex hormone concentrations and ovulation rate were determined and compared.. After 12 weeks of treatment, basal insulin level decreased from (18 +/- 8) to (12 +/- 7) mIU/L (P < 0.01), HOMA IR decreased from 4.3 +/- 1.2 to 2.6 +/- 0.7 (P < 0.01). Luteinizing hormone, free testosterone and androstenedione levels decreased [(15.4 +/- 4.4) versus (7.9 +/- 2.1) U/L, (12.5 +/- 1.9) versus (8.9 +/- 1.4) pmol/L, (9.8 +/- 1.7) versus (7.4 +/- 1.2) nmol/L respectively, P < 0.01]; Dehydroepiandrosterone sulfate level also decreased [(8.7 +/- 3.5) versus (6.9 +/- 2.1) micromol/L, P < 0.05]; Sex hormone binding globulin level increased [(39 +/- 3) versus (58 +/- 5) nmol/L, P < 0.01]. Plasma leptin level was decreased [(18 +/- 4) versus (13 +/- 3) microg/L, P < 0.01]. Ovulation rate increased to 50%.. Rosiglitazone might decrease plasma leptin level and improve insulin sensitivity, which led to alleviation of hyperandrogenism and resumption of ovulation and menses in patients with PCOS.

Topics: Administration, Oral; Adult; Androstenedione; Blood Glucose; Body Weight; Female; Follicle Stimulating Hormone; Humans; Hyperandrogenism; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Lipids; Luteinizing Hormone; Menstruation; Neuropeptide Y; Ovulation; Polycystic Ovary Syndrome; Rosiglitazone; Testosterone; Thiazoles; Thiazolidinediones; Treatment Outcome

To determine the clinical, hormonal and biochemical effect of 4-5 months of insulin-sensitizing therapy (hypocaloric diet+metformin) in obese patients with polycystic ovary syndrome (PCOS).. Prospective study.. Twenty-three obese patients with PCOS, 19 obese patients without menstrual disturbances and 11 healthy control women were recruited from the Department of Endocrinology and Endocrine Gynecology, Medical Academy, Bialystok, Poland. Obese patients received 500 mg metformin together with hypocaloric diet three times daily for 4-5 months, after baseline study. The clinical parameters, menstrual pattern and serum concentrations of insulin, leptin, IGF-I, insulin-dependent proteins (sex hormone-binding protein (SHBG), insulin-like growth factor-binding protein-1 (IGFBP-1)), gonadotropins and sex steroids were determined before and after treatment.. In the baseline study, obese patients with PCOS had significantly higher insulin, testosterone and LH concentrations in comparison with the other groups. The serum leptin, IGF-I, IGFBP-1 and SHBG were not different between the two groups of obese patients, but there was a significant difference in comparison with the control group. After metformin therapy a significant reduction in BMI, % of body fat and leptin concentration were observed in both groups of obese patients. Fasting insulin, testosterone and LH concentrations decreased significantly only in the PCOS group. Six out of 11 patients in the PCOS group had more regular menstrual cycles; two patients conceived.. Insulin-sensitizing therapy could be considered as an additional therapeutic option in obese women with PCOS.

Topics: Adult; Blood Glucose; Diet, Reducing; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Leptin; Metformin; Obesity; Polycystic Ovary Syndrome

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes

Topics: Abdomen; Adipose Tissue; Adult; Androgens; Body Composition; Combined Modality Therapy; Diet, Reducing; Double-Blind Method; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hypoglycemic Agents; Insulin; Leptin; Luteinizing Hormone; Metformin; Obesity; Placebos; Polycystic Ovary Syndrome; Progesterone; Sex Hormone-Binding Globulin; Viscera

Previous studies have suggested that metformin is clinically useful in the treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether the improvement of ovarian function achieved by metformin therapy is associated with changes in leptin concentrations. Twenty-six obese women with PCOS were treated with 500 mg metformin, x 3 daily, for 2 months; and 12 women continued the therapy for 4-6 months. A significant decrease in the serum leptin level was observed after 2 months of treatment in the whole study group (29.2 +/- 12.7 ng/mL vs. 25.7 +/- 10.9 ng/mL, P = 0.03). In the 12 women treated for 4-6 months, the mean serum leptin concentration decreased after 2 months (38.6 +/- 9.3 ng/mL vs. 30.2 +/- 8.1 ng/mL; P = 0.004) but slightly increased after 4-6 months of treatment (33.4 +/- 15.7 ng/mL; not significant). These results indicate that insulin sensitizing therapy with metformin decreases the leptin concentrations in obese PCOS women.

Topics: Adult; Analysis of Variance; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Leptin; Metformin; Obesity; Polycystic Ovary Syndrome; Proteins

The polycystic ovary syndrome (PCOS) is characterized by menstrual disturbances, chronic anovulation and hyperandrogenism and is associated with insulin resistance and hyperinsulinemia. Leptin, the product of the ob gene, is an adipocyte-secreted molecule that signals the magnitude of energy stores to the brain and has been recently shown to have important effects on the reproductive axis of rodents. To assess the potential contribution of leptin to the pathogenesis of PCOS, we measured leptin levels in 24 obese women with PCOS and 12 weight- and age-matched controls and determined whether alterations in hyperinsulinemia produced by administration of the insulin-sensitizing agent troglitazone had an effect on serum leptin levels. Leptin concentrations at baseline were not different in women with PCOS (38.1 +/- 2.15 ng/mL) and controls (33.12 +/- 2.39 ng/mL). Moreover, leptin concentrations remained unchanged after treatment with troglitazone (38.1 +/- 2.15 vs. 39.21 +/- 2.65 ng/mL). Baseline leptin correlated strongly with body mass index in both controls (r = 0.59; P < 0.05) and women with PCOS (r = 0.70; P = 0.0004). Leptin levels were not associated with baseline insulin, testosterone, non-sex hormone-binding globulin (SHBG)-bound testosterone, dehydroepiandrosterone sulfate, estradiol, or SHBG. Finally, despite significantly reduced insulin, non-SHBG-bound testosterone, and estradiol levels after troglitazone treatment of women with PCOS, their leptin levels remained unchanged. We conclude that circulating leptin levels in patients with PCOS do not differ from those in age- and weight-matched controls. Furthermore, increased circulating insulin due to insulin resistance does not appear to alter circulating leptin levels in women with PCOS.

Topics: Adult; Body Mass Index; Chromans; Double-Blind Method; Female; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Obesity; Osmolar Concentration; Polycystic Ovary Syndrome; Proteins; Thiazoles; Thiazolidinediones; Troglitazone

Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) that may augment metabolic disturbances. Serum fatty acids are important biomedical indicators of dyslipidemia. The aim of this study was to determine the distinct serum fatty acids in various PCOS subtypes and their association with metabolic risk in women with PCOS.. Fatty acids in the serum of 202 women with PCOS were measured using gas chromatography-mass spectrometry. Fatty acids were compared between PCOS subtypes and correlated with glycemic parameters, adipokines, homocysteine, sex hormones, and sex hormone-binding globulin (SHBG).. The levels of total monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) in the reproductive subtype of PCOS were lower than those in the metabolic subtype. Docosahexaenoic acid, a PUFA, was associated with higher SHBG after correction for multiple comparisons. Eighteen species of fatty acids emerged as potential biomarkers associated with the metabolic risk factors measured, independent of body mass index (BMI). Among them, myristic acid (C14:0), palmitoleic acid (C16:1), oleic acid (C18:1n-9C), cis-vaccenic acid (C18:1n-7), and homo-gamma-linolenic acid (C20:3n-6) were the strongest lipid species that were consistently associated with metabolic risk factors, particularly insulin-related parameters in women with PCOS. As for adipokines, 16 fatty acids were positively associated with serum leptin. Among them, C16:1 and C20:3n-6were significantly associated with leptin levels.. Our data demonstrated that a distinct fatty acid profile comprising high C14:0, C16:1, C18:1n-9C, C18:1n-7, and C20:3n-6levels is associated with metabolic risk in women with PCOS, independent of BMI.

Topics: Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Insulin; Leptin; Polycystic Ovary Syndrome

Topics: Female; Humans; Hypoglycemic Agents; Leptin; Metformin; Polycystic Ovary Syndrome; Pregnancy; Weight Gain

This study was designed to examine the effect of blue light exposure and exposure time on puberty in an animal model.. Eighteen 21-day-old female Sprague Dawley rats were divided into three equal groups which were: control group (CG); blue light-6 hours (BL-6); and blue light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The animals in BL-6 and BL-12 were exposed to blue light of wavelength 450-470 nm and intensity of 0.03 uW/cm. The median day of puberty start was 38, 32 and 30 for the CG, BL-6, and BL-12 groups, respectively (p=0.001). FSH, testosterone, DHEA-S, and leptin concentrations of all groups were similar. However, LH and estradiol concentrations in BL-6 were higher compared to CG (p=0.02). There was a negative correlation between blue light exposure, exposure time, and melatonin concentrations (r=-0.537, p=0.048). Ovarian tissue was compatible with puberty in all groups. As blue light exposure time increased, capillary dilatation and edema in the ovarian tissue increased. Prolonged exposure was associated with polycystic ovary-like (PCO) morphological changes and apoptosis in granulosa cells.. These results suggest that exposure to blue light and the duration of exposure induced earlier puberty in female rats. As the duration of blue light exposure increased, PCO-like inflammation, and apoptosis were detected in the ovaries.

Topics: Animals; Dehydroepiandrosterone; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leptin; Luteinizing Hormone; Melatonin; Polycystic Ovary Syndrome; Puberty; Rats; Rats, Sprague-Dawley; Testosterone

Insulin resistance and disrupted secretion of adipokines are the major contributors to the pathogenesis of polycystic ovary syndrome (PCOS). Previous research has indicated that adiponectin/leptin (A/L) and HOMA/adiponectin (H/A) ratios have a strong association with insulin resistance and metabolic syndrome. The current study aimed to assess the predictability of the A/L and H/A ratios for PCOS women infertility and recurrent pregnancy loss (RPL). In this study, we investigated the association of A/L and H/A ratios with PCOS, as well as infertility and RPL in Iranian women with PCOS.. This case-control study included 150 PCOS (60 infertile and 90 PCOS-RPL) and 50 non-PCOS women. Clinical, biochemical, and hormonal features were evaluated, and the A/L and H/A ratios were calculated.. The A/L and H/A ratios were significantly decreased and increased in women with PCOS, respectively. A significant association was observed between the A/L and H/A ratios with PCOS, as well as PCOS-infertile and PCOS-RPL, even after adjusting for potential confounders. Although there was no significant difference between PCOS-infertile and PCOS-RPL subgroups, ROC curve analysis showed that A/L and H/A ratios could strongly predict PCOS with the area under the curve (AUC) of 0.867 and 0.861, respectively.. The ratios of A/L and H/A may serve as biomarkers to distinguish women with PCOS from non-PCOS in the Iranian population. However, it seems that they are not discriminatory markers for PCOS-associated RPL and infertility.

Topics: Adiponectin; Body Mass Index; Case-Control Studies; Female; Humans; Infertility; Insulin; Insulin Resistance; Iran; Leptin; Polycystic Ovary Syndrome; Pregnancy

The authors determined the level of Expression of Leptin (LEP) in Polycystic Ovary Syndrome (PCOS) patients with or without obesity and in GCs treated with insulin.. LEP expression was first assessed in ovary cortex specimens collected from women with PCOS with or without obesity as well as from healthy controls. Ovarian Granulosa Cells (OGCs) induced by insulin extracted from a mouse model were used in further functional research.. Real-time PCR and western blotting indicated that LEP expression was upregulated in GCs induced by insulin, in comparison with that in GCs not induced by insulin. Furthermore, the knockdown of LEP resulted in a reduction in growth and multiplication and an increase in apoptosis and inflammation in GCs induced by insulin. Next, the authors evaluated the effect of LEP on three key pathways of inflammation (MAPK, NF-kB, and JAK1/STAT3); results showed that the JAK1/STAT3 pathway was induced by LEP knockdown, as evidenced by the upregulation of phosphor-JAK1, phosphor-STAT3, and nuclear STAT3 expression. Administration of curcumin, a specific inhibitor of STAT3, counteracted the effect of LEP knockdown on cell inflammation and apoptosis.. The present data suggest that upregulation of LEP expression in the PCOS granulosa cell model is essential for reducing apoptosis and inflammation by modulating the JAK1/STAT3 pathway axis.

Topics: Animals; Apoptosis; Female; Granulosa Cells; Humans; Insulin; Janus Kinase 1; Leptin; Mice; Obesity; Polycystic Ovary Syndrome; STAT3 Transcription Factor

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus and subsequently on the food intake and obesity in females.. A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus and primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR, respectively. The leptin levels in the serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of the hypothalamus.. The excessive prepuberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of neuropeptide Y and agouti-related peptide mRNAs was upregulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake.. Androgen excess increased food intake in rats and promoted obesity by downregulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

Topics: Androgens; Animals; Body Weight; Eating; Female; Humans; Hyperandrogenism; Hypothalamus; Insulin; Leptin; Neuropeptide Y; Obesity; Polycystic Ovary Syndrome; Rats; RNA, Messenger; Signal Transduction; Testosterone; Weight Gain

To explore mechanisms that modulate gestational weight gain (GWG) in women with polycystic ovary syndrome (PCOS) and healthy controls.. Sub-sample of randomised controlled trials (PCOS) combined with a prospective cohort (controls).. Eleven Norwegian, Swedish, and Icelandic hospitals.. Pregnant women with PCOS treated with metformin (PCOS-M, n = 36) or placebo (PCOS-P, n = 37), and healthy pregnant women (HC, n = 15).. Serum levels of the appetite regulating hormones leptin, ghrelin, allopregnanolone, and soluble leptin receptor (sOB-R) were determined in the first and third trimesters.. Excessive GWG (eGWG) relative to body mass index according to Institute of Medicine (IOM) guideline. Serum leptin/sOB-R ratio, or free-leptin-index (FLI), as biomarker of leptin sensitivity. Serum ghrelin and allopregnanolone levels.. The overall prevalence of eGWG was 44% (38/86). Women with eGWG had higher first and third trimester FLI (P < 0.001), and lower third trimester allopregnanolone levels (P = 0.003) versus women with non-eGWG. The prevalence of eGWG was lower in PCOS-M versus PCOS-P (28% versus 62%, odds ratio = 0.4, 95% CI 0.2-0.8, P = 0.005). FLI decreased during pregnancy in PCOS-M (P = 0.01), but remained unaltered in PCOS-P and HC. Ghrelin and allopregnanolone levels were comparable in PCOS-M, PCOS-P and HC throughout pregnancy.. Excessive GWG is associated with enhanced leptin resistance, and attenuated physiological increase in serum allopregnanolone levels during pregnancy. Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS.. Metformin counteracts excessive weight gain and leptin resistance in pregnant women with polycystic ovary syndrome.

Topics: Appetite; Body Mass Index; Cohort Studies; Female; Gestational Weight Gain; Ghrelin; Humans; Leptin; Metformin; Polycystic Ovary Syndrome; Pregnancy; Pregnanolone; Prospective Studies; Randomized Controlled Trials as Topic

Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovaries. Its pathogenesis is still unclear. This study aimed to investigate the relationship between kisspeptin, leptin, neuropeptide Y (NPY), and neurokinin B (NKB) levels for evaluating the pathogenesis of PCOS.. Levels of these parameters were analyzed in 20 patients with PCOS, and 16 healthy adolescents.. Serum NPY levels were significantly higher in the obese and non-obese PCOS group (p<0.01). There was a negative correlation between the kisspeptin and the NKB levels (p<0.01) in the PCOS group but not in the control group. This negative correlation was also found in both PCOS groups (p<0.01). In the obese PCOS group, serum kisspeptin levels were significantly lower than the control and non-obese PCOS groups (p<0.05) although serum leptin and NPY levels were significantly higher in the obese PCOS group (p<0.01).. The high NPY levels in both obese and non-obese patients with PCOS indicate that NPY plays a role in the pathogenesis independently from obesity. Significantly high leptin and low kisspeptin levels in the obese PCOS group suggested that they may be associated with obesity rather than PCOS.

Topics: Adolescent; Body Mass Index; Female; Humans; Kisspeptins; Leptin; Neurokinin B; Neuropeptide Y; Polycystic Ovary Syndrome

Leptin may have important implications in polycystic ovary syndrome (PCOS)-related metabolic disorders. However, the changes in serum leptin levels in patients with PCOS and its predictive value for PCOS remain obscure. We intend to analyze the association between leptin and PCOS in this study.. The study comprised 89 patients with PCOS and 139 individuals without PCOS. Each group was stratified as either normal- or hyper-fasting serum insulin (FSI), and lean or overweight/obese; and the patients were further categorized as normal- or hyper-androgenic. The validity of leptin toward the diagnosis of PCOS, or leptin combined with total testosterone, dehydroepiandrosterone sulfate (DHEAS), and free testosterone was estimated by receiver operating characteristic (ROC) curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. Associations between the clinical and metabolic variables and PCOS were analyzed. The serum leptin levels of patients with PCOS were significantly higher than that of the control, and especially the PCOS in hyper-FSI, hyperandrogenimic and overweight/obese subgroups. The area under the ROC curve (AUC) of leptin was 74%, with cutoff value, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) 11.58 ng/mL, 77.5%, 62.6%, 57.0%, and 81.3%, respectively. Combined leptin and anti-Müllerian hormone (AMH) had the highest AUC (92.3%), excellent sensitivity (93.3%), moderate specificity (78.3%), PPV (73.5%) and NPV (94.8%). Serum leptin levels of the patients were correlated with the FSI, fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone levels. Elevated serum leptin was associated with a high risk of PCOS [. Substantially elevated serum leptin is significantly associated with PCOS. These findings warrant further investigations into the function of leptin in the pathogenesis of PCOS.

Topics: Anti-Mullerian Hormone; Body Mass Index; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome

The aim of the study was to evaluate adrenal axis hyperactivation measuring hair cortisol levels, and its influence on the relationship among metabolic parameters, inflammation markers and androgens in adult women with PCOS. 44 women (18-34 years) with PCOS diagnosis and a control group of 49 healthy women (19-35 years) were included. In both gropus body mass index (BMI) was calculated and waist circumference (WC) was measured. Hair cortisol, total serum testosterone (TT), serum cortisol, 25 OH vitamin D (25OHD), insulin, high sensitivity C-reactive protein (hsCRP), triglycerides (TG), HDL cholesterol (HDL), glucose and leptin were measured. Bioavailable testosterone (bioT) was calculated. Hair cortisol concentration was higher and significantly different in PCOS patients compared to the control group (130 vs 63 pg/mg of hair, p < 0.001). Subsequently, patients with PCOS were divided into two groups according to hair cortisol levels: group 1 with normal hair cortisol concentration and group 2 with levels above the upper limit of the reference values (128 pg/mg of hair). In group 2, TT significantly correlated with 25OHD, hsCRP, TG/HDL index, BMI, WC, insulin and HOMA (p < 0.05); bioT correlated with hsCRP and leptin (p < 0.05). Finally, 25OHD was inversely correlated with leptin and with TG/HDL index (p < 0.05). High hair cortisol concentration in patients with PCOS confirmed hyperactivation of the HPA axis. The associations observed were only found in patients with PCOS with high hair cortisol levels (> 128 pg/mg of hair), showing a possible effect of HPA axis in these associations.

Topics: Adolescent; Adult; Body Mass Index; C-Reactive Protein; Female; Hair; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Insulin Resistance; Leptin; Obesity; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Testosterone; Young Adult

Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder, affecting 5-10% of females with hyperandrogenism and prolonged anovulation.. This study was done to understand the serum leptin role in women with PCOS and its link with the body mass index (BMI) and insulin resistance (IR).. This 1-year study was conducted in the Departments of Obstetrics and Gynecology as well as Infertility Unite in AL-Diwaniyah Maternity and Pediatrics Teaching Hospital, Iraq, in which 40 patients with PCOS (study group) and 40 healthy (non-PCOS) patients (control group) participated. After BMI assessment, both the study and control groups were further stratified into subgroups as normal weight and overweight patients. Blood samples were obtained for all patients for the serum leptin level (SLL), fasting blood glucose (FBG), and serum insulin level. The HOMA-IR equation was used to estimate insulin resistance for all patients.. SLL of the PCOS women (mean ± SD, 22.29 ± 10.96 ng/ml) was significantly (P < 0.05) higher (17.89 ± 8.29 ng/ml) when compared to that of the control group. Insulin level was significantly elevated in the obese control and PCOS women (16.87 ± 3.52) µ UI/L and (15.09 ± 5.27) µUI, respectively, compared to normal BMI control and PCOS patients (P ≤ 0.01). Insulin resistance was significantly higher in obese (control and PCOS) patients (2.47 ± 0.40 and 2.30 ± 0.43, respectively), compared to normal BMI (control and PCOS) patients (P ≤ 0.01).. In obese patients, serum leptin significantly correlated with BMI in the presence of hyperinsulinemia and elevated insulin resistance.

Topics: Body Mass Index; Child; Female; Humans; Insulin Resistance; Insulins; Leptin; Obesity; Polycystic Ovary Syndrome; Pregnancy

We investigated the effects of aerobic training on adipokine concentrations in women with polycystic ovary syndrome (PCOS).. 120 women, including 60 with PCOS and 60 without PCOS, were divided into six groups (n = 20) based on body fat percentages of 22%-27%, 28%-32%, and 33%-37%. All groups were submitted the same evaluations before and after 16 weeks of aerobic training. These included anthropometric and hemodynamic analyses, cardiopulmonary tests, and laboratory tests. Two-way analysis of variance was performed to evaluate the differences between women with and without PCOS, effect of the body fat percentage, and effect of aerobic training.. Body fat and PCOS were associated with high values of blood glucose, insulin, and testosterone. Body fat also reduced adiponectin levels and increased leptin, tumor necrosis factoralpha (TNF-α), and interleukin-6 (IL-6). In contrast, the PCOS increased only TNF-α and IL-6 levels. In the PCOS group, aerobic training reduced insulin, triglycerides, leptin, and IL-6 levels. It also promoted an increase in adiponectin and high-density lipoprotein levels. However, aerobic training did not alter TNF-α concentrations.. The body fat potentiates metabolic impairments that may be harmful to women with PCOS. Aerobic training appears to promote an important beneficial effect on the metabolic regulation of adipokines, except TNF-α.

Topics: Adipokines; Adiponectin; Adipose Tissue; Body Mass Index; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Polycystic Ovary Syndrome; Tumor Necrosis Factor-alpha

<b>Background and Objective:</b> Leptin is a hormone produced by fat cells in adipose tissue that plays a biological role in metabolism, immune system control and energy flow regulation. The study's objective was to investigate serum leptin levels in PCOS females and determine how they are related to immunological and hormonal parameters. <b>Materials and Methods:</b> Thirty PCOS women were chosen for the study and compared to thirty healthy women as control samples, with both case and normal samples ranging in age from 18-36 years. WBC count, absolute numbers of neutrophils, lymphocytes, monocytes, eosinophils, leptin, Prolactin and serum IgA levels were measured. <b>Results:</b> The results showed the mean WBC, lymphocytes and eosinophil absolute numbers in PCOS women were significantly different. However, there was no significant difference in the absolute numbers of neutrophils and monocytes. The findings also revealed a significant increase in BMI, IgA, leptin and prolactin levels in PCOS when compared to controls. The results showed strong positive correlation coefficients between BMI and IgA (1.000**), WBC with neutrophils, lymphocytes and monocytes (0.797**, 0.790**, 0.712**), respectively and finally leptin and prolactin (0.474**). The same test, on the other hand, revealed an inverse correlation coefficient between BMI, IgA and prolactin (-0.376*, -0.376*, respectively with p<u><</u>0.05). <b>Conclusion:</b> A rise in the levels of the hormones leptin and prolactin, which were positively associated with the body mass index in women with PCOS, was found in the current study. The findings revealed that the hormones leptin and prolactin have an effect on some immune parameters in women with PCOS.

Topics: Adolescent; Adult; Female; Humans; Immunity; Immunoglobulin A; Leptin; Obesity; Polycystic Ovary Syndrome; Prolactin; Young Adult

Polycystic ovary syndrome is an endocrinopathy that mainly affects adolescent girls and young women of childbearing age. In girls, the presence of clinical and biochemical symptoms of hyperandrogenism should be particularly considered. The role of vitamin D deficiency in insulin resistance, inflammation, dyslipidemia, and obesity, i.e. in diseases associated with PCOS, has been investigated, which may suggest its involvement in the pathophysiology of the syndrome. Leptin has been shown to stimulate the formation of FGF23 in bones. There is a relationship between the incidence of dyslipidemia, adipose tissue mass and the concentration of fibroblast growth factor 23. The main aim of the presented research project is to assess the concentration of vitamin D, calcium, and selected hormones as well as the concentration of adipokines (leptin) in girls diagnosed with polycystic ovary syndrome.. The study included a population of 85 girls and young women aged 14 to 22 years. The study group included 37 girls who were diagnosed with polycystic ovary syndrome according to the modified Rotterdam's criteria. The control group consisted of 48 completely healthy girls. In the first stage of the study participants were required to answer background questions. Next, anthropometric measurements were performed. The laboratory tests assessed: leptin, FGF23, FSH, SHGB, total testosterone, DHEA-S, 25-OH-D3, PTH, calcium, androstadiene, AMH, glucose, insulin.. The vitamin D level in the group with polycystic ovary syndrome was lower than in the control group, but there was no statistically significant difference. The level of anti-Müllerian hormone was significantly higher in the group of girls diagnosed with PCOS compared to the control group. Statistically significant differences between both groups were also noted in the HOMA-IR value. The concentration of calcium, parathyroid hormone, FGF23 and leptin in the study and control groups showed no statistically significant difference.. In the studied group of girls with PCOS, no correlation between the level of vitamin D and selected parameters such as: AMH leptin, HOMA-IR and FGF23 was confirmed. On this basis, it can be assumed that additional vitamin D supplementation would not reduce the symptoms of polycystic ovary syndrome.

