leptin and Endometriosis

The role of leptin in the development of endometriosis has been investigated previously. However, researches on the change of leptin levels in endometriosis remains controversial. So, we aimed to clarify changes of leptin levels in patients with endometriosis and their association with the progression of endometriosis. We searched PubMed, Embase, Web of Science, and The Cochrane Library to identify relevant studies published before May 25, 2020. The detected levels of leptin in patients with endometriosis versus controls were evaluated in this meta-analysis. Eighteen studies met our inclusion criteria, five studies detected serum, nine detected peritoneal fluid and another four detected both serum and peritoneal fluid leptin levels. The overall results showed that peritoneal fluid leptin levels in patients with endometriosis was significantly higher than that in the control group, but the serum and corrected peritoneal fluid leptin levels were comparable in both groups. Subgroup analysis failed to eliminate the high degree of heterogeneity included in the studies and showed that peritoneal fluid leptin levels were significantly elevated in both early and advanced endometriosis. In conclusion, peritoneal fluid rather than serum leptin levels was elevated in patients with endometriosis, which did not seem to be related to the severity of endometriosis, but was related to body mass index.

Topics: Ascitic Fluid; Biomarkers; Body Mass Index; Cross-Sectional Studies; Disease Progression; Endometriosis; Female; Humans; Leptin

Obesity and endometriosis are two very common entities, yet there is uncertainty on their exact relationship. Observational studies have repeatedly shown an inverse correlation between endometriosis and a low body mass index (BMI). However, obesity does not protect against endometriosis and on the contrary an increased BMI may lead to more severe forms of the disease. Besides, BMI is not accurate in all cases of obesity. Consequently, other anthropometric and phenomic traits have been studied, including body adiposity content, as well as the effect of BMI early in life on the manifestation of endometriosis in adulthood. Some studies have shown that the phenotypic inverse correlation between the two entities has a genetic background; however, others have indicated that certain polymorphisms are linked with endometriosis in females with increased BMI. The advent of metabolic bariatric surgery and pertinent research have led to the emergence of biomolecules that may be pivotal in understanding the pathophysiological interaction of the two entities, especially in the context of angiogenesis and inflammation. Future research should focus on three objectives: detection and interpretation of obesity-related biomarkers in experimental models with endometriosis; integration of endometriosis-related queries into bariatric registries; and multidisciplinary approach and collaboration among specialists.

Topics: Adiponectin; Adiposity; Anthropometry; Bariatric Surgery; Biomarkers; Body Mass Index; Case-Control Studies; Chemokines; Endometriosis; Female; Gene Expression Regulation; Gene-Environment Interaction; Ghrelin; Humans; Leptin; Obesity; Phenomics; Phenotype

Endometriosis is an inflammatory condition, affecting mainly women of reproductive age. Leptin is a regulator of food intake and energy expenditure, posing pleiotropic actions, and regulating immunity and fertility. The aim of this study was to systematically review the literature regarding leptin concentrations in biological fluids and tissues of women with endometriosis, and to investigate and propose a possible role of leptin in the pathophysiology of endometriosis.. A systematic search of the literature was conducted in two electronic databases (MEDLINE, COCHRANE) and grey literature for original research articles on humans, published in any language.. Twenty-nine studies with 1291 women with endometriosis and 1664 controls were included in the systematic review. Peritoneal fluid and follicular fluid leptin concentrations were higher in endometriosis compared with control group [mean difference (MD) 7.10, 95 % confidence interval (CI) 4.76 to 9.44 ng/mL, 18 studies), (MD 1.35, 95 % CI 0.54-2.17 ng/ml, 2 studies) respectively. No differences were evident in serum (MD 0.92, 95 % CI -0.84 to 2.68 ng/mL, 12 studies) or plasma (MD -0.95, 95 % CI -4.63 to 2.72 ng/mL, 3 studies) between the groups. No meta-analysis was conducted for ovarian tissue leptin (2 studies).. This meta-analysis provided evidence for increased leptin concentrations in both peritoneal fluid and follicular fluid of women with endometriosis compared with control; these differences were not present in the serum or plasma. The above results support a potential pathophysiologic role for leptin in the local microenvironment while declines its use as a blood diagnostic marker. Furthermore, we propose a possible role of leptin in the pathophysiology of endometriosis.

Topics: Ascitic Fluid; Biomarkers; Case-Control Studies; Endometriosis; Female; Follicular Fluid; Humans; Leptin

Endometriosis is one of the most common gynecological diseases that significantly reduce the life quality of affected women. Research results from the past decade clearly demonstrated that aberrant production of estrogen and cyclooxygenase-2-derived prostaglandin E2 play indispensable roles in the pathogenesis of this disease. However, the etiology of endometriosis remains obscure. Recent evidence reveals a new facet of endometriotic pathogenesis by showing that hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. These new findings shed lights on future investigations of delineating the etiology of endometriosis and designing new therapeutic strategy for endometriosis.

Topics: Cyclooxygenase 2; Endometriosis; Estrogens; Female; Humans; Hypoxia; Leptin; Neovascularization, Pathologic; Prostaglandins

The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation.

Topics: Ascitic Fluid; Autoantibodies; Cytokines; Endometriosis; Female; Growth Substances; Humans; Interleukins; Leptin; Macrophages; Matrix Metalloproteinases; Reactive Oxygen Species; Tumor Necrosis Factors

Initially described as an antiobesity hormone, leptin has subsequently been shown also to influence hematopoiesis, thermogenesis, reproduction, angiogenesis, and immune homeostasis. Leptin links nutritional status and proinflammatory T helper 1 immune responses, and the decrease in leptin plasma concentration during food deprivation leads to impaired immune function. This review focuses on the multiple roles of leptin in chronic inflammation and autoimmunity and suggests new possible therapeutic implications for leptin modulators.

Topics: Animals; Autoimmunity; CD4-Positive T-Lymphocytes; Endometriosis; Female; Humans; Immune System; Immunotherapy; Inflammation; Leptin; Neurosecretory Systems

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

Elevated expression of leptin in endometriotic tissue results in an increase in stromal cell proliferation and may contribute to the development of endometriosis. However, the underlying mechanism responsible for aberrant expression of leptin is not known. We hypothesize that aberrant expression of leptin in endometriotic stroma may be regulated by increased levels of hypoxia-inducible factor-1alpha (HIF-1alpha), the master transcription factor that controls gene expression in response to hypoxia. Herein we show that the mRNA and protein levels of HIF-1alpha were greater in ectopic endometriotic tissue compared with its eutopic counterpart. Exposure of eutopic endometrial stromal cells under hypoxic conditions or treated with desferrioxamine (DFO, chemical hypoxia) resulted in a time-dependent increase in leptin gene expression. A promoter activity assay demonstrated that HIF-1alpha induced leptin promoter activity after DFO treatment. Chromatin immunoprecipitation assay further demonstrated that binding of HIF-1alpha to leptin promoter was evident after DFO treatment. Finally, depletion of HIF-1alpha by short interference RNA abolished leptin expression in ectopic endometriotic stromal cells. Taken together, our data demonstrate that aberrant expression of leptin in ectopic endometriotic stromal cells is induced, at least in part, by an elevated level of HIF-1alpha in these cells, providing new insights into the etiology of endometriosis.

