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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. [ABSTRACT FROM AUTHOR]

We aimed to assay cytokines and growth factors in peritoneal fluid samples from women with and without endometriosis to understand the inflammatory milieu, and assess their potential diagnostic utility. This cross-sectional study conducted at a tertiary care hospital included 54 women, aged 20–45 years, with regular menstrual history and undergoing diagnostic/therapeutic laparoscopy for infertility and/or pain. Peritoneal fluid samples were collected after insertion of trocar & laparoscope but prior to other surgical intervention. A multiplex immunoassay of 27 cytokines and growth factors was performed. The concentration of FGF2 and CSF3 were significantly lower in women with endometriosis than without endometriosis (p =.043 and.003, respectively). The levels of CCL2 and IL1RN were significantly higher in moderate-severe than in minimal-mild endometriosis (p =.038 and.043, respectively). Phase-specific comparison revealed that in proliferative phase, the levels of CSF2 and CSF3 were lower in women with endometriosis than without the disease (p =.047 and.013, respectively). The ROC curve analysis provided a cutoff value 0.78 and 0.76 for FGF2 and CSF3, respectively. Cytokines and growth factors such as FGF2, CSF3, CSF2, CCL2 and IL1RN seem to contribute to the pathogenesis of endometriosis and may have a potential utility for the diagnosis of endometriosis. [ABSTRACT FROM AUTHOR]

Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors - Galectin-3 and Stimulation Expressed Gene 2 - in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis. 由于并未明确的发病机制,子宫内膜异位症成为一种令人困惑的疾病。一些研究认为腹腔液是子宫内膜异位发生和发展的关键炎症环境。本研究分析了两种炎症因子-- 半乳糖凝集素3及刺激表达基因2在15名患有子宫内膜异位症妇女和8名对照妇女腹腔液中的水平。腹腔液通过避免了任何污染的腹腔镜手术收集并妥善处理和保存，随后使用酶免疫分析法分析了浓缩腹腔液中的Gal-3和ST2。异位症组的Gal-3水平明显高于对照组(64.7 ± 52.34 比 21.05 ± 20.83 ng/ml,p=0.044)，而ST2水平在两组中并无明显差异。Gal-3与ST2水平存在明显的正相关，Gal-3水平与内异症的发展阶段、症状的持续时间、Marinoff及VAS评分正相关，而ST2与VAS评分呈正相关。我们的结果显示Gal-3和ST2或与内异症炎症发展过程有关。为确定子宫内膜异位症的早期诊断标记物及开展新的治疗方式仍需要进一步的研究。 [ABSTRACT FROM AUTHOR]

Objective: 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. Design and setting: 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. Results: 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). Conclusions: The results suggest that ghrelin and leptin might play a key role in pathophysiology of endometriosis, and leptin is associated with inflammation in endometriosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate serum and peritoneal fluid (PF) glycodelin-A concentrations in women with ovarian endometriosis. Ninety-nine matched pairs of serum and PF samples were included in our study. The case group comprised 57 women with ovarian endometriosis and the control group 42 healthy women undergoing sterilization or patients with benign ovarian cysts. Glycodelin-A concentrations were measured using ELISA. Endometriosis patients had significantly higher serum and PF glycodelin-A concentrations compared to controls, and this increase was observed in both proliferative and secretory cycle phases. Glycodelin-A concentrations were more than 10-fold higher in PF than in serum and correlated with each other. Intensity and frequency of menstrual pain positively correlated with glycodelin-A concentrations. Sensitivity and specificity of glycodelin-A as a biomarker for ovarian endometriosis were 82.1% and 78.4% in serum, and 79.7% and 77.5% in PF, respectively. These results indicate that Glycodelin-A has a potential role as a biomarker to be used in combination with other, independent marker molecules. [ABSTRACT FROM AUTHOR]

Objective: To study the levels of chitotriosidase activity in the peritoneal fluid and the plasma of patients with severe endometriosis and control subjects. Materials and methods: Twenty-five women with laparoscopically and histopathologically confirmed endometriosis (study group) and 27 control patients who had undergone laparoscopic surgery were included. Peritoneal fluid and peripheral blood were obtained from all the patients before the surgery. Chitotriosidase activities were measured. Results: Analysis of chitotriosidase activity in the peritoneal fluid of patients with endometriosis showed that there was no significant difference between endometriosis and control group, respectively (32.04 ± 64.20 vs. 15.25 ± 31.17 nmol/mL/h; p > 0.05). Analysis of chitotriosidase activity in plasma of patients with endometriosis showed significantly increased levels of chitotriosidase levels compared with the control group (74.81 ± 60.54 vs. 14.10 ± 26.17; p < 0.001), respectively. Conclusion: We found that the activity of chitotriosidase in plasma was statistically higher in severe endometriosis patients than women without endometriosis. [ABSTRACT FROM AUTHOR]

Objective. 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. Design and setting. 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. Results. 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. Conclusions. 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. [ABSTRACT FROM AUTHOR]

