Endometriotic lesions are known to be hyperinnervated, especially in lesions of deep endometriosis (DE), which are frequently in close proximity to various nerve plexuses. DE lesions typically have higher fibromuscular content than that of ovarian endometriomas (OE) lesions, but the underlying reason remains elusive. Aside from their traditional role of pain transduction, however, whether or not sensory nerves play any role in the development of endometriosis is unclear. Here, we show that, thorough their respective receptors neurokinin receptor 1 (NK1R), calcitonin receptor like receptor (CRLR), and receptor activity modifying protein 1 (RAMP-1), neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT) and further turn stromal cells into smooth muscle cells (SMCs) in endometriotic lesions, resulting ultimately in fibrosis. We show that SP and CGRP, or the rat dorsal root ganglia (DRG) supernatant, through the induction of NK1R and CGRP/CRLR/RAMP-1 signaling pathways, promoted EMT, FMT and SMM in endometriosis, resulting in increased migratory and invasive propensity, cell contractility, production of collagen, and eventually to fibrosis. Neutralization of NK1R and/or CGRP/CRLR/RAMP-1 abrogated these processes. Extended exposure of endometriotic stromal cells to SP and/or CGRP or the DRG supernatant induced increased expression of α-SMA, desmin, oxytocin receptor, and smooth muscle myosin heavy-chain. Finally, we show that DE lesions had significantly higher nerve fiber density, increased staining levels of α-SMA, NK1R, CRLR, and RAMP-1, concomitant with higher lesional fibrotic content than that of OE lesions. The extent of lesional fibrosis correlated positively with the staining levels of NK1R, CRLR, and RAMP-1, as well as the nerve fiber density in lesions. Thus, this study provides another piece of evidence that sensory nerves play an important role in promoting the development and fibrogenesis of endometriosis. It explains as why DE frequently have higher fibromuscular content than that of OE, highlights the importance of lesional microenvironment in shaping the lesional fate, gives more credence to the idea that ectopic endometrium is fundamentally wounds that go through repeated tissue injury and repair, and should shed much needed light into the pathophysiology of endometriosis.

Pains of various kinds--dysmenorrhea, chronic pelvic pain, and dyspareunia--are the major complaints from women with endometriosis, representing the most debilitating nature of the disease. Despite extensive research, our understanding as how endometriosis causes pain is still fragmentary. In this study, we examined transient receptor potential vanilloid 1 (TRPV1)-positive nerve fibers in ectopic endometrium from women with ovarian endometriomas and in endometrium from women without endometriosis and correlated the density with the severity of dysmenorrhea in cases. We also performed an immunohistochemistry analysis of TRPV1 in ectopic and control endometrium. After finding TRPV1 immunoreactivity in ectopic endometrial cells, we further examined whether TRPV1 is functional in ectopic endometrial stromal cells (EESCs). We found that the density of TRPV1-positive nerve fibers in ectopic endometrial implants is higher than that in control endometrium and correlates positively with the severity of dysmenorrhea in women with endometriosis. In addition, TRPV1 expression was also found to be elevated significantly in EESCs when stimulated with inflammatory mediators such as prostaglandin E2 (PGE(2) ) and tumor necrosis factor-α (TNF-α). Finally, we found that TRPV1 activation can induce the release of nitric oxide (NO) and interleukin 1β (IL-1β) in EESCs. The latter finding appears to be consistent with the reports of increased TRPV1 protein expression following peripheral inflammation. Our results suggest that the increased TRPV1-positive nerve fibers may integrate various stimuli on peripheral terminals or primary sensory neurons and generate hyperalgesia in endometriosis. The expression and functionality of TRPV1 in EESCs also suggest that TRPV1 may have neurosecretory functions that are yet to be elucidated.

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The Society of Radiologists in Ultrasound expert consensus provides recommendations for augmenting routine pelvic US examinations through additional maneuvers and imaging to improve diagnosis of deep endometriosis.

