·Evidence-Based Medicine· A Systematic Review of Guidelines and Expert Consensus on Endometriosis Pain Management

WAN Xie¹, TU Xulian², WU Liping¹, LIU Xia², LI Xiaoyan², LENG Mingyue², YANG Xueqing², LI Li²

¹School of Nursing, Peking Union Medical College, Beijing 100144, China
²Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China

*Corresponding authors: WU Liping, Professor; E-mail: wuliping@163.com
LIU Xia, Deputy Chief Nurse; E-mail: liuxia305@pumch.cn

【Abstract】 Background As understanding of pain management in endometriosis deepens, an increasing number of related guidelines and expert consensus have emerged domestically and internationally, providing significant guidance and reference for clinical practice. However, the quality of these guidelines and expert consensus is inconsistent, necessitating systematic review to guide clinical practice. Objective To systematically evaluate the quality of guidelines and expert consensus related to pain management in endometriosis, thereby providing an evidence base for developing pain management protocols. Methods Evidence-based guidelines involving recommendations for pain management in endometriosis were searched in CNKI, SinoMed, Wanfang Data, VIP, PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Guideline Central, GIN, as well as the official websites of ACOG, NICE, SIGN, WHO, IASP, APS, and BPS, plus other sources from inception to November 12, 2024. AGREE II was utilized to assess the quality of guidelines and expert consensus related to endometriosis pain management, and relevant recommendations were summarized. Results A total of 15 guidelines/expert consensus were ultimately included, of which 9 were guidelines and 6 were expert consensus. Seven guidelines/expert consensus originated from China and eight from abroad, with publication dates ranging from 2018 to 2024. Across the six domains of AGREE II, the mean standardized scores were: scope and purpose 83.15%, stakeholder involvement 71.11%, rigor of development 44.79%, clarity of presentation 65.74%, applicability 35.55%, and editorial independence 87.78%. Thirty-three recommendations were extracted and synthesized, covering six domains: general principles of pain management, pain assessment, pharmacological management, surgical management, non-pharmacological/non-surgical management, and health education. Conclusion The quality of included guidelines/expert consensus is moderate, providing reference for clinical practice, but further improvement is needed in rigor of development and applicability.

【Key words】 Endometriosis; Pain; Management; Guideline; Expert consensus; Quality appraisal

Funding: National Key R&D Program of China (2022YFC2704000); Central High-level Hospital Clinical Research Business Expenses (2022-PUMCH-B-085); 2025 Peking Union Medical College School of Nursing Research Project (PUMCSON202508)

Citation: XIE W, TU X L, WU L P, et al. A systematic review of guidelines and expert consensus related to endometriosis pain management[J]. Chinese General Practice, 2025. DOI: 10.12114/j.issn.1007-9572.2025.0016. [Epub ahead of print] [www.chinagp.net]

© Editorial Office of Chinese General Practice. This is an open access article under the CC BY-NC-ND 4.0 license.

1.1 Literature Sources

A computerized search was conducted across databases, guideline repositories, and professional society websites: CNKI, Chinese Biomedical Literature Database (SinoMed), Wanfang Data Knowledge Service Platform, VIP, PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Guideline Central, Guidelines International Network (GIN) database, as well as the official websites of the American College of Obstetricians and Gynecologists (ACOG), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), WHO, International Association for the Study of Pain (IASP), American Pain Society (APS), and British Pain Society (BPS). Additional relevant literature was supplemented through other approaches, such as reviewing references of included studies. The search timeframe spanned from database inception to November 12, 2024.

1.2 Literature Search Strategy

Based on database characteristics, a search strategy combining subject headings and free-text terms was employed. Chinese search terms included: "endometriosis," "endometrioma," "chocolate cyst," "pain," "dyspareunia," "pelvic pain," "dysmenorrhea," "abdominal pain," "painful defecation," "rectal pressure," "hyperalgesia," "central pain," "guideline," "statement," "recommendation," "expert recommendation," and "consensus." English search terms included: "endometriosis," "Endometrioses," "Endometrioma," "Endometriomas," "Pains," "Suffering, Physical," "Physical Suffering," "Physical Sufferings," "Sufferings, Physical," "Ache," "Aches," "painful intercourse," "dyspareunia," "menstrual cramps," "dysmenorrhea," "Painful Menstruation," "painful bowel movements," "Pain Management," "Management, Pain," and "Managements, Pain." Taking Wanfang Data Knowledge Service Platform as an example, the search strategy was as follows: Subject: ("endometriosis" OR "endometrioma" OR "chocolate cyst" OR "ovarian endometrioma") AND Subject: ("pain" OR "dyspareunia" OR "pelvic pain" OR "dysmenorrhea" OR "abdominal pain" OR "painful defecation" OR "rectal pressure" OR "hyperalgesia" OR "central pain" OR "management") AND Subject: ("guideline" OR "statement" OR "recommendation" OR "expert recommendation" OR "consensus").