Topics: Adult; Cell Hypoxia; Cells, Cultured; Deferoxamine; Endometriosis; Endometrium; Female; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leptin; Promoter Regions, Genetic; RNA, Small Interfering; Siderophores; Stromal Cells

Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by ectopic implants of endometrium in the peritoneal cavity and associated with increased secretion of proinflammatory cytokines and neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a role in food intake, basal metabolism, and reproductive function. Leptin levels are dynamically regulated, being elevated by inflammatory mediators and reduced by starvation. Leptin itself can influence the proinflammatory immune responses of CD4+ T lymphocytes, and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo. We investigated whether leptin concentrations in serum and peritoneal fluid (PF) differed between 13 patients with different stages of endometriosis and 15 age- and body mass index-matched controls. We found a statistically significant (P < 0.05) increase in leptin levels in serum (30.3 +/- 14.8 ng/mL) and PF (35.9 +/- 17.4 ng/mL) of patients with endometriosis, compared with our control population (serum, 15.6 +/- 8.4; PF, 17.5 +/- 7.2 ng/mL). Regression equations, relating leptin to body mass index, were also significantly different in endometriosis patients, compared with controls. Higher levels of leptin were observed in the earlier stages of endometriosis than advanced-stage disease. These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis.

Topics: Adult; Ascitic Fluid; Body Mass Index; C-Reactive Protein; Endometriosis; Female; Follicle Stimulating Hormone; Humans; Laparoscopy; Leptin; Luteinizing Hormone; Menstrual Cycle; Pelvic Inflammatory Disease

This study was undertaken to evaluate serum leptin concentrations in women with endometriosis during treatment with danazol and with leuprolide depot.. Twenty patients aged 18 to 42 years with regular menses and documented pelvic endometriosis were recruited from a university hospital setting. Treatment was 200 mg danazol 3 times daily for 6 months or 3.75 mg leuprolide depot every 28 days for 6 months. Serum leptin concentrations were measured before, during, and after treatment. A single blood sample was taken from each of 10 control women without endometriosis for comparison. Serum leptin level was measured with a radioimmunoassay kit with human leptin, and analysis of variance and paired t tests were used for statistical analysis.. Serum leptin levels were almost the same among women with endometriosis as in the control group. Leptin levels were higher among women with endometriosis during treatment with danazol and leuprolide(P <.001). Three months after treatment, leptin values remained moderately higher than before treatment.. Danazol and leuprolide increased serum leptin levels. The mechanism of leptin increase is unclear. Further studies are needed to determine whether an adipogonadal axis exists.

Topics: Adolescent; Adult; Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Infertility, Female; Leptin; Leuprolide

The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (

Topics: Ascitic Fluid; Biomarkers; C-Peptide; Dipeptidyl Peptidase 4; Endometriosis; Female; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Leptin; Macrophages; Nicotinamide Phosphoribosyltransferase; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Resistin

We tested the hypothesis that enriched environment (EE), consisting of enlarged space, and increased physical activity and social interactions, hinders the development of endometriosis through attenuated adrenergic signaling, enhanced autophagy, and reduced leptin levels. Two mouse experiments were performed. In Experiment 1, 40 female Balb/C mice were randomly divided into four equal-sized groups, the SE (standard environment), EE, p-EE (EE instituted after endometriosis induction), and the d-EE (SE housing but received uterine fragments from EE donors) groups. Housing intervention was initiated 3 weeks before the induction of endometriosis and continued for 3 weeks after induction. In Experiment 2, 20 female mice were randomly divided into SE and EE groups, and the plasma leptin levels were measured. We measured lesion weight and hotplate latency and performed Masson trichrome staining as well as immunohistochemistry analysis of β2 adrenergic receptor (ADRB2), dopamine receptor D2 (DRD2), vascular endothelial growth factor (VEGF), and microtubule-associated protein light chain 3 (LC3). We found that EE reduced the lesion weight by 40.8% as compared with SE mice, but the reduction in p-EE and d-EE mice did not reach statistical significance. EE significantly reduced staining levels of ADRB2 and VEGF as well as the extent of lesional fibrosis but increased staining levels of LC3 and DRD2 in lesions as compared with the SE group. EE mice had reduced plasma leptin levels as compared with SE mice. Thus, EE decelerates the development of endometriosis and fibrogenesis and improved generalized hyperalgesia, possibly through increased DRD2 expression but decreased expression of ADRB2 and VEGF as well as enhanced autophagy and reduced leptin level.

Topics: Animals; Endometriosis; Environment; Female; Housing, Animal; Leptin; Mice; Mice, Inbred BALB C; Physical Conditioning, Animal; Social Interaction; Vascular Endothelial Growth Factor A

Endometriosis is one of the most common reproductive diseases of women, with some important biochemical changes in the serum. Curcumin was reported to have anti-endometriosis, anti-inflammatory and antioxidant activity. This study explores the changes of serum levels of Cancer Antigen 125 (CA125), leptin, resistin, homocysteine, and total antioxidant capacity (TAC) in a rat model of endometriosis and the effect of curcumin treatment on these factors. Fifty female Sprague-Dawley rats (220-250 gr body weight) were randomly divided into control (received 0.3 mL of the vehicle), sham(stress of surgery + 0.3 mL of the vehicle) and three endometriosis groups as danazol treatment (7.2 mg/kg BW, IP), curcumin treatment (48 mg/kg BW, IP) and test (received 0.3 mL of the vehicle). Endometriosis was induced by surgically auto-transplantation of uterine tissue to the abdominal wall and intestinal mesentery. The animals were treated for 4 weeks. On the last day, the blood sample was collected by heart puncture, and the above-mentioned factors were measured in the sera. Leptin in the curcumin treatment group was markedly higher than all of the studied groups, except the danazol group, while there were no significant differences between other groups (P < 0.05). Level of resistin in endometriosis groups did not show significant differences with the control group (P < 0.05). There was no significant difference in the serum levels of homocysteine and CA 125 between all of the studied groups (P > 0.05). The serum levels of TAC in the control group were significantly higher than all of the studied groups (P < 0.05). Curcumin could prevent the growth of endometriosis, while there was no significant alteration on measured factors in the serum of rat with induced endometriosis. Hence follow up of these parameters in serum may not be a proper indicator to evaluate the status of endometriosis in the rat model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Curcumin; Endometriosis; Female; Homocysteine; Leptin; Proteins; Rats; Rats, Sprague-Dawley; Resistin

To investigate whether and how human chorionic gonadotropin (HCG) treatment ameliorates endometriosis in an endometriotic rat model.. Twenty-four endometriosis rats were established and were randomly divided into four groups, and then the rats were treated with 19.4, 25.8, and 51.6 IU/100 g weight/day of HCG, respectively. The control group was treated with 0.9% NaCl. After 15 days (3 estrous cycles), the ectopic lesion volume and the expression of leptin protein in eutopic and ectopic endometrium were investigated.. After HCG treatment, the volumes of endometriotic lesions were significantly smaller than those before treatment. During endometriosis development, the expression of leptin protein in eutopic and ectopic endometrium was remarkably increased. HCG administration reversed leptin upregulation in endometriotic tissues.. HCG therapy appears to be an effective treatment for endometriosis in rats through down-regulation of leptin expression in eutopic and ectopic endometrium.