Topics: Adipokines; Adolescent; Androstadienes; Anti-Mullerian Hormone; Calcium; Dehydroepiandrosterone; Female; Fibroblast Growth Factor-23; Follicle Stimulating Hormone; Glucose; Humans; Insulin; Leptin; Parathyroid Hormone; Polycystic Ovary Syndrome; Testosterone; Vitamin D; Vitamins; Young Adult

We aimed to investigate the metabolic effects of HIIT exercise on PCOS patients and how it affects adiponectin, vaspin and leptin.. Twenty women with PCOS were included in the study and were divided into two groups. HIIT program was applied for 10 PCOS and Medium Intensity Continuous Training (MICT) program was applied for other 10 PCOS. At the beginning and at the end of the study, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride(TG), insulin, Adiponectin, Leptin, Vaspin levels of both PCOS groups were evaluated.. When PCOS patients by performed HIIT exercise for 12 weeks, we found that the levels of leptin and vaspin did not change while adiponectin levels increased. Moreover serum levels of insulin, TG, total cholesterol, LDL-C decreased but levels of HDL-C increased.. HIIT increased in the adiponectin levels in women with PCOS and provided more weight loss.

Topics: Adiponectin; Body Mass Index; Case-Control Studies; Female; High-Intensity Interval Training; Humans; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Serpins

Polycystic ovary syndrome (PCOS) affects over 10% of women. Insulin resistance, elevated free fatty acids (FFAs) and increased adiposity are key factors contributing to metabolic dysfunction in PCOS. We hypothesised that aberrant adipogenesis during adolescence, and downstream metabolic perturbations, contributes to the metabolic phenotype of adult PCOS. We used prenatally androgenised (PA) sheep as a clinically realistic model of PCOS. During adolescence, but not during fetal or early life of PA sheep, adipogenesis was decreased in subcutaneous adipose tissue (SAT) accompanied by decreased leptin, adiponectin, and increased FFAs. In adulthood, PA sheep developed adipocyte hypertrophy in SAT paralleled by increased expression of inflammatory markers, elevated FFAs and increased expression of genes linked to fat accumulation in visceral adipose tissue. This study provides better understanding into the pathophysiology of PCOS from puberty to adulthood and identifies opportunity for early clinical intervention to normalise adipogenesis and ameliorate the metabolic phenotype.

Topics: Adipogenesis; Adiponectin; Aging; Animals; Biomarkers; Disease Models, Animal; Fatty Acids; Female; Leptin; Polycystic Ovary Syndrome; RNA, Messenger; Sexual Maturation; Sheep; Subcutaneous Fat; Transcription, Genetic

For many patients, weight loss is a first-line measure recommended to reduce comorbidities associated with polycystic ovary disease. When lifestyle modifications such as diet and exercise are insufficient at achieving this goal, the addition of weight loss medications has proven effective for many patients. In patients with severe obesity, bariatric surgery is often used when other methods have been unsuccessful and has shown promising results for improving health and fertility in patients with polycystic ovary disease.

Topics: Bariatric Surgery; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome

Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of "adiposopathy.". A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program.. Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group.. The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction ("adiposopathy") in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

Topics: Acanthosis Nigricans; Adiponectin; Adipose Tissue; Adolescent; Adult; Asian People; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; India; Insulin Resistance; Interleukin-6; Leptin; Polycystic Ovary Syndrome; Tumor Necrosis Factor-alpha; Young Adult

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous complex disorder of defined aetiology. Some studies report its association with various endocrine, metabolic and immunological abnormalities. The hunger hormones ghrelin and leptin affect the pathogenesis of PCOS and might lead to the development of Metabolic Syndrome (MS) in obese women.. The study aims at evaluating the role of ghrelin and leptin level in females with polycystic ovary syndrome as a biochemical marker for the diagnosis and monitoring progression.. The study included one hundred PCOS patients and fifty apparently healthy subjects with regular menstrual cycle, visiting gynecology outpatient clinic of Kalar General Hospital, from the beginning of February 2015 to the end of June 2015. Body Mass Index (BMI) along with serum ghrelin, leptin, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and testosterone levels were measured for both groups. Serum leptin was determined using sandwich ELISA, while serum ghrelin was determined using competitive ELISA. Differences between patient and control groups were assessed by using a t-test. Also, one-way Anova was used to test the relationships among different groups.. A significant decrease in ghrelin level and an increase in leptin levels in women with PCOS were observed compared to the control group. Also, a significant elevation in serum levels of LH, Testosterone, Prolactin, and a decrease in serum FSH in PCOS patients were observed, when compared to the control group. Additionally, serum ghrelin decreased and serum leptin level increased significantly in women with PCOS compared to controls in all age and BMI groups.. A significant decrease in ghrelin and an increase in leptin in PCOS patients were observed than in controls, indicating that they are at high risk for metabolic syndrome development.

Topics: Adolescent; Adult; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Follicle Stimulating Hormone; Ghrelin; Humans; Iraq; Leptin; Luteinizing Hormone; Metabolic Syndrome; Middle Aged; Polycystic Ovary Syndrome; Testosterone; Young Adult

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinopathy among reproductive-aged women and related with body mass and insulin resistance. Adipocytokines produced by adipose tissue seems to take part in the hormonal and metabolic alterations that arise in PCOS. Fat mass and obesity associated (FTO) gene is linked with body mass index (BMI) and diabetes. Aims - To investigate the association between fat mass related adipocytokines and single nucleotide polymorphisms (SNPs) (rs9939609 T/A) in the FTO gene in women with PCOS. Study design - Cross-sectional study MATERIAL AND METHODS: FTO+rs9939609 gene polymorphism and serum spexin, adiponectin and leptin levels were determined in 91 PCOS women and 86 healthy controls. Study participants were subdivided according to BMI and comparisons were made within each group.. Serum spexin levels were not differed between study groups. Serum levels of adiponectin were found to be decreased in PCOS women with BMI lower than 25 kg/m2 (10.1 ± 5.6 vs 14.1 ± 9.1, p = 0.015). Serum leptin levels were elevated in obese PCOS women compared to healthy control group (2197.9 ± 596.3 pg/mL vs 1535.9 ± 812.1 pg/mL, p = 0.001). The prevalence of A risk allele of SNP rs9939609 was more frequent in PCOS patients than in the control group. PCOS risk was found to increase 3 times more in AA genotype when compared with TT genotype (OR = 3.04 95% CI: 1.243-7.309; p = 0.013).. Serum adiponectin and leptin levels may serve as independent markers for PCOS diagnosis. Moreover, the FTO+rs9939609 gene polymorphism increase susceptibility to PCOS development independent from serum adipocytokine levels.

Topics: Adiponectin; Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Genotype; Humans; Insulin Resistance; Leptin; Peptide Hormones; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide

Topics: Adult; Animals; Anti-Mullerian Hormone; Female; Humans; Hyperinsulinism; Insulin Resistance; Insulin Secretion; Leptin; Polycystic Ovary Syndrome; Rats; Young Adult

Adipokine leptin plays a crucial role in metabolic and reproductive functions. Leptin receptor has a soluble form that binds to leptin, thus modulating its level in the circulation. It has been indicated that the levels of leptin and leptin receptor and also LEP rs7799039 and LEPR rs1137101 polymorphisms are associated with metabolic disorders. In the present study, we assessed the levels of leptin and soluble leptin receptor (sOB-R), and also the frequency of rs7799039 and rs1137101 polymorphisms in healthy fertile women and patients with polycystic ovary syndrome (PCOS), inclusive of PCOS-infertile and PCOS-recurrent pregnancy loss (RPL) subjects.. A total of 324 PCOS patients- including 199 infertile cases and 125 patients with a history of RPL- and 144 healthy controls were enrolled in this study. Biochemical parameters and plasma leptin and sOB-R levels were measured by ELISA and the genotypes of rs7799039 and rs1137101 polymorphisms were determined using PCR- RFLP.. Plasma leptin and sOB-R levels were significantly higher and lower in PCOS, PCOS-infertile and PCOS RPL groups, respectively. The GG genotype frequencies of rs7799039 and rs1137101 polymorphisms were significantly different between PCOS-infertile women and non-PCOS subjects (P = 0.043, OR = 0.47, 95% CI = 0.22-0.97, and P = 0.01, OR = 0.31, 95% CI = 0.12-0.75, respectively). Increased LEP levels were associated with the risk of PCOS and RPL in women with PCOS (P = 0.039, OR = 1.203, 95%CI = [1.009-1.435] and P = 0.012, OR = 1.267, 95% CI = [1.054-1.522], respectively).. Polymorphisms rs7799039 and rs1137101 and circulating leptin and sOB-R levels were associated with infertility in Iranian women with PCOS. Further studies are needed to reveal the role of leptin in PCOS pathogenesis.

Topics: Adult; Female; Humans; Infertility, Female; Leptin; Polycystic Ovary Syndrome; Pregnancy; Receptors, Leptin

The present study was designed to elucidate the underlying mechanisms of Bao Gui capsule (BGC) against hyperandrogenism, insulin resistance and leptin resistance of PCOS. Letrozole was used to induce a PCOS model in rats, which were then randomly divided into four groups (n=9): Control, Model, high‑dose BGC (BGC‑H) and low‑dose BGC (BGC‑L) group. Serum levels of follicle‑stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), insulin, leptin, and interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α (TNF‑α) in the hypothalamus were determined by ELISA. Protein levels of cytochrome P450c17α and cytochrome P450 aromatase (P450arom) in ovaries were determined by immunohistochemistry and western blot analysis. Additionally, the expression of GLUT4 in uterus and muscle tissue, and NF‑κB, IKKβ and SOCS3 mRNA levels in the hypothalamus were evaluated. BGC significantly reduced body weight gain and decreased serum levels of LH/FSH, T, log T/E2, insulin and leptin compared with the PCOS model rats. Furthermore, BGC markedly reduced the expression of P450c17α and significantly increased the expression of P450arom in ovaries, and increased the expression of GLUT4 in uterus and muscle tissues. BGC also effectively reduced the level of IL‑6 and TNF‑α, and the expression of IKKβ, NF‑κB and SOCS3 in the hypothalamus of PCOS model rats. These results suggest that BGC may effectively improve hyperandrogenism, insulin resistance, endometrial receptivity and the low‑grade chronic inflammation in the hypothalamus.

Topics: Animals; Cytokines; Drugs, Chinese Herbal; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Glucose Transporter Type 4; Hyperandrogenism; Hypothalamus; Insulin; Insulin Resistance; Leptin; Luteinizing Hormone; Phytotherapy; Plant Preparations; Polycystic Ovary Syndrome; Rats; Testosterone; Uterus

Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10.

Topics: 17-alpha-Hydroxyprogesterone; Adiponectin; Adipose Tissue; Adolescent; Adult; Androgens; Biomarkers; Body Mass Index; Case-Control Studies; Female; Follicle Stimulating Hormone; Glucose; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Luteinizing Hormone; Metabolic Diseases; Polycystic Ovary Syndrome; Risk Factors; Sedentary Behavior; Tumor Necrosis Factor-alpha; Young Adult

Clinical and experimental evidences indicate that epigenetic modifications induced by the prenatal environment are related to metabolic and reproductive derangements in polycystic ovary syndrome (PCOS). Alterations in the leptin and adiponectin systems, androgen signalling and antimüllerian hormone (AMH) levels have been observed in PCOS women and in their offspring. Using a targeted Next-Generation Sequencing (NGS), we studied DNA methylation in promoter regions of the leptin (

Topics: Adiponectin; Adult; DNA Methylation; Epigenesis, Genetic; Female; Humans; Infant; Leptin; Male; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Receptors, Adiponectin; Receptors, Androgen; Receptors, Leptin

Since polycystic ovarian syndrome (PCOS) is prevalent in reproductive women with obesity and insulin resistance, adipocytokines are often accused and investigated for pathophysiology. The aim of this study was to evaluate the adiponectin and leptin levels in normal-weight women with PCOS.. Forty women with PCOS and 40 age and body mass index (BMI) matched controls were included in the study. Adiponectin and leptin levels in addition to other biochemical parameters were measured.. Leptin levels were statistically significantly higher in the study group compared to the control group (6.53 ± 2.670 vs 3.37 ± 2.002 ng/mL, p < 0.001 respectively). Although Adiponectin levels were lower in the study group compared to the control group (28.89 ± 16.124 μg/mL vs 31.05 ± 20.507, p = 0.714 respectively) the difference did not reach statistical significance. Leptin levels were positively correlated with fasting glucose, fasting insulin, free testosterone levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. Adiponectin levels were negatively correlated with BMI.. Adiponectin and leptin have been suggested to play a crucial role in the pathogenesis of PCOS. Different adipocytokine levels in the normal weight PCOS group compared to age and BMI matched controls support the idea that adipose tissue in this group of women has some distinctive features not only in high BMI subgroup but also in normal weight subgroup.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Case-Control Studies; Female; Humans; Insulin; Leptin; Polycystic Ovary Syndrome

Our study aimed to explore the relationship between leptin and IFN-γ in PCOS patients, and confirmed the effect of leptin-induced IFN-γ on granulosa cells furtherly.. 29 patients with PCOS and 36 healthy controls were enrolled. Leptin level and the proportion of Th1 cells were detected and association between them were analyzed. Meanwhile, peripheral blood mononuclear cells (PBMCs) isolated from PCOS patients were treated with leptin and then the proportion of Th1 was analyzed. Besides that, the apoptotic level of KGN cells was monitored after IFN-γ treatment.. In the circulation of PCOS patients, leptin level dramatically increased compared with controls. And, this was associated with upregulated Th1 cells proportion and IFN-γ level.. Our results indicated that leptin takes part in process of PCOS

Topics: Adult; Apoptosis; Case-Control Studies; Cell Line, Tumor; Female; Follicle Stimulating Hormone; Granulosa Cells; Humans; In Vitro Techniques; Inflammation; Interferon-gamma; Leptin; Leukocytes, Mononuclear; Luteinizing Hormone; Polycystic Ovary Syndrome; Prolactin; Receptors, Leptin; Testosterone; Th1 Cells

Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.

Topics: Adiposity; Animals; Body Weight; Diet; Dietary Carbohydrates; Estrous Cycle; Female; Fibrosis; Glucose Intolerance; Insulin Resistance; Leptin; Lipid Metabolism; Ovarian Follicle; Ovarian Reserve; Ovary; Oxidative Stress; Polycystic Ovary Syndrome; Rats; Rats, Wistar

Women with polycystic ovary syndrome (PCOS) are at an increased risk of developing insulin resistance and abdominal obesity in the state of an improper diet balance. Leptin is a peptide considered to be a satiety hormone that plays an important role in the long-term energy balance, whereas ghrelin is a hormone that controls short-term appetite regulation and is considered a hunger hormone. The aim of the present study was to assess the relationship between serum leptin and ghrelin concentrations and the dietary macronutrient content in PCOS women. We examined 73 subjects: 39 women diagnosed with PCOS by the Rotterdam criteria and 34 healthy controls, matched by the body mass index. The subjects completed a consecutive three-day dietary diary to identify the macronutrient and micronutrient intake. Serum concentrations of leptin and total ghrelin were measured and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The studied groups did not differ significantly in terms of the intake of macronutrients (proteins, fats, and carbohydrates) and serum concentrations of ghrelin and leptin (all

Topics: Adult; Body Mass Index; Case-Control Studies; Diet Records; Dietary Fats; Eating; Energy Metabolism; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Micronutrients; Nutrients; Polycystic Ovary Syndrome; Young Adult

To assess the variability and predictability of adiponectin, leptin, resistin and their ratios in non-obese and obese women with anovulatory polycystic ovary syndrome (aPCOS).

Topics: Adiponectin; Adult; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Predictive Value of Tests; Resistin; ROC Curve

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.

Topics: Animals; Blood Pressure; Body Composition; Body Weight; Disease Models, Animal; Drug Evaluation, Preclinical; Eating; Female; Glucagon-Like Peptide-1 Receptor; Heart Rate; Hyperandrogenism; Insulin Resistance; Leptin; Lipids; Liraglutide; Metabolic Syndrome; Polycystic Ovary Syndrome; Postmenopause; Random Allocation; Rats, Sprague-Dawley; Renin-Angiotensin System

BACKGROUND Intestinal dysbiosis, or dysbacteriosis, is an abnormal interaction between the intestinal microbiota and the host cells due to altered microbial diversity. This study aimed to investigate the metabolic effects and changes in the intestinal microbiota in newborn rats following exposure to increased levels of maternal androgens in a rat model of maternal polycystic ovary syndrome (PCOS). MATERIAL AND METHODS The administration of androgen developed the rat maternal PCOS model during pregnancy. Maternal rat ovarian follicles were counting and assessed by histology. The metabolic phenotype of newborn rats was evaluated and included an insulin tolerance test, a glucose tolerance test, and measurement of serum levels of triglyceride, insulin, cholesterol, adiponectin, and leptin. Expression of pro-inflammatory cytokines was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), serum levels were measured by enzyme-linked immunosorbent assay (ELISA), and proteins associated with adipose tissue remodeling and adipocyte differentiation were measured by Western blot. RESULTS Markers of systemic inflammation were significantly increased in the female offspring but not in the male offspring born to rat in the PCOS model. Following birth, newborn rats that received antibiotics showed an improved metabolic phenotype, with reduced serum lipid levels, insulin resistance, body weight, inflammation of adipose tissue, and serum levels of inflammatory cytokines compared with controls. Probiotics had no significant effects on these parameters in newborn rats. CONCLUSIONS In a rat model of maternal PCOS, exposure to androgens in utero resulted in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn female rats.

Topics: Adipose Tissue; Androgens; Animals; Animals, Newborn; Body Weight; China; Disease Models, Animal; Dysbiosis; Female; Gastrointestinal Microbiome; Glucose; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Male; Metabolic Diseases; Obesity; Ovarian Follicle; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley

The aim of the study was to investigate whether altered adipose tissue secretion of various adipokines is secondary to obesity, hyperandrogenism, and hyperinsulinemia or intrinsic to polycystic ovary syndrome (PCOS). This cross-sectional study included 151 women diagnosed with PCOS by the Rotterdam criteria and 95 healthy women matched by age, body mass index (BMI), and waist-to-hip ratio (WHR). Clinical, biochemical, and hormonal characteristics were assessed. Serum concentrations of ghrelin and adiponectin were found to be significantly lower and concentrations of leptin and resistin significantly higher in women with PCOS than in healthy women matched by age, BMI, and WHR. A PCOS diagnosis made the largest contribution to predicting serum levels of leptin, adiponectin, resistin, and ghrelin in all stepwise multiple regression models, which included PCOS diagnosis, BMI, WHR, luteinizing hormone, total testosterone, free testosterone and homeostatic model assessment of insulin resistance as independent predictors. Leptin, adiponectin, ghrelin and resistin levels may serve as independent biomarkers for the diagnosis of PCOS.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; Cross-Sectional Studies; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Resistin; Waist-Hip Ratio; Young Adult

Polycystic ovarian syndrome (PCOS) is of frequent occurrence in Saudi females and is often associated with obesity, insulin resistance, hypogonadotropic hypogonadism, and infertility. Since these features are also associated with leptin receptor (LEP-R) deficiency, several studies have attempted to link LEP-R gene polymorphisms to PCOS.. The purpose of this study is to assess the possible association of LEP-R gene polymorphism (rs1137101) with the main obesity-linked metabolic parameters in Saudi female patients affected by PCOS. A cohort of 122 Saudi female subjects, attending the outpatient's clinics at Makkah, Saudi Arabia and diagnosed with PCOS was investigated. Metabolic parameters in serum samples, including lipidogram, glucose, leptin, ghrelin and insulin and obesity markers (BMI, W/H ratio, HOMA) were assayed and compared with values from 130 healthy female volunteers (controls). The genotyping of rs1137101 polymorphism in the leptin receptor gene by amplification (PCR) followed by DNA sequencing, was conducted in both groups (PCOS and controls).. Waist/hip ratio (W/H ratio), leptin serum levels and triglycerides appeared to be associated with PCOS but, aside from W/H ratio (AA s GG p = 0.009), this association also occurred for controls. No significant association in the leptin gene polymorphic locus rs1137101 with PCOS was seen in the results of the present study. In the control group, BMI, W/H ratio, leptin, Insulin, and HOMA-IR were significantly higher in the GG genotype compared to AA.. Despite previous suggestion about a relationship between rs1137101, serum leptin levels, and PCOS, our studies do not show any statistical association and further investigations; possibly by also evaluating obese patients should be needed to elucidate this issue better.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Genotype; Humans; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Receptors, Leptin; Saudi Arabia

Epidemiological studies suggested that ethnic/racial background influences the associations of altered leptin secretion and leptin gene (LEP) polymorphisms with polycystic ovary syndrome (PCOS). We investigated the association between LEP variants and plasma leptin levels with PCOS in Tunisian and Bahraini Arab women.. Retrospective case-control study, involving 255 PCOS cases and 253 control subjects from Bahrain, and 320 women PCOS cases and 447 controls from Tunisia. LEP genotyping was done by allele exclusion on real-time PCR.. Minor allele frequencies of rs10487506, rs7799039, rs2167270, rs12706832, and rs10954173 LEP variants were not significantly different between PCOS cases and control women among Bahraini and Tunisians, even before applying the Bonferroni correction. Similarly, the genotype distribution of the tested LEP variants was comparable between women with PCOS and control women among Bahraini and Tunisian subjects. None of the tested LEP variants was linked with altered leptin serum concentrations. However, five-locus haplotype analysis identified GGGGG and GAGGG haplotypes to be positively, and haplotype AAGGG to be negatively associated with PCOS in Bahraini women, after adjusting for HOMA-IR. No LEP haplotype associated with PCOS was identified in Tunisians.. This is the first study to document differential contribution of LEP gene variants with PCOS according to ethnic/racial background of study subjects, highlighting the need for controlling for ethnicity in genetic association studies.

Topics: Adult; Arabs; Bahrain; Case-Control Studies; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Humans; Leptin; Linkage Disequilibrium; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Retrospective Studies; Tunisia

Polycystic ovary syndrome (PCOS) is an androgen excess disorder associated with obesity and adipose tissue disturbances. Our aim was to evaluate gene expression of adipocytokines and adipocyte characteristics in abdominal subcutaneous adipose tissue (SAT) of PCOS women.. Twelve PCOS (PCOSw) and 12 control (Cw) premenopausal women (BMI 20-35 kg/m. Both groups were comparable in age and BMI. Trunk fat mass amount (p = .043), serum and SAT leptin/adiponectin ratio (p = .034 and p = .028, respectively) and adipocyte area (p = .015) were higher in PCOSw compared to Cw. Interestingly, trunk fat mass was positively correlated with adipocyte area in PCOSw (r = 0.821, p = .023), while the inverse correlation was found in Cw (r = -0.786, p = .021). Only in PCOSw, adipocyte area was positively correlated with serum testosterone (r = 0.857, p = .014) and visceral adipose tissue volume (r = 0.857, p = .014).. Our results indicate that PCOS women present adipose tissue dysfunction in the subcutaneous compartment, characterized by an alteration in adipocyte size and leptin/adiponectin expression and secretion, probably associated with higher androgen concentrations.

Topics: Adipocytes; Adipokines; Adiponectin; Adult; Body Composition; Female; Humans; Hyperandrogenism; Intra-Abdominal Fat; Leptin; Polycystic Ovary Syndrome; Subcutaneous Fat

To examine the role of high-molecular-weight (HMW) adiponectin and its relationship to sympathetic activity in women with polycystic ovary syndrome (PCOS).. Cross sectional study using biobanked samples.. Not applicable.. Premenopausal women with PCOS (n = 46, Rotterdam diagnostic criteria) and without PCOS (n = 22).. None.. High-molecular-weight adiponectin levels with secondary outcomes of sympathetic activity and leptin levels.. The high-molecular-weight adiponectin level was lower in women with PCOS (median 2.2 [interquartile range (IQR)2.3] μg/mL) than in controls (median 3 [IQR2.5] μg/mL) (age and BMI adjusted), and it correlated inversely with the values measured for homeostatic model of assessment of insulin resistance (HOMA-IR), fasting insulin, triglycerides, and free androgen index and positively with sex hormone-binding globulin (SHBG) and high-density lipoprotein cholesterol in all participants and in the PCOS group. In the PCOS group, sympathetic activity (burst frequency) was statistically significantly higher than in controls (median 26 [IQR11] vs. median 22 [IQR14], respectively) and correlated inversely with HMW adiponectin (r = -0.230). The leptin levels were similar between the women with PCOS and controls and did not statistically significantly correlate with HMW adiponectin or sympathetic activity. On multiple regression analysis, burst frequency and SHBG explained 40% of the HMW adiponectin variability (B = -0.7; 95% CI -1.2 to -0.2; and B = 0.01; 95% CI 0.004-0.01) in PCOS.. Alongside insulin resistance, increased sympathetic activity is associated with and may modulate HMW adiponectin levels in women with PCOS.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Linear Models; Lipids; Logistic Models; Molecular Weight; Multivariate Analysis; Polycystic Ovary Syndrome; Premenopause; Randomized Controlled Trials as Topic; Sex Hormone-Binding Globulin; Sympathetic Nervous System; Testosterone; Young Adult

Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin resistance and vascular pathologies. A total of 67%-85% of hyperandrogenic women suffer also from vitamin D deficiency. We aimed to check a potential interplay between hyperandrogenism and vitamin D deficiency in producing insulin resistance and effects on coronary resistance arteries. Adolescent female rats were divided into four groups, 11-12 animals in each. Transdermal testosterone-treated and vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D-supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin D plasma levels were measured, and oral glucose tolerance test was performed. In coronary arterioles, insulin receptor and vitamin D receptor expressions were tested by immunohistochemistry, and insulin-induced relaxation was measured in vitro on isolated coronary resistance artery segments. Testosterone impaired glucose tolerance, and it diminished insulin relaxation but did not affect the expression of insulin and vitamin D receptors in vascular tissue. Vitamin D deficiency elevated postprandial insulin levels and homeostatic model assessment insulin resistance. It also diminished insulin-induced coronary arteriole relaxation, while it raised the expression of vitamin D and insulin receptors in the endothelial and medial layers. Our conclusion is that both hyperandrogenism and vitamin D deficiency reduce sensitivity of coronary vascular tissue to insulin, but they do it with different mechanisms.