1.3 Inclusion and Exclusion Criteria

Inclusion criteria: (1) Guideline literature involving pain management in patients with endometriosis, including clinical guidelines and expert consensus; (2) Guidelines/expert consensus containing relevant recommendations for endometriosis pain management; (3) For revised guidelines, the most recent version was included; (4) Language limited to Chinese or English.

Exclusion criteria: (1) Guidelines/expert consensus for which full text could not be obtained; (2) Duplicate publications of guidelines/expert consensus; (3) Literature translating or interpreting guidelines/expert consensus; (4) Guidelines/expert consensus rated as Grade C by AGREE II evaluation.

1.5 Quality Evaluation of Included Guidelines/Expert Consensus

The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument [8] was used independently for literature quality evaluation. The evaluation encompassed six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence, comprising 23 main items plus two overall assessment items. Each item was scored on a 1-7 scale, where 1 indicated complete non-compliance and 7 indicated full compliance. The standardized score for each domain was calculated as: (actual score - minimum possible score) / (maximum possible score - minimum possible score) × 100%. Based on scoring results, guidelines or expert consensus with standardized percentages >60% across all six domains were classified as "strongly recommended" (Grade A); those with standardized percentages between 30%-60% in the majority of domains (≥3) were classified as "recommended" (Grade B); and those with standardized percentages <30% in the majority of domains (>3) were classified as "not recommended" (Grade C) [9].

Two researchers independently evaluated guideline quality using AGREE II. To assess inter-rater consistency, intraclass correlation coefficient (ICC) analysis was performed using SPSS 25.0, with ICC ≥ 0.80 considered acceptable for evaluation [10].

2.1 Guideline/Expert Consensus Screening Process and Results

A total of 1,936 articles were initially identified. After screening according to inclusion and exclusion criteria, 15 evidence-based guidelines/expert consensus were ultimately included [11-25]. The screening process and results are shown in Figure 1 [FIGURE:1].

2.2 Basic Characteristics of Included Guidelines/Expert Consensus

Literature was retrieved from databases or relevant websites (n=1,933): CNKI (n=23), Wanfang Data Knowledge Service Platform (n=119), VIP (n=25), PubMed (n=126), SinoMed (n=79), CINAHL (n=25), Embase (n=609), Cochrane Library (n=12), NICE (n=14), GIN (n=2), Guideline Central (n=2), Web of Science (n=891), IASP (n=4), and ACOG (n=2). Additional relevant literature was obtained through other sources (n=3). After removing duplicates (n=443), titles, abstracts, and keywords were reviewed for initial screening (n=1,493). Excluded literature (n=1,437) included: irrelevant studies (not mentioning endometriosis, diagnosis, etc.) (n=875), non-guideline articles (systematic reviews, meta-analyses, reviews, original studies, etc.) (n=530), translations, commentaries, or interpretations of guidelines (n=27), and non-Chinese/English literature (n=5). Full-text review was conducted for secondary screening (n=56). Further exclusions (n=41) included: literature not addressing endometriosis pain management (n=18), guidelines with unobtainable full text (n=3), outdated versions of guidelines (n=18), and guideline summaries (n=2). Ultimately, 15 guidelines were evaluated using AGREE II and included in the final analysis [FIGURE:1].

Among the 15 included guidelines/expert consensus, 9 were guidelines [11-13,17-20,22,25] and 6 were expert consensus [14-16,21,23-24]. Seven [11-15,23-24] originated from China and eight [16-22,25] from abroad, with publication dates ranging from 2018 to 2024. Eight guidelines/expert consensus [11-13,17-18,22-23,25] explicitly described evidence grading, and seven [11,13,17-18,22-23,25] specified recommendation strength. Detailed information on the included guidelines/expert consensus is presented in Table 1 [TABLE:1].

2.3 Quality Evaluation Results of Included Guidelines/Expert Consensus

Across the six domains of AGREE II, the mean standardized scores for the 15 guidelines/expert consensus were: scope and purpose 83.15%, stakeholder involvement 71.11%, rigor of development 44.79%, clarity of presentation 65.74%, applicability 35.55%, and editorial independence 87.78%. Among the 15 included guidelines/expert consensus, 1 received Grade A recommendation [19] and 14 received Grade B recommendations [11-18,20-25]. Details are provided in Table 2 [TABLE:2].