Topics: Animals; Blotting, Western; Chorionic Gonadotropin; Disease Models, Animal; Down-Regulation; Endometriosis; Endometrium; Female; Fluorescent Antibody Technique; Humans; Leptin; Rats; Rats, Sprague-Dawley

CA-125 protein is used as a marker in clinical practice for the diagnosis of endometriomas. The aim of this study was to determine whether endometriomas are accompanied by an increased level of urocortin, ghrelin, and leptin, as well as the increased parameters of blood cell count, fibrinogen, and CA-125.. The study included 86 women aged 18-38 years who had been treated laparoscopically for lesions in the adnexa with the characteristics of endometriomas and mature teratoma, during the period September 2009 to November 2012. The statistical analysis was performed using the nonparametric Mann-Whitney U test and the Spearman rank correlation coefficients (p ≤ 0.05).. The medians were 105.31 pg/mL versus 120.84 pg/mL for urocortin, 7.16 pg/mL versus 9.13 pg/mL for leptin and 584.33 pg/mL versus 657.82 pg/mL for ghrelin (p > 0.05), respectively. Analyzing the parameters of blood cell count, statistically significant differences were shown in the respective groups for leucocyte level (5.35 × 10(9)/L vs. 6.7 × 10(9)/L; p = 0.029), fibrinogen level (3.12 mg% vs. 2.57 mg%; p = 0.001), and CA-125 (36.50 U/mL vs. 15.08 U/mL; p = 0.001).. In conclusion, the prognostic values for CA-125, leukocytes, and fibrinogen may prove a very useful tool for the diagnosis of lesions in the adnexa of the type endometriomas.

Topics: Adolescent; Adult; Biomarkers; CA-125 Antigen; Endometriosis; Female; Fibrinogen; Ghrelin; Humans; Leptin; Leukocyte Count; Ovarian Neoplasms; Sensitivity and Specificity; Teratoma; Urocortins; Young Adult

The aim of this study was to evaluate the leptin levels in the serum and peritoneal fluid (PF) and the protein expression in three different peritoneal ectopic implants in patients who underwent surgery for deep infiltrating endometriosis.. All patients had been treated at the Department of Gynecology of the Pedro Ernesto University Hospital, Rio de Janeiro. The study group consisted of 15 patients who underwent surgery for adnexal masses and infertility, while the control group consisted of ten women who underwent surgery for tubal ligation. Peritoneal fluid and samples tissues were collected during surgery. Serum samples were obtained before anesthesia. In this study, the leptin levels in the serum and peritoneal fluid (PF) were evaluated by ELISA. The protein expression of leptin and its receptors (ObR) and aromatase enzyme were evaluated by Western blot analysis of the intestine, uterosacral ligament and vaginal septum in the ectopic implants. The t-test and one-way ANOVA with Holm-Sìdak post-test were used, and p < 0.05 was considered to be statistically significant.. Compared to the controls, the serum leptin levels (control = 14.7 ng/mL ± 2.63, endometriosis = 19.2 ng/mL ± 1.84, p < 0.0001) were increased, while in PF, there was no difference (control = 6.68 ng/mL ± 0.43, endometriosis = 7.71 ng/mL ± 0.59, p = 0.18). Comparing women with and without ovarian implants, the leptin levels in both the serum and PF were significantly higher in women without ovarian implants (serum: with ovarian implant = 15.85 ± 1.99; without ovarian implant = 23.14 ± 2.60; ng/mL, p = 0.04; PF: with ovarian implant = 4.28 ± 1.30; without ovarian implant = 11.18 ± 2.98;ng/mL, p = 0.048). The leptin, ObR and aromatase protein expression levels were increased in lesions in the vaginal septum and were decreased in the intestine lesions.. This study reports several interesting associations between the leptin levels in serum, peritoneal fluid, and tissue samples and the localization of the ectopic endometrium. Although this study does not provide a clear picture of the role of leptin in the development and progression of peritoneal implants, it contributed new data that might be useful to elucidating the enigma that is the role of leptin in endometriosis disease.

Topics: Adult; Aromatase; Ascitic Fluid; Body Mass Index; Endometriosis; Female; Gene Expression Regulation, Neoplastic; Humans; Infertility, Female; Laparoscopy; Leptin; Peritoneum; Receptors, Leptin; Vagina

Endometriosis pain is a very common and extremely disabling condition whose mechanism is still poorly understood. While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain. Rats implanted with autologous uterine tissue onto the gastrocnemius muscle developed endometriosis-like lesions and local chronic pain. Compared to eutopic uterine tissue, leptin mRNA and protein were up-regulated in the endometriosis-like lesions. Intramuscular injection of recombinant leptin in naive rats produced dose-dependent local mechanical hyperalgesia and nociceptor sensitization to mechanical stimulation. Ovariectomy attenuated the mechanical hyperalgesia induced by recombinant leptin, in rats treated with vehicle compared to those treated with 17β-estradiol replacement, at 1 and 24 h after leptin injection. Finally, intralesional injections of a pegylated leptin receptor (Ob-R) antagonist or of an inhibitor of Janus kinase2, which transduces the Ob-R signal, markedly attenuated pain in the endometriosis model. Taken together these data support the hypothesis that leptin, generated in ectopic endometrial lesions produces mechanical hyperalgesia by acting on nociceptors innervating the lesion. This sensitivity to leptin is dependent on estrogen levels. Thus, interventions targeting leptin signaling, especially in combination with interventions that lower estrogen levels, might be useful for the treatment of endometriosis pain.

Topics: Animals; Chronic Pain; Disease Models, Animal; Endometriosis; Endometrium; Enzyme Inhibitors; Estradiol; Estrogens; Female; Hyperalgesia; Janus Kinase 2; Leptin; Muscle, Skeletal; Nociceptors; Ovariectomy; Rats; Rats, Sprague-Dawley; Receptors, Leptin; RNA, Messenger; Touch; Uterus

This study was designed to investigate leptin levels in the fluid in ovarian endometriomas (OEs) and to compare the expression of leptin and its receptors (OBR) in ovarian tissue affected by endometrioma in infertile women to its expression in the normal ovarian tissue of fertile controls without endometriosis.. In this case-control observational study, ovarian tissue, blood samples and peritoneal fluid were obtained from 20 women (10 fertile controls without endometriosis or any ovarian disease, who were undergoing tubal ligation surgery, and 10 infertile women with severe endometriosis and OE). The ovarian endometriomal fluid (EF) was aspirated, and peritoneal-implant (PI) biopsies were performed. The tissues removed during the surgeries were immediately frozen in liquid nitrogen to determine expression levels by western blot and leptin levels by ELISA.. OBR was expressed at higher levels in the ovarian tissue affected by endometrioma than in the normal ovarian tissue (control = 0.38 ± 0.05, study = 0.60 ± 0.09, p = 0.03), but there was no significant difference in leptin levels between these groups (control = 0.57 ± 0.1, study = 0.35 ± 0.1, p = 0.18). Positive and significant correlations were observed between leptin and OBR in the OE (r = 0.85, p = 0.004) and in the PI (r = 0.87, p = 0.001). ELISA results demonstrate a greater leptin concentration within the EF compared with the serum and the PF (serum = 14.25 ± 1.63, PF = 5.98 ± 2.0, EF = 73.8 ± 16.2, p = 0.0001), but there was no correlation between these variables. A positive, significant and strong correlation was observed between PF leptin levels and the expression of leptin and OBR in PI (leptin: r = 0.78, p = 0.007/OBR: r = 0.68, p = 0.04) and between the EF leptin levels and the expression of leptin and OBR in the OE (leptin: r = 0.88, p = 0.008/OBR: r = 0.89, p = 0.005).. These data suggest that leptin may play an important role in the physiopathology of OE through a modulatory interaction with its active receptor.