Topics: Animals; Arterioles; Biomarkers; Blood Glucose; Coronary Artery Disease; Coronary Vessels; Disease Models, Animal; Female; Glucose Tolerance Test; Gonadal Steroid Hormones; Hyperandrogenism; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Rats, Wistar; Time Factors; Vascular Resistance; Vasodilation; Vitamin D; Vitamin D Deficiency

Polycystic ovary syndrome (PCOS) is considered as one of the most frequently encountered hormonal pathologies in women during their reproductive years. Leptin and ghrelin, peptide hormones with adipostatic and orexigenic effect, respectively, seem to be involved in the metabolic changes that occur in PCOS. The aim of this study was to determine serum ghrelin and leptin levels in obese and lean Saudi women with PCOS and to investigate their relationship to the metabolic profiles in these women.. This study was conducted as a prospective, observational, cross-sectional, case-control study, at the Department of Obstetrics and Gynecology, Al-Noor Hospital, Makkah, Kingdom of Saudi Arabia. The study population included 252 women [130 women with PCOS (diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus, 2003) and 122 normo-ovulatory women as matched controls] attending the outpatient Gynecology Clinic. Demographic details were recorded, blood was extracted following overnight fast and serum was used for the determination of serum ghrelin and leptin levels and other hormonal and biochemical parameters including total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, and insulin. Insulin resistance and sensitivity were calculated as HOMA-IR and HOMA-S.. No significant differences in ghrelin (P = 0.1830) and leptin (P = 0.8329) levels were detected between the PCOS and control groups. However, ghrelin levels were significantly lower; and leptin levels were significantly higher in obese PCOS patients in comparison with lean patients (P = 0.0001 for both). In the PCOS group, there were significant correlations between ghrelin and leptin levels with Body Mass Index (BMI), waist-hip ratio, total cholesterol, triglycerides, HDL, LDL and insulin levels. Multiple regression analysis demonstrated that insulin was the main determinant for ghrelin (R. Although serum ghrelin and leptin levels were found to be normal in women with PCOS; yet, there is a relationship, possibly linked to obesity, hyperinsulinemia and insulin resistance between these levels and metabolic profile of Saudi PCOS.

Topics: Adult; Case-Control Studies; Female; Ghrelin; Homeostasis; Humans; Insulin Resistance; Leptin; Metabolomics; Obesity; Polycystic Ovary Syndrome; Saudi Arabia; Thinness

The plasma leptin-adiponectin ratio (L:A) has been suggested as a one of the potentially independent predictor of metabolic risk and Insulin resistance in women with polycystic ovarian syndrome (PCOS).. This is a case-control study, total 439 female subjects, comprises in to two group 223 cases (PCOS) and 216 control (non-PCOS women) according to their clinical characteristics. Further both case and control group were sub-grouped in PCOS and non-PCOS with metabolic syndrome (wMetS) and without metabolic syndrome (woMetS) as per National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Anthropometrical measurements and biochemical analysis were done. Leptin and adiponectin level were estimated by enzyme-linked immunosorbent assay.. Results indicated that SAD, WHR, BMI, BP, lipid profile, FPG, fasting plasma insulin, IR (HOMA-IR), leptin and L:A ratio were significantly higher (p=<0.001) in PCOS women compare to non PCOS. Furthermore anthropometrical values and level of FPG, TC, TG, Insulin, IR (HOMA-IR) and L:A ratio were significantly high (p=<0.001) in PCOS wMetS compare woMetS, however HDL (p=<0.001) and adiponectin level (p=<0.001) were significantly low. The same trend was also found in comparison between with and without MetS among non-PCOS women. The correlation between L:A Ratio with different metabolic risk markers, L:A ratio was positively significant with SAD (r=0.97, p <0.001), FPG (r=0.96, p<0.001), TC (r=0.44, p<0.001), insulin (r=0.98, p<0.001), IR (r=0.97, p<0.001), Adiponectin (r=0.21, p<0.01) and negatively significant with HDL(r=-0.42, p<0.001) in PCOS wMetS whereas L:A ratio was also positively correlated with SAD, BMI, TG in PCOS woMetS.. Study concluded L:A ratio may be one of the potential biomarker for metabolic syndrome and insulin resistance which is independent for presence of PCOS disease.

Topics: Adiponectin; Adult; Biomarkers; Case-Control Studies; Female; Follow-Up Studies; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Polycystic Ovary Syndrome; Prognosis

We aim to assess the effects of metformin treatment on metabolic and endocrine parameters and genes expression related to the insulin-responsive pathway in polycystic ovary syndrome (PCOS). This study comprises twenty-eight obese mice divided into three metformin-treated groups for seven and twenty days and eight nonobese and nontreated ones. We found a significant decrease in glycemia after metformin treatment at days seven and twenty. However, we did not observe differences in body weight measurement. Histologically, after twenty days we observed follicular development with regression of androgenic effects. Levels of IGF-1R protein expression were low after twenty days of treatment, but LEP proteins showed an overexpression in the ovarian stroma. We assessed the IGF-1R and LEP mRNAs levels; data showed a significant overexpression of LEP after seven days of treatment, while the IGF-1R was downregulated. Metformin therapy seems to exert a beneficial effect on histological and anovulatory features, reducing follicular number and pyknosis formation, possibly involved in the reversion of androgenic stimulus. Expression of IGF-1 and LEPR indicates a relevant role in androgenic features reversion present in PCOS, hormonal equilibrium, body weight regulation, and glucose metabolism, therefore, under phenotype obesity and infertility regulation in this model.

Topics: Animals; Blood Glucose; Body Weight; Female; Gene Expression Regulation; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Metformin; Mice; Mice, Obese; Polycystic Ovary Syndrome; Receptor, IGF Type 1; Receptors, Leptin

To investigate the association of LEPR polymorphisms and plasma leptin and soluble leptin receptor (sOB-R) levels with polycystic ovary syndrome (PCOS) in Chinese women.. LEPR Lys109Arg (rs1137100) and Gln223Arg (rs1137101) polymorphisms of PCOS patients and the controls were genotyped. Plasma leptin and sOB-R levels of two groups were measured.. The genotypic distributions of Lys109Arg (rs1137100) differed between the PCOS and control groups. Plasma sOB-R levels increased significantly in PCOS patients and were associated with PCOS independent of BMI. Furthermore, luteinizing hormone, triglyceride and fasting blood glucose correlated significantly to PCOS patients' sOB-R levels.. LEPR Lys109Arg (rs1137100) was associated with PCOS susceptibility and genotype AA was deduced to be a protective factor for PCOS; sOB-R levels might be recognized as a new indicator for the severity of PCOS.

Topics: Adult; Alleles; Asian People; Case-Control Studies; China; Ethnicity; Female; Gene Expression; Gene Frequency; Genotype; Humans; Leptin; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Receptors, Leptin

Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high-intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development.

Topics: Animals; Aromatase Inhibitors; Body Weight; Disease Models, Animal; Female; Follicle Stimulating Hormone; Insulin; Leptin; Letrozole; Nitriles; Obesity; Physical Conditioning, Animal; Polycystic Ovary Syndrome; Progesterone; Rats; Testosterone; Triazoles

To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls.. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed.. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT.. This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Brain; Female; Ghrelin; Glucagon-Like Peptide 1; Gray Matter; Humans; Leptin; Magnetic Resonance Imaging; Obesity; Organ Size; Polycystic Ovary Syndrome; Young Adult

The objective of this study is to measure serum chemerin levels in women with polycystic ovary syndrome (PCOS) and assess their relationship with clinical, metabolic, and hormonal parameters. One hundred eighteen PCOS women and 114 healthy women were recruited in this study. Their blood pressure, body mass index (BMI), waist circumference and waist-to-hip ratio (WHR), fasting insulin (FIN), fasting plasma glucose (FPG), blood serum sex hormone, and blood lipid were measured. Serum chemerin, leptin, and adiponectin were measured by ELISA. Serum chemerin was significantly higher in the obese PCOS group (47.62 ± 11.27 ng/mL) compared with non-obese PCOS (37.10 ± 9.55 ng/mL) and the obese (33.71 ± 6.17 ng/mL) and non-obese (25.78 ± 6.93 ng/mL) control groups (p < 0.05). Serum chemerin was positively related to BMI, waist circumference, WHR, testosterone (T), FPG, FIN, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), LDL-C/high-density lipoprotein(HDL-C), TC/HDL-C and serum leptin, while negatively related to glucose-to-insulin ratio (G/I), HDL-C, and adiponectin levels. Multiple linear regression analysis revealed HOMA-IR, leptin, and TC were the significant influencing factors of chemerin levels (p < 0.05). Increased serum chemerin in PCOS woman with or without obesity suggested that chemerin may be involved in the development of the pathogenesis of PCOS.

Topics: Adiponectin; Adolescent; Adult; Blood Glucose; Blood Pressure; Body Mass Index; Case-Control Studies; Chemokines; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Linear Models; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Testosterone; Triglycerides; Waist Circumference; Waist-Hip Ratio; Young Adult

Due to the complex relationship between kisspeptin and the hypothalamic-pituitary-gonadal axis, the study was planned to measure the kisspeptin levels in polycystic ovary syndrome (PCOS) and to analyze the correlations between kisspeptin and PCOS-related reproductive, metabolic changes.. The study was designed as a prospective study in Dokuz Eylul University between December 2011 and September 2013. A total of 285 PCOS cases and 162 controls were recruited. After the antropometric measeruments and physcial examination, blood samples were taken for biochemical analysis.. In this study, kisspeptin had a positive correlation with LH and leptin levels in PCOS. In fact, the serum levels of kisspeptin and leptin does not differ statistically between PCOS and healthy women. There are limited data in the literature with regard to changes in kisspeptin levels and its relation with metabolic and hormonal disturbances.

Topics: Adult; Female; Humans; Kisspeptins; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Prospective Studies; Young Adult

Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats.

Topics: Animals; Body Weight; Eating; Female; Hypothalamus; Inflammation; Leptin; Letrozole; Nitriles; Ovary; Polycystic Ovary Syndrome; Rats, Sprague-Dawley; Suppressor of Cytokine Signaling 3 Protein; Triazoles

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS.. Cross-sectional study.. Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status.. Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic-hyperinsulinaemic clamp.. The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0.04) and women with PCOS (P = 0.01).. Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS.

Topics: Adult; Biomarkers; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Overweight; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Predictive Value of Tests; Resistin; Young Adult

Adipocytokines may alter normal metabolic function and play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). We prospectively evaluated a cohort of obese and non-obese women with PCOS and non-PCOS controls for both novel (chemerin and omentin-1) and established (leptin and adiponectin) adipokines. Compared with age-matched controls, non-obese women with PCOS had decreased serum omentin-1 (191.1 ng/ml versus 269.7 ng/ml, p = 0.0001), while serum chemerin was not significantly altered in women with PCOS (53.95 ng/ml versus 48.61 ng/ml, p = 0.11). The findings were similar in the entire group of women with PCOS. However, in women with PCOS, chemerin correlated with leptin (r = 0.508, p = 0.004), adiponectin (r = -0.36, p = 0.014), and the leptin/adiponectin (L/A) ratio (r = 0.605, p < 0.0001), while there were no such correlations with omentin-1. In women with PCOS, chemerin correlated with BMI (r = 0.317, p = 0.034), abdominal subcutaneous fat (r = 0.451, p = 0.0019), and insulin resistance (HOMA-IR, r = 0.428, p = 0.0034), while omentin-1 did not correlate with any parameter. These data suggest that chemerin although not significantly elevated in women with PCOS correlates with adiposity and insulin resistance, and it is the single best adipokine measured in this regard. Chemerin, through its inflammatory role as a chemo-attractant in adipose tissue, may be an important determinant of insulin resistance in PCOS.

Topics: Adiponectin; Adipose Tissue; Adiposity; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Chemokines; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Polycystic Ovary Syndrome

The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS).. This was a retrospective study.. Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated.. Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated.. Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women.. Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; Down-Regulation; Female; Glucose Metabolism Disorders; Hospitals, Urban; Humans; Insulin Resistance; Leptin; Medical Records; Obesity; Overweight; Polycystic Ovary Syndrome; Retrospective Studies; Risk; Taiwan; Up-Regulation; Young Adult

The aim of the study was to analyse the relationship between nutritional status, selected adipokines and plasma anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).. A prospective, cross-sectional study, involving 87 PCOS (48 obese) women and 67 non-PCOS women (36 obese). Anthropometric parameters were measured, and body composition was determined by the bioimpedance method. Fasting serum glucose, androgens, FSH, LH, SHBG, insulin, AMH, apelin-36, adiponectin, leptin and omentin-1 were measured.. Plasma AMH levels were significantly higher in PCOS compared to the non-PCOS group (7.8 ± 4.3 ng/ml vs 44 ± 2.4 ng/ml; P < 0.001). Furthermore, AMH levels were higher in both PCOS and non-PCOS normal weight than in obese subgroups (8.9 ± 4.4 ng/ml vs 7.0 ± 4.0 ng/ml; P < 0.05 and 5.1 ± 2.4 ng/ml vs 3.9 ± 2.3 ng/ml; P < 0.05). There were negative correlations between AMH levels and anthropometric parameters (body mass, BMI, fat mass and percentage, as well as waist circumference) and plasma omentin-1 concentrations (R = -0.28, P < 0.001; R = -0.30, P < 0.001; R = -0.36, P < 0.001; R = -0.34, P < 0.001; R = -0.23, P < 0.01; and R = -0.20, P < 0.05, respectively) in all study groups. In multiple regression analysis, circulating AMH level variability was explained by omentin-1 levels and anthropometric parameters (excluding waist circumference).. In this observational study, nutritional status appears to be the main factor influencing circulating AMH levels independent of PCOS. The observed AMH association with omentin-1 levels suggests that this adipokine may be a link between hormonal dysfunction of adipose tissue related to obesity and decreased AMH secretion.

Topics: Adipokines; Adiponectin; Adult; Androgens; Anti-Mullerian Hormone; Apelin; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Follicle Stimulating Hormone; GPI-Linked Proteins; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Lectins; Leptin; Luteinizing Hormone; Nutritional Status; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Sex Hormone-Binding Globulin; Young Adult

Almost 50% of the women with polycystic ovary syndrome (PCOS) are obese. Obesity in PCOS affects reproduction via various mechanisms. Hyperandrogenism, increased luteinizing hormone (LH) and insulin resistance play a pivotal role. Several substances produced by the adipose tissue including leptin, adiponectin, resistin and visfatin may play a role in the pathophysiology of PCOS. Infertility in PCOS is related to anovulation. For induction of ovulation, clomiphene citrate and human gonadotrophins are first- and second-line treatments, respectively. Other treatment modalities include the use of insulin sensitizers, such as metformin as well as aromatase inhibitors and laparoscopic ovarian drilling, while in vitro fertilization is the last resort. Obesity can adversely affect infertility treatment in PCOS. Diet and lifestyle changes are recommended for the obese women before they attempt conception. The use of anti-obesity drugs and bariatric surgery in PCOS require further evaluation.

Topics: Adipokines; Adiponectin; Female; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Infertility, Female; Insulin Resistance; Leptin; Life Style; Luteinizing Hormone; Metformin; Nicotinamide Phosphoribosyltransferase; Obesity; Ovulation Induction; Polycystic Ovary Syndrome; Resistin

Thuja occidentalis L. (Cupressaceae) has been used in folk medicine for the treatment of rheumatism, amenorrhea, cystitis, and uterine carcinomas, and as an abortifacient and contraceptive.. The present study aimed to determine whether T. occidentalis oil and α-thujone could be beneficial in the treatment of polycystic ovary syndrome (PCOS).. T. occidentalis oil and α-thujone were administered to rats with letrozole-induced PCOS for 21 days. At the end of 21 days, the rats were sacrificed and blood samples were taken by cardiac puncture. The levels of serum gonadotropins, steroids, blood lipid, leptin, and glucose and the values of antioxidant parameters were measured.. The results demonstrated that estradiol and progesterone levels significantly increased, while luteinizing hormone (LH) and testosterone levels decreased in the T. occidentalis- and α-thujone-administered groups. The plasma low-density lipoprotein-cholesterol (LDL-C), leptin, and glucose concentrations were also significantly decreased in the T. occidentalis and α-thujone groups when compared to the control group. Histopathological findings demonstrated that the T. occidentalis and α-thujone groups displayed good healing. According to the phytochemical analyses, 25 compounds were identified in the T. occidentalis oil. The main constituents of the oil were the monoterpene ketones α- and β-thujone, fenchone, and sabinene, as well as the diterpenes beyerene and rimuene.. T. occidentalis essential oil and its active component, α-thujone, can be used for the treatment of PCOS without inducing osteoporosis.

Topics: Animals; Bicyclic Monoterpenes; Blood Glucose; Catalase; Estradiol; Female; Glutathione Peroxidase; Leptin; Letrozole; Lipids; Luteinizing Hormone; Malondialdehyde; Monoterpenes; Nitriles; Oils, Volatile; Osteoporosis; Phytotherapy; Polycystic Ovary Syndrome; Progesterone; Rats, Sprague-Dawley; Superoxide Dismutase; Testosterone; Thuja; Triazoles

To evaluate the association of changes in adipokine ratios with polycystic ovary syndrome (PCOS) and related features as altered levels of the adipokines adiponectin, leptin, and resistin were linked with the pathogenesis of PCOS.. Case-control retrospective study.. Outpatient obstetrics/gynecology and adult endocrinology clinics.. Unrelated women with PCOS (n = 211) and age-matched control women (n = 215).. None.. Utility of adiponectin/leptin and adiponectin/resistin ratios as potential biomarkers of PCOS and associated features.. Significant differences in adiponectin but not leptin or resistin serum levels were seen between women with PCOS and control women. Ratios of adiponectin/leptin and adiponectin/resistin, but not leptin/resistin ratios, were statistically significantly different between PCOS cases and control women. Receiver operated characteristics area under the curve demonstrated sensitivity and specificity for adiponectin/leptin and adiponectin/resistin but not leptin/resistin ratios or individual adipokines as predictors of PCOS. Adiponectin/leptin and adiponectin/resistin ratios negatively correlated with body mass index, homeostatic model assessment, insulin resistance, and free insulin, testosterone, and sex hormone-binding globulin. In addition, adiponectin/resistin ratio negatively correlated with menarche.. Ratios of adiponectin/leptin and adiponectin/resistin constitute novel predictor factors to explain PCOS and associated features and thus may present target for novel therapeutics in PCOS.

Topics: Adiponectin; Adult; Biomarkers; Case-Control Studies; Female; Humans; Leptin; Polycystic Ovary Syndrome; Predictive Value of Tests; Resistin; Retrospective Studies; Young Adult

Polycystic ovary syndrome (PCOS) is clinically heterogeneous endocrine disorders. Insulin resistance-related proteins play a role in the etiopathogenesis of PCOS. Irisin is a newly identified myokine which act like adipokines. Irisin has been shown to be associated with the insulin resistance and metabolic syndrome. The purpose of this study was to determine the serum levels of irisin in PCOS patients and evaluate the correlations with other metabolic and hormonal parameters.. Thirty-five PCOS patients and 35 matched healthy controls were enrolled to study. Serum irisin levels, anthropometric, hormonal and metabolic parameters including HOMA-IR were measured. Linear regression analysis was employed to study the relationship between irisin and hormonal and metabolic parameters.. Serum irisin level in PCOS patients (mean value; 0.491±0.145 µg/mL) was significantly elevated when compared to control group (mean value 0.281±0.138 µg/mL) (p < 0.001). Linear regression analysis showed that serum irisin was positively associated with body mass index, luteinizing hormone, fasting insulin and total cholesterol in the overall patient population but not for PCOS group alone (p < 0.05).. Serum irisin level of PCOS patients was high compared to that of healthy control subjects. In patients with PCOS, this situation may be due to insulin resistance, when there is leptin resistance or metabolic syndrome.

Topics: Adipokines; Adult; Anthropometry; Biomarkers; Body Mass Index; Cholesterol; Female; Fibronectins; Humans; Insulin; Insulin Resistance; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Young Adult

Small for gestational age (SGA) birth has been associated with adipocyte dysfunction during later phases of life. Because SGA women are at a higher risk of developing polycystic ovary syndrome (PCOS), adipocyte dysfunction detected in patients with PCOS may be associated with SGA birth.. To determine whether SGA birth is related to altered serum markers of adipose tissue dysfunction during the third decade of life in Brazilian women. A secondary objective was to relate the presence of PCOS with serum markers of adipose tissue dysfunction.. Prospective cohort observational study.. A total of 384 women born at 37 to 42weeks of gestation from June 1, 1978 to May 31, 1979 in Ribeirão Preto, State of São Paulo, Brazil. After exclusion, 165 women participated in the study. Of these women, 43 were in the SGA group and 122 were in the adequate for gestational age group based on birth weight determined from cohort files.. Body mass index (BMI), arterial systolic and diastolic pressures, abdominal circumference and serum concentrations of total testosterone, fasting glucose and insulin, lipid profile, adiponectin, leptin and necrosis factor alpha tumor (TNFα).. BMI was an independent predictor of lower adiponectin (adjusted coefficient=-0.02, p=0.01) and higher leptin (adjusted coefficient=0.06, p=0.01) concentrations. The serum insulin concentration was associated with higher leptin (adjusted coefficient=0.03, p=0.02) and TNF-α (adjusted coefficient=0.01, p=0.03) concentrations. Having PCOS or being born SGA did not predict any markers of adipocyte dysfunction.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Cohort Studies; Female; Gestational Age; Humans; Infant, Small for Gestational Age; Insulin; Leptin; Lipids; Male; Polycystic Ovary Syndrome; Prospective Studies; Term Birth; Testosterone; Tumor Necrosis Factor-alpha

We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF).. We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17- β -estradiol (17 β -E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin).. In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW.. Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

Topics: Adult; Body Mass Index; Female; Follicular Fluid; Humans; Insulin; Leptin; Ovulation Induction; Polycystic Ovary Syndrome

The aim of this study was to estimate serum fetuin-A levels in lean and obese women with polycystic ovary syndrome (PCOS) and to find possible relationships between fetuin-A, metabolic factors and androgens in these patients.. In 25 lean (18-38 years, BMI 17.5-25.0 kg/m2) and 15 obese women (20-41 years, BMI 28.1-53.2 kg/m2) with PCOS, anthropometric indices and body composition were measured. Fasting serum fetuin-A, adiponectin, leptin, glucose, lipids, hsCRP, insulin, androgens and SHGB levels were estimated.. There was no significant difference in serum fetuin-A levels between lean and obese patients: 0.54 ± 0.13 g/L and 0.60 ± 0.14 g/L, respectively. We noted a correlation between BMI and leptin levels (r = 0.88; p < 0.0001) and a nearly significant negative correlation between BMI and adiponectin levels (r = -0.53; p = 0.11) in all subjects. In lean patients, we found a correlation between fetuin-A levels and ALT activity (r = 0.44; p < 0.05). In all participants, fetuin-A correlated directly with DHEA-S levels (r = 0.44; p < 0.03).. Serum fetuin-A levels were similar in lean and obese women with PCOS. We found an association between fetuin-A levels and ALT activity in lean patients and between fetuin-A levels and DHEA-S in all women. The role of fetuin-A in the mechanisms of insulin resistance, and its potential impact on androgenic hormones production in women with PCOS, need to be tested in further studies.

Topics: Adiponectin; Adult; alpha-2-HS-Glycoprotein; Biomarkers; Body Composition; Body Mass Index; Female; Humans; Insulin; Leptin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Risk Factors; Young Adult

The aim of the study was to estimate potential associations of vitamin D concentration with metabolic and hormonal indices in women with polycystic ovary syndrome (PCOS) presenting abdominal and gynoidal type of obesity.. Twenty-six women with PCOS (19-49 years old, BMI: 26.8-53.8 kg/m2), presenting predominantly abdominal and gynoidal type of obesity were recruited. Anthropometric measures, body composition using dual-energy absorptiometry, fasting serum 25-hydroxyvitamin D, leptin, glucose, insulin, homeostatic model of assessment (HOMA), lipids, androgens and sex hormone-binding globulin (SHGB) were estimated.. Vitamin D insufficiency was found in 2, and deficiency or deep deficiency in 12 patients. Levels of vitamin D were lower in obese than non-obese women, and in patients with abdominal as compared to gynoidal obesity (9.60±3.7 vs. 16.02±3.3 ng/mL, p<0.04). In obese women, vitamin D correlated negatively with all, except for gynoidal fat, measures of obesity fasting glucose levels, and HOMA. No correlations with androgens were found. In women with abdominal obesity vitamin D correlated with luteinizing hormone/follicle-stimulating hormone ratio (LH/FSH) and SHBG.. We demonstrated that women with PCOS are often vitamin D deficient. Its concentration was lower in patients with predominantly abdominal obesity as compared to subjects with gynoidal fat excess. In overweight/obese subjects with PCOS, vitamin D correlated with fasting glucose and HOMA. The correlation with LH/FSH suggests that vitamin D status may contribute to hormonal dysregulation. Further studies are needed to elucidate a potentially different impact of abdominal and subcutaneous fat on vitamin D metabolism.

Topics: Adult; Androgens; Blood Glucose; Female; Humans; Leptin; Metabolic Syndrome; Middle Aged; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Vitamin D; Vitamin D Deficiency; Young Adult

To analyze the level of serum leptin and its relations with insulin resistance in patients with polycystic ovary syndrome (PCOS) so as to investigate the clinical effect of aciesis in PCOS under treatment of metformin.. 86 cases with PCOS (observation group) and 100 non-PCOS women (as controls) were chosen as the objects for the study. Body mass index (BMI), serum leptin, fasting blood glucose, insulin and IR index were measured and the relativity analyzed. PCOS patients were randomly divided into group A and group B, with clinical effect of metformin observed.. Both serum leptin and insulin levels and the IR index in observation group were significantly higher than those in the control group (P < 0.001). In the PCOS group, leptin levels in patients with insulin resistance was significantly higher than that in patients who were without (P < 0.001). The leptin levels were positive correlated to BMI, insulin and IR index (P < 0.05), but not to fasting plasma glucose (P > 0.05). The rate of ovulation was 58.1% in group B, much higher than that in group A 27.9% (P < 0.05). The rate of pregnancy as 25.6% in group B was also much higher than that in group A 9.3% (P < 0.05).. In patients with PCOS, the levels of leptin and insulin were significantly elevated if the elevation of leptin levels was inherent in obesity. Both resistances on insulin and leptin might exist at the same time. The serum leptin was positively correlated with BMI, insulin and IR index. It seemed worthwhile to treat the patients with metformin in aciesis of PCOS to improve both the rates on ovulation and pregnancy.

Topics: Body Mass Index; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Metformin; Obesity; Polycystic Ovary Syndrome; Pregnancy

We reviewed emerging evidence linking serum levels and adipose tissue expression of leptin and adiponectin in women with polycystic ovary syndrome (PCOS). Previous data obtained by our group from a sample of overweight/obese PCOS women and a control sample of normal weight controls, both stratified by BMI, were reanalyzed. Circulating levels of leptin and adiponectin were determined by commercially available enzyme-linked immunosorbent assays. Adipose tissue total RNA was reserve-transcripted into complementary DNA samples, which were used as templates for quantitative real-time PCR amplification. Positive correlations were found between serum and mRNA levels for both leptin (r = 0.321; P = 0.005) and adiponectin (r = 0.266; P = 0.024). Determination of leptin and adiponectin serum levels could serve as an indirect method to assess adipocyte production, since leptin and adiponectin are predominantly produced by subcutaneous adipocytes in women.