To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas.All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated.Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was 'an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable.Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy.(c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Background: Endometriosis is a common condition which causes pain and reduced fertility. Treatment can be difficult, especially for severe disease, and an accurate preoperative assessment would greatly help in the managment of these patients. The objective of this study is to assess the accuracy of pre-operative transvaginal ultrasound scanning (TVS) in identifying the specific features of pelvic endometriosis and pelvic adhesions in comparison with laparoscopy.;Methods: Consecutive women with clinically suspected or proven pelvic endometriosis, who were booked for laparoscopy, were invited to join the study. They all underwent a systematic transvaginal ultrasound examination in order to identify discrete endometriotic lesions and pelvic adhesions. The accuracy of ultrasound diagnosis was determined by comparing pre-operative ultrasound to laparoscopy findings.;Results: 198 women who underwent preoperative TVS and laparoscopy were included in the final analysis. At laparoscopy 126/198 (63.6%) women had evidence of pelvic endometriosis. 28/126 (22.8%) of them had endometriosis in a single location whilst the remaining 98/126 (77.2%) had endometriosis in two or more locations. Positive likelihood ratios (LR+) for the ultrasound diagnosis of ovarian endometriomas, moderate or severe ovarian adhesions, pouch of Douglas adhesions, and bladder deeply infiltrating endometriosis (DIE), recto-sigmoid colon DIE, rectovaginal DIE, uterovesical fold DIE and uterosacral ligament DIE were > 10, whilst for pelvic side wall DIE and any ovarian adhesions the + LH was 8.421 and 9.81 respectively.;The negative likelihood ratio (LR-) was: < 0.1 for bladder DIE; 0.1-0.2 for ovarian endometriomas, moderate or severe ovarian adhesions, and pouch of Douglas adhesions; 0.5-1 for rectovaginal, uterovesical fold, pelvic side wall and uterosacral ligament DIE. The accuracy of TVS for the diagnosis of both total number of endometriotic lesions and DIE lesions significantly improved with increasing total number of lesions.;Conclusions: Our study has shown that the TVS diagnosis of endometriotic lesion is very specific and false positive results are rare. Negative findings are less reliable and women with significant symptoms may still benefit from further investigation even if TVS findings are normal. The accuracy of ultrasound diagnosis is significantly affected by the location and number of endometriotic lesions.

To estimate the diagnostic value of transvaginal ultrasonography in the detection of pelvic adhesions in women suspected of having endometriomas at ultrasonography.Prospective observational study.Academic Department of Obstetrics and Gynecology.One hundred thirteen women who underwent surgery for an endometrioma.All patients underwent transvaginal ultrasonography before surgery, and at ultrasonography the presence of fixation of the ovary to the uterus was considered characteristic of the presence of pelvic adhesions.Sensitivity, specificity, and likelihood ratios were calculated with 95% confidence intervals (CIs).The sensitivity and specificity of the fixation to the uterus of at least one ovary were respectively 89% (95% CI 84%-92%) and 90% (95% CI 76%-97%). The likelihood ratio for fixation of at least one ovary to the uterus was 8.92 (95% CI 3.04-26) and for a "normal" ultrasound examination 0.12 (95% CI 0.06-0.23). The pretest probability of pelvic adhesions was 74%, and this probability increased to 96% when fixation of at least one ovary to the uterus was present and fell to 27% when this ultrasonographic finding was absent.Transvaginal ultrasonography seems to be able to detect or exclude the presence of adhesions in women with ultrasonographic suspicion of endometrioma.Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

To evaluate preoperative real-time dynamic transvaginal sonography (TVS) in the prediction of pouch of Douglas (POD) obliteration in women undergoing laparoscopy for suspected endometriosis.This was a multicenter prospective observational study undertaken from January 2009 to November 2011. All women with symptoms suggestive of endometriosis who were scheduled for laparoscopy underwent detailed preoperative TVS, in particular to ascertain whether the POD was obliterated. POD obliteration was assessed using a real-time TVS technique called the 'sliding sign'. Preoperative TVS sliding sign findings were then compared to gold standard laparoscopic POD findings.One hundred consecutive women with preoperative TVS and laparoscopic outcomes were included in the final analysis. Mean age was 32.8 years and mean age at diagnosis of endometriosis was 27.4 years. At laparoscopy, 84/100 (84%) were found to have some form of endometriosis (73% peritoneal endometriosis, 35% ovarian endometrioma(s), 33% deep infiltrating endometriosis). At laparoscopy, 30/100 (30%) had an obliterated POD and 19/30 (63.3%) of these women also had evidence of bowel endometriosis. The sonographic sliding sign technique had an accuracy of 93.0%, sensitivity of 83.3%, specificity of 97.1%, positive predictive value of 92.6%, negative predictive value of 93.2%, positive likelihood ratio of 29.2 and negative likelihood ratio of 0.17 in the prediction of POD obliteration (P = 1.8E-16).Preoperative real-time dynamic TVS evaluation using the sliding sign seems to establish with a high degree of certainty whether the POD is obliterated. Given the increased risk of deep infiltrating endometriosis in women with POD obliteration, the TVS sliding sign technique may also be useful in the identification of women who may be at a higher risk for bowel endometriosis.Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.