Endometriosis affects 10-20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-α (TNF-α), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-α and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-α and glycodelin when compared with the other patients (no or moderate pain). TNF-α and glycodelin may thus play a role in endometriosis and the severity of menstrual pain. [ABSTRACT FROM AUTHOR]

Aim. Endometriosis is often associated with lower abdominal pain, dysmenorrhea, dyspareunia, and chronic pelvic pain. There is no correlation between the extent of endometriosis and the intensity of pain. The mechanism of pain in endometriosis is unknown. The aim of our study was to investigate the influence of peritoneal fluid (PF) from endometriosis patients on cultured neural cells that are the morphological basis of nociception, and to determine whether there was a relationship between the rAFS staging and an elevation of TGF-β1 production by these cells. Methods. Different human neuroblastoma cell lines were grown to 3/4 confluence and then cultured in presence of PF pooled according to the presence of no, mild, or severe endometriosis. After 6 and 24 h of incubation, the morphological changes were assessed and the metabolic activity was determined. Results. The different cell lines showed strongly varying proliferation and aggregation patterns. The metabolic activity was also varying between cell lines, but no consistently increased cell turnover in the PF when compared with the control medium nor associated to a particular, endometriosis-derived PF pool could be shown. In this experimental setting, we have observed that the cell proliferation in the presence of PF was inhibited, and not enhanced as it might have been expected. Measurement of TGF-β1 showed higher production rates for this cytokine under exposure to PF than in controls for some but not all tested cell lines, but there was no association with the stage (rAFS) of the disease. Conclusion. The neuronal cell culture model may become a useful tool to investigate the endometriosis-derived pain, but different endpoints and cell lines may have to be introduced. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. Endometriosis has a wide range of severity but molecular factors associated with variable extension of the disease have not been widely investigated. The present study compares the peritoneal fluid (PF) proteome of 109 women with endometriosis and different disease stage as defined by the American Society for Reproductive Medicine (ASRM). Methods. PF samples were subjected to two-dimensional gel electrophoresis; protein spots of interest were identified by liquid chromatography tandem mass spectrometry. Results. Over 470 protein spots were analyzed. One isoform of haptoglobin α chain, α-1b-glycoprotein and one unknown protein had higher expression in PF of women with ASRM stage I-II endometriosis. Four isoforms of α1-antitrypsin, three isoforms of α-1b-glycoprotein, one isoform of S100-A8 and serotransferrin had higher expression in PF of women with ASRM stage III-IV disease. Conclusions. Several protein isoforms have different expression in PF of women with ASRM stage I-II endometriosis than in those with ASRM stage III-IV disease; most of these molecules are involved in inflammation and immune response. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic estrogen-dependent gynecological disease, characterized by pelvic pain and infertility, defined as the presence of endometrial glands and stroma within the pelvic peritoneum and other extrauterine sites. In the peritoneal cavity endometrial cells adhere, proliferate and induce an inflammatory response. Despite a long history of clinical and experimental research, the pathogenesis of endometriosis is still controversial. Abnormal immunological activation, the endocrine milieu and the peritoneal environment all dramatically affect endometriotic tissue function. Recent studies suggest that the peritoneal fluid of women with endometriosis contains an increased number of activated macrophages and other immune cells that secrete various local products, such as growth factors and cytokines, which exert a paracrine action on endometriotic cells. Since the peculiar biological characteristics of eutopic endometrium from women with endometriosis differ from endometrium of normal subjects, an important role in the pathogenesis of this complex disease has been suggested. All of these factors contribute to enhanced proliferative and angiogenic activity and a number of functional and structural changes, resulting in the particular behavior of this tissue. [ABSTRACT FROM AUTHOR]

Objective . It is becoming more and more evident that different types of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the pathogenesis of endometriosis. The aim of the present study was to measure levels of the active forms of MMP-13 and membrane type-1 matrix metalloproteinase (MT1-MMP)/MMP-14 as well as TIMP-2 in the peritoneal fluid of women with endometriosis. Study design . We determined the levels of the active forms MMP-13 and MT1-MMP/MMP-14 as well as TIMP-2 in the peritoneal fluid of 20 women with endometriosis and 18 controls by different types of enzyme-linked immunosorbent assay. Results . We found that the concentrations (mean ± standard deviation) of total active MMP-13 and endogenous active MT1-MMP/MMP-14 in the peritoneal fluid of patients with endometriosis were 1.69 ± 0.67 and 3.12 ± 1.07 ng/ml, respectively. In control women the corresponding values were 3.02 ± 0.43 and 4.45 ± 1.03 ng/ml. The differences were statistically significant ( p < 0.0001 and p < 0.0004 for MMP-13 and MMP-14, respectively). Levels of TIMP-2 did not differ significantly. Conclusions . Decreased concentrations of active MMP-13 and MT1-MMP/MMP-14 may imply that the proteolytic activity of the peritoneal milieu of women with endometriosis is disturbed, which may have implications in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]