Topics: Adiponectin; Case-Control Studies; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Subcutaneous Fat

To compare plasma kisspeptin, serum leptin, and serum retinol-binding protein 4 (RBP4) levels in women with and without polycystic ovary syndrome (PCOS) and to correlate these among each other and with clinical, hormonal, and metabolic parameters.. Ninety women, including 54 women with PCOS and 36 without PCOS, participated in this study. For all patients, history and physical examinations were performed and blood samples were collected between days 3 and 8 of a spontaneous bleeding episode in the PCOS group and during normal menses of controls. Plasma kisspeptin, serum leptin, and serum RBP4 levels were measured using specific commercial assays.. Kisspeptin, leptin, and RBP4 levels were significantly higher in the PCOS group than in controls. Kisspeptin and RBP4 levels were significantly higher among obese PCOS patients than controls. Leptin levels were higher among obese PCOS patients than non-obese PCOS patients or controls. Kisspeptin and leptin levels of PCOS patients were significantly correlated with RBP4 levels. When only obese PCOS patients were analyzed, kisspeptin levels correlated with only the free androgen index.. These findings suggest that kisspeptin, leptin, and RBP4 are associated with metabolic disturbances in women with PCOS.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Female; Gonadal Steroid Hormones; Humans; Insulin; Kisspeptins; Leptin; Obesity; Polycystic Ovary Syndrome; Retinol-Binding Proteins, Plasma; Young Adult

To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2.. Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters.. Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers.. A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Diabetes Mellitus; Female; Humans; Insulin Resistance; Lamin Type A; Leptin; Lipodystrophy, Familial Partial; Middle Aged; Mutation; Pedigree; Polycystic Ovary Syndrome; Sequence Analysis, DNA; Young Adult

Hyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships.. Blood sampling from overweight postmenopausal women (25 PCOS and 24 age- and BMI-matched controls) at baseline and during oral glucose tolerance test for measurement of insulin and glucose levels, baseline leptin, adiponectin, visfatin, retinol-binding protein 4, lipocalin-2, androgen, and high-sensitivity C-reactive protein (hs-CRP) levels and for calculation of insulin sensitivity (glucose-to-insulin ratio (G/I), quantitative insulin sensitivity check index, and insulin sensitivity index (ISI)), resistance (homeostasis mathematical model assessment-insulin resistance (HOMA-IR)), secretion (Δ of the area under the curve of insulin (ΔAUCI), first-phase insulin secretion (1st PHIS), and second-phase insulin secretion (2nd PHIS)), and free androgen indices (FAI).. PCOS women had higher insulin secretion indices, hs-CRP, androgen, and FAI levels than controls without differing in baseline glucose, insulin and adipocytokines levels, insulin sensitivity, and resistance indices. In PCOS women, FAI levels correlated positively with baseline insulin, ΔAUCI, HOMA-IR, and ΔAUCG and negatively with G/I; hs-CRP levels correlated positively with ΔAUCI and negatively with ISI. PCOS status, waist circumference, and 17-hydroxyprogesterone (17-OHP) levels were positive predictors for ΔAUCI. In all women, waist circumference was a negative predictor for ISI; 17-OHP and FAI levels were positive predictors respectively for baseline insulin levels and for 1st PHIS and 2nd PHIS.. Early postmenopausal PCOS women are characterized by hyperinsulinemia but attenuated insulin resistance. PCOS status and waist circumference are predictors of hyperinsulinemia while insulin sensitivity correlates negatively with FAI. The differences reported in adipocytokine levels between PCOS and non-PCOS women in reproductive years seem to disappear after menopause.

Topics: Adipokines; Androgens; Blood Glucose; Carbohydrate Metabolism; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Middle Aged; Nicotinamide Phosphoribosyltransferase; Polycystic Ovary Syndrome; Postmenopause

To evaluate the differences in adipokines, namely adiponectin, leptin, and ghrelin, in obese adolescent girls with or without polycystic ovary syndrome (PCOS).. Case-control study.. University hospital.. 38 adolescent girls (age 15-20 years). Group I: 17 Obese adolescent girls with PCOS (BMI ≥ 30 kg/m(2)); Group II: Control group of 21 obese adolescent girls (BMI ≥ 30 kg/m(2)).. Adiponectin, leptin, and ghrelin measurements.. LH, LH/FSH, and cortisol levels were significantly higher in the obese PCOS girls compared to the obese controls (6.94 ± 3.28 vs 4.44 ± 1.79; 1.50 ± 0.72 vs 0.90 ± 0.36; 16.02 ± 4.28 vs 12.46 ± 5.29; P < .05, respectively). Adiponectin, leptin, and ghrelin levels were similar between the obese PCOS girls and the obese controls (11.13 ± 6.00 vs 15.26 ± 12.66; 23.66 ± 11.54 vs 23.11 ± 11.17; 665.69 ± 402.12 vs 650.22 ± 467.73, respectively). Adiponectin negatively correlated with BMI (r = -0.32; P = .04) and positively correlated with fasting glucose (r = 0.40; P = .01). Leptin positively correlated with BMI (r = 0.534; P = .001), estradiol (r = 0.354; P = .02), and TSH (r = 0.374; P = .02). No significant correlation was found between ghrelin and the test parameters.. Among obese adolescents with PCOS, adiponectin, and leptin levels do not seem to be determined by the existence of PCOS, while ghrelin presents no significant correlation.

Topics: Adiponectin; Adolescent; Case-Control Studies; Female; Ghrelin; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Young Adult

The aim of the study was to analyse relationships between plasma apelin-36 and apelin-12 levels, nutritional status, insulin resistance and hormonal disturbances, as well as plasma adiponectin, leptin and resistin concentrations in PCOS women.. A cross-sectional study involving 87 PCOS (48 obese) and 67 non-PCOS women (36 obese). Anthropometric parameters and body composition were determined. Serum glucose, androgens, FSH, LH, SHBG, insulin, apelin-36, apelin-12, adiponectin, leptin and resistin were measured in the fasting state.. Plasma apelin-36 and apelin-12 levels were significantly higher in normal weight women than in the obese women with PCOS (3·1 ± 2·2 vs 1·2 ± 0·7 μg/l, P < 0·001; 2·9 ± 2·4 vs 0·5 ± 0·7 μg/l; P < 0·001 respectively). Both plasma apelin-36 and -12 levels correlated positively with adiponectin levels, and inversely with leptin or resistin levels. There was a negative correlation between plasma apelin-36, apelin-12 and serum LH levels. In addition, an inverse correlation between apelin-12 level and LH to FSH ratio was found. In multiple regression analysis 9% of LH variability was explained by apelin-12 levels (β = -0·14; P < 0·001).. Nutritional status seems to have different effects on apelin release, particularly, its active isoform, in women with PCOS compared with women without PCOS. This may be partially caused by changes in leptin and resistin secretion and may enhance pituitary-ovarian axis disturbances. The association between both isoforms of apelin and insulin resistance seems to be bidirectional.

Topics: Adiponectin; Adult; Apelin; Blood Glucose; Cross-Sectional Studies; Fasting; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Luteinizing Hormone; Nutritional Status; Obesity; Polycystic Ovary Syndrome; Resistin

The main purpose of the research is to compare serum leptin (Lep) levels and adipose tissue percentage in adolescents diagnosed with polycystic ovary syndrome (PCOS) and those in healthy subjects. The results showed a greater percentage of patients with increased adipose tissue and significantly higher serum Lep levels in the PCOS group compared to the healthy controls. It was proved that there is a correlation between Lep and body mass index, body adipose tissue, waist circumference and HOMA index. PCOS in adolescents is a condition related to highly predominant overweight and obesity with exceeding level of body adipose tissue and higher serum Lep levels compared to healthy age-matched controls.

Topics: Adipose Tissue; Adolescent; Body Composition; Estradiol; Female; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Prolactin; Testosterone; Waist Circumference

Five to ten percent of women of reproductive age suffer from polycystic ovary syndrome (PCOS). Leptin, NPY, galanin, cholecystokinin (CCK) are involved in the regulation of eating behavior. PPARγ are receptors that are probably involved in hyperandrogenism. This study was designed to assess associations between the Pro12Ala PPARγ2 gene polymorphism and satiety factors in PCOS. Fifty-four PCOS women and 51 healthy women were studied. Leptin, NPY, galanin, CCK levels, and genetic studies to detect Pro12Ala PPARγ2 gene polymorphism were assessed. The leptin levels in the PCOS women carrying Pro12Ala genotype were higher than in those with Pro12Pro and Ala12Ala. The PCOS women had higher leptin and NPY levels and lower galanin levels. Obese PCOS patients had lower CCK levels.. In the PCOS women, a single Ala allele may have a protective role as far as hyperleptinemia is concerned. The PCOS women may reveal a disrupted central leptin/NPY feedback loop with some shifts in food intake.

Topics: Adult; Body Mass Index; Cholecystokinin; Female; Galanin; Genotype; Humans; Hyperandrogenism; Insulin Resistance; Leptin; Neuropeptide Y; Obesity; Polycystic Ovary Syndrome; Polymorphism, Genetic; PPAR gamma; Satiation

Hyperinsulinemia and adipokines such as leptin and adiponectin with respective proatherogenic and antiatherogenic properties are reported to be the major contributors to pathogenesis of polycystic ovary syndrome (PCOS), including to the development of type 2 diabetes and coronary artery disease. In this study, the association of hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, high leptin-to-adiponectin (L/A) and adiponectin-to-leptin (A/L) ratios as risk factors associated with PCOS in Bahraini women was investigated.. Serum levels of insulin, leptin, adiponectin, cholesterol, triglyceride, A/L and L/A ratios were compared in women with PCOS and controls to investigate tentative and potential diagnostic markers for women with PCOS.. Insulin was significantly higher in PCOS cases than controls (15.0±3.0 vs. 6.5±1.72, P<0.001). Leptin was significantly higher in PCOS cases than in controls (39.9±4.6 vs. 26.4±3.4, P<0.001), whereas adiponectin was significantly lower in PCOS cases than in controls (8.7±3.0 vs. 11.1±3.6, P<0.001). In addition, L/A ratios were significantly higher in PCOS cases than in controls (4.8±2.7 vs. 2.3±1.6, P<0.001), whereas A/L ratios were significantly lower in PCOS cases than in controls (0.25±0.08 vs. 0.50±0.1, P<0.001). In multivariate logistic regression analyses, insulin [odds ratio (OR)=2.1, confidence interval (CI) 1.2-3.8, P=0.01], A/L (OR=1.6, CI 1.4-7.2, P=0.03), and L/A (OR=1.4, CI 1.2-2.0, P=0.04) were independently associated with PCOS. Receiver operating characteristic analyses showed that the best predictive markers for PCOS were insulin [area under the curve (AUC)=0.937, CI 0.887-0.989] L/A and A/L ratios (AUC=0.861, CI 0.786-0.936), indicating their high sensitivity and specificity for diagnosis of PCOS.. In Bahraini women with PCOS, insulin, L/A, and A/L ratios seem to be the best markers to distinguish women with and without PCOS.

Topics: Adiponectin; Adolescent; Adult; Bahrain; Biomarkers; Case-Control Studies; Diagnostic Techniques, Endocrine; Female; Humans; Insulin; Leptin; Polycystic Ovary Syndrome; Risk Factors; Sensitivity and Specificity; Young Adult

To evaluate in a cross-sectional study adiponectin and leptin levels in prepubertal and pubertal daughters of women with PCOS and their relationship to insulin sensitivity and reproductive features.. We studied 92 daughters of PCOS women (PCOSd) and 76 daughters of control women (Cd) matched by age and body mass index SD scores and distributed according to breast Tanner stage: prepuberty (Tanner 1), early puberty (Tanner 2-3) or late puberty (Tanner 4-5). In all girls an oral glucose tolerance test was performed. Leptin, adiponectin, sex steroids, SHBG, glucose, insulin and lipid profile were determined. Leptin-adiponectin ratio, free androgen index and insulin sensitivity (HOMA-IR and ISI composite) were then calculated.. Prepubertal PCOSd showed lower serum adiponectin compared to Cd (p=0.028), whereas during puberty no differences were observed between the groups. Leptin concentrations were similar in both groups in all Tanner stages. In addition, in PCOSd during early puberty, adiponectin showed a negative correlation with testosterone and leptin showed a negative correlation with ISI composite, which were independent of BMI SDS (r=-0.39; p=0.02 and r=-0.42; p=0.01).. These observations suggest that during the prepubertal period PCOSd exhibit abnormal adiponectin levels, independently of BMI. Moreover, leptin and adiponectin may be related to metabolic and reproductive abnormalities observed in PCOSd during the early stages of sexual development.

Topics: Adiponectin; Adolescent; Blood Glucose; Child; Cross-Sectional Studies; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Nuclear Family; Polycystic Ovary Syndrome; Puberty; Sex Hormone-Binding Globulin

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women in their reproductive age, is characterized by both reproductive and metabolic features. Recent studies in human, nonhuman primates, and sheep suggest that hyperandrogenism plays an important role in the development of PCOS. We investigated whether chronic dihydrotestosterone (DHT) exposure in mice reproduces both features of PCOS. Such a model would allow us to study the mechanism of association between the reproductive and metabolic features in transgenic mice. In this study, prepubertal female mice received a 90 d continuous release pellet containing the nonaromatizable androgen DHT or vehicle. At the end of the treatment period, DHT-treated mice were in continuous anestrous, their ovaries contained an increased number of atretic follicles, with the majority of atretic antral follicles having a cyst-like structure. Chronic DHT-exposed mice had significantly higher body weights (21%) than vehicle-treated mice. In addition, fat depots of DHT-treated mice displayed an increased number of enlarged adipocytes (P < 0.003). Leptin levels were elevated (P < 0.013), adiponectin levels were diminished (P < 0.001), and DHT-treated mice were glucose intolerant (P < 0.001). In conclusion, a mouse model of PCOS has been developed showing reproductive and metabolic characteristics associated with PCOS in women.

Topics: Adiponectin; Animals; Body Weight; Dihydrotestosterone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Humans; Immunohistochemistry; Insulin; Leptin; Lipid Metabolism; Luteinizing Hormone; Mice; Mice, Inbred C57BL; Ovarian Follicle; Ovary; Phenotype; Polycystic Ovary Syndrome; Reproduction; Reverse Transcriptase Polymerase Chain Reaction

Modulation of sex steroid pre-receptor in adipose tissue is important for the development of metabolic diseases, but its roles in the pathogenesis of polycystic ovary syndrome (PCOS) has not been fully characterized. Herein we compared the expression of key sex steroid converting enzymes in the subcutaneous adipose tissue (SAT) between patients with PCOS and the matched controls. Most of the sex steroid converting enzymes were highly expressed in the SAT, except 17α-hydroxylase (CYP17A1). Compared with the controls, PCOS patients showed significantly higher levels of 3β-hydroxysteroid dehydrogenase1-2 (3β-HSD1-2), aldo-keto reductase 1C 1-3 (AKR1C1-3) and leptin, but lower level of P450 aromatase and 5α-reductase 1. Interestingly, leptin was positively correlated to AKR1C2 expression and negatively to 5α-reductase1 as well as peroxisome proliferator-activated receptor γ (PPARγ). In summary, the expression of enzymes synthesizing testosterone and enzymes inactivating DHT and progesterone was higher in SAT of PCOS patients compared to controls. Correlation analysis indicated that increased leptin expression may be negatively related to local DHT level. These data suggested that sex steroid converting enzymes expression was different in SAT of PCOS patients that might contribute to abnormal testosterone and leptin level of PCOS patients.

Topics: Adiponectin; Adipose Tissue; Adult; Dihydrotestosterone; Female; Humans; Leptin; Oxidoreductases; Polycystic Ovary Syndrome; PPAR gamma; RNA, Messenger; Testosterone; Young Adult

The objective was to investigate whether the associations between leptin, adiponectin, andadiposity reported in classic polycystic ovary syndrome (PCOS) are also observed in elderly women with a novel putative postmenopausal PCOS phenotype. We studied 713 postmenopausal community-dwelling women. Diagnosis of the novel phenotype required the presence of ≥3 diagnostic features including: 1) a personal history of oligomenorrhea; 2) history of infertility or miscarriage; 3) current or past clinical or hormonal evidence of hyperandrogenism; 4) central obesity; 5) biochemical evidence of insulin resistance. Women in the control group had ≤2 of these components. Mean age (±SD) was 74±8 years for the study cohort. Sixty-six women (9.3%) had the putative PCOS phenotype. Serum leptin was higher (mean 25.70±15.67 vs 14.94+9.89 ng/mL, P<.01) and adiponectin lower (mean 11.72±4.80 vs 17.31±7.45 μg/mL, P<.01) in cases vs controls. Leptin was positively, and adiponectin inversely, associated with an increasing number of phenotype features (P<.01 for linearity). In age-adjusted regression analysis, adjustment for waist circumference eliminated the association between leptin and the PCOS phenotype, but not the association between adiponectin and the PCOS phenotype. In this novel postmenopausal PCOS phenotype, adipocytokine profiles and their associations with adiposity parallel those reported in younger women with classic PCOS. These results support our hypothesis that a putative phenotype analogous to PCOS can be identified in postmenopausal women using clinical and biochemical criteria. Use of this novel phenotype could provide a basis for studies of the delayed consequences of PCOS in older women.

Topics: Abortion, Spontaneous; Adiponectin; Aged; Biomarkers; Body Mass Index; Female; Humans; Hyperandrogenism; Infertility, Female; Insulin Resistance; Leptin; Medical History Taking; Middle Aged; Obesity; Obesity, Abdominal; Oligomenorrhea; Phenotype; Polycystic Ovary Syndrome; Postmenopause; Premenopause

To investigate the role of adipocytokines in the pathophysiology of polycystic ovary syndrome (PCOS) by analyzing the messenger RNA (mRNA) expression and plasma levels of adipocytokines.. Cross sectional study.. Hospital.. Thirty-six women with PCOS, 17 lean (LP) and 19 obese (OP), and 24 age- and weight-matched controls, 8 lean (LC) and 16 obese (OC).. Subcutaneous adipose tissue and fasting plasma samples collected from 60 women, and insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance index (HOMA-IR).. mRNA expression of adiponectin, leptin, and interleukin-6 (IL-6) in adipose tissue, and plasma levels of leptin, adiponectin, resistin, visfatin, and tumor necrosis factor α (TNF-α).. The baseline data on body mass index (BMI), age, androgen levels, and insulin sensitivity was published previously. We found no independent effect of PCOS on the adipose expression of leptin, adiponectin, or IL-6 or on the plasma levels of adiponectin, leptin, resistin, visfatin, and TNF-α. Obesity was associated with increased mRNA expression of leptin, lower expression of adiponectin, and increased plasma levels of leptin.. Obesity is per se associated with increased adipose expression and plasma levels of leptin, lower expression of adiponectin, and marginally elevated expression of IL-6, but PCOS does not appear to have an independent effect on the adipose expression of leptin, adiponectin, and IL-6 or the circulating adipocytokines.. NCT00975832.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Gene Expression; Humans; Interleukin-6; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Polycystic Ovary Syndrome; Resistin; RNA, Messenger; Thinness; Tumor Necrosis Factor-alpha

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS).. We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet.. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group.. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Topics: Adipokines; Adiponectin; Adult; Anti-Obesity Agents; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Polycystic Ovary Syndrome; Resistin; Waist Circumference; Weight Loss; Young Adult

Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR.. The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR).. The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity.. The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

Topics: Adipokines; Adiponectin; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Case-Control Studies; CD11c Antigen; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Gene Expression Regulation; Humans; Insulin Resistance; Leptin; Macrophages; Obesity; Phenotype; Polycystic Ovary Syndrome; PPAR gamma; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; RNA, Messenger; Subcutaneous Fat; Tumor Necrosis Factor-alpha

Insulin resistance (IR) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS), but identification of insulin-resistant individuals is difficult. The homeostasis model assessment (HOMA), a surrogate marker of IR, is available in 2 computational models: HOMA1-IR (formula) and HOMA2-IR (computer program), which differ in incorporated physiological assumptions. This study evaluates the associations of the 2 models as markers of IR, the metabolic syndrome (MS), and PCOS.. Anthropometric, hormonal, and biochemical parameters were measured in 92 PCOS women and 110 controls. HOMA1 and HOMA2 were used to assess IR. Regression analyses were used to find the associations of the 2 models with different variables, MS, and PCOS.. The cutoff levels for definition of IR were HOMA1-IR ≥2.9 and HOMA2-IR ≥1.7. Mean HOMA1-IR (2.79) and HOMA2-IR (1.42) differed substantially. The difference (HOMA1-IR - HOMA2-IR) was significantly correlated with insulin, fasting plasma glucose, triglycerides, HDL cholesterol, waist circumference, leptin, and adiponectin (all P < 0.05). HOMA1-IR and HOMA2-IR were significantly associated with MS (odds ratio 5.7 and 4.2, respectively) and PCOS (odds ratio 3.7 and 3.5, respectively).. HOMA computational methods significantly affect the associations and cutoff values used for definition of IR. The correlations of the difference in the computational methods corroborate differences in captured physiological mechanisms. As precise identification of IR in PCOS patients is of practical importance, practitioners and researchers should be aware of these differences in the HOMA computational methods.

Topics: Adiponectin; Adolescent; Adult; Blood Glucose; Body Weights and Measures; Cholesterol, HDL; Computer Simulation; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Models, Biological; Polycystic Ovary Syndrome; Risk Assessment; Triglycerides; Young Adult

Luteinizing hormone (LH) concentrations and pulsatility are increased in obese women with polycystic ovary syndrome (PCOS). In addition, patients have hyperandrogenemia and insulin resistance. The mechanisms involved in aberrant hormone regulation in PCOS are still unclear. We investigated 15 obese PCOS women with a body mass index between 30 and 54 kg/m(2) and 9 healthy obese controls (body mass index, 31-60 kg/m(2)) with regular menstrual cycles. Subjects underwent 24-hour blood sampling at 10-minute intervals for later measurements of LH, leptin, testosterone, and insulin concentrations. Data were analyzed with a new deconvolution program, approximate entropy (and bivariate approximate entropy), and a cross-correlation network. Patients had increased LH pulse frequency and more than 2-fold greater daily LH secretion, with diminished pattern regularity. Testosterone secretion was increased 2-fold, but pattern regularity was similar to that in controls. In the network construct, insulin was correlated positively with LH, whereas leptin and testosterone were correlated negatively with LH. Bivariate synchrony of LH with insulin was decreased. Short-term caloric restriction paradoxically increased LH secretion by 1.5-fold and pattern irregularity, and reduced interpulse variability. Testosterone secretion and fasting concentrations of estradiol and sex hormone-binding globulin levels remained unchanged. Correlations between LH and insulin, leptin, and calculated free testosterone decreased. This study demonstrates marked alterations in the control of LH secretion in PCOS in the fed and calorie-restricted states. The ensemble results point to abnormal feedback control of not only the GnRH-gonadotrope complex, but also LH's relationships with leptin, insulin, and testosterone.

Topics: Adult; Female; Humans; Insulin; Leptin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Testosterone

To determine leptin and adiponectin serum levels and gene expression in subcutaneous adipose tissue from women with polycystic ovary syndrome (PCOS) and nonhirsute, ovulatory women; and leptin/adiponectin (L/A) ratio.. Case-control study.. University hospital gynecologic endocrinology unit.. Thirty-one women with PCOS and 57 controls.. Anthropometric, hormonal, and metabolic assessment; subcutaneous adipose tissue biopsy.. Leptin and adiponectin serum levels, L/A ratio, controlled by age, and gene expression in women with PCOS and controls, stratified by body mass index and variables associated with androgen excess and insulin resistance.. Serum leptin was higher in overweight/obese patients with PCOS than in all normal-weight control women. Adiponectin levels were similar in all subgroups. The L/A ratio was lower in normal-weight controls (1.80; range 0.94-3.72) than in overweight/obese controls (5.27; range 2.66-13.58) and patients with PCOS (7.73; range 3.81-15.04). Subcutaneous leptin messenger RNA was higher in overweight/obese women with PCOS than in normal-weight controls (2.316 [range 1.987-2.580] vs. 1.687 [range 1.518-2.212]). Adiponectin gene expression was similar in all groups. Positive correlations were found between serum and messenger RNA levels for both leptin and adiponectin. On multiple regression analysis, percentage of body fat contributed significantly to L/A ratio in PCOS, independently of body mass index and free androgen index.. In PCOS, altered adipocyte secretion seems to relate to adiposity rather than to androgen excess.

Topics: Adiponectin; Adiposity; Adolescent; Adult; Case-Control Studies; Female; Gene Expression; Humans; Insulin Resistance; Leptin; Obesity; Overweight; Polycystic Ovary Syndrome; Subcutaneous Fat, Abdominal; Validation Studies as Topic; Young Adult

The relationship between serum adipocytokines level and insulin resistance (IR) in polycystic ovary syndrome (PCOS) is unclear. Sixty-one patients with PCOS were divided into an IR group (n = 31) and a non-IR group (n = 30) using homeostasis model assessment (HOMA). Serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, total testosterone, insulin, glucose, and adipocytokines were measured by radioimmunoassay or enzyme-linked immunosorbent assay. The serum adiponectin level in women with PCOS and IR was lower than that of non-IR PCOS patients (P < 0.05); however, there were no significant differences between the two groups with regard to resistin, leptin, and leptin receptor levels (P > 0.05). And the levels of adipocytokines and IR are significantly correlated; consequently, adipocytokines may be involved in the development of IR in PCOS patients.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; China; Female; Follicle Stimulating Hormone; Humans; Insulin Resistance; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Progesterone; Receptors, Leptin; Resistin; Testosterone; Young Adult

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated.. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model.. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined.. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression.. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension.