To evaluate whether the presence of uterorectal adhesions demonstrated by transvaginal sonography (TVS) could aid as a simple sonographic predictor for deep infiltrating endometriosis (DIE) of the rectum in patients with symptoms suggestive of endometriosis.This was a prospective multicenter study of women scheduled for laparoscopy because of symptoms suggestive of endometriosis. Patients were assessed prospectively using TVS before laparoscopy and radical resection of disease followed by histological confirmation. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, accuracy and positive (LR+) and negative (LR-) likelihood ratios were calculated for the observation of a negative uterine 'sliding sign' on TVS in predicting the presence of DIE of the rectum.In total, 117 patients underwent laparoscopy and resection. Thirty-four (29%) patients had DIE of the rectum. A negative sliding sign on TVS predicted DIE of rectum with a sensitivity of 85%, specificity of 96%, PPV of 91%, NPV of 94%, accuracy of 93.1%, LR + of 23.6 and LR- of 0.15.Sonographic demonstration of uterorectal adhesions reflected by a negative uterine sliding sign is an easy and practical method for prediction of the presence of DIE involving the rectum. This could be a valuable 'red flag' sign for triaging patients to tertiary referral centers and specialized clinics for detailed investigation.Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Endometriosis is a common gynaecological condition of unknown aetiology that primarily affects women of reproductive age. The accepted first-line imaging modality is pelvic ultrasound. However, magnetic resonance imaging (MRI) is increasingly performed as an additional investigation in complex cases and for surgical planning. There is currently no international consensus regarding patient preparation, MRI protocols or reporting criteria. Our aim was to develop clinical guidelines for MRI evaluation of pelvic endometriosis based on literature evidence and consensus expert opinion. This work was performed by a group of radiologists from the European Society of Urogenital Radiology (ESUR), experts in gynaecological imaging and a gynaecologist expert in methodology. The group discussed indications for MRI, technical requirements, patient preparation, MRI protocols and criteria for the diagnosis of pelvic endometriosis on MRI. The expert panel proposed a final recommendation for each criterion using Oxford Centre for Evidence Based Medicine (OCEBM) 2011 levels of evidence.• This report provides guidelines for MRI in endometriosis. • Minimal and optimal MRI acquisition protocols are provided. • Recommendations are proposed for patient preparation, best MRI sequences and reporting criteria.

To investigate the efficacy and safety of oral dienogest 2mg compared with placebo in the treatment of endometriosis-associated pelvic pain (EAPP).This was a 12-week, randomized, double-blind, placebo-controlled, multicenter (n=33) study in Germany, Italy, and Ukraine of 198 women aged 18-45 years with laparoscopically confirmed endometriosis and EAPP score > or =30 mm on a visual analog scale (VAS). Dienogest 2mg or placebo was administered orally once daily. The primary efficacy variable was absolute change in EAPP from baseline to Week 12, as determined by the target variables of change in VAS score and change in intake of supportive analgesic medication (ibuprofen) for pelvic pain.Mean reductions in VAS score between baseline and Week 12 in the full analysis set were 27.4 mm and 15.1mm in the dienogest and placebo groups, respectively-a significant score difference of 12.3 mm in favor of dienogest (P<0.0001). Changes in intake of supportive analgesic medication were modest in both groups. The primary efficacy measure of absolute change in EAPP demonstrated the superiority of dienogest over placebo. Dienogest was generally well tolerated and few adverse events were associated with therapy.Dienogest at a dose of 2mg daily for 12 weeks was significantly more effective than placebo for reducing EAPP.Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Although there are various hormone therapies, including gonadotropin‐releasing hormone agonist, danazol, levonorgestrel‐releasing intrauterine system, dienogest, and low‐dose estrogen progestin, no consensus opinion has been reached in terms of which medication should be used and for how long it should be administered. We aimed to determine whether dienogest or goserelin is the better postoperative therapy to prevent recurrence of endometriosis.

