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BACKGROUND: Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is medical therapy with gonadotrophin-releasing hormone analogues (GnRHas) to reduce pain due to endometriosis. One of the adverse effects of GnRHas is a decreased bone mineral density. In addition to assessing the effect on pain, quality of life, most troublesome symptom and patients' satisfaction, the current review also evaluated the effect on bone mineral density and risk of adverse effects in women with endometriosis who use GnRHas versus other treatment options. OBJECTIVES: To assess the effectiveness and safety of GnRH analogues (GnRHas) in the treatment of painful symptoms associated with endometriosis and to determine the effects of GnRHas on bone mineral density of women with endometriosis. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and the trial registries in May 2022 together with reference checking and contact with study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared GnRHas with other hormonal treatment options, including analgesics, danazol, intra-uterine progestogens, oral or injectable progestogens, gestrinone and also GnRHas compared with no treatment or placebo. Trials comparing GnRHas versus GnRHas in conjunction with add-back therapy (hormonal or non-hormonal) or calcium-regulation agents were also included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodology as recommended by Cochrane. Primary outcomes are relief of overall pain and the objective measurement of bone mineral density. Secondary outcomes include adverse effects, quality of life, improvement in the most troublesome symptoms and patient satisfaction. Due to high risk of bias associated with some of the studies, primary analyses of all review outcomes were restricted to studies at low risk of selection bias. Sensitivity analysis including all studies was then performed. MAIN RESULTS: Seventy-two studies involving 7355 patients were included. The evidence was very low to low quality: the main limitations of all studies were serious risk of bias due to poor reporting of study methods, and serious imprecision. Trials comparing GnRHas versus no treatment We did not identify any studies. Trials comparing GnRHas versus placebo There may be a decrease in overall pain, reported as pelvic pain scores (RR 2.14; 95% CI 1.41 to 3.24, 1 RCT, n = 87, low-certainty evidence), dysmenorrhoea scores (RR 2.25; 95% CI 1.59 to 3.16, 1 RCT, n = 85, low-certainty evidence), dyspareunia scores (RR 2.21; 95% CI 1.39 to 3.54, 1 RCT, n = 59, low-certainty evidence), and pelvic tenderness scores (RR 2.28; 95% CI 1.48 to 3.50, 1 RCT, n = 85, low-certainty evidence) after three months of treatment. We are uncertain of the effect for pelvic induration, based on the results found after three months of treatment (RR 1.07; 95% CI 0.64 to 1.79, 1 RCT, n = 81, low-certainty evidence). Besides, treatment with GnRHas may be associated with a greater incidence of hot flushes at three months of treatment (RR 3.08; 95% CI 1.89 to 5.01, 1 RCT, n = 100, low-certainty evidence). Trials comparing GnRHas versus danazol For overall pain, for women treated with either GnRHas or danazol, a subdivision was made between pelvic tenderness, partly resolved and completely resolved. We are uncertain about the effect on relief of overall pain, when a subdivision was made for overall pain (MD -0.30; 95% CI -1.66 to 1.06, 1 RCT, n = 41, very low-certainty evidence), pelvic pain (MD 0.20; 95% CI -0.26 to 0.66, 1 RCT, n = 41, very low-certainty evidence), dysmenorrhoea (MD 0.10; 95% CI -0.49 to 0.69, 1 RCT, n = 41, very low-certainty evidence), dyspareunia (MD -0.20; 95% CI -0.77 to 0.37, 1 RCT, n = 41, very low-certainty evidence), pelvic induration (MD -0.10; 95% CI -0.59 to 0.39, 1 RCT, n = 41, very low-certainty evidence), and pelvic tenderness (MD -0.20; 95% CI -0.78 to 0.38, 1 RCT, n = 41, very low-certainty evidence) after three months of treatment. For pelvic pain (MD 0.50; 95% CI 0.10 to 0.90, 1 RCT, n = 41, very low-certainty evidence) and pelvic induration (MD 0.70; 95% CI 0.21 to 1.19, 1 RCT, n = 41, very low-certainty evidence), the complaints may decrease slightly after treatment with GnRHas, compared to danazol, for six months of treatment. Trials comparing GnRHas versus analgesics We did not identify any studies. Trials comparing GnRHas versus intra-uterine progestogens We did not identify any low risk of bias studies. Trials comparing GnRHas versus GnRHas in conjunction with calcium-regulating agents There may be a slight decrease in bone mineral density (BMD) after 12 months treatment with GnRHas, compared to GnRHas in conjunction with calcium-regulating agents for anterior-posterior spine (MD -7.00; 95% CI -7.53 to -6.47, 1 RCT, n = 41, very low-certainty evidence) and lateral spine (MD -12.40; 95% CI -13.31 to -11.49, 1 RCT, n = 41, very low-certainty evidence). AUTHORS' CONCLUSIONS: For relief of overall pain, there may be a slight decrease in favour of treatment with GnRHas compared to placebo or oral or injectable progestogens. We are uncertain about the effect when comparing GnRHas with danazol, intra-uterine progestogens or gestrinone. For BMD, there may be a slight decrease when women are treated with GnRHas, compared to gestrinone. There was a bigger decrease of BMD in favour of GnRHas, compared to GnRHas in conjunction with calcium-regulating agents. However, there may be a slight increase in adverse effects when women are treated with GnRHas, compared to placebo or gestrinone. Due to a very low to low certainty of the evidence, a wide range of outcome measures and a wide range of outcome measurement instruments, the results should be interpreted with caution.