Topics: Angiotensinogen; Animals; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Dihydrotestosterone; Disease Models, Animal; Estradiol; Female; Glomerular Filtration Rate; Glucose Tolerance Test; Kidney Diseases; Leptin; Metabolic Syndrome; Oxidative Stress; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System

The present study investigated the role of IGF1 in lactating lean and non-lactating obese dairy cows by injecting 1 μg IGF1 into the ovaries prior to superovulation. This amount of IGF1 has been linked with pregnancy loss in women with the polycystic ovary syndrome (PCOS) and was associated with impaired bovine oocyte competence in vitro. Transcript abundance and protein expression of selected genes involved in apoptosis, glucose metabolism, and the IGF system were analyzed. Plasma concentrations of IGF1 and leptin, and IGF1 in uterine luminal fluid (ULF), were also measured. IGF1 treatment decreased embryo viability in lean cows to the levels observed in obese cows. Obese cows were not affected by IGF1 treatment and showed elevated levels of IGF1 (in both plasma and ULF) and leptin. Blastocysts from lean cows treated with IGF1 showed a higher abundance of SLC2A1 and IGFBP3 transcripts. IGF1 treatment reduced protein expression of tumor protein 53 in blastocysts of lean cows, whereas the opposite was observed in obese cows. IGF1 in plasma and ULF was correlated only in the control groups. Blastocyst transcript abundance of IGF1 receptor and IGFBP3 correlated positively with IGF1 concentrations in both plasma and ULF in lean cows. The detrimental microenvironment created by IGF1 injection in lean cows and the lack of effect in obese cows resemble to a certain extent the situation observed in PCOS patients, where IGF1 bioavailability is increased in normal-weight women but reduced in obese women, suggesting that this bovine model could be useful for studying IGF1 involvement in PCOS.

Topics: Animals; Blastocyst; Cattle; Disease Models, Animal; Embryo Loss; Female; Gene Expression Regulation, Developmental; Glucose Transporter Type 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lactation; Leptin; Obesity; Oogenesis; Polycystic Ovary Syndrome; Pregnancy; Receptor, IGF Type 1; RNA, Messenger; Superovulation; Thinness; Tumor Suppressor Protein p53; Uterus

The aim was to analyze the effect of adipose tissue transplantation on growth differentiation factor-9 (GDF-9), insulin growth factor 1 receptor (IGF1R), and leptin receptor (LEPR) protein expression in ovaries of obese anovulatory mice. Leptin-deficient female (ob/ob) and wild-type mice were divided into untreated ob/ob mice and gonadal white adipose tissue transplanted ob/ob mice, with evaluation after 7, 15, and 45 days and compared to control wild-type mice. The corporal weight and glycemia levels increased in the obese group concomitant with polymicrocyst formation and abundant estrone, mimicking anovulatory disease. In the treated group after 45 days, glycemia, weight, ovarian size, and number of follicles were decreased and corpora lutea were decreased. The analysis of GDF-9 revealed that, whereas control ovaries presented follicular localization, the obese ovary lacked this protein. On the other hand, obese ovaries showed elevated expression of IGF1R that was normalized after the transplantation. Finally, LEPR was reduced in obese ovaries, and adipose tissue transplantation was efficient in returning it to normal levels. In conclusion, the adipose tissue transplantation, especially after 45 days, seems to stimulate ovulation, supported by the fact that several proteins involved in ovulation returned to basal levels.

Topics: Animals; Anovulation; Corpus Luteum; Female; Fertility; Growth Differentiation Factor 9; Intra-Abdominal Fat; Leptin; Mice; Mice, Knockout; Mice, Obese; Obesity; Organ Size; Ovary; Ovulation; Polycystic Ovary Syndrome; Receptor, IGF Type 1; Receptors, Leptin; Subcutaneous Tissue; Transplantation, Heterotopic

The causes of anxiety and depression in women with polycystic ovary syndrome (PCOS) remain elusive. To identify steps linking androgen signaling to the regulation of affective symptoms in vivo, we compared behavioral responses in female rats continuously exposed to DHT from puberty (a model of DHT-induced PCOS) and in rats exposed to DHT for 1week. Continuous and 1week of DHT exposure resulted in a general decrease in locomotor activity and time spent on the open arms in the elevated plus maze, indicating anxiety-like behavior. Rats with DHT-induced PCOS have increases in adiposity and circulating leptin levels accompanied by leptin resistance. One week of DHT exposure decreased androgen receptor (AR) expression in the hypothalamus and leptin synthesis and function in adipocytes; it also inhibited signal transducer and activator of transcription 3 (STAT3) and attenuated leptin activity by increasing levels of soluble leptin receptor, a leptin-binding protein, in the hypothalamus. This may affect the androgen-induced anxiety-related behavior in female rats. In conclusion, our results highlight the central role of androgens in behavioral function in female rats and suggest that androgens directly regulate the AR by decreasing its hypothalamic expression. Androgens also increase leptin synthesis in adipocytes, which drives central leptin signaling, and may regulate anxiety-related behaviors. Elucidating mechanisms by which androgens modulate female anxiety-like behavior may uncover useful approaches for treating women with PCOS who have symptoms of anxiety.

Topics: Androgens; Animals; Behavior, Animal; Body Weight; Brain; Cell Physiological Phenomena; Dihydrotestosterone; Disease Models, Animal; Female; Humans; Leptin; Maze Learning; Organ Size; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Receptors, Androgen

Obesity has an overall negative impact on fertility, affecting both women and men. Not only are obese individuals more likely to experience infertility, they are less likely to benefit from fertility treatment. Moreover, achieving pregnancy may place obese women at high risk for serious complications. It is important that obese individuals understand the effects that their obesity can have on reproductive function.

Topics: Adult; Female; Fertility; Humans; Infertility, Female; Insulin Resistance; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Pregnancy

To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS).. We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles.. Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH.. An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.

Topics: Adiponectin; Adult; Anti-Mullerian Hormone; Female; Humans; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Regression Analysis; Retinol-Binding Proteins, Plasma

We sought to verify if an oral contraceptive (OC) containing drospirenone affects the cardiovascular risk of patients with polycystic ovary syndrome (PCOS).. A total of 28 women with PCOS (16 lean [group A] and 12 overweight [group B]) were assessed at baseline and after 6 months therapy with an OC. Leptin, homocysteine, endothelin-1, and flow-mediated dilatation of brachial artery were measured.. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, did not change in group A; it improved significantly in group B after 6 months of treatment. At baseline and after therapy the plasma levels of homocysteine and endothelin-1 did not differ among the groups. Leptin was significantly lower at baseline in group A compared to group B.. The OC containing drospirenone does not seem to affect the surrogate markers of cardiovascular risk in lean patients with PCOS.

Topics: Adolescent; Adult; Androstenes; Brachial Artery; Cardiovascular Diseases; Contraceptives, Oral; Endothelin-1; Female; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Mineralocorticoid Receptor Antagonists; Obesity; Pilot Projects; Polycystic Ovary Syndrome

We previously demonstrated that low birth weight (BW) infant girls show increased serum anti-Müllerian hormone (AMH) concentrations and poststimulated estradiol levels compared to normal-BW infants, suggesting an altered follicular development. However, the impact of high BW on reproductive function is less known.. To evaluate the effect of BW on AMH, we determined the concentrations of this hormone in low-BW, normal-BW, and high-BW female infants during the first 3 months of life.. Twenty-seven low-BW, 29 normal-BW, and 28 high-BW infant girls were studied. We measured serum gonadotropins, steroid hormones, AMH, glucose, insulin, free fatty acids, IGF-I, and adiponectin in a fasting blood sample. In addition, in a subgroup of normal-BW (n = 23) and high-BW infants (n = 10), a GnRH analog leuprolide acetate test was performed.. Serum concentrations of AMH were higher in low-BW and high-BW infants compared to normal-BW infants (P = 0.028 and 0.022, respectively). In addition, in high-BW infants, adiponectin concentrations were lower (P = 0.018), and poststimulated FSH and estradiol levels were higher compared to normal-BW infants (P = 0.024 and 0.047, respectively).. Serum AMH and poststimulated estradiol concentrations are increased in low-BW and high-BW female infants, suggesting that these girls may show evidence of an altered follicular development. However, the increased poststimulated FSH levels and low adiponectin concentrations observed in high-BW infants suggest that ovarian function is perturbed through a different mechanism from that in low-BW infants.

Topics: Adiponectin; Adult; Anti-Mullerian Hormone; Birth Weight; Female; Follicle Stimulating Hormone; Humans; Infant; Infant, Newborn; Leptin; Polycystic Ovary Syndrome; Pregnancy

High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations.. Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS.. This was a cross-sectional study.. A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs).. A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8).. Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFalpha, PPARgamma, and AR were assessed.. HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFalpha (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls.. HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional/translational modification contributes to reduced HMW adiponectin in PCOS.

Topics: Adiponectin; Adult; Anthropometry; Blood Glucose; Body Composition; Body Mass Index; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Resistin; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Sex Hormone-Binding Globulin; Statistics, Nonparametric

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

Obesity and hyperandrogenaemia are key features of polycystic ovary syndrome (PCOS). The aim of this study was to investigate whether leptin and androgens are associated with obesity in PCOS subjects and identify whether there exist any genetic alterations in leptin gene in women with PCOS. The results reveal that leptin levels are elevated in women with PCOS and associate with BMI. However, irrespective of the obesity status leptin levels are higher in PCOS cases indicating that increased BMI/obesity may not be the only factor contributing to elevated levels of leptin. With regard to testosterone and androstenedione, the levels were increased in obese individuals irrespective of PCOS status. No correlation between leptin and androstenedione or testosterone was observed in controls and PCOS subjects. The single-nucleotide polymorphism G19A detected in the untranslated exon 1 of leptin gene was not associated with PCOS and does not contribute to elevated levels of leptin. The results overall suggest that androgen and leptin levels are increased in PCOS and obesity. It demonstrates that obesity is a confounding factor for hyperandrogenaemia irrespective of their PCOS status. The study rules out role of obesity status and leptin genotype in increase in leptin levels observed in PCOS cases.

Topics: Adult; Androstenedione; DNA; Female; Genotype; Humans; Leptin; Linear Models; Obesity; Polycystic Ovary Syndrome; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Testosterone

To assess metabolic parameters in the cord blood of newborns of women with polycystic ovary syndrome (PCOS) and to correlate these parameters with those of mothers with PCOS during midgestation.. Case-control study.. Unit of Endocrinology and Reproductive Medicine.. Thirty newborns of mothers with PCOS (PCOSn) and 34 newborns of control mothers (Cn) were studied.. A sample of cord blood was obtained at delivery. In all mothers, an oral glucose tolerance test (oGTT) with measurement of glucose and insulin was performed at 22-28 weeks of gestation. In cord blood and in the fasting sample of the oGTT, serum leptin, adiponectin, insulin, glucose, and lipids (triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) were determined.. PCOSn showed significantly higher leptin concentrations than Cn. Moreover, in PCOSn, leptin concentrations in cord blood were correlated with birth weight (r = 0.495) and body mass index of the mother at midpregnancy (r = 0.644).. The metabolic parameters in the cord blood of PCOSn are similar to those observed in controls, except for leptin concentrations, which are significantly higher. The latter could be related to the fetal adiposity or the metabolic condition of the mother.

Topics: Birth Weight; Blood Glucose; Body Mass Index; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Leptin; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Reference Values; Skull

To examine the serum visfatin, adiponectin and leptin levels in patients with polycystic ovarian syndrome (PCOS), and to explore the basis of the pathogenesis of PCOS.. A PCOS group (n=73) and a healthy control group (n=75) were included in the study, which were matched in age and body mass index (BMI). Serum visfatin, adiponectin, leptin, sex hormone levels, and metabolic parameters were measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA).. Serum levels of fasting insulin(Fins), homeostatic model assessment for insulin resistance (HOMA-IR), testosterone (T), luteinizing hormone (LH), and prolactin (PRL) in the PCOS group were significantly higher than those in the healthy group(all P<0.05),and follicle-stimulating hormone (FSH) level was significantly decreased in the PCOS group. The visfatin and leptin levels in the PCOS group increased significantly than those in the healthy group [PCOS group: (95.30+/-31.90) and (11.10+/-3.87) microg/L; healthy group: (73.20+/-20.30) and (7.21+/-2.47) microg/L,P<0.001]. The adiponectin level was significantly lower than that in the healthy group [PCOS group: (4.21+/-1.17) mg/L; healthy group:( 6.39+/-1.53) mg/L,P<0.001]. Pearson correlation analysis showed that visfatin level was negatively related to adiponectin levels (r=-0.452 and -0.378, P<0.01), but positively related to leptin and HOMA-IR levels in both the PCOS group and the healthy group (r=0.379-0.556, all P<0.01). The correlation remained between the visfatin and HOMA-IR levels in the PCOS group after correcting the influence of BMI. CONCLUSION Patients with PCOS have high visfatin and leptin levels but low adiponectin levels. Visfatin levels are positively related to insulin resistance.

Topics: Adiponectin; Adolescent; Adult; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Polycystic Ovary Syndrome; Young Adult

To compare serum leptin levels in women with polycystic ovary syndrome (PCOS) and healthy subjects, and to evaluate the relationship between leptin concentration and insulin resistance.. Forty-five women with PCOS and 20 controls were included in the study. Serum levels of leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, LH and FSH were measured. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed.. Serum leptin levels in PCOS patients were higher than in the control group independently of BMI, WHR and waist circumference. In PCOS patients there was a strong positive correlation between leptin and IRI (r = 0.592, p < 0.01) on the one hand, and leptin and HOMA-IR, on the other (r = 0.637, p < 0.01). In PCOS patients with more pronounced insulin resistance (IR) the correlation between leptin levels and HOMA-IR is independent of BMI, WHR and waist circumference. We did not find any correlation between leptin and other hormonal indices in PCOS patients.. Our study confirms the existence of a significant positive correlation between serum leptin levels and clinical and hormonal indices of IR. The hyperleptinaemia is probably due to leptin resistance and may be characteristic of the syndrome. The lack of correlation with other hormonal parameters is probably due to the heterogeneity of the PCOS group.

Topics: Adolescent; Adult; Body Mass Index; Case-Control Studies; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Leptin; Logistic Models; Obesity; Polycystic Ovary Syndrome; Statistics, Nonparametric; Testosterone; Waist Circumference; Waist-Hip Ratio; Young Adult

To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels.. Prospective case-control study.. Endocrine clinics in the community.. Forty-four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1.645] with PCOS; 16 were lean (BMI SDS <1.036) with PCOS; and 14 were lean (BMI SDS <1.036) without PCOS. Intervention Blood samples were collected from all girls between 8 and 11 am, after an overnight fast.. Serum levels of adiponectin, leptin, insulin, Müllerian-inhibiting substance, luteinizing hormone, follicle-stimulating hormone, testosterone, 17-alpha-hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17beta-oestradiol.. Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10.5 +/- 5.5 mug/ml) compared with that in lean girls with or without PCOS (16.9 +/- 8.64 and 18.0 +/- 7.4 mug/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12.3 +/- 12.2 vs. 4.5 +/- 2.9, P < 0.05), and compared with that in normal weight PCOS adolescents (7.4 +/- 4.9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin.. Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.

Topics: 17-alpha-Hydroxyprogesterone; Adiponectin; Adolescent; Body Mass Index; Case-Control Studies; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Humans; Insulin; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Prospective Studies; Testosterone

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovarian morphology and is a complex endocrine disorder that also presents with features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia. These latter symptoms form cardiometabolic risk factors predisposing individuals to the development of type 2 diabetes and cardiovascular disease (CVD). To date, animal models to study PCOS in the context of the metabolic syndrome and CVD risk have been lacking. The aim of this study was to investigate the JCR:LA-cp rodent as an animal model of PCOS associated with the metabolic syndrome. Metabolic indices were measured at 6 and 12 wk, and reproductive parameters including ovarian morphology and estrous cyclicity were assessed at 12 wk or adulthood. At 6 wk of age, the cp/cp genotype of the JCR:LA-cp strain developed visceral obesity, insulin resistance, and dyslipidemia (hypertriglyceridemia and hypercholesterolemia) compared with control animals. Serum testosterone concentrations were not significantly different between groups at 6 wk of age. However, at 12 wk, the cp/cp genotype had higher serum testosterone concentrations, compared with control animals, and presented with oligoovulation, a decreased number of corpora lutea, and an increased number of total follicles, in particular atretic and cystic follicles. The cardiometabolic risk factors in the cp/cp animals were exacerbated at 12 wk including obesity, insulin resistance, and dyslipidemia. The results of this study demonstrate that the JCR:LA-cp rodent may be a useful PCOS-like model to study early mechanisms involved in the etiology of cardiometabolic risk factors in the context of both PCOS and the metabolic syndrome.

Topics: Animals; Blood Glucose; Disease Models, Animal; Estrous Cycle; Fasting; Female; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Liver; Metabolic Syndrome; Ovary; Polycystic Ovary Syndrome; Rats; Receptors, Leptin; Risk Factors; Triglycerides

To investigate the correlations between adipocytokines and insulin resistance in women with polycystic ovary syndrome.. Sixty women with polycystic ovary syndrome aged 19-34 years old were divided into 2 groups: group A [n = 36, BMI > or = 25 kg/m(-2) or WHR (waist height ratio) > 0.85] and group B (n = 24, BMI < 25 kg/m(-2) and WHR < or = 0.85). Twenty-six healthy infertile women with a mean age of 26 + or - 8 years old served as controls and they were named as group C (n = 26, BMI < 25 kg/m(-2) and WHR < or = 0.85). Anthropometric measurements, hormonal profiles and metabolic profiles were compared between three groups. Plasma leptin, CRP and free fatty acid were measured by enzyme-linked immunosorbent assay (ELISA). Adiponectin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by radioimmunoassay. Insulin resistance was estimated by homeostasis model assessment (HOMA).. (1) Adiponectin and TNF-alpha levels were significantly higher in group B (17 + or - 9) mg/L and (1.0 + or - 0.3) mg/L respectively than in group A (10 + or - 7) mg/L and (0.8 + or - 0.2) mg/L respectively. Leptin was lower in group B (24 + or - 13) microg/L and group C than in group A (42 + or - 21) microg/L (all P < 0.01). IL-6 was higher in group A (173 + or - 184) ng/L and group B (184 + or - 44) ng/L than in group C (P < 0.05 and P < 0.01 respectively). No significant difference of circulating level of CRP was found between these 3 groups. (2) Leptin was positively correlated with BMI, WHR and HOMA-IR (all P < 0.01) whereas adiponectin was negatively correlated with BMI, WHR and HOMA-IR (P < 0.01; P < 0.01, P < 0.05 respectively). Multivariate regression showed that adiponectin was the most significant predictor of HOMA-IR and it explained 16.5% of variance.. The higher levels of leptin and TNF-alpha, the lower level of adiponectin in obese PCOS and the higher level of TNF-alpha and IL-6 in non-obese PCOS suggested different adipocytokines play different roles of insulin resistance in PCOS.

Topics: Adipokines; Adiponectin; Adult; Case-Control Studies; Female; Humans; Insulin Resistance; Interleukin-6; Leptin; Polycystic Ovary Syndrome; Tumor Necrosis Factor-alpha; Young Adult

Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin.

Topics: Adipokines; Adiponectin; Adult; Anovulation; Body Fat Distribution; C-Reactive Protein; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Lipids; Nicotinamide Phosphoribosyltransferase; Ovulation; Phenotype; Polycystic Ovary Syndrome; Retinol-Binding Proteins, Plasma; Waist Circumference

To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls.. Prospective case-control study.. University-based practice.. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]).. Cardiovascular risk markers and hormonal parameters were assessed.. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS.. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D.. Weight and PCOS are two independent variables affecting the endothelial function.

Topics: Adult; Androgens; Blood Flow Velocity; Brachial Artery; Case-Control Studies; Endothelin-1; Endothelium, Vascular; Female; Fibrinogen; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Menstruation; Overweight; Polycystic Ovary Syndrome; Progesterone; Vasodilation; Young Adult

To compare ghrelin and leptin levels in women with PCOS and healthy subjects and to evaluate the relationship between them and the heterogeneity of clinical and biochemical manifestations of women with polycystic ovary syndrome (PCOS).. 45 women with PCOS and 20 controls were included in the study. Serum levels of ghrelin, leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, LH and FSH were measured. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed.. Serum ghrelin levels in PCOS patients were lower (21.78 +/- 2.12 ng/ml vs. 34.67 +/- 3.57 ng/ml; p = 0.04) and leptin levels were higher (15,03 +/- 2,9 ng/ml vs. 6,16 +/- 0,60 ng/ml p = 0,048) than the control group. In group with PCOS negative correlation exists between ghrelin and testosterone (r = -0.315; p < 0.05) and between ghrelin and leptin levels (r = -0.306; p < 0.05). The latter correlation disappeared after partial correlation analysis controlling for BMI, WHR and HOMA-IR. In PCOS patients there were strong positive correlation between leptin and IRI (r = 0.592, p < 0.01) and HOMA-IR (r = 0.637, p< 0.01). In PCOS patients with more pronounced insulin resistance the correlation between leptin levels and HOMA-IR is independent of BMI, WHR and waist circumference.. Our study confirms the strong association that exists between serum leptin levels and clinical and hormonal indices of IR. The ghrelin level in women with PCOS reflects the metabolic and hormonal changes which are characteristics of the syndrome. The inverse correlation between ghrelin and leptin in these women is mediated through metabolic factors.

Topics: Adolescent; Adult; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome

The aim of the present study was to investigate the levels of leptin, resistin and ghrelin in polycystic ovary syndrome (PCOS), and to assess their possible correlations with the hormonal and metabolic features of PCOS.. Sixteen obese (ObPCOS) and 12 lean (LeanPCOS) subjects with PCOS and 19 obese control subjects were enrolled in the study.. Ghrelin, leptin and resistin concentrations were similar between groups when body mass index (BMI) was used as a covariate (P > 0.05). Mean androgen, SHBG, luteinizing hormone (LH) levels and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio tended to be similar between polycystic ovary syndrome (PCOS) groups. However, when compared with the control group, SHBG was lower and androgen, LH levels and LH/FSH ratio were higher in the PCOS groups. Free testosterone levels significantly correlated with resistin (r = -0.38), SHBG correlated significantly with body mass index (BMI) (r = -0.45) and resistin (r = -0.67), LH/FSH ratio was significantly correlated with ghrelin (r = -0.52) and estradiol (E2) levels (r = 0.51).. ObPCOS and LeanPCOS groups having higher LH/FSH ratios and lower SHBG levels suggest that there could be factors other than adiposity responsible for the clinical features of PCOS patients. In the light of our results, those factors can be suggested as ghrelin and E2 for the elevated LH/FSH ratio and resistin for the lowered SHBG.

Topics: Adolescent; Female; Ghrelin; Humans; Leptin; Polycystic Ovary Syndrome; Resistin

To compare ghrelin levels in women with polycystic ovary syndrome (PCOS) and healthy subjects and to evaluate the relationships between circulating ghrelin and the heterogeneity of clinical and biochemical manifestations of PCOS women.. Forty-five women with PCOS and 20 controls were included in the study. Serum levels of ghrelin, leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, luteinizing hormone and follicle-stimulating hormone were measured. Free androgen index and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.. Serum ghrelin levels in PCOS patients were lower than in the control group (mean+/-standard error of the mean: 21.78+/-2.12 vs. 34.67+/-3.57 ng/ml; p = 0.04). In women with PCOS, a strong negative correlation was observed between ghrelin values and the clinical (BMI, WHR, waist circumference) and hormonal indices of insulin resistance (IRI and HOMA-IR). The negative correlative relationship between ghrelin and HOMA-IR disappeared after partial correlation analysis when controlling for WHR and BMI. Negative correlation existed between ghrelin and testosterone (r = -0.315; p<0.05) and between ghrelin and leptin levels (r = -0.306; p<0.05). The latter correlation disappeared after partial correlation analysis controlling for BMI, WHR and HOMA-IR.. The ghrelin level in women with PCOS reflects the metabolic and hormonal changes which are characteristics of the syndrome. The inverse correlation between ghrelin and leptin in these women is mediated through metabolic factors.

Topics: Adolescent; Adult; Anthropometry; Body Mass Index; Case-Control Studies; Female; Ghrelin; Hormones; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Waist Circumference; Young Adult

To assess message expression of adiponectin and leptin in visceral and SC fat in women with polycystic ovary syndrome (PCOS) and in control women.. Prospective clinical trial.. Academic medical centers in Mexico City, Mexico and New York, New York.. Women with PCOS and control women.. Surgical biopsies of visceral (omental) and subcutaneous (SC) adipose tissue, fasting blood samples, and ultrasound measurements of visceral and SC fat.. Messenger RNA assessment of adiponectin and leptin in adipose tissue samples; serum measurements of adiponectin, leptin, glucose, insulin, and hormone levels; measurements of fat quantity by ultrasound. Correlative analyses as well as comparisons between women with PCOS and control women were performed.. Confirming previous data, women with PCOS had more insulin resistance, similar serum leptin, but lower serum adiponectin compared with control women. When control women were divided into quartiles by body mass index (BMI), messenger RNA expression of leptin and adiponectin decreased with increasing BMI. Adiponectin and leptin expression was significantly lower in women with PCOS; in weight-matched patients and control women, leptin and adiponectin expression was statistically significantly lower in SC tissue, and adiponectin expression was statistically significantly lower in omental tissue in women with PCOS. In control women, there was greater expression in SC tissue compared with in visceral tissue. There were significant negative correlations between visceral and SC fat mass by both ultrasound as well as adiponectin and leptin expression in women with PCOS. Serum adiponectin correlated statistically significantly with visceral adiponectin expression (r = 0.64) in women with PCOS, and there was a statistically significant correlation between SC adiponectin expression and the Quantitative Insulin-Sensitivity Check Index as a marker of insulin resistance (r = 0.43).. Adipocytokine expression in fat tissue appears to be down-regulated by an increased fat mass; this is particularly evident in the case of adiponectin expression in women with PCOS. It is probable that insulin resistance is a factor that may contribute, in part, to these findings.

Topics: Abdominal Fat; Adiponectin; Adult; Blood Glucose; Body Mass Index; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Mexico; New York; Polycystic Ovary Syndrome; Prospective Studies; RNA, Messenger; Subcutaneous Fat; Ultrasonography

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. Pharmacotherapy is often unsatisfactory. This study evaluates the effects of low-frequency electro-acupuncture (EA) and physical exercise on metabolic disturbances and adipose tissue mRNA expression of selected genes in a rat PCOS model characterized by insulin resistance and adiposity. Dihydrotestosterone (inducing PCOS) or vehicle (control) was administrated continuously, beginning before puberty. At age 10 wk, PCOS rats were randomly divided into three groups; PCOS, PCOS EA, and PCOS exercise. PCOS EA rats received 2-Hz EA (evoking muscle twitches) three times/wk during 4-5 wk. PCOS exercise rats had free access to a running wheel for 4-5 wk. EA and exercise improved insulin sensitivity, measured by clamp, in PCOS rats. Exercise also reduced adiposity, visceral adipocyte size, and plasma leptin. EA increased plasma IGF-I. Real-time RT-PCR revealed increased expression of leptin and IL-6 and decreased expression of uncoupling protein 2 in visceral adipose tissue of PCOS rats compared with controls. EA restored the expression of leptin and uncoupling protein 2, whereas exercise normalized adipose tissue leptin and IL-6 expression in PCOS rats. Thus, EA and exercise ameliorate insulin resistance in rats with PCOS. This effect may involve regulation of adipose tissue metabolism and production because EA and exercise each partly restore divergent adipose tissue gene expression associated with insulin resistance, obesity, and inflammation. In contrast to exercise, EA improves insulin sensitivity and modulates adipose tissue gene expression without influencing adipose tissue mass and cellularity.