Endometriosis is a common, chronic gynecological disease that affects women’s fertility potential. Dydrogesterone is an effective and safe drug that is under-utilized due to limited clinical research. The purpose of this evidence mapping is to identify, describe, and analyze the current available evidence regarding dydrogesterone for the treatment of endometriosis.

To evaluate the effectiveness of a levonorgestrel-releasing IUD as therapy for endometriosis of the rectovaginal septum.Prospective therapeutic non-randomized, self-controlled clinical trial analyzing changes in pain symptoms and size of lesions induced by the levonorgestrel-releasing IUD over 12 months.Tertiary referral center for treatment of deep endometriosis.Eleven symptomatic patients with rectovaginal endometriosis.A levonorgestrel-releasing IUD was inserted and maintained for 12 months.Severity of dysmenorrhea, pelvic pain, and deep dyspareunia were assessed before insertion of the IUD and throughout treatment. The size of rectovaginal endometriotic lesions were evaluated by using transrectal and transvaginal ultrasonography.Dysmenorrhea, pelvic pain, and deep dyspareunia greatly improved and the size of the endometriotic lesions was significantly reduced by treatment.Insertion of a levonorgestrel-releasing IUD alleviates pain and reduces the size of lesions in patients with endometriosis of the rectovaginal septum.

To determine whether the frequency and severity of dysmenorrhea are reduced in women with symptomatic endometriosis in whom a levonorgestrel-releasing intrauterine device (Lng-IUD) is inserted after operative laparoscopy compared with those treated with surgery only.Open-label, parallel-group, randomized, controlled trial.A tertiary care and referral center for patients with endometriosis.Parous women with moderate or severe dysmenorrhea undergoing first-line operative laparoscopy for symptomatic endometriosis.Randomization to immediate Lng-IUD insertion or expectant management after laparoscopic treatment of endometriotic lesions. Proportions of women with recurrence of moderate or severe dysmenorrhea in the two study groups 1 year after surgery and overall degree of satisfaction with treatment. Moderate or severe dysmenorrhea recurred in 2 of 20 (10%) subjects in the postoperative Lng-IUD group and 9/20 (45%) in the surgery-only group. Thus, a medicated device inserted postoperatively will prevent the recurrence of moderate or severe dysmenorrhea in one out of three patients 1 year after surgery. A total of 15/20 (75%) women in the Lng-IUD group and 10/20 (50%) in the expectant management group were satisfied or very satisfied with the treatment received.Insertion of an Lng-IUD after laparoscopic surgery for symptomatic endometriosis significantly reduced the medium-term risk of recurrence of moderate or severe dysmenorrhea.

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.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.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.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.

Endometriosis is a chronic benign disease that affects women of reproductive age. Medical therapy is often the first line of management for women with endometriosis in order to ameliorate symptoms or to prevent post-surgical disease recurrence. Currently, there are several medical options for the management of patients with endometriosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of chronic inflammatory conditions, being efficacious in relieving primary dysmenorrhea. Combined oral contraceptives (COCs) and progestins, available for multiple routes of administration, are effective first-line hormonal options. In fact, several randomized controlled trials (RCTs) demonstrated that they succeed in improving pain symptoms in the majority of patients, are well tolerated and not expensive. Second-line therapy is represented by gonadotropin-releasing hormone (GnRH) agonists. Even if these drugs are efficacious in treating women not responding to COCs or progestins, they are not orally available and have a less favorable tolerability profile (needing an appropriate add-back therapy). The use of danazol is limited by the large availability of other better-tolerated hormonal drugs. Because few data are available on long-term efficacy and safety of aromatase inhibitors they should be administered only in women with symptoms refractory to other conventional therapies in a clinical research setting. Promising preliminary data have emerged from multicenter Phase III trials on elagolix, a new oral GnRH antagonist but non-inferiority RCT data are required to compare elagolix with first-line therapies for endometriosis.