Topics: Adult; Ascitic Fluid; Case-Control Studies; Endometriosis; Female; Humans; Infertility, Female; Leptin; Ovarian Diseases; Ovary; Receptors, Leptin; Up-Regulation

The objective of the present study was to evaluate the levels of leptin, ghrelin, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in peritoneal fluid in patients with endometriosis and infertility, and study their correlation.. This cross-sectional study included women undergoing diagnostic and/or therapeutic laparoscopy for endometriosis with chief complaint of infertility and/or pain at a tertiary care hospital. Based upon laparoscopic and histopathological findings, patients were categorized as with endometriosis and no endometriosis. Of the 50 patients with infertility (age 23-41 years), 19 had endometriosis while 31 had no endometriosis. The markers were assessed using ELISA kits.. The median levels of leptin in patients with endometriosis (10.20 ng/mL) were higher (p = 0.04) and median levels of ghrelin in patients with endometriosis (150.4 pg/mL) were lower (p = 0.037) versus patients with no endometriosis (5.07 ng/mL and 229.6 pg/mL, respectively). The median levels of IL-6 and VEGF in patients with endometriosis were not different between the groups. The correlation analyses showed that leptin levels and IL-6 were positively correlated (p = 0.0001).. The results suggest that ghrelin and leptin might play a key role in pathophysiology of endometriosis, and leptin is associated with inflammation in endometriosis.

Topics: Adult; Ascitic Fluid; Cross-Sectional Studies; Endometriosis; Female; Ghrelin; Humans; Infertility, Female; Interleukin-6; Leptin; Vascular Endothelial Growth Factor A; Young Adult

To evaluate the expression of leptin, leptin receptor (ObR), adiponectin, and adiponectin receptor (AdipoR) in ovarian endometriomas compared with normal endometrium, and to analyze relationships among adipokines and their receptors.. Experimental study.. A clinic for the treatment of endometriosis and basic research laboratories.. Forty-four women with endometriosis and 42 age-matched women with no laparoscopic evidence of endometriosis as control subjects.. Endometrial tissue samples were obtained during laparoscopic surgery.. Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed with the use of tissue microarray. Clinical characteristics were reviewed from the patient's medical records. The effect of leptin on the expression of adiponectin was evaluated in endometriotic cell line using real-time reverse-transcription polymerase chain reaction.. Positive expression rates of leptin and ObR were significantly higher in ovarian endometrioma compared with normal endometrium, but those of adiponectin and AdipoR were similar (ovarian endometrioma vs. normal endometrium, respectively: leptin 100% vs. 59.5%; ObR 72.7% vs. 33.3%; adiponectin 31.8% vs. 42.9%; AdipoR 88.6% vs. 73.8%). Expression of adipokines and their receptors did not show any correlation with disease stage. A positive correlation was found between expression of ObR and adiponectin (correlation coefficient 0.488; P=.001). Leptin treatment in endometriotic cells induced mRNA expression of adiponectin.. These data suggest that leptin and its receptor are induced in ovarian endometriomas, and that the leptin/ObR system regulates adiponectin gene expression in endometriotic cells.

Topics: Adiponectin; Adult; Biomarkers; Cell Line, Transformed; Endometriosis; Female; Gene Expression Regulation, Neoplastic; Humans; Leptin; Ovary; Receptors, Adiponectin; Receptors, Leptin

Leptin acts as a potential growth stimulator in several normal and neoplastic cells. Recent studies have shown the presence of increased levels of leptin in the peritoneal fluid of patients with endometriosis, implicating leptin in the pathogenesis of endometriosis. However, the specific function of leptin in the induction of mitogenesis in endometriosis is not known. This study investigated the expression of the leptin receptor (ObR) in endometrioma tissues and immortalized endometriotic cells, and the effect of leptin on cell growth. ObR expression was higher in endometriomas than in the normal endometrium, and it was detected in 74% of epithelial and 30% of stromal endometrioma tissues. In addition, human endometriotic epithelial cells (11Z and 12Z) showed a high level of ObR when compared with endometrial cells and endometriotic stromal cells (22B). Furthermore, leptin treatment stimulated the growth of 11Z and 12Z cells, but not that of 22B cells. Knockdown of the ObR in 11Z and 12Z cells impaired the ability of leptin to induce cell growth. Leptin induced the activation of Janus Kinases 2 (JAK2), signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) in endometriotic epithelial cells. Moreover, pretreatment with the JAK2/STAT3 inhibitor AG490 and the ERK inhibitor PD98059 significantly inhibited leptin-induced cell growth. The present results show that the ObR is induced in endometriosis, and that leptin stimulates the growth of endometriotic epithelial cells through the JAK2/STAT3 and ERK pathways.

Topics: Adult; Cell Proliferation; Cells, Cultured; Endometriosis; Endometrium; Enzyme Inhibitors; Epithelial Cells; Female; Flavonoids; Gene Expression Regulation; Humans; Janus Kinase 2; Leptin; MAP Kinase Signaling System; Middle Aged; Receptors, Leptin; RNA, Small Interfering; STAT3 Transcription Factor; Stromal Cells; Tyrphostins

