Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis

Objectives: To investigate whether there is an association between vascular endothelial growth factor (VEGF) levels in serum and peritoneal fluid, and the presence of pelvic endometriosis and its clinical symptoms. Methods: Blood and peritoneal fluid sample levels of VEGF were measured in 46 women undergoing laparoscopy: 32 with suspected endometriosis and 14 with confirmed endometriosis. Data were analyzed according to phase of the menstrual cycle, symptoms, disease stage, and disease site. Results: There were no significant associations between serum and peritoneal fluid levels of VEGF and the presence of endometriosis, even when controlling for the menstrual phase. However, among the women with confirmed endometriosis, there was a significant increase (P=0.002) in the mean peritoneal. VEGF level. in those in the late secretory phase compared with those in the proliferative and early secretory phases. Conclusions: Measuring VEGF levels in symptomatic patients is not helpful to differentiate those with endometriosis from those with a different condition. However, in the late secretory and menstrual phases, mean VEGF levels were higher in women with confirmed endometriosis than in those suspected of having the disease. (C) 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.991333

Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis

BACKGROUND: The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months. METHODS: Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period. RESULTS: CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life. CONCLUSIONS: Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.2071993199

Quality of Life after Segmental Resection of the Rectosigmoid by Laparoscopy in Patients with Deep Infiltrating Endometriosis with Bowel Involvement

Study Objective: To estimate the quality of life of patients undergoing laparoscopic resection of a segment of the rectosigmoid for the treatment of deep infiltrating endometriosis with bowel involvement. Design: Prospective application of the SF-36 Health Status Questionnaire to 151 women before and 1 year after surgical intervention (Canadian Task Force Design Classification II). Setting: Department of Obstetrics and Gynecology, University of Sao Paulo Medical School, and Samaritano Hospital, Sao Paulo, Brazil. Patients: A total of 151 women (mean age 34.05 +/- 5.65 years) with deep infiltrating endometriosis underwent resection of a segment of the rectosigmoid by laparoscopy between 2002 to 2009. Interventions: All the patients had historical data collected and underwent clinical examination and transvaginal ultrasonography with prior bowel preparation for resection of a segment of the rectosigmoid by laparoscopy indicated for patients with symptoms (pelvic pain) with 1 or more lesions of more than 3 cm in length or multifocal lesions. Measurements and Main Results: Wilcoxon signed rank test verified differences between the degrees of the symptoms and the SF-36 scores before and 1 year after laparoscopic treatment. There was a significant improvement (p < .001) in all pain-related symptoms, as well as a significant increase (p < .001) in scores in all the SF-36 domains and in the sum of the components comprising both physical and mental health. Conclusion: Laparoscopic segmental resection of the rectosigmoid fulfills its essential objective of treating endometriosis with bowel involvement and improving patients' QoL to a significant extent. Journal of Minimally Invasive Gynecology (2011) 18, 730-733 (C) 2011 AAGL. All rights reserved.18673073

Interleukin-12 but not interieukin-18 is associated with severe endometriosis

Objective: To evaluate interleukin (IL)-12 and IL-18 levels in the serum and peritoneal fluid of women with and without endometriosis. Design: Cross-sectional survey. Setting: University hospital. Patients: Interleukin-12 and IL-18 levels were compared in 105 patients submitted to laparoscopy because of symptoms suggestive of endometriosis (pain and/or infertility). The disease was confirmed in 72 patients (study group), while in 33 patients findings were not compatible with endometriosis (control group). Intevention(s): Blood sample and peritoneal fluid were obtained from patients during videolaparoscopy. Main Outcome Measure(s): The levels of IL-12 and IL-18 in peripheral blood and peritoneal fluid were determined and compared with the stage and site of the disease and histologic classification. Result(s): IL-12 levels measured in peritoneal fluid were higher inpatients with endometriosis compared with the control group. A significant increase in IL-12 levels was found when the more advanced stages of the disease were compared with the initial stages. No statistically significant differences were found in IL-18 levels, either in serum or in peritoneal fluid samples. Conclusion(s): Patients with severe endometriosis have higher IL-12 levels irrespective of IL-18 levels, suggesting that in this disease an alternative pathway is involved in induction of the Th1 immune response. (Fertil Steril (R) 2009;91:320-4. (C)2009 by American Society for Reproductive Medicine.)Foundation for the Support of Research in the State of Sao Paulo (FAPESP