To evaluate the efficacy of laparoscopic resection of the uterosacral ligaments in women with endometriosis and predominantly midline dysmenorrhea.Randomized controlled trial.Two academic departments. One hundred eighty patients undergoing operative laparoscopy as first-line therapy for stage I to IV symptomatic endometriosis.Operative laparoscopy including uterosacral ligament resection or conservative surgery alone.Proportion of women with recurrence of moderate or severe dysmenorrhea 1 year after surgery.No complications occurred. Among the patients who were evaluable 1 year after operative laparoscopy, 23 of 78 (29%) women who had uterosacral ligament resection and 21 of 78 (27%) women who had conservative surgery only reported recurrent dysmenorrhea. The corresponding numbers of patients at 3 years were 21 of 59 (36%) women and 18 of 57 (32%) women, respectively. Time to recurrence was similar in the two groups. Pain was substantially reduced, and patients in both groups experienced similar and significant improvements in health-related quality of life, psychiatric profile, and sexual satisfaction. Overall, 68 of 90 (75%) patients in the uterosacral ligament resection group and 67 of 90 (74%) patients in the conservative surgery group were satisfied at 1 year.Addition of uterosacral ligament resection to conservative laparoscopic surgery for endometriosis did not reduce the medium- or long-term frequency and severity of recurrence of dysmenorrhea.

To determine whether the immediate initiation of estrogen replacement therapy (ERT) in the postoperative period increases the incidence of symptom recurrence following total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) for the treatment of endometriosis.In a retrospective cohort study, 95 women who underwent TAH with BSO for endometriosis at the Johns Hopkins Hospital during 1979-1991 and who subsequently received ERT were identified by computer search. Follow-up information was obtained from medical records, outpatient charts, and telephone surveys. Pain recurrence in patients who started ERT within 6 weeks after surgery and in those who delayed ERT for more than 6 weeks was compared and adjusted for length of patient follow-up and other covariates.Sixty women began ERT within the immediate postoperative period, and four (7%) of them had recurrent pain; 35 women began ERT more than 6 weeks after surgery, and seven (20%) of them had recurrent pain. The mean length of follow-up was 57 months. The difference in the crude rate of symptom recurrence following early and delayed initiation of ERT after TAH with BSO was not statistically significant (P =.09). Controlling for length of patient follow-up, no significant differences were observed between the two groups. Adjusting for covariates of stage, age, and postoperative adjunct medroxyprogesterone therapy, those who started ERT more than 6 weeks after surgery had a relative risk of 5.7 (95% confidence interval 1.3, 25.2) for pain recurrence.Although the number of patients in the study was too small to reach statistical significance in all analyses, these findings suggest that patients who begin ERT immediately after TAH with BSO are at no greater risk of recurrent pain than those who delay ERT for more than 6 weeks.

To evaluate the efficacy of the GnRH agonist (GnRH-a) nafarelin compared with placebo administered for 6 months after reductive laparoscopic surgery for symptomatic endometriosis.Randomized, prospective, placebo-controlled, multicenter clinical trial.Thirteen clinics including private practice and university centers.One hundred nine women aged 18-47 with laparoscopically proven endometriosis and pelvic pain who had undergone reductive laparoscopic surgery for endometriosis.Patients were randomized to receive either the GnRH-a nafarelin (200 micrograms twice daily) or placebo for 6 months.Time to initiation of alternative treatment (the length of time from beginning study medication to receiving alternative therapy or to deeming that the study drug was ineffective) and patient-reported and physician-assessed pelvic pain scores.The median time to initiation of alternative treatment was > 24 months in the nafarelin group versus 11.7 months in the placebo group. Fifteen (31%) of 49 nafarelin-treated patients required alternative therapy, compared with 25 (57%) of 44 placebo-treated patients. The patients' pelvic pain scores dropped significantly in the nafarelin and placebo groups after 6 months of treatment. Physician summary ratings showed significant improvement in the nafarelin group and no significant changes in the placebo group after 6 months of treatment.Compared with placebo, nafarelin administered after reductive laparoscopic surgery for endometriosis significantly delays the return of endometriosis symptoms requiring further treatment.