2.4 Consistency Testing of Guideline/Expert Consensus Evaluation

In this study, the consistency between the two reviewers' assessments for all guidelines/expert consensus was >0.8, indicating good inter-rater agreement. Results are shown in Table 3 [TABLE:3].

2.5 Summary of Main Recommendations

Thirty-three recommendations related to endometriosis pain management were extracted and synthesized from the 15 guidelines/expert consensus, covering six domains: general principles of pain management, pain assessment, pharmacological management, surgical management, non-pharmacological/non-surgical management, and health education. Specific recommendations are detailed in Table 4 [TABLE:4].

3.1 Quality Analysis of Guidelines/Expert Consensus

The overall quality of guidelines/expert consensus was moderate. Among the six domains, the highest mean scores were for editorial independence and scope and purpose, followed by stakeholder involvement and clarity of presentation, while rigor of development and applicability scored relatively lower.

In the "applicability" domain, eight guidelines/expert consensus [11-16,20,24] had standardized scores below 30%, primarily because they failed to specify implementation barriers and cost considerations. Barriers and associated costs are particularly critical for long-term management of endometriosis pain, as endometriosis not only poses significant health threats but also creates substantial social and economic burdens, causing $22 billion annually in productivity losses and direct healthcare costs in the United States [26]. In China, endometriosis similarly consumes considerable social resources [27] and significantly impacts patients, their families, and the economy [28]. Only one guideline [19] reported medication dosages and prices, while four guidelines/expert consensus [14,16-17,22] mentioned cost considerations but without specific details. Future guideline development should incorporate these economic and social factors to ensure feasibility and cost-effectiveness of recommendations, thereby reducing financial pressure on patients and society. One guideline [22] scored below 60% only in applicability, reporting medication dosages and prices but lacking specification of monitoring and/or audit criteria; improvements in this area could potentially elevate it to Grade A recommendation status.

In the "rigor of development" domain, five guidelines/expert consensus [14-16,23-24] had standardized scores below 30%, mainly due to absence of detailed search methodology, evidence strengths and limitations, recommendation formulation processes, external review procedures, and guideline update specifications. This deficiency makes it difficult to assess the completeness and systematicity of included evidence and the scientific validity and impartiality of recommendations, thereby compromising guideline rigor, objectivity, authority, and sustained applicability, and limiting trust in and application of recommendations by clinicians and patients.

Only four guidelines [18-19,22,25] mentioned search methods, with some merely listing searched databases without specific search strategies. Future guideline development should document and transparently report search strategies, including databases used, search terms, and screening processes, to ensure comprehensive and systematic evidence coverage. Additionally, all included evidence should undergo quality assessment with explicit reporting of evidence strengths and limitations. Furthermore, external review should be implemented by inviting external experts to review guideline drafts, with review processes and results reported in the final guideline, along with explicit update plans including mechanisms for monitoring new evidence, update frequency, and procedures to ensure guideline timeliness and validity, thereby enhancing guideline quality and credibility [29].

In the "clarity of presentation" domain, two guidelines [11,13] had standardized scores below 40% because key recommendations were not easily identifiable. Only one guideline [22] used pictures and tables to highlight important recommendations. Visual presentation can help readers understand complex information more intuitively, enhance content visualization, and improve information transmission efficiency and persuasiveness [30]. To improve guideline clarity and operability, future guideline development should adopt more visual presentation methods such as charts and diagrams to enhance information transmission efficiency and effectiveness.

3.2 Analysis of Recommendations

As a chronic disease requiring long-term management, endometriosis causes debilitating symptoms, with pain significantly impacting women's quality of life and work capacity [19], making pain management particularly important [31]. Analysis revealed that recommendations across included guidelines were generally consistent, all emphasizing the importance of pharmacological management in endometriosis pain management. Overall, pharmacological management of endometriosis pain requires comprehensive consideration of efficacy, safety, and patient quality of life. However, current guidelines lack explicit long-term management strategies, including duration of pharmacological management and post-discontinuation management. Pharmacological management for endometriosis must be long-term, as pain recurrence rates are high after discontinuation [32]. Future guideline development should provide more explicit guidance and recommendations. Additionally, controversy remains regarding preoperative medication use; some studies suggest preoperative hormones may help reduce intraoperative bleeding and postoperative adhesions, while others worry this may affect lesion identification and complete excision [32]. Three guidelines [17,19-20] do not recommend preoperative medication, warranting further research.