Topics: Adipocytes; Adipose Tissue; Animals; Animals, Newborn; Dihydrotestosterone; Electroacupuncture; Female; Gene Expression Regulation; Insulin-Like Growth Factor I; Interleukin-6; Ion Channels; Leptin; Mitochondrial Proteins; Physical Conditioning, Animal; Polycystic Ovary Syndrome; Random Allocation; Rats; Reverse Transcriptase Polymerase Chain Reaction; Uncoupling Protein 2

Insulin resistance and obesity play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). It is known that experimentally induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion. It is not yet known whether the long-term insulin resistance as found in PCOS patients alters the leptin response to hypo- and hyperglycaemia.. We induced hyper- and hypoglycaemia by glucose clamp technique in 7 patients with PCOS and 20 healthy controls. After a plasma glucose level of 8.8 mmol/l was reached, the plasma glucose level was reduced stepwise to 6.8, 4.8 and 2.8 mmol/l.. The PCOS patients required lower glucose infusion rates to reach the glycaemic targets (P < 0.05). Serum insulin and C-peptide concentrations increased significantly during the clamp compared with the baseline in both groups (P < 0.001 for insulin, and P < 0.001, P < 0.005 for C-peptide control and PCOS, respectively) and increased significantly more in PCOS patients compared with the control group (both P < 0.05). Basal leptin levels were significantly higher in the PCOS group than in the control group (P = 0.005). In the controls, the leptin concentration increased significantly during the clamp (P < 0.001 for each glycaemic target), whereas in the PCOS group, leptin secretion increased only during hypoglycaemia (P = 0.04).. Compared with the healthy controls, the response of leptin secretion to hyper- and hypoglycaemia was diminished in PCOS patients. Changes in leptin secretion seem not to be caused by hyper- and hypoglycaemia, but rather by hyperinsulinaemia. Reduced insulin sensitivity seems to be responsible for the diminished leptin response, which might contribute to the obesity found in PCOS patients.

Topics: Adult; Blood Glucose; C-Peptide; Female; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome

The aim of this study was to investigate serum leptin, oxidized low density lipoprotein (ox-LDL) and asymmetric dimethylarginine (ADMA) levels and their interaction with dyslipidaemia in adolescents with polycystic ovary syndrome (PCOS).. The study group consisted of 23 obese (obPCOS) and 21 nonobese girls with PCOS (nPCOS), and 31 lean healthy controls. PCOS was defined by the National Institutes of Health (NIH) criteria as the presence of chronic oligoanovulation and hyperandrogenism. Fasting leptin, ox-LDL, ADMA and detailed lipid-lipoprotein profile were determined. Atherogenic index (AI) was calculated as [Total cholesterol - HDL cholesterol/HDL cholesterol]. Logarithmic transformations were made for ox-LDL.. Total cholesterol, triglycerides, LDL cholesterol, very low density lipoprotein (VLDL) cholesterol, apolipoprotein B, lipoprotein A levels and AI were higher and apolipoprotein AI was lower in obPCOS compared to those in controls (P < 0.05). LDL cholesterol, apolipoprotein B and lipoprotein A levels were higher in nPCOS compared to controls (P < 0.05). ADMA and ox-LDL levels did not differ in the three groups. Leptin was significantly higher in obPCOS compared with that in the other two groups (P < 0.001) and it was correlated with triglycerides (r = 0.62), VLDL cholesterol (r = 0.45), lipoprotein A (r = 0.38) and AI (r = 0.43) in the PCOS group (P < 0.05).. Our data demonstrate that ADMA and ox-LDL levels in adolescent PCOS subjects were not different than those in controls. Abnormal lipid profile was shown in obese and nonobese girls with PCOS and leptin was related with these lipid abnormalities in the PCOS subjects.

Topics: Adolescent; Apolipoproteins B; Arginine; Biomarkers; Case-Control Studies; Cholesterol; Cholesterol, LDL; Dyslipidemias; Female; Humans; Leptin; Lipoprotein(a); Lipoproteins, LDL; Lipoproteins, VLDL; Multivariate Analysis; Obesity; Polycystic Ovary Syndrome; Triglycerides

Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndrome (PCOS) through the dysregulated production of various adipokines. Polycystic ovary syndrome has also been described as a low-grade inflammation state characterized by elevated levels of C-reactive protein (CRP). Furthermore, CRP is a strong independent predictor of the metabolic syndrome and cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been proposed as a potential atherogenic index in obese type 2 diabetic patients. The aim of this study was to evaluate the potential role of the A/L ratio in the metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with PCOS (38 normal-weight and 36 overweight-obese women). The A/L ratio was negatively correlated with BMI (r = -0.79 P < .001), homeostasis model assessment (r = -0.642, P < .001), triglycerides (r = -0.67, P < .001), and total cholesterol (r = -0.38, P < .01), and positively correlated with high-density lipoprotein cholesterol (r = 0.38, P < .01) and sex hormone-binding globulin (r = 0.39, P = .001). After controlling for BMI, the A/L ratio was independently associated with insulin resistance indexes and triglycerides. Furthermore, the A/L ratio was negatively correlated with CRP (r = -0.746, P < .0001). Multiple regression analysis revealed that BMI and the A/L ratio were the only independent significant determinants of CRP (beta = .436, P = .003 and beta = -.398, P = .007, respectively). Studying normal-weight and overweight-obese women separately, we found an independent association between the A/L ratio and CRP in both groups (beta = -.460, P = .009 in normal-weight women and beta = -.570, P = .001 in overweight-obese women). In conclusion, the A/L ratio may serve as a biomarker of both insulin resistance and low-grade inflammation, providing the link between these cardiovascular risk factors in women with PCOS.

Topics: Adiponectin; Adolescent; Adult; C-Reactive Protein; Cholesterol, HDL; Female; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a familial endocrine-metabolic dysfunction, increasingly recognized in adolescent girls with hyperandrogenism. However, it is difficult to establish whether the metabolic abnormalities described in PCOS are present before the onset of hyperandrogenism. In children, a strong association of adiponectin levels with metabolic parameters of insulin resistance has been described.. The objective of the study was to evaluate adiponectin serum concentrations and metabolic parameters in prepubertal and pubertal daughters of women with PCOS to identify girls with increased metabolic risk.. Fifty-three prepubertal and 22 pubertal (Tanner stages II-V) daughters of PCOS women (PCOSd) and 32 prepubertal and 17 pubertal daughters of control women (Cd) were studied. In both groups, an oral glucose tolerance test was performed with measurement of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, sex steroids, and lipids were determined in the fasting sample.. Both groups had similar chronological ages, body mass index sd score, and Tanner stage distribution. In the prepubertal girls, 2-h insulin was higher (P = 0.023) and adiponectin levels were lower (P = 0.004) in the PCOSd group, compared with the Cd group. In the pubertal girls, triglycerides (P = 0.03), 2-h insulin (P = 0.01), and serum testosterone concentrations were higher (P = 0.012) and SHBG lower (P = 0.009) in PCOSd, compared with Cd, but adiponectin levels were similar in both groups.. Some of the metabolic features of PCOS are present in daughters of PCOS women before the onset of hyperandrogenism. Adiponectin appears to be one of the early markers of metabolic derangement in these girls.

Topics: Adiponectin; Adult; Anthropometry; Biomarkers; Blood Glucose; C-Reactive Protein; Child; Child, Preschool; Estradiol; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Phenotype; Polycystic Ovary Syndrome; Radioimmunoassay; Risk Assessment; Sex Hormone-Binding Globulin; Testosterone

Our objective was to evaluate whether polycystic ovarian syndrome (PCOS)-associated infertility is related to alterations of leptin, leptin receptor (Ob-R), and the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signal 3 (SOCS3) system in the ovary.. A case-control study was conducted in a university hospital.. Thirty-one infertile PCOS women with oligoovulation plus polycystic ovarian morphology and 79 infertile women with tubal blockage (control) participated in the study. The subjects were stratified according to in vitro fertilization outcomes: successful and failed subgroups.. Serum and follicular fluid (FF) leptin levels were measured with ELISA. RT-PCR and Western blotting were performed to assess expression of mRNA encoding leptin and Ob-R and proteins of p-STAT3 and SOCS3 in granulosa cells (GCs).. Leptin levels in serum and FF of PCOS women were significantly higher than those of control (P < 0.01). There were no significant differences in expression of leptin mRNA and short and long Ob-Rs between PCOS and control (P > 0.05). The p-STAT3 level was decreased in PCOS compared with control (P < 0.01), whereas SOCS3 remained significantly unchanged (P > 0.05). Further analysis showed that serum and FF leptin levels were significantly higher, whereas p-STAT3 in GCs was lower in the failed subgroup of PCOS than those in the successful subgroup of PCOS (P < 0.05).. Hyperleptinemia and high FF leptin are important pathologies of PCOS with infertility. Lower levels of p-STAT3 in GCs may be related to ovarian leptin resistance and fecundity in PCOS women. Relatively high serum and FF leptin and low p-STAT3 in GCs may account for decreased fertilization, implantation, and pregnancy rates of in vitro fertilization in PCOS women.

Topics: Actins; Adult; Blotting, Western; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Fertility; Fertilization in Vitro; Follicular Fluid; Granulosa Cells; Humans; Infertility, Female; Leptin; Polycystic Ovary Syndrome; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

Leptin secretion exhibits a pulsatile, circadian pattern and may play a role in reproduction. No previous studies have compared leptin secretory burst characteristics in normal eumenorrheic women and women with polycystic ovary syndrome (PCOS) who are appropriately matched for body mass index (BMI). To determine if leptin secretory burst characteristics and/or the relationships of BMI, insulin, or testosterone to these characteristics differ between PCOS and normal women, we studied 9 normal eumenorrheic women and 9 women with PCOS. Each woman underwent blood sampling every 10 minutes for 24 hours to measure leptin and insulin under controlled conditions. Leptin secretory bursts were identified and characterized using multiparameter deconvolution procedures (Deconv), and the 24-hour periodicity of leptin was characterized with cosinor analysis. Relationships between BMI, area under the curve (AUC) insulin, and testosterone and leptin secretory burst characteristics in PCOS and normal women were sought using linear regression. There were no significant differences in mean serum leptin concentrations or in secretory burst characteristics between PCOS and normal women. Although the 24-hour serum leptin concentration correlated with BMI in both normal and PCOS women, leptin secretory burst mass correlated with BMI only in normal women. Similarly, the 24-hour serum leptin concentration correlated with serum insulin AUC in both normal and PCOS women; but insulin AUC correlated with leptin burst mass only in normal women. Although there was a strong trend toward a correlation between both mean 24-hour serum leptin concentration and leptin secretory burst mass with the serum testosterone concentration in normal women, such trends were not seen in PCOS women. Both normal and PCOS women exhibited a diurnal rhythm of leptin secretion with the peak occurring at night. However, neither the peak amplitude nor the timing of the peak amplitude differed between normal and PCOS women. The presence of strong relationships between BMI and insulin with both mean serum leptin and leptin secretory burst mass in normal women as opposed to PCOS women suggests that the mechanisms subserving leptin secretion differ in these 2 groups.

Topics: Body Mass Index; Case-Control Studies; Female; Humans; Insulin; Leptin; Polycystic Ovary Syndrome; Regression Analysis

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level.. We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 +/- 5.7 years) and 81 healthy controls (aged 25 +/- 4.0 years).. Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism.. In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 +/- 20.7 vs 45.4 +/- 25.0 vs 67.7 +/- 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 +/- 3.4 vs 6.4 +/- 2.5 vs 5.7 +/- 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 +/- 3.4 vs 12.7 +/- 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 +/- 3.9 vs 2.8 +/- 2.2, P = 0.0285).. Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.

Topics: Adult; Androstenedione; Blood Glucose; Body Composition; Body Mass Index; Cholesterol; Estradiol; Female; Humans; Hydrocortisone; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Obesity; Polycystic Ovary Syndrome; Receptors, Cell Surface; Receptors, Leptin; Sex Hormone-Binding Globulin; Statistics, Nonparametric; Testosterone; Thyrotropin

Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines.. A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured.. PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters.. These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors.

Topics: Adipocytes; Adiponectin; Adult; Blood Flow Velocity; Blood Glucose; Body Fat Distribution; Body Mass Index; Brachial Artery; Carotid Arteries; Case-Control Studies; Cytokines; Endothelium, Vascular; Female; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Peptide Hormones; Polycystic Ovary Syndrome; Prospective Studies; Resistin; Tunica Intima; Tunica Media; Vasodilation

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

To determine whether the infertile patients with polycystic ovarian syndrome (PCOS) is related to dysregulation of peritoneal fluid and serum leptin concentration, and to investigate the relationship between the leptin and some endocrine hormones in PCOS.. Twenty subjects with PCOS and 20 control women were included in the study. Peritoneal fluid and serum concentration of leptin, insulin, insulin-antibody, testosterone (T), estrogen (E(2)), and progestogen (P) were measured by radioimmunoassay (RIA).. Peritoneal fluid concentrations of leptin, insulin, T and insulin-antibody in PCOS patients were significantly higher than those of the control group (P<0.05). There was no statistically significant difference in peritoneal fluid E(2) and P between PCOS and the control group (P>0.05). The serum concentrations of leptin and T in PCOS were significantly higher than those of the control group (P<0.05), but the levels of insulin, E(2), P and insulin-antibody were not significantly different between the 2 groups (P>0.05). With the BMI> or =23 kg/m(2) subgroup in PCOS patients, the peritoneal fluid and serum concentrations of leptin, insulin and T were significantly higher than those of BMI 23 kg/m(2) subgroup (P<0.01). There was no significant difference in E(2)and insulin-antibody between the 2 subgroups (P>0.05). Pearson correlation analysis indicated that peritoneal fluid and serum leptin levels were positively correlated with BMI, insulin, T and insulin-antibody, but negatively correlated with E(2), with no significant correlation with P. Multiple stepwise regression analysis indicated that the factors that influenced the peritoneal fluid and serum leptin levels were BMI, insulin, T and E(2) ordinally.. Peritoneal fluid and serum leptin concentration and insulin,T, Ins-antibody level are abnormal in PCOS patients. Leptin may play an important role in the pathogenesis of PCOS. BMI is the main factor to correlate with leptin.

Topics: Adult; Ascitic Fluid; Autoantibodies; Estrogens; Female; Humans; Insulin; Leptin; Polycystic Ovary Syndrome; Progesterone; Testosterone

Authors estimate the influence of body mass on the leptin serum concentrations changes in course of 24 hours in twelve women with polycystic ovary syndrome (PCOS).. The course of leptin pulses was analysed in two volunteers' six-persons groups, both with PCOS. first group with BMI < 22 kg/m2 and the second group with BMI >26 kg/m2. The blood samples (0,5 ml) were taken from cubital vein in 15-20 minutes intervals through 48 hours. In the first day of clinical experiment three meals were accepted but in the second day the women were starved and they could drink only mineral water.. The significant difference in average leptin concentration in any woman's group between each experimental day was observed. The value of leptin pulses amplitude compared between both women's group on each experimental daytime was significant too. The results we got relating number of leptin pulses and their duration time compared between both women's group and into groups between night and day were not statistically significant.. For leptin pulses detection in blood the cluster method was applied, which confirmed the pulses appearance in leptin secretion in both woman's group.

Topics: Adult; Body Mass Index; Cluster Analysis; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Pulse

To identify the effect of IGF-1 and leptin on the hyperinsulinemia (HI) of patients with polycystic ovarian syndrome (PCOS).. The case-control compared method was applied to the study. Ninety-two PCOS and 92 control subjects were involved in the study. The group of PCOS was further divided into two subgroups of 46 PCOS-HI and 46 PCOS-NHI. The leptin, IGF-1 and other hormones such as serum testosterone, DHT, DHEA, DHEA-S were measured by RIA method.. Leptin and IGF-1 were higher in PCOS group (16.8 +/- 9.8 ng/mL, 214.8 +/- 131.6 ng/mL) than those in control group (11.6 +/- 6.8 ng/ mL, 118.0 +/- 82.9 ng/mL respectively, P < 0.05). Serum leptin level was higher in hyperinsulinemia group (9.2 +/- 10.2 ng/mL) than that in normal insulin group (12.5 +/- 7.6 ng/mL, P < 0.05). IGF-1 (208.7 +/- 109.7 ng/mL vs. 151.7 +/- 120.0 ng/mL, P = 0.66) and fasting glucose (5.1 +/- 0.5 mmol/L vs. 4.9 +/- 0.4 mmol/L, P = 0.15) had no significant difference between two groups. Multiple logistic regression showed that after the body mass index (BMI) adjusted, the testosterone, LH/FSH, DHT, DHEA, and DHEA-S, leptin and IGF-1 showed to be the independent risk factor for PCOS, but not to be for hyperinsulinemia in patients with PCOS.. The leptin and IGF-1 may contribute to the pathogenesis of PCOS, but the relationship between leptin, IGF-1 and hyperinsulinemia needs more researches to confirm.

Topics: Adult; Case-Control Studies; Female; Glucose; Humans; Hyperinsulinism; Insulin-Like Growth Factor I; Leptin; Logistic Models; Polycystic Ovary Syndrome; Risk Factors

Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes.. Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin, adiponectin, and resistin) as well as hormonal parameters and markers of insulin resistance as assessed by the quantitative insulin-sensitivity check index. Body mass index (BMI) was stratified into obese, overweight, and normal subgroups for comparisons between PCOS and controls.. Adiponectin was lower (P < 0.05) and resistin was higher (P < 0.05) while leptin was similar to matched controls. Breakdown of the groups into subgroups showed a strong body mass relationship for leptin with no changes in resistin although adiponectin was lower in PCOS, even controlling for BMI. In controls, leptin and adiponectin and leptin and resistin correlated (P < 0.05) but not in PCOS. In controls, all adipocytokines correlated with markers of insulin resistance but not in PCOS.. When matched for BMI status, decreased adiponectin in PCOS represent the most marked change. This alteration may be the result of altered adipose tissue distribution and function in PCOS but no correlation with insulin resistance was found.

Topics: Adipocytes; Adiponectin; Adult; Body Mass Index; Case-Control Studies; Female; Hormones, Ectopic; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Polycystic Ovary Syndrome; Resistin

To investigate the expression of leptin mRNA in luteinized granulose cells and the leptin level in serum and follicular fluid of non-obese patients with polycystic ovary syndrome (PCOS).. Granulosa cells were collected from the puncture fluid of follicle of 16 obese infertile patients with PCOS to undergo external fertilization. Fasting venous blood was collected while collecting the ova. RT-PCR was used to detect the expression of leptin mRNA in the granulosa cells. ELISA was used to detect the leptin level in the serum and follicular fluid. Twenty normal women undergoing external fertilization because of male infertility of their husbands were used as controls.. The expression of leptin mRNA (A value) was 1.5 +/- 0.4 in the obese infertile patients with PCOS and was 1.8 +/- 0.6 (P > 0.05) in the controls. Both the leptin levels of serum and follicular fluid were not different between the obese infertile patients with PCOS and controls (both P > 0.05). The leptin level in follicular fluid was significantly correlated with both the serum leptin level in the obese infertile patients with PCOS (r(s) = 0.838, P = 0.000) and the control group (r(s) = 0.712, P = 0.000). The expression level of leptin mRNA in the luteinized was not correlated with the leptin level of follicular fluid in both the obese infertile patients with PCOS and the control group (both P > 0.05). The fertility rate was not different between the obese infertile patients with PCOS (7/16) and the controls (9/24) (P = 0.693).. The expression of leptin mRNA is normal in the follicular fluid of the obese infertile patients with PCOS. The leptin levels in serum and follicular fluid of the obese infertile patients with PCOS are similar to those of normal women. The leptin level in follicular fluid depends mainly on the circulating leptin level.

Topics: Adult; Female; Follicular Fluid; Granulosa Cells; Humans; Infertility, Female; Leptin; Polycystic Ovary Syndrome; RNA, Messenger

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

Adiponectin is regarded as a possible link between adiposity and insulin resistance. Ghrelin and leptin are considered as signals of energy status. We evaluated the relationships between these peptides, androgens and insulin sensitivity in women affected by polycystic ovary syndrome.. Thirty-six women with PCOS were examined with euglycemic hyperinsulinemic clamp (to determine M/I, index of insulin sensitivity). Leptin, ghrelin, adiponectin, androgens, and SHBG were determined. Statistics was done using correlation analysis and backward stepwise multiple regression.. The positive correlation of adiponectin with testosterone remains significant even after adjustment for BMI (p = 0.01), M/I (p = 0.009) and for both M/I and BMI (p = 0.02). In multiple regression with testosterone, M/I, leptin and ghrelin as independent variables, the model including testosterone (p = 0.03) and ghrelin (p = 0.002) explained 49% of the variability (p < 0.0012) of adiponectin.. Both adiponectin and ghrelin can be involved in the pathophysiology of PCOS but their relation must be delineated further.

Topics: Adiponectin; Adult; Androgens; Biomarkers; Body Mass Index; Female; Ghrelin; Glucose Clamp Technique; Humans; Insulin Resistance; Leptin; Middle Aged; Peptide Hormones; Polycystic Ovary Syndrome; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone

The genetic property of subclinical eating behaviour (SEB) and the link between SEB and polycystic ovary syndrome (PCOS) has been studied before but the role of leptin within this connection has never been investigated. The objective of this study was 1). to study the genetic property of SEB. 2). To find a link between leptin, SEB and PCOS. One hundred and fifty four (77 pairs) female-female Iranian twins including 96 MZ individuals (48 pairs) and 58 DZ individuals (29 pairs) participated in the study. Clinical, biochemical and ultrasound tools were used to diagnose polycystic ovary syndrome. BITE questionnaire was filled out for subjects. Eight percent of subjects were diagnosed for subclinical eating disorder. No significant difference was found between intraclass correlation of MZ and DZ (z = 0.57, P = 0.569). Serum leptin level correlated significantly with bulimia score (P < 0.007). The mean (+/-SD) value for bulimia score was found to be higher among PCOS(positive) subjects (3.27 +/- 5.51) in comparison with PCOS(negative) subjects (2.06 +/- 4.48) (P < 0.001). The genetic property of subclinical eating disorder was not confirmed as shared environment might have played a major role in likeliness of DZ twins as well as MZ. Leptin is linked with both subclinical eating disorder and PCOS.

Topics: Adult; Bulimia Nervosa; Feeding and Eating Disorders; Female; Humans; Iran; Leptin; Polycystic Ovary Syndrome; Reference Values; Risk Assessment; Risk Factors; Surveys and Questionnaires; Twins, Dizygotic; Twins, Monozygotic

Patients with polycystic ovary syndrome (PCOS) usually are obese, insulin resistant and hyperinsulinemic. The known association between leptin, obesity and insulin action suggests that leptin may have a role in PCOS but this has only been addressed peripherally. This study was designed to assess the relationship between serum leptin and the anthropometric, metabolic and endocrine variables of obese (body mass index, BMI (3)30 kg/m(2)) and non-obese (BMI <30 kg/m(2)) PCOS patients. Twenty-eight PCOS patients and 24 control women subdivided into obese and non-obese groups were evaluated. Leptin, androgens, lipids, gonadotrophins and insulin-glucose response to the oral glucose tolerance test were measured by radioimmunoassay in all participants. The assays were done all in one time. The areas under the insulin curve (AUC-I) and the glycemia curve were calculated to identify patients with insulin resistance. Mean leptin levels were not significantly higher in patients with PCOS compared to the control group (21.2 +/- 10.2 vs 27.3 +/- 12.4 ng/ml). Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS (26.9 +/- 9.3 vs 14.1 +/- 7.0 ng/ml) and in the control group (37.3 +/- 15.5 vs 12.9 +/- 5.8 ng/ml). The leptin of the PCOS group was correlated with BMI (r = 0.74; P < 0.0001) and estradiol (r = 0.48; P < 0.008) and tended to be correlated with the AUC-I (r = 0.36; P = 0.05). Of the parameters which showed a correlation with leptin in PCOS, only estradiol and probably insulinemia (AUC-I) did not show a significant correlation with BMI, suggesting that the other parameters were correlated with leptin due to their correlation with BMI. Estradiol correlated with leptin in PCOS patients regardless of their weight.

Topics: Adolescent; Adult; Area Under Curve; Biomarkers; Body Constitution; Body Mass Index; Case-Control Studies; Estradiol; Female; Humans; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Prospective Studies

Insulin levels, insulin resistance, and leptin levels were evaluated in 47 women who developed ovarian hyperstimulation syndrome (OHSS) after participation in assisted reproduction technologies programs and in 47 matched controls who did not develop such a complication. Analysis of the results in relation to underlying polycystic ovarian syndrome and hyperinsulinemia revealed no association of insulin levels, insulin resistance, and leptin levels with the development of OHSS.

Topics: Adult; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy with symptoms such as obesity, insulin resistance and hyperandrogenemia. PCOS might be the result of a genetic disorder. Genetic discrepancy in the production of leptin, a product of the obesity gene, may lead to various endocrinopathies such as PCOS. The objective of this study was first, to ascertain the incidence of PCOS, using the gold standard; second, to ascertain the genetic property of leptin; and third, to evaluate the association between leptin concentration and PCOS. A total of 154 Tehran-resident female-female twins were studied. They included 48 pairs of monozygotic (MZ) and 29 pairs of dyzygotic (DZ) twins, aged 15-45 years. Clinical, ultrasound and biochemical findings were used to diagnose PCOS. The incidence of PCOS using biochemical and clinical features was 16.2%. The correlation coefficient between serum leptin levels of MZ twins was higher than that of the DZ twins. The serum level of leptin was similar between subjects with or without PCOS, irrespective of their zygosity. It was concluded that the incidence of PCOS is high among twins, and that leptin is likely to be genetically determined, although the effect of environmental factors cannot be denied. This study did not find any association between the diagnosis of PCOS and leptin level. However, the link between the two may lie with other entities such as eating disorders and/or obesity.