To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post-operative hormonal therapy compared with women treated with surgery only. Pregnancy rates and time to conception in women wanting children were also evaluated.A multicentre, prospective, randomised controlled study.Nineteen Italian academic departments and teaching hospitals specialising in reparative and reconstructive surgery.A total of 269 women undergoing conservative surgery for mild to severe symptomatic endometriosis.After surgery the women were assigned to treatment with subcutaneous goserelin depot injections for six months or to expectant management. Dysmenorrhoea, deep dyspareunia, nonmenstrual pain and general discomfort were graded according to a verbal rating scale from 0 (absent) to 3 (severe) and the scores summed to give a total symptoms score. Only patients with at least one preoperative moderate or severe symptom were enrolled. The women were evaluated regularly for two years.Post-operative pain recurrences (total symptoms scores > or = 5), time to recurrence, pregnancy rates and time to conception in the two study groups.At one- and two-year follow up visits, 14/107 (13.1%) and 19/81 (23.5%) patients had moderate or severe symptoms recurrence in the goserelin group compared with, respectively, 22/103 (21.4%) and 27/74 (36.5%) in the expectant management group (P = 0.143 at 1 year and 0.082 at 2 years). Time to symptoms recurrence was significantly longer in the goserelin group according to survival analysis (Wilcoxon test, P = 0.041). Among women wanting children, few conceptions occurred in both the goserelin (8/69, 11.6%) and the expectant management group (14/76, 18.4%). There was no significant difference at survival analysis (Wilcoxon test, P = 0.427).Post-operative treatment with goserelin significantly prolonged the pain-free interval after conservative surgery for symptomatic endometriosis and did not influence reproductive prognosis.

To ascertain whether long-term reduction of pain is obtained by continuous administration of an oral contraceptive (OC) in women with endometriosis-associated recurrent dysmenorrhea that does not respond to cyclic OC use.Prospective, therapeutic, self-controlled clinical trial.A tertiary care and referral center for patients with endometriosis.Fifty women who underwent surgery for endometriosis in the previous year and experienced recurrent dysmenorrhea despite cyclic OC use.Continuous use of an OC containing ethinyl estradiol (0.02 mg) and desogestrel (0.15 mg) for 2 years.Dysmenorrhea variation during cyclic and continuous OC use, evaluated with a 100-mm visual analog scale and a 0- to 3-point verbal rating scale, and degree of satisfaction with continuous OC treatment.In the study period, amenorrhea, spotting, and breakthrough bleeding were reported by 19 (38%), 18 (36%), and 13 (26%) women. The mean +/- SD number of >7-day bleeding episodes with consequent 7-day OC suspension was 5.5 +/- 2.1. The mean +/- SD dysmenorrhea visual analog scale and verbal rating scale scores were 75 +/- 13 and 2.4 +/- 0.5 at baseline and 31 +/- 17 and 0.7 +/- 0.6 at 2-year follow-up, respectively. Moderate or severe side effects were reported by 7/50 (14%) women. At final evaluation, 13 (26%) women were very satisfied, 27 (54%) were satisfied, 1 (2%) was uncertain, 8 (16%) were dissatisfied, and 1 (2%) was very dissatisfied.Long-term continuous OC use can be proposed to women with symptomatic endometriosis and menstruation-related pain symptoms.

Despite standard medical treatment endometriosis is often associated with disabling pain and poor quality of life (QoL). Studies indicate that psychological interventions (PIs) may improve pain and QoL, yet studies on the effects of PIs for women with endometriosis are sparse and limited by low-quality study designs. Therefore, this study aimed, in a rigorous three-armed design, to evaluate the effect of PIs on chronic pelvic pain (CPP) and QoL in women with endometriosis.This three-armed parallel, multi-center randomized controlled trial included fifty-eight endometriosis patients reporting severe CPP [≥ 5 for pain intensity measured on a 0-10-point numeric rating scale (NRS)]. Patients were randomly assigned to (1) Specific mindfulness- and acceptance-based psychological intervention (MY-ENDO), (2) Carefully matched non-specific psychological intervention (Non-specific), or (3) A wait-list control group (WL). The primary outcome was pelvic pain intensity/unpleasantness measured on NRS. Secondary outcomes included endometriosis-related quality of life, workability, pain acceptance, and endometriosis-related symptoms. Differences in outcomes between groups at post-treatment follow-up were analyzed using mixed linear models. Analyses were performed on an intention-to-treat basis.Compared to WL, psychological intervention (MY-ENDO + Non-specific) did not significantly reduce pain. However, psychological intervention did significantly improve the QoL-subscales 'control and powerlessness', 'emotional well-being', and 'social support' as well as the endometriosis-related symptoms 'dyschezia' and 'constipation'. MY-ENDO was not superior to Non-specific.Women with endometriosis may have significant and large effects of psychological intervention on QoL despite an ongoing experience of severe CPP.12 April 2016, clinicaltrials.gov (NCT02761382), retrospectively registered.© 2023. The Author(s).