Do higher leptin levels and lower adiponectin levels predict subsequent development of endometriosis?. Plasma leptin and adiponectin levels were not associated with laparoscopically confirmed endometriosis when collected prior to disease diagnosis.. Case-control studies have identified altered levels of the inflammatory adipokines leptin and adiponectin in women with endometriosis, but it remains unclear whether inflammation results in endometriosis or whether the presence of endometriosis creates an inflammatory state.. Nested, matched, case-control study within the prospective Nurses' Health Study II (NHS II) cohort. Blood samples were collected between 1996 and 1999 from 29 611 female nurses within the cohort. Women who reported endometriosis before blood collection were excluded.. Plasma leptin and adiponectin levels were assayed by ELISA. Three hundred and fifty cases of laparoscopically confirmed endometriosis were matched 1:2 with 694 controls of comparable race, age, infertility history, menopausal status and time of blood draw. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models adjusting for matching factors and BMI.. After adjusting for BMI, there were no statistically significant associations between endometriosis and leptin [RR = 1.2; 95% CI = 0.7-2.0; P-value, test for linear trend (P(trend)) = 0.72], adiponectin (RR = 0.8; 95% CI = 0.5-1.2; P(trend) = 0.48) or the leptin to adiponectin ratio (RR = 0.8; 95% CI = 0.4-1.4; P(trend) = 0.14) when comparing the upper with the lower quartile. Results were unaltered when analyses were stratified by BMI or restricted to cases diagnosed ≥ 4 years after blood draw. To evaluate statistical significance and limit the role of chance to the gold standard of 5%, we present 95% CIs about the RRs, and for P-values calculated for linear tests of trend and tests of heterogeneity, we have set the α-level to be 0.05 (i.e. <0.05 is considered to be statistically significant).. A limitation of this study is the inability to differentiate the time of endometriosis 'diagnosis' from the time of disease 'onset' due to the impossibility in identifying a precise time point at which the disease process was first initiated at a molecular or cellular level. Additional limitations include lack of information regarding stage of endometriosis and the possibility of asymptomatic disease in the control population.. The mean age at diagnosis of endometriosis in the study population is 41.7, ≈ 10 years older than the mean age of diagnosis in the general population. While this may limit the generalizability of the results, there is no reason to suspect that the association between adipokines and endometriosis risk should differ at a younger age of diagnosis in an adult population.

Topics: Adiponectin; Adult; Case-Control Studies; Endometriosis; Female; Humans; Leptin; Middle Aged; Prospective Studies; Risk Factors

Pelvic endometriosis is a chronic inflammatory disease with an immunological background. Yet there is paucity of contemporary research exploring both the angiogenic cytokines, leptin and IL-8 for a possible role in its pathophysiology.. To compare levels of both leptin and IL-8 in peritoneal fluid (PF) in women with endometriosis vs. fertile controls and correlate with disease stage, type and symptoms.. PF from 58 women with endometriosis and 28 women undergoing tubal ligation was collected at laparoscopy and leptin and IL-8 levels were measured using ELISA. Results showed significantly higher levels of both cytokines in women with endometriosis. Significantly higher leptin and IL-8 levels were demonstrated in patients with early peritoneal (ASRM stage I and II) and advancing disease (ASRM stage III and IV), respectively. Levels of leptin/IL-8 were significantly lower in patients with endometrioma (4.8 ng/mL/32 pg/mL) vs. implants (13.0 ng/mL/68 pg/mL). There was no correlation of infertility or chronic pelvic pain with these levels.. Both leptin and IL-8 levels are raised in PF of women with endometriosis reflecting inflammation and dysregulated immunomodulation. Higher levels of leptin were seen in early stages; IL-8 seems to stimulate the disease in a dose-dependent manner.

Topics: Adult; Ascitic Fluid; Case-Control Studies; Endometriosis; Female; Humans; Infertility, Female; Interleukin-8; Leptin; Ovarian Diseases; Pelvic Pain; Peritoneal Diseases

To explore the roles of leptin, monocyte chemotactic protein (MCP)-1, and tumour necrosis factor (TNF)-α in the peritoneal fluid (PF) in the pathogenesis of endometriosis-associated infertility.. Leptin, MCP-1, and TNF-α levels in the PF from 28 infertile women with endometriosis (study group), 23 women with fallopian-associated infertility (controls), and 24 women with myoma (controls) were determined by performing enzyme-linked immunosorbent assay (ELISA).. Leptin and TNF-α levels in the PF showed no significant difference among three groups. The MCP-1 level in patients with endometriosis was higher than those in fallopian-associated infertility group and myoma group (P < 0.01). There was a positive correlation between leptin and MCP-1 levels in the PF of patients with endometriosis (P < 0.05).. Peritoneal leptin and MCP-1 play important roles in the pathogenesis of infertility in the early stage of endometriosis.

Topics: Adult; Ascitic Fluid; Chemokine CCL2; Endometriosis; Enzyme-Linked Immunosorbent Assay; Fallopian Tubes; Female; Humans; Infertility, Female; Leptin; Myoma; Tumor Necrosis Factor-alpha

The expression of cyclooxygenase (COX)-2 is considered as a marker of macrophage activation and has been implicated in the development of endometriosis. Leptin is an immunomodulator, which may also affect the development of endometriosis. However, how leptin contributes to these pathological processes has not been completely understood. The aim of this study was to investigate the effects of leptin on peritoneal macrophages and its relationship with endometriosis.. Peritoneal fluid from 60 women of reproductive age was obtained while they underwent laparoscopy. Forty patients had endometriosis and 20 patients did not have endometriosis. The concentration of leptin in the peritoneal fluid and prostaglandin F(2alpha) levels was measured by ELISA, and the other protein expression using Western blot when peritoneal macrophages were stimulated with leptin.. Concentration of leptin in peritoneal fluid was increased in patients with endometriosis compared with disease-free normal control. Functional leptin receptor was present in peritoneal macrophages. Treatment of peritoneal macrophages with leptin induced COX-2 expression. Production of prostaglandin F(2alpha) by peritoneal macrophages was increased after leptin stimulation in women with endometriosis.. Elevated concentration of leptin in peritoneal fluid may contribute to the pathological process of endometriosis through activation of peritoneal macrophages.

Topics: Adult; Ascitic Fluid; Cyclooxygenase 2; Dinoprost; Endometriosis; Female; Humans; Interleukin-1; Leptin; Macrophage-Activating Factors; Macrophages, Peritoneal; Receptors, Interleukin-1; STAT3 Transcription Factor; Taiwan

Endometriosis is a leading cause of infertility, and recent studies suggest that leptin and adiponectin may have a role in its causation and progression. This study assessed levels of leptin and adiponectin in serum and peritoneal fluid (PF) in patients with endometriosis and infertility.. This cross-sectional study included women undergoing diagnostic and/or therapeutic laparoscopy for endometriosis with chief complaint of infertility. Following laparoscopy, patients diagnosed with endometriosis served as cases while patients with no endometriosis served as controls. Patients with polycystic ovarian syndrome, diabetes, thyroiditis and patients on prior therapy with danazol or leuprolide were excluded from the study. Leptin and adiponectin levels were analysed in blood and PF using commercially available ELISA kits.. Of the 50 patients (aged 22-41 years), 15 had endometriosis (cases) while 35 had no endometriosis (controls). The median PF leptin level was significantly higher in cases as compared to controls (27.7 vs. 15.6 ng/ml, p = 0.019), and this remained significant even when PF leptin was BMI-normalised (p = 0.004). However, median serum leptin and adiponectin levels remained comparable between the two groups.. This study confirmed the role of PF leptin in causation and progression of endometriosis. However, this would have been definitive if healthy fertile females were included in this study.