Topics: Adolescent; Adult; Diseases in Twins; Female; Humans; Incidence; Iran; Leptin; Middle Aged; Polycystic Ovary Syndrome; Twins, Dizygotic; Twins, Monozygotic

Topics: Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Metformin; Obesity; Polycystic Ovary Syndrome; Progestins; Risk Factors

To examine serum leptin concentrations in obese and lean patients with polycystic ovary syndrome (PCOS) to assess whether the changes in leptin levels are due to obesity or hormonal alterations.. Controlled clinical study.. Academic research environment.. Obese and lean women with PCOS.. Blood samples were collected before and after food consumption.. Serum leptin and insulin levels.. Serum leptin concentrations were significantly correlated with body mass index (r = 0.649) and also with HOMA (r = 0.535). However, after controlling for body mass index in a partial correlation analysis, no significant correlation was found between serum leptin levels and HOMA or hyperinsulinemia. While lean patients with PCOS had a significant correlation between leptin concentrations and obesity parameters, they did not show any significant correlation with insulin resistance parameters.. Although leptin concentrations in women with PCOS correlate with insulin resistance/hyperinsulinemia, this is related only to obesity.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Homeostasis; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome

To evaluate leptin levels in a sample of obese women with PCOS and compare the results with obese and non-obese control, to be ultimately correlated with BMI, and insulin sensitivity.. Leptin and insulin assays by immuno-radiometric method, glucose assay by enzymatic colorimetric method.. Leptin levels were significantly different between obese and non-obese subjects, and were significantly different between insulin resistant and non-insulin resistant obese PCOS, but were not significantly different between obese non-insulin resistant PCOS, and obese controls.. Body mass index and insulin resistance are the two main factors governing serum leptin levels.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Body Composition; Body Constitution; Body Mass Index; Body Weight; C-Peptide; Cyproterone Acetate; Dehydroepiandrosterone Sulfate; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin; Insulin Resistance; Leptin; Lipoprotein(a); Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

Our aim was to determine whether serum leptin level is regulated by thyroid hormones, lipid metabolic products and insulin resistance status in women with polycystic ovary syndrome (PCOS). A prospective case-controlled study was carried out in Istanbul University, Cerrahpasa School of Medicine in 25 lean PCOS (L-PCOS) women, 19 obese PCOS (O-PCOS) women and 28 normal women. The diagnosis of PCOS was established according to the clinical, hormonal (elevated luteinizing hormone and serum androgens) and ultrasonographic findings. Fasting serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), fasting glucose, insulin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C) and leptin were measured and compared in the three groups and the correlations between serum levels of leptin and other parameters were evaluated. Serum leptin levels were higher in the O-PCOS group, while its level was comparable between the L-PCOS and control groups. Serum levels of FT4 were significantly lower in both L-PCOS and O-PCOS groups than the control group. Women in both L-PCOS and O-PCOS groups were found to be significantly hyperinsulinemic and insulin resistant. Serum levels of TC, VLDL-C and TG were significantly higher in the O-PCOS group, while serum HDL-C level was lower. There was a poor correlation between serum leptin, and FT4, TC, TG, HDL-C and VLDL-C levels. A significant correlation was observed between serum leptin levels and both BMI and insulin resistance status in PCOS. We believe that, although thyroid hormones and lipid metabolic products do not seem to participate in the regulation of serum leptin levels, BMI and insulin resistance status may have a key role in women with PCOS.

Topics: Adult; Blood Glucose; Body Mass Index; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Polycystic Ovary Syndrome; Prospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine

To study the expression of leptin and long form of leptin receptors (Ob-R(L)) messenger ribonucleic acid (mRNA) and protein in endometrium during mid-luteal phase of patients with polycystic ovary syndrome (PCOS).. The expression of leptin and Ob-R(L) mRNA in endometrium during mid-luteal phase from 15 normal controls and 14 PCOS related anovulatory patients who underwent ovulation induction therapy were studied by in situ hybridization, and levels of leptin and Ob-R(L) protein were investigated by immunohistochemical methods.. The expression of Ob-R(L) mRNA and protein in endometrial glands of most patients with PCOS were weak or moderate positive, whereas the levels of Ob-R(L) mRNA and protein were moderate or strong positive in those of the controls, there was significant difference between the two groups; leptin mRNA and protein expression in endometrium of patients with PCOS and controls were not significantly different between the groups.. The expression of Ob-R(L) decreased in endometrium of mid-luteal phase in patients with PCOS during induced ovulation, which may be related to low pregnancy rate of patients with PCOS.

Topics: Adult; Endometrium; Female; Humans; Leptin; Polycystic Ovary Syndrome; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger

Topics: Female; Humans; Leptin; Polycystic Ovary Syndrome

The aim of this study was to evaluate serum leptin levels in women with polycystic ovary syndrome (PCOS) and in controls with normal or abnormal body mass index (BMI), since the literature data are contradictory. The study population comprised 34 women with PCOS and 30 regularly cycling women, with normal or abnormal BMI. PCOS was defined by clinical, ultrasonographic, and hormonal findings. The women were divided into four groups according to the diagnosis of PCOS and their BMI values. In all women serum levels of FSH, LH, prolactin, testosterone, androstenedione, DHEA-S, 17alpha-OH progesterone, SHBG, insulin, glucose and leptin were determined. It was found that: (a) there was a significant interaction between BMI and PCOS in increasing serum leptin levels; (b) the dominant factor for serum leptin levels in women of all Groups was BMI, followed by insulin; (c) once we corrected for BMI, it was found that there was a significant correlation between serum leptin levels and insulin values, as well as between serum leptin levels and testosterone concentrations; and (d) the QUICKI IR formula presented the most significant correlation with serum leptin levels than the other measures of insulin sensitivity. Our results showed that serum leptin levels in a subgroup of overweight women with PCOS and insulin resistance were higher than those expected for their BMI, and therefore leptin might interfere in the pathogenesis of this syndrome.

Topics: Adolescent; Adult; Analysis of Variance; Biomarkers; Body Composition; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Probability; Prognosis; Reference Values; Regression Analysis; Risk Assessment; Severity of Illness Index

Obesity affects about 44% of women with polycystic ovary syndrome (PCOS). Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the genes involved in the differentiation of adipose tissue. In an attempt to shed light on the high percentage of obesity in PCOS, we examined polymorphisms at exons 6 and 2 of the PPAR-gamma gene in 100 PCOS patients and in 100 healthy controls matched for age and body mass index (BMI). The T allele frequency of exon 6 was significantly higher (P < 0.05) in PCOS patients compared with control women. In addition, the BMI and leptin levels were significantly higher (P < 0.05) in PCOS patients carrying the C-->T substitution than in controls. There was no significant difference in leptin levels after normalization for BMI. The Pro(12)Ala polymorphism at exon 2 was unrelated to BMI and/or leptin levels in PCOS women. In conclusion, the higher frequency of the C-->T substitution in exon 6 of the PPAR-gamma gene in PCOS women suggests that it plays a role in the complex pathogenetic mechanism of obesity in PCOS, whereas the Pro(12)Ala polymorphism does not seem to affect BMI in PCOS women.

Topics: Adult; Alleles; Body Mass Index; Case-Control Studies; Cytosine; Exons; Female; Gene Frequency; Humans; Leptin; Polycystic Ovary Syndrome; Polymorphism, Genetic; Receptors, Cytoplasmic and Nuclear; Thymine; Transcription Factors

To evaluate the effects of metformin on gonadotropin-induced ovulation in patients with polycystic ovary syndrome (PCOS).. Forty patients with PCOS (study group) and 20 women with normal weight and menstrual cycle (control group) were enrolled. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), fasting glucose (FG), fasting insulin (FINS) and fasting leptin were measured before and after treatment. In the study group, 20 cases (group A) were assigned to take 500 mg of metformin three times daily for 12 weeks, if pregnancy did not occur, high purified FSH (FSH-HP) was added for one cycle; another 20 cases (group B) were induced ovulation with FSH-HP alone for one cycle.. There were significant high FINS and leptin levels in the study group as compared with the control group [(20 +/- 16) vs (12 +/- 6) nmol/L, P < 0.05; (14 +/- 16) vs (8 +/- 4) mg/L, P < 0.05]. The obese PCOS group had markedly higher serum FINS and leptin than the non-obese PCOS group [(24 +/- 18) vs (14 +/- 8) nmol/L, P < 0.05; (20 +/- 22) vs (8 +/- 4) mg/L, P < 0.05], but serum FINS and FG were not significantly different between the non-obese PCOS and the control group (P > 0.05). After administration of metformin for 12 weeks, serum LH, T, leptin and FINS decreased significantly (P < 0.05 - 0.01), serum FSH levels and body mass index showed a slight decrease, whereas no change was found in FG. In the study group, 3 cases conceived during metformin therapy, the remaining 37 were induced ovulation with FSH-HP or FSH-HP and metformin, 7 cases obtained pregnancy. The rates of ovulation and pregnancy in group A were higher than those in group B (88% vs 70%, 24% vs 15%), but no significant difference was found.. Metformin therapy in PCOS can decrease the FINS and leptin levels, normalize the endocrine abnormalities, resumes ovulation and pregnancy in some patients, and may improve the ovarian response to gonadotropin.

Topics: Adult; Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Insulin; Leptin; Metformin; Ovulation; Polycystic Ovary Syndrome; Pregnancy

Up to now it is unclear whether there is a relationship between insulin resistance and circulating leptin levels (LEP) in women with polycystic ovary syndrome (PCOS). To assess the role of LEP in PCOS and to clarify the relationship between plasma LEP levels and insulin resistance (IR) in PCOS patients, we studied 49 women with PCOS and 14 normal premenopausal women. All subjects were evaluated by a 2 hours, 75 g, oral glucose tolerance test. Fasting plasma LEP, insulin, glucose, insulin sensitivity indexes and LEP:body mass index (BMI) were determined. Results were analyzed by ANOVA and the Pearson's correlation test when appropriate. The results indicate that: 1) no differences were found in basal plasma LEP levels (ng/ml) between normal (17.6 +/- 4.9) and PCOS (21.9 +/- 2.8) women; 2) in PCOS patients, a significant (P < 0.01) correlation between plasma LEP levels and BMI and insulin sensitivity indexes were found; and 3) seventeen PCOS patients were insulin resistant (IR) and showed higher basal plasma LEP levels (32.8 +/- 4.3, P < 0.01) and LEP:BMI (0.95 +/- 0.09, P < 0.05) than non insulin resistant (non IR) PCOS subjects (16.2 +/- 3.2 and 0.61 +/- 0.08, respectively). Our results suggest that PCOS seems to be associated with normoleptinemia, however, if IR are analyzed separately from non IR PCOS patients, there is a clear relationship between IR PCOS and hyperleptinemia, regardless of the BMI. The present study strongly supports bi-directional relationship between fat and carbohydrate metabolisms under a very particular physiopathological condition (PCOS).

Topics: Adolescent; Adult; Biomarkers; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Polycystic Ovary Syndrome

To evaluate the relationships between leptin, body composition, insulin resistance, androgens, and reproductive indices among women with polycystic ovary syndrome (PCOS).. Matched case-control study.. Academic reproductive endocrine practice; school of public health.. Forty-six Caucasian women with PCOS and 46 population-based controls matched by age and body mass index (BMI).. None.. Leptin, insulin, androgenic hormones, body composition parameters; reproductive parameters.. Overall, leptin levels among women with PCOS did not differ significantly from those of control women (20.4 +/- 14.9 vs. 21.9 +/- 14.3 ng/mL). However, within the lowest BMI tertile, women with PCOS had significantly lower leptin levels (9.6 vs. 18.3 ng/mL), comparable insulin, and higher testosterone concentrations than controls of similar body mass. Within the overweight and obese subgroups, both insulin and testosterone levels were increased among women with PCOS; leptin levels, although higher among obese cases, were not statistically different than those in controls.. Below a certain BMI, hyperandrogenic women with PCOS have lower leptin levels than controls. Conversely, overweight and obese PCOS subjects appear to produce insufficient leptin for a given fat mass, relative to the degree of hyperinsulinemia, potentially because of the competing effects of adipocyte insulin resistance and androgens on leptin.

Topics: Adult; Body Composition; Body Mass Index; Body Weight; Case-Control Studies; Female; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Obesity; Pennsylvania; Polycystic Ovary Syndrome; Reference Values; Reproduction; Thinness; White People

To elucidate whether the negative effect of obesity on the serum inhibin B level that we previously reported is specific or not to polycystic ovary syndrome (PCOS) and whether it may explain the wide interindividual variability in serum inhibin B levels found in patients with PCOS.. Prospective study.. Reproductive endocrinology unit of an academic medical center.. One hundred thirty-four consecutive patients with PCOS (mean age, 27.4 +/- 4.7 years; mean body mass index [BMI], 28.3 +/- 7.6 kg/m(2); BMI > 25, 53%) and in 78 control women (mean age, 30.1 +/- 4.1 years; mean BMI, 24.3 +/- 4.9; BMI > 25, 34%).. Blood sampling was performed in the early follicular phase in patients and in control women.. BMI and waist circumference (WC), serum levels of inhibin B, LH, FSH, E(2), androstenedione, T, fasting insulin, and leptin were assessed in all subjects.. No difference was observed in the mean inhibin B level between patients and controls. The BMI and WC correlated negatively with inhibin B in patients with PCOS and in controls, with similar regression slopes, thus indicating that the influence of obesity on inhibin B is not specific to PCOS. In addition, we found a positive relationship between serum LH and inhibin B levels in PCOS. There was no significant interaction between the effects of BMI and LH on the serum inhibin B levels by analysis of variance (ANOVA). The mean serum inhibin B level in patients with PCOS with high serum LH (i.e., >the 90th percentile of LH in controls) was significantly higher than in those patients with normal LH or in controls. The highest mean inhibin B level was noted in nonobese patients with PCOS with high LH levels (121.0 +/- 51.2 pg/mL), while nonobese patients with PCOS with normal LH levels and obese patients with normal LH or high LH levels had similar mean levels (94.5 +/- 40.0, 84.9 +/- 34 and 91.6 +/- 51.7 pg/mL, respectively).. We confirm that obesity has a negative effect on inhibin B serum level, which is not specific to PCOS. Obesity and excess LH, acting oppositely and independently on inhibin B production, may explain the discrepancies between the previous reports studying serum inhibin B level in patients with PCOS. Further work is required to elucidate the mechanisms underlying the antagonistic effects of LH and obesity on inhibin B production in patients with PCOS.

Topics: Adolescent; Adult; Androstenedione; Body Mass Index; Estradiol; Female; Follicle Stimulating Hormone; Humans; Immunoenzyme Techniques; Inhibins; Insulin; Leptin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Testosterone

We hypothesized that short-term calorie restriction would blunt luteinizing hormone (LH) hypersecretion in obese women with polycystic ovary syndrome (PCOS) and thereby ameliorate the anovulatory endocrine milieu. To test this hypothesis, 15 obese patients with PCOS and nine age- and body mass index-matched healthy women underwent 24-h blood sampling to quantitate plasma LH, leptin, and insulin levels. PCOS subjects were prescribed a very low caloric liquid diet (4.2 MJ/day) for 7 days and were then resampled. Basal and pulsatile LH secretion was threefold higher in PCOS subjects, but plasma insulin and leptin levels were not different in the calorie-replete state. Contrary to expectation, calorie restriction enhanced basal and pulsatile LH secretion even further. As expected, plasma glucose, insulin, and leptin concentrations decreased by 18, 75, and 50%, respectively. Serum total testosterone concentration fell by 23%, whereas serum estrone, estradiol, sex hormone-binding globulin (SHBG), and androstenedione concentrations remained unchanged. Enhanced LH secretion in the presence of normal metabolic and hormonal adaptations to calorie restriction points to anomalous feedback control of pituitary LH release in PCOS.

Topics: Adult; Androstenedione; Blood Glucose; Body Mass Index; Diet, Reducing; Energy Intake; Estradiol; Estrone; Female; Humans; Insulin; Leptin; Luteinizing Hormone; Obesity; Periodicity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin

To determine whether polycystic ovary syndrome (PCOS) is related to leptin dysregulation.. Prospective study.. Department of Obstetrics and Gynecology in a university hospital.. Fifty patients with PCOS (33 nonobese and 17 obese) and 32 control women (19 nonobese and 13 obese) were included in the study.. Serum leptin levels were measured in patients with PCOS and the controls. Correlations between leptin levels and serum hormone levels (FSH, LH, free testosterone, androstenedione, DHEA-S and fasting insulin) were studied.. Serum leptin levels and correlations between leptin levels and the hormonal parameters.. Mean serum leptin levels were not significantly higher in patients with PCOS compared to the control group. Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS and in the control women. Leptin levels were found to be higher in obese patients with PCOS compared to obese controls; however, when the levels were evaluated again with covariance analysis excluding body mass index, there was no statistically significant difference. Leptin levels had a positive correlation with body mass index, both in patients with PCOS and the controls.. Leptin levels were not higher in patients with PCOS compared to the control group; the leptin level was correlated with the amount of fat tissue not only in patients with PCOS but also in healthy women.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Prospective Studies

Several studies have suggested that leptin modulates hypothalamic-pituitary-gonadal axis function. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting that leptin may modulate the episodic secretion of LH. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin during lactational amenorrhoea in fully breastfeeding normal and PCOS women at 4 and 8 weeks postpartum, in order to establish LH-leptin interactions in the reactivation of the gonadal axis during this period. Six lactating PCOS patients and six normal lactating women of similar age and body mass index were studied. During a 12 h period on the 4th and 8th weeks postpartum, blood samples were collected at 10 min intervals for 12 h (22:00-10:00). Serum LH and leptin concentrations were measured in all samples. For pulse analysis, the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of co-pulsatility was employed. LH concentrations tended to increase in both groups between the 4th and 8th weeks postpartum; however, serum leptin concentrations were not modified. Leptin pulse frequencies were similar at the 4th and 8th weeks postpartum, and did not differ between groups. Moreover, leptin pulse frequency was higher than LH pulse frequency in both groups, and in the two study periods. There was no synchronicity between LH and leptin pulses, and there were no increments in leptin concentration during the night. The fact that leptin concentrations were not modified and no synchronicity between LH and leptin pulses was observed suggests that, during lactational amenorrhoea, circulating leptin is probably not involved as a primary signal in promoting the reactivation of pulsatile LH secretion.

Topics: Adult; Amenorrhea; Breast Feeding; Case-Control Studies; Female; Humans; Lactation; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Postpartum Period

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

The present study probes putative disruption of hypothalamic control of multihormone outflow in polycystic ovarian syndrome by quantitating the joint synchrony of leptin and LH release in adolescents with this syndrome and eumenorrheic controls. To this end, hyperandrogenemic oligo- or anovulatory patients with polycystic ovarian syndrome (n = 11) and healthy girls (n = 9) underwent overnight blood sampling every 20 min for 12 h to monitor simultaneous secretion of leptin (immuno-radiometric assay), LH (immunofluorometry), and androstenedione and T (RIA). Synchronicity of paired leptin-LH, leptin-androstenedione, and leptin-T profiles was appraised by two independent bivariate statistics; viz., lag-specific cross-correlation analysis and pattern-sensitive cross-approximate entropy. The study groups were comparable in chronological and postmenarchal age, body mass index, fasting plasma insulin/glucose ratios, and serum E2 concentrations. Overnight mean (+/- SEM) serum leptin concentrations were not distinguishable in the two study groups at 30 +/- 4.8 (polycystic ovarian syndrome) and 32 +/- 7.4 microg/liter (control). Serum LH concentrations were elevated at 9.5 +/- 1.4 in girls with polycystic ovarian syndrome vs. 2.8 +/- 0.36 IU/liter in healthy subjects (P = 0.0015), androstenedione at 2.8 +/- 0.30 (polycystic ovarian syndrome) vs. 1.2 +/- 0.11 ng/ml (control) (P = 0.0002), and T at 1.56 +/- 0.29 (polycystic ovarian syndrome) vs. 0.42 +/- 0.06 ng/ml (P < 0.0001). Cross-correlation analysis shows that healthy adolescents maintained a positive relationship between leptin and LH release, wherein the latter lagged by 20 min (P < 0.01). No such association emerged in girls with polycystic ovarian syndrome. In eumenorrheic volunteers, leptin and androstenedione concentrations also covaried in a lag-specific manner (0.0001 < P < 0.01), but this linkage was disrupted in patients with polycystic ovarian syndrome. Anovulatory adolescents further failed to sustain normal time-lagged coupling between leptin and T (P < 0.01). Approximate entropy calculations revealed erosion of orderly patterns of leptin release in polycystic ovarian syndrome (P = 0.012 vs. control). Cross-entropy analysis of two-hormone pattern regularity disclosed marked disruption of leptin and LH (P = 0.0099), androstenedione and leptin (P = 0.0075) and T-leptin (P = 0.019) synchrony in girls with polycystic ovarian syndrome. In summary, hyperandrogenemic nonobese adolescents with oligo- or ano

Topics: 17-alpha-Hydroxyprogesterone; Activity Cycles; Adolescent; Androgens; Androstenedione; Dehydroepiandrosterone Sulfate; Estradiol; Estrone; Female; Follicle Stimulating Hormone; Humans; Leptin; Luteinizing Hormone; Ovary; Polycystic Ovary Syndrome; Reference Values; Sex Hormone-Binding Globulin; Testosterone

Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. Although the role of leptin in the control of reproduction is unclear, it may be involved in the control of ovulation. The aim of this cross-sectional study was to determine the relationship between circulating leptin concentrations, and anthropometric, metabolic and endocrine variables as well as to examine a possible role of leptin in ovarian dysfunction associated with PCOS.. Prospective observational study.. Seventy-one subjects with PCOS and 23 body mass index (BMI)-matched control subjects were recruited from infertility clinics. The association between serum leptin concentrations and the above variables was measured outwith the luteal phase. A subgroup of 24 PCOS subjects underwent more frequent blood sampling to monitor follicular growth and ovulation. The association between variables was measured by univariate, multivariate and partial correlation analyses.. Serum leptin concentrations were not different in subjects with PCOS and controls, and were strongly associated with BMI in both groups. Twelve patients ovulated during the study period. There was no significant difference in serum leptin concentrations between ovulatory and anovulatory subjects. The relationship between BMI and leptin was similar in both groups.. The results indicated that circulating leptin concentrations relate principally to total body fat in subjects with PCOS and controls, and that this is not associated with the facility for follicular development and ovulation in these patients.

Topics: Adult; Androgens; Body Constitution; Body Mass Index; Estradiol; Female; Humans; Insulin; Leptin; Luteinizing Hormone; Ovary; Ovulation; Polycystic Ovary Syndrome; Prospective Studies; Testosterone

Leptin may play a role in the regulation of menstrual cycle acting either directly on ovaries or at the level of the hypothalamic-pituitary axis. Peritoneal fluid is a biologically active environment that influences ovarian function but, on the other hand, concentration of many substances in peritoneal fluid can reflect the functional status of ovaries. In our study, we estimated leptin concentration in peritoneal fluid in relation to serum leptin concentration in infertile patients. A study group consisted of 31 infertile patients that underwent laparoscopy. In 15 patients, laparoscopy did not solve the problem and they were grouped as unexplained infertility, in eight patients we found endometriosis and eight patients were diagnosed as polycystic ovary syndrome (PCOS). We found significantly higher peritoneal fluid leptin concentrations in patients with unexplained infertility and endometriosis compared to those with PCOS. The plasma leptin concentration did not differ between the groups studied. There was no correlation between peritoneal fluid and plasma leptin concentrations in any patient group. Taking into account our results, the role of leptin in reproduction should be emphasized but further investigation is needed to determine its mechanism of action.

Topics: Adult; Ascitic Fluid; Female; Humans; Infertility, Female; Leptin; Polycystic Ovary Syndrome

Leptin, the 'obese' protein, is found in cultured granulosa cells derived from human pre-ovulatory follicles. However, the occurrence of leptin has not been studied in intact ovaries, either normal or polycystic, until now. Paraffin sections from 25 human ovaries of different cycle stages and 25 wedge resections of polycystic ovaries were investigated by means of immunochemistry. Additionally, three ovaries were available for reverse transcription-polymerase chain reaction analysis. Leptin-positive cells were located in the granulosa cells of pre-antral follicles, and distinctly in the thecal layer of intact and regressing antral follicles. In the corpus luteum (CL) in the developmental stage, the former epithelioid leptin-positive thecal cells became fibroblast-like in the septum. In the CL of the secretory stage, single leptin-positive cells were detected between luteal cells. In polycystic ovaries, leptin-positive cells were noted both in the hypertrophied thecal layer and in the luteinized granulosa layer. Our findings on leptin expression at the protein level were confirmed by a positive mRNA signal for leptin in granulosa cells and in the CL. Additionally, mRNA of the full-length leptin receptor OB-R and of the short isoforms B219.1-B219.3 was identified in granulosa cells and the CL, as well as in the cortex and medulla. We conclude that leptin is produced in the ovary and may act in autocrine and paracrine ways.

Topics: Adolescent; Adult; Carrier Proteins; Corpus Luteum; Female; Granulosa Cells; Humans; Immunohistochemistry; Leptin; Ovarian Follicle; Ovary; Polycystic Ovary Syndrome; Protein Isoforms; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Theca Cells

Leptin is an adipocyte-derived hormone which plays a central role in the regulation of body weight and energy homeostasis and in signalling to the brain that adequate energy stores are available for reproduction. Although leptin may affect reproduction by regulating the hypothalamic-pituitary-gonadal axis, recent in-vitro observations indicate that leptin may also have direct intra-ovarian actions. Leptin concentrations were measured in women who succeeded in becoming pregnant within three cycles of in-vitro fertilization (IVF) or gamete intra-fallopian transfer (n = 53), in women who failed to become pregnant within three cycles (n = 50), and in women with polycystic ovarian syndrome (PCOS) (n = 22). It was found that lower follicular fluid leptin concentrations were a marker of assisted reproduction treatment success in normal women. Women with PCOS had higher leptin concentrations than women without such a diagnosis, but this was due to their higher body mass index (BMI). After adjustment for age and BMI, women with PCOS who became pregnant tended to have lower mean follicular fluid leptin concentrations than women with PCOS who did not succeed at becoming pregnant. Further studies exploiting the strengths of the IVF model are needed to assess whether the prognostic role for follicular fluid leptin in human reproduction is independent of other factors, and to elucidate the underlying mechanisms.