Furthermore, recommendations primarily focus on measures taken by healthcare professionals. Support for non-pharmacological/non-surgical management is also crucial for improving pain in endometriosis patients, with six guidelines [11-12,17-20] mentioning non-pharmacological/non-surgical management. The NICE guideline [19] noted that high-quality studies on the effectiveness of lifestyle interventions such as diet or exercise in pain reduction have not been identified. Although some guidelines include non-pharmacological/non-surgical management, some measures lack supporting evidence. To successfully self-manage endometriosis pain, patients need evidence-based, accessible information about the disease and non-pharmacological/non-surgical management methods. Future high-quality relevant studies should be conducted to provide more scientific evidence supporting the effectiveness of non-pharmacological/non-surgical management approaches and help patients better manage their pain.

3.3 Current Status and Optimization Recommendations for Chinese Endometriosis Pain Management Guidelines

This study included seven Chinese guidelines related to endometriosis pain management, which demonstrated significant advantages in multiple aspects. In terms of professional authority, the expert panels involved in development were robust, comprising authoritative experts from renowned obstetrics and gynecology departments across China. Regarding content comprehensiveness, the guidelines detailed the incidence, types, and characteristics of endometriosis-related pain, comprehensively covering various pain symptoms including dysmenorrhea, chronic pelvic pain, and dyspareunia, with particular attention to pain management in adolescent endometriosis patients through detailed descriptions of clinical features, diagnosis, and long-term management, demonstrating consideration for individual differences in special populations. Chinese endometriosis pain management guidelines have made substantial progress; however, compared with international guidelines, they still have room for further optimization and improvement. First, Chinese guidelines could be enhanced in terms of systematicity of evidence-based medicine evidence. Although domestic clinical research has increased in recent years, the number of systematic reviews and high-quality randomized controlled trials remains in a gradual accumulation phase, leaving the evidence base for some recommendations in need of further strengthening. Additionally, international guidelines provide more detailed and specific recommendations regarding medication selection and surgical options, including dosages, treatment courses, indications, and contraindications for different drugs. In contrast, some domestic guidelines offer relatively general recommendations in these areas without similarly detailed treatment course guidance or specific information on target populations, possibly because domestic guidelines emphasize comprehensiveness and general applicability to accommodate diverse healthcare environments and resource conditions. Finally, both domestic and international guidelines have relatively limited discussion on multidisciplinary management; research shows that patients managed through multidisciplinary approaches experience significantly reduced pain levels, and this area is expected to improve as clinical practice continues to evolve.

To construct high-quality Chinese endometriosis pain management guidelines and better assist patients in managing pain, we recommend increasing systematic reviews and conducting high-quality randomized controlled trials to enhance the scientific validity and reliability of evidence. National research project support can facilitate high-quality research development, and guidelines should explicitly list the evidence sources and quality grades for each recommendation. Regarding guideline recommendations, detailed treatment protocols should be provided, including medication selection, dosages, treatment courses, indications, and contraindications. Chinese guideline development teams should thoroughly study advanced international guidelines, such as the 2024 NICE updated guideline [19], drawing on its detailed pharmacological treatment protocols and surgical indications. Concurrently, multidisciplinary expert seminars can be organized to develop precise recommendations on drug dosages and treatment courses based on domestic healthcare realities, reducing uncertainty in clinical judgment and improving treatment standardization and effectiveness. For multidisciplinary management, guidelines should specify the composition and roles of multidisciplinary teams and workflow processes, coordinating medical resources across departments and integrating multidisciplinary perspectives [34] to provide clearer guidance for clinical practice and help healthcare institutions more effectively establish and manage multidisciplinary teams.

3.4 Limitations

This study has several limitations. The AGREE II guideline evaluation tool assesses only the quality of guidelines/expert consensus without in-depth analysis of the reasonableness of evidence grades and recommendation strengths within the guidelines, and the evaluation process may be subject to some degree of subjective influence. More than half of the included guidelines/expert consensus originated from abroad, potentially limiting the applicability of findings to the Chinese context. Appropriate adaptation and localization are needed to ensure relevance and effectiveness.

Author contributions: WAN Xie conceptualized the study, designed the research protocol, and proposed the research question, design, concepts, or methods. TU Xulian, LIU Xia, LI Xiaoyan, LENG Mingyue, YANG Xueqing, and LI Li were responsible for data collection, acquisition, cleaning, statistical analysis, and figure/table preparation. WAN Xie and TU Xulian drafted the manuscript. WU Liping and LIU Xia revised the final version and take responsibility for the paper.

Conflict of interest: None declared.

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(Received date: 2025-01-15; Revised date: 2025-04-20)
(This article editor: JIA Mengmeng)