Topics: Adiponectin; Adult; Ascitic Fluid; Biomarkers; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Diet, Vegetarian; Disease Progression; Endometriosis; Female; Humans; Infertility, Female; Laparoscopy; Leptin; Menstrual Cycle; Pelvis; Young Adult

Some studies have suggested a possible role of leptin, an active cytokine produced by adipocytes, in the pathogenesis of pelvic endometriosis. The present study was designed to assess leptin levels in the peritoneal fluid (PF) of women with the 'deep' or 'superficial' types of ovarian endometriosis. Twenty-seven women with a single ovarian endometrioma having a mean diameter between 3 and 5 cm were included in the study. Patients were divided into two groups according to the type of ovarian endometriosis: Group A (n = 11) consisted of women with 'superficial' endometriomas located at the ovarian surface; Group B (n = 16) included patients with 'deep' intra-ovarian endometriomas. Women undergoing laparoscopy for unexplained infertility and not affected by pelvic and/or ovarian endometriosis were considered as controls (Group C, n = 10). Patients with an ovarian endometrioma had significantly increased PF leptin concentrations than endometriosis-free controls (Groups A and B vs. Group C, p < 0.01). Patients with 'superficial' endometriomas had significantly higher PF leptin levels compared with patients with 'deep' endometriomas (Group A vs. B, p < 0.01). This difference remained significant after correction for the BMI; moreover, a positive correlation between PF leptin and BMI was observed in Groups B and C, but not in women with 'superficial' endometrioma (Group A). Our observations suggest that: (a) leptin could play an active role in promoting the development of 'superficial' ovarian endometriomas and (b) 'superficial' and 'deep' ovarian endometriomas could have a different pathogenesis.

Topics: Analysis of Variance; Ascitic Fluid; Endometriosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Ovarian Diseases; Ovary; Patient Selection; Regression Analysis

Endometriosis is a common, complex and chronic disease related to ectopic implantation and growth of endometrial tissue that may manifest by pelvic inflammatory reactions, chronic pelvic pain and subfertility. Endometriosis may be associated with increased peritoneal fluid leptin levels. Leptin is known to exert immunomodulatory effects; however, an association between leptin and inflammatory reactions in endometriosis has not been documented. Therefore, the aim of this study was to investigate a relationship between leptin concentrations in peritoneal fluid and the levels of peritoneal fluid inflammatory cytokines and mononuclear leukocyte subpopulations.. Peritoneal fluid was aspirated by laparoscopy from 46 women in whom endometriosis had been confirmed by clinical and histopathological examinations and from 10 control women qualified for ART in whom pelvic pathology has been excluded. Concentrations of leptin and inflammatory cytokines (IL-1beta, IL-6, IFN-gamma and TNF) in peritoneal fluid were evaluated by specific ELISAs. Percentage of peritoneal leukocyte subpopulations (CD3+, CD4+, CD8+ and CD14+) was analyzed by FACS using specific monoclonal antibodies.. Leptin concentrations in peritoneal fluid correlated negatively with concentrations of IL-1beta and IFN-gamma (r(s)=-0.38, p=0.01 and r(s)=-0.31, p=0.03, respectively) and correlated positively with the percentage of CD3+ pan-T cells (r(s)=0.69, p=0.009) and CD4+ T helper cells (r(s)=0.74, p=0.036).. Increased leptin levels in peritoneal fluid from endometriosis patients may affect local inflammatory/immune reactions, especially infiltration of CD4+ T helper cells. Thus, leptin may play an important role in the immunopathogenesis of endometriosis.

Topics: Adult; Ascitic Fluid; Cytokines; Endometriosis; Female; Humans; Leptin; Lymphocyte Subsets

Endometriosis is a common, complex and chronic disease related to ectopic implantation and growth of endometrial tissue that may manifest by pelvic pain, and accounts for over 20% of all cases of infertility in women. Endometriosis may be associated with increased levels of leptin in peritoneal fluid. However, the association of leptin with infertility has not been definitely documented. Therefore, the aim of the present study was to search for a relationship between concentrations of peritoneal-fluid leptin and patients' clinical status. The study included 56 patients being diagnosed for infertility and/or pelvic pain. Peritoneal fluid was aspirated during routine laparoscopic examination. Concentrations of leptin in peritoneal fluid were evaluated by a specific enzyme-linked immunosorbent assay. The results revealed that the levels of peritoneal-fluid leptin did not correlate with different stage of endometriosis. However, they correlated with body mass index. Leptin levels were significantly higher in infertile patients than in patients with pelvic pain (p = 0.0023 by Mann-Whitney U test or p = 0.0045 by analysis of variance). It may suggest that increased leptin levels in the peritoneal fluid may play a role in pathogenesis of infertility.

Topics: Adult; Ascitic Fluid; Body Mass Index; Endometriosis; Female; Humans; Infertility, Female; Leptin; Pelvic Pain; Peritoneal Diseases; Up-Regulation

To evaluate whether a combination of putative markers of inflammation and CA-125 could serve as a multiple-marker screening test for endometriosis in a heterogeneous population of patients.. Case-control evaluation of a diagnostic test.. University medical center.. Consenting women of reproductive age undergoing laparoscopy for indications of pain, infertility, elective tubal ligation, tubal reanastomosis, or other benign indications.. Diagnostic laparoscopy and peripheral venipuncture.. Serum concentrations of interleukin-6, tumor necrosis factor-alpha, macrophage migration inhibitory factor, macrophage chemotactic protein-1, interferon-gamma, leptin, and CA-125 measured by using ELISA assays; surgical staging of endometriosis.. Concentrations of the seven markers were compared between the 63 women with surgically confirmed stage II-IV endometriosis and 78 women who were surgically confirmed to be free of endometriosis. The individual diagnostic performance of each of the markers, based on receiver operating characteristic curves, was poor. When combinations of markers were evaluated by using classification tree analysis, a three-marker panel of CA-125, macrophage chemotactic protein-1, and leptin could diagnose 51% of subjects as to the presence of endometriosis with 89% accuracy. A four-marker panel of CA-125, macrophage chemotactic protein-1, leptin, and macrophage migration inhibitory factor could diagnose 48% of subjects with 93% accuracy. The remaining subjects would have no definitive diagnosis on the basis of the algorithm and would need to undergo standard evaluation.. This large study evaluates the combined use of putative serum markers for the diagnosis of endometriosis, rather than the use of each singly. Using the serum concentration of four markers in a two-tiered decision rule, nearly half of the subjects in this population would have been diagnosed (and could have avoided surgery) with 93% accuracy.

Topics: Adolescent; Adult; Algorithms; Biomarkers; CA-125 Antigen; Case-Control Studies; Chemokine CCL2; Cytokines; Endometriosis; Female; Humans; Interferon-gamma; Interleukin-6; Intramolecular Oxidoreductases; Leptin; Macrophage Migration-Inhibitory Factors; Middle Aged; Predictive Value of Tests; Tumor Necrosis Factor-alpha

Leptin, a 16-kDa cytokine, has been implicated in several reproductive processes and disorders. Notably, elevated leptin levels in the peritoneal fluid of women with mild endometriosis has been demonstrated, suggesting a role for this cytokine in the early stages of disease establishment. To gain insight into the functional significance of leptin during the initial requisite proliferative and neovascularization events involved in endometriosis, we investigated the effect of disruption of in vivo leptin signaling on the establishment and/or maintenance of an endometriosis-like lesion in a syngeneic immunocompetent mouse model of endometriosis. Findings of this study show that the disruption of leptin signaling by ip injection of the pegylated leptin peptide receptor antagonist (LPrA) impairs the establishment of endometriosis-like lesions (derived from uteri of C57BL/6 female siblings) and results in a reduction of viable organized glandular epithelium, vascular endothelial growth factor-A expression, and mitotic activity. LPrA treatment resulted in a significant reduction of microvascular density in endometriosis-like lesions after continuous and acute courses. Endometriosis-like lesions (derived from tissue with functional leptin receptor) of Lepr(db) hosts (nonfunctional leptin receptor) were phenotypically similar to those of LPrA-treated mice. Our results confirm that leptin signaling is a necessary component in lesion proliferation, early vascular recruitment, and maintenance of neoangiogenesis in a murine model of endometriosis.