Topics: Adult; Biomarkers; Body Weight; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility, Female; Leptin; Polycystic Ovary Syndrome; Predictive Value of Tests; Pregnancy; Pregnancy Rate; Reference Values; Reproductive Techniques; Smoking

To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation.. Prospective analysis.. University IVF program.. Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12).. Controlled ovarian hyperstimulation and IVF.. Serum estradiol, testosterone, and leptin.. Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively).. Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.

Topics: Adult; Body Weight; Case-Control Studies; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leptin; Menotropins; Obesity; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Testosterone

To determine whether leptin is involved in ovarian function.. Fasting serum samples were obtained from 20 women with normal menstrual cycles who were either obese or non-obese: 12 non-obese patients with polycystic ovary syndrome (PCOS), 8 obese patients with PCOS, 10 patients with stress-related hypothalamic amenorrhea, and 8 patients with weight loss-related hypothalamic amenorrhea.. Serum leptin levels were strongly related to body mass index (BMI) in each group, but there was no difference in the mean serum leptin levels among the BMI-matched study groups. A significant difference in the mean serum leptin levels was found between the non-obese and obese control groups (P<0.001) and between the non-obese and obese PCOS groups (P<0.001).. These findings indicate that circulating leptin levels in women with normal menstrual cycles and those with ovarian dysfunction are strongly related to BMI. Leptin does not appear to be primarily involved in regulating ovarian function.

Topics: Adult; Amenorrhea; Body Mass Index; Female; Humans; Hypothalamus; Leptin; Obesity; Ovary; Polycystic Ovary Syndrome; Reference Values; Regression Analysis

It is well known that a strong exponential relationship exists between leptin levels and body mass index (BMI). The different serum leptin levels, however, that are observed for each BMI value, suggest that other factors, as well, interfere with leptin secretion. This study was designed in order to estimate serum leptin levels in patients with polycystic ovary syndrome (PCOS), before and after long-term treatment with conjugated estrogens and antiandrogens. Sixteen women with PCOS were included in the study. They were divided into two groups: the first group comprised 11 non-obese women (BMI 21.6 +/- 0.5 kg/m2), aged 23.5 +/- 1.1 years; the second consisted of five obese women (BMI 28.9 +/- 1.5 kg/m2), aged 22.8 +/- 1.9 years. Blood samples for leptin measurement were drawn before and 2, 4, 6, 9 and 12 months after administration of conjugated estrogens and antiandrogens. Our results showed that obese women exhibited higher serum leptin levels in all blood samples. Moreover, the administration of conjugated estrogens and antiandrogens caused an increase in serum leptin levels in the 2nd, 4th, 6th and 9th month in both groups of women. Finally, leptin concentrations during the 12th month of the treatment returned to basic levels in both groups of women with PCOS. Our results support the view that BMI is the main variable that influences serum leptin levels, and that the effect of conjugated estrogens and antiandrogens on serum leptin concentrations is poor.

Topics: Adolescent; Adult; Androgen Antagonists; Body Mass Index; Estrogens, Conjugated (USP); Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Time Factors

Polycystic ovarian syndrome (PCOS) is often associated with obesity and insulin resistance, both of which are features that are linked to the leptin and leptin receptor (LEPR) genes. Analysis of the leptin gene by sequencing samples from 38 well-characterized patients with PCOS revealed no mutations of the coding exons. In single-stranded conformational polymorphism (SSCP) analysis and subsequent sequencing of the LEPR gene revealed previously identified amino acid variants in exons 2, 4 and 12 as well as the pentanucleotide insertion in the 3'-untranslated region (3'-UTR). The allele frequencies of these polymorphisms did not differ from those in the general population, as assessed in 122 female controls. Compared with non-carriers, serum insulin concentrations tended to be lower in the carriers of the variant LEPR exon 12 allele as well as in the carriers of the variant LEPR 3'-UTR allele, a marker previously suggested to be associated with serum insulin concentrations. In conclusion, PCOS is not commonly a consequence of mutations of the leptin or LEPR genes. However, our data support the hypothesis that variations in the LEPR gene locus have an effect on insulin regulation.

Topics: Adult; Blood Glucose; Body Mass Index; Carrier Proteins; DNA Mutational Analysis; Exons; Female; Gene Frequency; Humans; Insulin; Leptin; Middle Aged; Polycystic Ovary Syndrome; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Receptors, Cell Surface; Receptors, Leptin; Testosterone

Several studies suggest that leptin modulates the reproductive axis function. Leptin may stimulate release of GnRH from hypothalamus and of gonadotrophins from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting a relationship between the episodic secretion of LH and leptin. In vitro experimental studies have demonstrated that leptin administration promotes GnRH-LH release. However it is not established whether GnRH promotes the episodic secretion of leptin.. To assess the response of LH and leptin to the administration of a GnRH bolus in hyperandrogenic and healthy women.. Eleven hyperandrogenic and eleven healthy women of similar age and body mass index (BMI) were studied. Under basal conditions three blood samples were collected every 30 min before and after the administration of a GnRH bolus (100 micrograms). LH and leptin concentrations were measured in all samples. Testosterone, SHBG and estradiol were determined in the first sample. For data analysis, the increment of LH and leptin between 0-30 and 0-60 min was calculated. The LH and leptin areas under the curve (AUC) before and after GnRH administration were also calculated in both groups.. After GnRH administration an increment in LH concentrations was observed in both groups; however, leptin concentrations were not modified. In both groups LH area under the curve increased after GnRH administration; however, the leptin area was not modified.. These results suggest that circulating leptin concentration is not modulated by GnRH-LH.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Statistics, Nonparametric; Time Factors

The author exposes the present concept of metabolic syndrome X, which is a complex of Type II diabetes, obesity, hypertension and vascular problems. This syndrome has been known for many years, but it has been individualized as such only recently. This is due to the huge importance that obesity is reaching in developed countries, especially in the U.S.A. Today this is a very important health problem. In this work, in addition to the description of the syndrome, which is purely an internal medicine issue, its relation to some women-specific problems is also explained, especially to the so-called polycystic ovary.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Leptin; Menopause; Myocardial Ischemia; Obesity; Phenotype; Polycystic Ovary Syndrome; Syndrome

To investigate the clinical importance of leptin's intraovarian effects, we studied the concentration of leptin and leptin binding activity in the plasma and in the follicular fluid of PCOS patients (n=20; median BMI: 27.1 kg/m2, range 19.7-36.3) undergoing controlled ovarian stimulation with long-term GnRH agonist, recombinant FSH, and in vitro fertilization. Follicular fluid and blood samples were collected during follicle aspiration for IVF. Total leptin concentration was measured by radioimmunoassay, and specific leptin binding activity was accessed by a gel filtration column assay. Follicular fluid and plasma leptin levels were similar (median 1135 pmol/l vs. 1409 pmol/l; p=0.81). Follicular fluid to plasma leptin ratio was independently associated with cumulative FSH dose (r=0.63; p=0.006) and insulin resistance index (r=-0.45; p=0.04). Specific leptin binding activity was higher in the plasma than in the follicular fluid [median 7.94% vs. 3.49%; p<0.001]. When multivariate analysis was used to predict FSH consumption, only follicular fluid leptin levels were significantly associated with cumulative FSH dose (r=0.46; p=0.04). We infer that at least in part by increased intrafollicular leptin levels, obesity directly affects ovarian function in PCOS, and may induce a relative resistance to gonadotropin stimulation. This intraovarian effect of leptin can be even more profound because of low leptin binding activity in the preovulatory follicle of obese patients.

Topics: Adult; Body Mass Index; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Humans; Infertility, Female; Insulin Resistance; Leptin; Ovarian Follicle; Ovulation; Polycystic Ovary Syndrome; Protein Binding; Recombinant Proteins

Recent data raised the possibility that high leptin levels may contribute to infertility in some women with PCOS.. To assess changes in leptin levels and its relationship to some hormonal changes (insulin, testosterone, SHBG, FSH, LH, and prolactin) associated with PCOS in obese (n = 27) and nonobese (n = 18) patients when compared to obese and nonobese normal controls (n = 20).. Leptin concentration were significantly higher in PCOS than in controls, p < 0.05, with 81% sensitivity and 50% specificity. Whereas, high serum insulin levels were found in obese and nonobese women with PCOS, high serum leptin, FAI together with reduced SHBG were found in obese rather than nonobese PCOS women. Moreover, hyperleptinemia in PCOS women was not correlated to hyperinsulinemia (r = -0.13 and -0.4 in obese and nonobese PCOS women, respectively). In the patient's group correlation analysis between fasting serum leptin and different studied variables showed some correlation with body mass index (BMI) only (r = 0.413) suggesting that high leptin levels could be a characteristic of the obese PCOS. However, multiregression analysis showed that together with testosterone, leptin can successfully predict the presence or absence of PCOS.. The potential significance of leptin for the pathophysiology of PCOS will await direct studies of the effects of exogenous leptin and/or its inhibitors on the reproductive axis of women, including those with PCOS.

Topics: Adolescent; Adult; Female; Follicle Stimulating Hormone; Humans; Insulin; Leptin; Luteinizing Hormone; Middle Aged; Obesity; Polycystic Ovary Syndrome; Prolactin; Proteins; Sex Hormone-Binding Globulin; Testosterone

Animal and human studies suggest that leptin modulates hypothalamic-pituitary-gonadal axis functions. Leptin may stimulate gonadotrophin-releasing hormone (GnRH) release from the hypothalamus and luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women, suggesting that leptin probably also regulates the episodic secretion of LH. In some pathological conditions, such as polycystic ovarian syndrome (PCOS), LH-leptin interactions are not known. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin in PCOS patients compared to regularly menstruating women. Six PCOS patients and six normal cycling (NC) women of similar age and body mass index (BMI) were studied. To assess episodic hormone secretion, blood samples were collected at 10-min intervals for 6 h. LH and leptin concentrations were measured in all samples. For pulse analysis the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of copulsatility was employed. LH concentrations were significantly higher in the PCOS group in comparison to NC women, however serum leptin concentrations and leptin pulse characteristics for PCOS patients did not differ from NC women. A strong synchronicity between LH and leptin pulses was observed in NC women; 11 coincident leptin pulses were counted with a phase shift of 0 min (P = 0.027), 18 pulses with a phase shift of -1 (P = 0.025) and 24 pulses with a phase shift of -2 (P = 0.028). PCOS patients also exhibited a synchronicity between LH and leptin pulses but weaker (only 20 of 39 pulses) and with a phase shift greater than in normal women, leptin pulses preceding LH pulses by 20 min (P = 0.0163). These results demonstrate that circulating leptin and LH are synchronized in normal women and patients with PCOS. The real significance of the apparent copulsatility between LH and leptin must be elucidated, as well as the mechanisms that account for the ultradian leptin release.

Topics: Adult; Body Weight; Female; Humans; Insulin; Leptin; Luteinizing Hormone; Menstrual Cycle; Periodicity; Polycystic Ovary Syndrome; Proteins; Sex Hormone-Binding Globulin; Testosterone

Although serum leptin is principally influenced by body mass, to understand the role of insulin and androgens in the regulation of serum leptin in normal weight women.. Prospective observational study.. Academic practice in reproductive endocrinology.. Twenty-one women with polycystic ovary syndrome (PCOS) of normal body weight, 8 apparently normal women with polycystic-appearing ovaries (PAO), and 21 normal women.. Fasting blood levels of luteinizing hormone, follicle-stimulating hormone, testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), insulin, insulin growth factor-binding protein-1 (IGFBP-1), and leptin.. Comparisons of measured hormones in the different groups and correlative analysis. Women with PCOS had higher levels of serum luteinizing hormone, T, unbound T, DHEAS and insulin, and lower levels of IGFBP-1 compared with the normal controls, but they had similar leptin levels. Normal women with PAO had increased levels of insulin and leptin compared with controls, whereas IGFBP-1 was lower in PAO. In normal weight women with PCOS and PAO, leptin correlated positively with body weight and insulin, and negatively with IGFBP-1 and DHEAS.. In normal weight patients serum leptin levels may be regulated in part by insulin. Androgens, on the other hand, may play a role in suppressing serum leptin.

Topics: Adult; Androgens; Case-Control Studies; Dehydroepiandrosterone Sulfate; Female; Humans; Insulin; Leptin; Luteinizing Hormone; Polycystic Ovary Syndrome; Testosterone

It has been reported that polycystic ovary syndrome (PCOS) is very frequently associated with obesity, insulin resistance and hyperinsulinemia. However, metabolic disorders may lead to suppression of reproductive hormone secretion during undernutrition and in obesity. Some neuropeptides, such as neuropeptide Y (NPY) and galanin, modulate the control of appetite and play an important role in the mechanism of luteinizing hormone-releasing hormone (LHRH) secretion. NPY and galanin regulate appetite via both central and peripheral mechanisms. The interaction between central and peripheral signals for the control of food intake is due to leptin. Leptin can modulate the activity of NPY and other peptides in the hypothalamus that are known to affect eating behavior. In order to evaluate the relationship between NPY, galanin and leptin, 28 women with PCOS, 32 obese women (non-PCOS) and 19 lean healthy women (control group) were investigated. Obese women with PCOS were divided into two groups: PCOS (A) overweight (body mass index, BMI 26-30 kg/m2), and PCOS (B) obese (BMI 31-40 kg/m2). Plasma NPY, galanin and leptin concentrations were measured by radioimmunoassay. Plasma leptin levels in obese women with PCOS (groups A and B) were significantly higher than those in the control group (p < 0.05, p < 0.05, respectively). A significant positive correlation between plasma leptin and BMI in women with PCOS was found (r = 0.427, p < 0.01). A positive correlation was demonstrated between leptin and testosterone in PCOS (r = 0.461, p < 0.01). Plasma galanin concentrations in PCOS were higher than in the control group but the differences were not significant. Plasma NPY levels were significantly elevated in both non-obese (normal) and obese women with PCOS (group A) (p < 0.01, p < 0.005, respectively). However, in obese non-PCOS women plasma NPY levels gradually increased with increase in BMI. No significant correlations were found between galanin, NPY and percentage change in response of LH to LHRH, as well as between NPY and insulin, and galanin and testosterone. Plasma insulin concentrations in women with PCOS (group B) were significantly higher than in the control group (p < 0.001). Increased plasma NPY levels are found in both obese and non-obese women with PCOS. The increase in NPY is independent of the increase in BMI. In obese women with PCOS, plasma leptin is increased compared with control lean women. Serum insulin concentration is increased in obese women with P

Topics: Adolescent; Adult; Body Mass Index; Estradiol; Female; Follicle Stimulating Hormone; Galanin; Humans; Immunoenzyme Techniques; Insulin; Leptin; Luteinizing Hormone; Neuropeptide Y; Obesity; Polycystic Ovary Syndrome; Prolactin; Radioimmunoassay; Testosterone

The relationship between leptin and insulin sensitivity, sexual steroids and insulin concentrations in women with polycystic ovary syndrome is still controversial. The objective of this study was to assess the relationship between insulin levels, insulin resistance parameters and serum leptin concentrations in healthy and polycystic ovary syndrome women.. 33 hyperandrogenic polycystic ovary syndrome women (GHA) and 27 healthy women (GS) were included in this study. Leptin, insulin, sex-hormone binding globulin (SHBG), testosterone and estradiol concentrations were determined in a basal sample. Body mass index, waist diameter and waist to hip ratio were recorded. Insulin sensitivity was calculated by means of insulin tolerance test and glycemia/insulinemia ratio.. The leptin concentration was not different between GHA and GS. Insulin levels and free testosterona index (FTI) were higher in GHA than GS (p < 0.01). The glycemia/insulinemia ratio, SHBG levels, and insulin sensitivity were lower in GHA (p < 0.01). In both groups positive correlations between leptin concentration and body mass index (p < 0.01), waist diameter (p < 0.01), insulin levels (p < 0.01) and glycemia/insulinemia ratio (p < 0.01) were observed. Only GHA showed correlation between insulin sensitivity and leptin concentration (p < 0.02). SHBG and leptin levels were not correlated.. The leptin concentration was not different between GHA and healthy women, although they are metabolically different. This phenomenon could be due to the fact that in hyperandrogenic women the effects of insulin resistance and hyperandrogenemia counteract each other.

Topics: Adolescent; Adult; Blood Glucose; Estradiol; Female; Humans; Hyperandrogenism; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone

The aim of the present study was to estimate the leptin role in the pathogenesis of polycystic ovary syndrome.. The study was carried out in 21 obese women with PCO, 18 obese women without menstrual disturbances and 9 normal-weight healthy women.. In all patients antropomethric parameters: weight, height, % of body fat, waist and hip girths were measured and than BMI and WHR were calculated. Plasma concentrations of leptin, insulin, LH, FSH, testosterone, cortisol, PRL, estradiol were estimated.. There were no statistical significant difference between plasma leptin concentrations in obese patients with PCO in comparison to obese women with normal menstrual cycle. In both groups of obese patients plasma leptin concentrations was significantly higher than in control group (p < 0.001, p < 0.001). There were significant correlation between plasma leptin and % body fat, BMI and waist girth in all studied groups.. We conclude that leptin is not directly involved in observed hormonal disturbances in polycystic ovary syndrome. The main predictor of plasma leptin concentrations in patients with PCO is amount of body fat.

Topics: Adult; Female; Humans; Leptin; Obesity; Polycystic Ovary Syndrome

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.

Topics: Adolescent; Adult; Androgens; Body Composition; Body Constitution; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins; Skinfold Thickness

Leptin is a hormone produced in the adipose tissue and its concentrations in peripheral blood are significantly correlated with the amount of body fat. Whether other factors, including the pattern of body fat distribution and several hormones (such as insulin, sex steroids, and glucocorticoids), may be involved in the regulation of circulating blood leptin levels is controversial. Women with the polycystic ovary syndrome (PCOS) are hyperandrogenic and most of them are characterized by hyperinsulinemia, insulin resistance, and obesity, particularly the visceral phenotype. To assess the potential contribution of anthropometric factors, androgens, and insulin in determining leptin levels, we examined their relationship with body-mass index (BMI), visceral (VAT) and subcutaneous (SAT) adipose tissue areas, basal androgen levels, and fasting and glucose-stimulated (AUC) insulin in different groups of obese women with PCOS (n = 23) and of age-matched obese (n = 16) and non-obese (n = 10) otherwise healthy controls. The VAT/SAT ratio was measured as a parameter of body fat distribution. Serum leptin levels were significantly higher in obese PCOS women than in obese and normal-weight healthy controls and, within the controls, in the obese than in the non-obese group. In all women considered together, and in each group separately, leptin concentrations were highly significantly correlated with BMI. In addition, after adjusting for BMI, both VAT and the VAT/SAT ratio were positively and significantly correlated with leptin. Partial correlations with the VAT/SAT ratio remained significant in both the obese PCOS group and in controls considered separately, whereas the correlation with the SAT value was significant only in the control group. After adjusting for BMI, no correlation between leptin, androgens and fasting or stimulated (like AUC) insulin was found. These findings indicate that leptin levels in obese women with PCOS are higher than those observed in obese and non-obese controls. Moreover, they suggest that, other than BMI, the pattern of body fat distribution may be an independent factor related to circulating leptin levels, which, on the contrary, do not appear to be related to either androgen or insulin concentrations.

Topics: Adipose Tissue; Adult; Androgens; Blood Glucose; Body Constitution; Body Weight; Case-Control Studies; Female; Gonadal Steroid Hormones; Humans; Insulin; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins

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 ana

Topics: Adipose Tissue; Administration, Oral; Adult; Diazoxide; Drug Administration Schedule; Female; Humans; Leptin; Polycystic Ovary Syndrome; Proteins

To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS).. Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17-36 years, body mass index (BMI) 29.9 +/- 0.9 kg/m2, mean +/- SD) and 18 control women (25-47 years, BMI 25 +/- 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations.. Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay.. Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/ hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 +/- 1.3 vs 12.1 +/- 2.3 micrograms/l, mean +/- SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups.. Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.

Topics: Adolescent; Adult; Androstenedione; Body Mass Index; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Lipoproteins, HDL; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Progesterone; Proteins; Regression Analysis; Testosterone

Topics: Female; Humans; Leptin; Polycystic Ovary Syndrome; Proteins; Reference Values

Polycystic ovary syndrome (PCOS) is associated with chronic anovulation, hyperandrogenemia, insulin resistance (IR)/hyperinsulinemia, and a high incidence of obesity. Thus, PCOS serves as a useful model to assess the role of IR and chronic endogenous insulin excess on leptin levels. Thirty-three PCOS and 32 normally cycling (NC) women of similar body mass index (BMI) were studied. Insulin sensitivity (S(I)) was assessed by rapid ivGTT in a subset of 28 PCOS and 29 NC subjects; percent body fat was determined by dual-energy x-ray absorptiometry (DEXA) in 14 PCOS and 17 NC. Fasting (0800 h) and 24-h mean hourly insulin levels were 2-fold higher (P < 0.0001), and S(I) was 50% lower (P = 0.005) in PCOS than in NC, while serum androstenedione (A), testosterone (T), 17-alpha hydroxyprogesterone (17OHP), and estrone (E1) levels were elevated (P < 0.0001), and sex hormone-binding globulin (SHBG) levels were decreased (P < 0.01). Twenty-four hour LH pulse frequency, mean pulse amplitude, and mean LH levels were elevated in PCOS (P < 0.001) as compared with NC. Serum leptin levels for PCOS (24.1 +/- 2.6 ng/mL) did not differ from NC (21.5 +/- 3.5 ng/mL) and were positively correlated with BMI (r = 0.81) and percent body fat (r = 0.91) for the two groups (both P < 0.0001). Leptin levels for PCOS and NC correlated positively with fasting and 24-h mean insulin levels (r = 0.81, P < 0.0001 for both PCOS and NC) and negatively with S(I) and SHBG levels. Leptin concentrations for PCOS, but not NC, correlated positively with 24-h mean glucose levels and inversely with 24-h mean LH levels and 24-h mean LH pulse amplitude. Leptin levels were not correlated with estrogen or androgen levels for either PCOS or NC, although leptin levels were positively related to the ratios of E1/SHBG and E2/SHBG for both PCOS and NC and to the ratio of T/SHBG for PCOS only. In stepwise multivariate regression with forward selection, only 24-h mean insulin levels contributed significantly (P < 0.01) to leptin levels independent of BMI and percent body fat for both PCOS and NC. Given this relationship and the presence of 2-fold higher 24-h mean insulin levels in PCOS, the expected elevation of leptin levels in PCOS was not found. This paradox may be explained by the presence of adipocyte IR specific to PCOS, which may negate the stimulatory impact of hyperinsulinemia on leptin secretion, a proposition requiring further study.

Topics: Adipose Tissue; Adolescent; Adult; Body Composition; Body Mass Index; Endocrine Glands; Female; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Osmolar Concentration; Polycystic Ovary Syndrome; Proteins

The role of gonadotropins, androgens, and insulin in the regulation of circulating leptin levels is obscure. In order to clarify the relationships of these parameters we studied serum leptin levels in 19 healthy control subjects and in 35 hyperandrogenic and hyperinsulinemic patients with polycystic ovary syndrome (PCOS). Serum leptin concentrations did not differ significantly between PCOS patients and control subjects. When PCOS and control groups were analyzed together by univariate analysis, serum leptin was positively correlated with body mass index (BMI), body weight, serum insulin, serum triglyceride, and serum free testosterone concentrations. Serum leptin was inversely correlated with serum sex hormone binding globulin (SHBG) concentrations. There were no significant correlations between serum leptin and testosterone, androstenedione, or gonadotropin concentrations. Serum insulin, triglyceride, and free testosterone concentrations were positively correlated, and serum SHBG was negatively correlated with BMI. However, when BMI on one hand and serum insulin, triglyceride, free testosterone, or SHBG on other hand were used as independent variables in the partial correlation analysis with leptin, BMI turned out to be the variable primarily responsible for all of the correlations with leptin. In conclusion, the concept that circulating leptin levels would be different in PCOS patients than in regularly menstruating control subjects is not supported by our data.

Topics: Adult; Body Mass Index; Female; Humans; Insulin; Leptin; Osmolar Concentration; Polycystic Ovary Syndrome; Proteins; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

The study was conducted to assess leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome (PCOS). Twenty-two women with PCOS and 19 control healthy women were included in the study, divided into obese and non-obese groups. Leptin was determined using Linco Research radio-immunoassay while insulin sensitivity was calculated from intravenous glucose tolerance tests with frequent blood sampling using MINMOD analysis. Significantly higher basal leptin levels were found in obese compared to non-obese PCOS (31.76 +/- 3.06 vs. 10.42 +/- 2.31 ng/ml; p < 0.05) as well as in obese in comparison to non-obese controls (29.16 +/- 5.06 vs 8.51 +/- 0.88 ng/ml; p < 0.05). A negative correlation was found between insulin sensitivity and leptin levels in both obese (r = -0.2480; p > 0.05) and non-obese PCOS groups (r = -0.4620; p > 0.05). In conclusion, high serum leptin, insulin and testosterone levels together with reduced insulin sensitivity were found in obese PCOS women, suggesting that high leptin levels could be a characteristic of the obese PCOS phenotype.

Topics: Adult; Body Mass Index; Female; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins; Testosterone

Recent data in the mouse demonstrate that leptin, a protein hormone produced by fat cells, is required for fertility. In the absence of leptin the mice become obese, diabetic and infertile. Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is associated with obesity and insulin resistance. Because of the increased frequency of PCOS in obese women we tested the hypothesis that alterations in serum leptin concentrations might be associated with PCOS. Immunoreactive leptin concentrations were measured in 58 women with PCOS and 70 regularly menstruating (control) women. As has previously been shown there was a positive correlation between leptin levels and body mass index (BMI). Although the leptin levels in the majority of women with PCOS fell within the control range, 29% of PCOS women had leptin levels above the 99% prediction interval for their BMI and none had low leptin levels. There were also positive correlations of leptin levels with free testosterone and insulin sensitivity in control women. In women with PCOS, 13% and 9.5% exhibited higher than expected leptin concentrations with respect to free testosterone and insulin sensitivity, respectively. Insulin resistant PCOS women had higher leptin levels than controls. The data demonstrate that a substantial proportion of women with PCOS have leptin levels that are higher than expected for their BMI, free testosterone and insulin sensitivity. These results suggest that abnormalities in leptin signaling to the reproductive system may be involved in certain cases of PCOS.

Topics: Adult; Animals; Case-Control Studies; Female; Hormones; Humans; Insulin Resistance; Leptin; Mice; Obesity; Polycystic Ovary Syndrome; Proteins