Supplemental material, sj-pdf-1-jop-10.1177_0269881120965915 for A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis by Benjamin JG Illingworth, Declan J Lewis, Andrew T Lambarth, Kate Stocking, James MN Duffy, Luke A Jelen and James J Rucker in Journal of Psychopharmacology

© 2019 Royal College of Obstetricians and Gynaecologists Objective: To quantify the effect of different methodological decisions on the identification of potential core outcomes to inform the development of recommendations for future core coutcome set developers. Design: Mixed methods study. Setting: A core outcome set for pre-eclampsia was used as an exemplar. Sample: A long list of potential core outcomes was developed by undertaking a systematic review of pre-eclampsia trials and performing a thematic analysis of in-depth patient interviews. Methods: Specific methods used to generate long lists of potential core outcomes were evaluated. Results: Different methodological decisions had a substantial impact on the identification of potential core outcomes. Extracting outcomes from published pre-eclampsia trials was an effective way of identifying 48 maternal, eight fetal, 25 neonatal outcomes, and eight patient-reported outcomes. Limiting the extraction of outcomes to primary outcomes or outcomes commonly reported in pre-eclampsia trials reduced the number and diversity of potential core outcomes identified. Thematic analysis of in-depth patient interviews ensured an additional five patient reported outcomes and six outcomes related to future child health were identified. Conclusions: Future core outcome set developers should use quantitative and qualitative methods when developing a long list of potential core outcomes. Tweetable abstract: @OfficialNIHR research published in @BJOGtweets informs new recommendations for future @coreoutcomes developers.

Background: An evaluation of outcome reporting is required to develop a core outcome set. Objectives: To assess primary outcomes and outcome measure reporting in pre-eclampsia trials. Search strategy: Five online databases were searched from inception to January 2016 using terms including “preeclampsia” and “randomized controlled trial”. Selection criteria: Randomized controlled trials evaluating treatments for pre-eclampsia published in any language were included. Data collection and analysis: Primary outcomes and data on outcome measure reporting were systematically extracted and categorized. Main results: Overall, 79 randomized trials including data from 31 615 women were included. Of those, 38 (48%) reported 35 different primary outcomes; 28 were maternal outcomes and seven were fetal/neonatal outcomes. Three randomized trials reported composite outcomes, incorporating between six and nine outcome components. The method of definition or measurement was infrequently or poorly reported. Even when outcomes were consistent across trials, different methods of definition or measurement were frequently described. Conclusions: In randomized trials evaluating interventions for pre-eclampsia, critical information related to the primary outcome, including definition and measurement, is regularly omitted. Developing a core outcome set for pre-eclampsia trials would help to inform primary outcome selection and outcome measure reporting.

Background\ud \ud Pre-eclampsia is a serious complication of pregnancy and contributes to maternal and offspring mortality and morbidity. Randomised controlled trials evaluating therapeutic interventions for pre-eclampsia have reported many different outcomes and outcome measures. Such variation contributes to an inability to compare, contrast, and combine individual studies, limiting the usefulness of research to inform clinical practice. The development and use of a core outcome set would help to address these issues ensuring outcomes important to all stakeholders, including patients, will be collected and reported in a standardised fashion.\ud \ud Methods\ud \ud An international steering group including healthcare professionals, researchers, and patients, has been formed to guide the development of this core outcome set. Potential outcomes will be identified through a comprehensive literature review and semi-structured interviews with patients. Potential core outcomes will be entered into an international, multi-perspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and patients will be invited to participate. The modified Delphi method encourages whole and stakeholder group convergence towards consensus ‘core’ outcomes. Once core outcomes have been agreed upon it is important to determine how they should be measured. The truth, discrimination, and feasibility assessment framework will assess the quality of potential outcome measures. High quality outcome measures will be associated with core outcomes. Mechanisms exist to disseminate and implement the resulting core outcome set within an international context.\ud \ud Discussion\ud \ud Embedding the core outcome set within future clinical trials, systematic reviews, and clinical practice guidelines could make a profound contribution to advancing the usefulness of research to inform clinical practice, enhance patient care, and improve maternal and offspring outcomes. The infrastructure created by developing a core outcome set for pre-eclampsia could be leveraged in other settings, for example selecting research priorities and clinical practice guideline development.\ud Prospective registration\ud \ud [1} Core Outcome Measures in Effectiveness Trials (COMET) registration number: 588\ud \ud [2] International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42015015529.