Topics: Animals; Disease Models, Animal; Endometriosis; Female; Green Fluorescent Proteins; Leptin; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neovascularization, Pathologic; Phenotype; Signal Transduction; Uterus

Leptin influences the proinflammatory immune responses and has angiogenic activity in vitro and in vivo. The objective of this study was to evaluate the peritoneal fluid levels of leptin in patients with endometriosis and idiopathic infertility and compare them with a control group of tubal ligation/reanastomosis patients.. In this observational, prospective controlled study, peritoneal fluid from 108 women was obtained while they underwent laparoscopy for pelvic pain, infertility, tubal ligation or sterilization reversal. We measured the concentration of leptin in the peritoneal fluid and compared the levels among women who were divided into groups according to their post-surgical diagnosis. Sixty patients were diagnosed with endometriosis, 10 with idiopathic infertility and 38 had undergone tubal ligation or reanastomosis (control group).. Peritoneal fluid leptin was significantly higher in endometriosis 14.62+/-9.79 (mean+/-SD) ng/ml compared to idiopathic infertility [0.92+/-1.57 ng/ml (P=0.0007)] and to controls [0.78+/-1.94 ng/ml (P<0.0001)]. Leptin levels were positively correlated with the stage of endometriosis (r=0.45; P=0.03), and with pelvic pain in endometriosis patients (r=0.49; P=0.001). Peritoneal fluid leptin levels in patients with idiopathic infertility were comparable to controls.. Higher levels of leptin were observed in peritoneal fluid of patients with endometriosis compared to those without the disease. These data suggest that the proinflammatory and neoangiogenic action of leptin may contribute to the pathogenesis of endometriosis. Moreover, leptin may play a role in endometriosis-associated pain.

Topics: Ascitic Fluid; Biomarkers; Body Mass Index; Endometriosis; Female; Humans; Infertility, Female; Inflammation; Leptin; Pain; Pelvis; Sterilization Reversal; Sterilization, Tubal

Changes in peritoneal fluid (PF) composition may affect fertilization as well as early embryonic development. Leptin, an adipocyte hormone, has been shown to act as a link between adipose tissue and the reproductive system. Therefore, we decided to assess peritoneal and serum leptin levels in infertile endometriotic patients.. Seventy-two women were studied, including 30 fertile and 18 infertile women with ovarian endometriotic cysts and, as a reference group, 24 patients with unexplained infertility.. No significant difference in the peritoneal and leptin levels was found between the studied groups. Significantly higher PF leptin concentration was observed in patients with stages III and IV of endometriosis as compared to those with minimal stage of the disease. In fertile patients with endometriosis a positive correlation has been found between PF and serum leptin concentrations.. No differences in peritoneal or serum leptin levels between infertile and fertile women with endometriosis suggest that this cytokine is not involved in pathophysiology of endometriosis-related infertility.

Topics: Adolescent; Adult; Ascitic Fluid; Endometriosis; Female; Humans; Infertility, Female; Leptin

To investigate the concentrations of steroid hormones (estradiol, progesterone), pregnancy-associated protein-A, IGF-binding protein-4 and leptin in the follicular fluid of infertile patients with and without endometriosis.. Follicular fluid of IVF patients with and without endometriosis was aspirated, centrifuged and stored to analyze the above mentioned hormones and to compare their concentrations between women with and without endometriosis.. Follicular fluid estradiol levels were significantly higher in controls than in affected women. The concentrations of the other markers did not differ between the two groups.. Since not only the follicular fluid concentration of estradiol, but also the oocyte quality is decreased in women with endometriosis, we suggest that estradiol can be considered as a marker not only of oocyte maturity but also of oocyte quality.

Topics: Adult; Case-Control Studies; Endometriosis; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility, Female; Insulin-Like Growth Factor Binding Protein 4; Leptin; Oocytes; Pregnancy-Associated Plasma Protein-A; Progesterone; Treatment Outcome

Topics: Adult; Endometriosis; Endometrium; Female; Humans; Infertility, Female; Leptin

The leptin system has been implicated in reproductive function, acting at endocrine and paracrine levels. Recently, deregulation of this gene family has been linked to endometrial changes caused by endometriosis. In the present study, we compare the expression of leptin receptor mRNA during the pre-receptive (LH+2) and receptive (LH+9) phases in the eutopic endometrium from patients with severe/moderate endometriosis (n = 30) versus fertile controls (n = 12). In each patient, two endometrial samples were obtained at LH+2 and LH+9 in their natural cycles. When real-time quantitative fluorescent PCR was performed, an up-regulation of OB-RL and all the isoforms investigated was observed at LH+9 versus LH+2 in patients with and without endometriosis. However, no difference was found in the expression pattern of the total leptin receptor OB-RT, or in its long OB-RL and soluble HuB219.3 forms when the eutopic endometria of patients with severe/moderate endometriosis and fertile controls were compared. By means of in situ hybridization, total leptin receptor mRNA was localized in the luminal epithelium and the glands of the endometrium. The immunohistochemical analysis of the long form of leptin receptor was also performed in order to confirm these findings at the protein level. Finally, we have also shown similar leptin mRNA expression in both the control group and patients with endometriosis. In conclusion, we have not identified differences in the endometrial expression and localization of leptin and the leptin receptor when comparing the eutopic endometrium of women with severe/moderate endometriosis and fertile controls.

Topics: Adult; Endometriosis; Endometrium; Female; Gene Expression; Humans; In Situ Hybridization; Leptin; Protein Isoforms; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

The aims of this retrospective study were to investigate whether the quantification of ovarian stromal blood flow and/or leptin concentration are predictive of in vitro fertilization (IVF) outcomes in women after laparoscopic ovarian cystectomy for large endometriomas.. Twenty-two women undergoing IVF after laparoscopic surgery for ovarian endometriomas (> 6 cm) comprised the study group. Twenty-six women with tubal factor infertility constituted the control group. Ovarian stromal blood flow was evaluated by three-dimensional (3D) power Doppler ultrasound imaging using virtual organ computer-aided analysis (VOCAL( trade mark )). Serum and follicular fluid (FF) leptin concentrations were quantified using an enzyme-linked immunosorbent assay kit.. There were significantly decreased ovarian stromal blood flow parameters (including vascularization index, flow index (FI), and vascularization flow index) in the endometriosis group without an evident difference in total ovarian volume on the day of human chorionic gonadotropin. The value of FF leptin demonstrated a negative correlation with ovarian stromal FI in the control group, but there was a loss of this effect in the endometriosis group.. Quantification of ovarian stromal blood flow by 3D power Doppler ultrasound in women with endometriosis may provide an important prognostic indicator in those undergoing IVF.

Topics: Adult; Blood Flow Velocity; Endometriosis; Female; Fertilization in Vitro; Humans; Imaging, Three-Dimensional; Infertility, Female; Leptin; Ovary; Retrospective Studies; Treatment Outcome; Ultrasonography, Doppler, Color

The role of leptin in reproductive processes has received increasing attention. Because leptin has intrinsic angiogenic properties, may be induced by inflammatory cytokines and induces matrix metalloproteinases, we examined peritoneal fluid (PF) leptin concentrations in women with endometriosis.. PF samples were collected from 60 women undergoing laparoscopy for endometriosis, and 18 controls undergoing tubal sterilization. Fifty of the women with endometriosis had received no prior hormonal treatment, while 10 with moderate- severe endometriosis were using GnRH agonists.. Women with untreated endometriosis had significantly higher (mean +/- SD) PF leptin levels (34.9 +/- 7.9 ng/ml) than controls (17.9 +/- 4.1 ng/ml; P < 0.001). However, PF leptin levels were inversely correlated with the stage of disease (r = -0.62; P < 0.001). Nevertheless, women with stage III-IV endometriosis maintained significantly higher PF leptin levels (26.3 +/- 4.8 ng/ml; P < 0.001) than controls. Although PF leptin levels were significantly higher in the secretory versus proliferative phase of the menstrual cycle, they remained higher in both phases in women with untreated endometriosis. PF leptin levels in women on GnRH agonists were similar to controls.. PF leptin levels are elevated in women with endometriosis, but inversely correlated with extent of disease. These findings suggest a potential role for leptin in the pathogenesis of peritoneal endometriosis.

Topics: Adult; Ascitic Fluid; Endometriosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infertility, Female; Laparoscopy; Leptin; Menstrual Cycle; Pelvic Pain

It has been recently reported that serum concentrations of the adipocyte-derived hormone leptin are increased in patients affected by endometriosis. On the basis of these findings, the present study was undertaken to evaluate whether the protein may be used as a new serum marker of the disease. A consecutive series of 67 reproductive-age women who underwent laparoscopy for benign gynecological pathologies were enrolled prospectively for the study. Serum leptin concentrations, as evaluated by a conventional RIA kit, were related to baseline clinical characteristics and surgical and histologic diagnosis. Endometriosis was documented in 42 women (stage I-II in 19 patients and stage III-IV in 23 patients). Twenty-five women of similar age and body mass index, who had no laparoscopic evidence of the disease, served as control group. Serum levels of leptin resulted similar between women without and with endometriosis at any stage (mean +/- SEM, 12.5 +/- 9.4 ng/ml and 12.1 +/- 8.0 ng/ml, respectively). No significant association with leptin concentrations was observed in regard to stage of the disease, number of endometriotic implants, presence/absence of an endometriotic cyst or peritoneal deep endometriosis, and presence/absence of specific symptoms. Therefore, our results do not support the possibility to employ leptin measurement as a diagnostic tool for endometriosis. Further studies are needed to elucidate the relationship between leptin and endometrial system and determine the potential contribution of the molecule in implantation and early pregnancy development.

Topics: Adult; Biomarkers; Endometriosis; Female; Humans; Leptin; Middle Aged; Osmolar Concentration; Prospective Studies; Reference Values

Endometriosis is a polygenic disease with complex, multifactorial aetiologies affecting approximately 10% of women of reproductive age. Leptin is the product of the ob gene, which is related to reproductive function and immunological alteration. The angiogenic and mitogenic action of leptin may influence the formation of endometriosis. This study was aimed at determining whether leptin and leptin receptor expression differs in eutopic and ectopic endometria collected from laparoscopy and at investigating the pathophysiological role of leptin in the development of endometriosis. Leptin mRNA was undetectable in seven out of 14 eutopic endometria and only a minute amount was detected in the remaining samples. In contrast, there was a marked increase in leptin mRNA and protein expression in ectopic endometriotic lesions of patients with endometriosis (P < 0.05). Receptors for leptin were immunologically stained in eutopic endometrium as well as in ectopic endometriotic implants. However, the levels of mRNA for the long and total forms of leptin receptors were suppressed in association with the severity of endometriosis (P < 0.05). Administration of leptin stimulated its own mRNA expression in ectopic endometriotic stromal cells but decreased steady-state concentrations of mRNA encoding for leptin receptor (n = 6). In addition, leptin significantly enhanced both eutopic and ectopic endometrial stromal cell proliferation (P < 0.05). In conclusion, the differential distribution of mRNA for leptin and its receptor suggests an important autocrine and paracrine role for leptin in human endometriosis. The mitogenic and auto-augmentation effects of leptin may further contribute to the pathogenesis of endometriosis.

Topics: Adult; Cell Division; Cells, Cultured; Endometriosis; Female; Gene Expression Regulation; Humans; Leptin; Receptors, Cell Surface; Receptors, Leptin; Stromal Cells; Up-Regulation

This study was designed to measure leptin concentrations in the peritoneal fluid (PF) of women with different aspects of pelvic endometriosis. Among 36 consecutive women undergoing laparoscopy, nine were diagnosed as having minimal-mild endometriosis (stage I-II). Among nine other subjects with advanced stage (III-IV) disease, six showed one or more ovarian endometriotic cysts as the only operative finding. The remaining 18 unaffected women constituted the control group. Patients with endometriosis had significantly higher PF leptin concentrations (32.6 +/- 16.2 versus 17.1 +/- 6.6 ng/ml, P = 0.002); this difference remained significant when corrected for body mass index (BMI) (PF leptin/BMI ratio 1.41 +/- 0.67 versus 0.76 +/- 0.28, P = 0.001). Furthermore, the PF leptin/BMI ratio was significantly higher in women with peritoneal implants than in those in whom no implant was found at laparoscopy (1.6 +/- 0.7 versus 0.83 +/- 0.33, P = 0.007). Conversely, patients with one or more ovarian endometriomata as the only finding, had a PF leptin/BMI ratio comparable with that in women where no cyst was found (1.05 +/- 0.4 versus 1.1 +/- 0.65). In women with stage I-II endometriosis, a higher mean PF leptin/BMI ratio was found compared with those affected by stage III-IV (1.78 +/- 0.68 versus 1.05 +/- 0.43, P = 0.01). These results show that during endometriosis the presence of peritoneal disease, and not of ovarian endometriotic cysts, influences leptin concentrations in PF. The data suggest that leptin may play a role in the development of peritoneal endometriosis, and that different biochemical phenomena might be involved in the pathogenesis of the ovarian form of the disease.

Topics: Adult; Ascitic Fluid; Body Mass Index; Endometriosis; Female; Humans; Laparoscopy; Leptin; Ovarian Diseases; Peritoneal Diseases; Regression Analysis