GUIDELINES

Diagnosis and management of endometriosis:summary of NICE guidanceLaura Kuznetsov systematic reviewer 1, Katharina Dworzynski guideline lead 1, Melanie Daviesclinical advisor and consultant gynaecologist 1 2, Caroline Overton chair of Guideline Committee andconsultant gynaecologist, subspecialist in reproductive medicine and laparoscopic surgery 3

1National Guideline Alliance, Royal College of Obstetricians and Gynaecologists, London NW1 4RG, UK; 2University College London Hospitals,London, UK; 3St Michael’s University Hospital, Bristol, UK

Endometriosis is one of the most common gynaecologicaldisorders, affecting an estimated 10% of women in thereproductive age group (usually 15-49 years old), and in theUK it is the second most common gynaecological condition(after fibroids).1 Endometriosis is hormone mediated and isassociated with menstruation. The precise cause is not known,but it is widely accepted that endometrial cells deposited in thepelvis by retrograde menstruation are capable of implantationand development. It is a long term condition causing pelvicpain, painful periods, and subfertility. Endometriosis presentsa diagnostic and clinical challenge, with many women leftundiagnosed, often for many years. Small observational studieshave reported delays of 4-10 years in diagnosis,2 3 which canresult in decreased quality of life4 and disease progression.5 Thediagnostic delay is not limited to adults; endometriosis is alsooften missed in adolescent girls,6 and this guideline aims toimprove care by highlighting this age group in somerecommendations.This article summarises the most recent recommendations fromthe National Institute for Health and Care Excellence (NICE)on diagnosis and management of endometriosis.7 Therecommendations were based on consideration of the availableevidence, which was mostly of very low quality and seldom ofmoderate or high quality, and the expert opinion of the GuidelineCommittee (GC).The overall aim of the guideline is to improve the diagnosis andmanagement of endometriosis in community services,gynaecology services, and specialist endometriosis services(endometriosis centres). It includes women with confirmed orsuspected endometriosis, including recurrent endometriosis,and women who do not have symptoms but have endometriosisdiscovered incidentally. The guideline also addresses the careof adolescent girls. This summary focuses on investigation,early management, and referral for women with suspected

endometriosis, and is aimed mainly at general practitioners andhealthcare professionals in community services where womenwill first present.RecommendationsNICE recommendations are based on systematic reviews of thebest available evidence and explicit consideration of costeffectiveness. When minimal evidence is available,recommendations can be based on the Guideline Committee’s(GC) experience and opinion of what constitutes good practice.Evidence levels for the recommendations are given in italic insquare brackets.

When to suspect endometriosisRecommendations on endometriosis symptoms and signs aresummarised in box 1, and a pathway for initial management ofsuspected endometriosis is presented in the infographic (the fullNICE pathway for diagnosis and management of suspectedendometriosis is available in appendix 1 on bmj.com).

Investigating suspected endometriosis•Do not exclude the possibility of endometriosis if the

abdominal or pelvic examination, ultrasound scan, ormagnetic resonance imaging is normal. If clinical suspicionremains or symptoms persist, consider referral for furtherassessment and investigation (see below). [Based on lowto very low quality evidence from quantitative studies andthe experience and opinion of the GC]

Imaging: ultrasound scanning•Consider transvaginal ultrasound:–To investigate suspected endometriosis even if the pelvic

and abdominal examination is normal

Correspondence to: M Davies mdavies@rcog.org.uk

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BMJ 2017;358:j3935 doi: 10.1136/bmj.j3935 (Published 2017 September 06) Page 1 of 4

Practice

PRACTICE

What you need to know• Endometriosis can be difficult to diagnose, with some studies showing a delay in diagnosis of 4-10 years, resulting in decreased quality

of life and disease progression• Endometriosis cannot be ruled out by a normal examination and pelvic ultrasound• Hormonal treatments for endometriosis suppress menstruation and reduce pain. They are contraceptive but have no effect on

subsequent fertility after discontinuation• Refer women to a gynaecology service if they have severe, persistent, or recurrent symptoms of endometriosis, if they have pelvic

signs of endometriosis, or if initial management is not effective, not tolerated, or is contraindicated• Endometriosis can be a long term condition, with substantial physical, sexual, psychological, and social impact

Box 1: Endometriosis symptoms and signs• Suspect endometriosis in women (including young women aged ≤17 years) presenting with one or more of:

– Chronic pelvic pain– Period related pain (dysmenorrhoea) affecting daily activities and quality of life– Deep pain during or after sexual intercourse– Period related or cyclical gastrointestinal symptoms, in particular painful bowel movements– Period related or cyclical urinary symptoms, in particular blood in the urine or pain passing urine– Infertility in association with one or more of the above.– [Based on moderate quality evidence from quantitative studies and the experience and opinion of the GC]

• Inform women with suspected or confirmed endometriosis that keeping a pain and symptom diary can aid discussions. [Based on theexperience and opinion of the GC]

• Offer an abdominal and pelvic examination to women with suspected endometriosis to identify abdominal masses and pelvic signs,such as reduced organ mobility and enlargement, tender nodularity in the posterior vaginal fornix, and visible vaginal endometrioticlesions. [Based on moderate quality evidence from quantitative studies and the experience and opinion of the GC]

–To identify endometriomas and deep endometriosisinvolving the bowel, bladder, or ureter.[Based on low to very low quality evidence fromquantitative studies and the experience and opinion ofthe GC]

• If a transvaginal scan is not appropriate (for example, inwomen who have never had sexual intercourse), considera transabdominal ultrasound scan of the pelvis. [Based onlow to very low quality evidence from quantitative studiesand the experience and opinion of the GC]

Imaging: magnetic resonance imaging (MRI)•Do not use pelvic MRI as the primary investigation to

diagnose endometriosis in women with symptoms or signssuggestive of endometriosis. [Based on very low qualityevidence from quantitative studies and the experience andopinion of the GC]

•Consider pelvic MRI to assess the extent of deependometriosis involving the bowel, bladder, or ureter.[Based on very low quality evidence from quantitativestudies and the experience and opinion of the GC]

•Ensure that MRI scans are interpreted by a healthcareprofessional with specialist expertise in gynaecologicalimaging. [Based on the experience and opinion of the GC]

Blood tests: cancer antigen 125 (CA-125)•Do not use serum CA-125 to diagnose endometriosis.

[Based on very low quality evidence from quantitativestudies and the experience and opinion of the GC]

• If a coincidentally reported serum CA-125 level isavailable, be aware that:–A raised serum CA-125 titre (≥35 IU/mL) may be

consistent with having endometriosis

–Endometriosis may be present despite a normal serumCA-125 level (<35 IU/mL).[Based on very low quality evidence from quantitativestudies and the experience and opinion of the GC]

Diagnostic laparoscopy•Consider laparoscopy to diagnose endometriosis in women

with suspected endometriosis, even if the ultrasound scanwas normal. [Based on moderate to very low qualityevidence from quantitative studies and the experience andopinion of the GC]

•During a diagnostic laparoscopy, a gynaecologist withtraining and skills in laparoscopic surgery should performa systematic inspection of the pelvis. [Based on theexperience and opinion of the GC]

Initial management of suspectedendometriosisIf endometriosis is suspected after a thorough history andexamination and if an initial trial with paracetamol ornon-steroidal anti-inflammatory drug (NSAID), or both, andmanagement with hormonal treatment are ineffective or nottolerated, it is recommended that primary health care doctorscould consider a referral to a gynaecology, paediatric andadolescent gynaecology, or specialist endometriosis service. Inwomen for whom fertility is a priority, consider managingendometriosis related subfertility in a multidisciplinary teamwith input from a fertility specialist.

Analgesics•For women with endometriosis related pain, health

professionals should discuss the benefits and risk ofanalgesics, taking into account any comorbidities and thewoman’s preferences. Consider a short trial (for example,3 months) of paracetamol or NSAID, alone or incombination, for first line management of endometriosis

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PRACTICE

related pain. If this does not provide adequate pain relief,consider other forms of pain management and referral forfurther assessment. [Based on the experience and opinionof the GC]

Hormonal treatments•Explain to women with suspected or confirmed

endometriosis that hormonal treatment for endometriosiscan reduce pain and has no permanent negative effect onsubsequent fertility. [Based on high to low quality evidencefrom quantitative studies and the experience and opinionof the GC]

•Offer hormonal treatment (such as combined oralcontraceptive or a progestogen) to women with suspected,confirmed, or recurrent endometriosis. [Based on high tolow quality evidence from quantitative studies and theexperience and opinion of the GC]Not all combined oral contraceptives and progestogenshave UK authorisation for this indication. Prescribersshould follow relevant professional guidance forprescribing unlicensed medicines.

•Do not offer hormonal treatment to women withendometriosis who are trying to conceive, because it doesnot improve spontaneous pregnancy rates. [Based on highto low quality evidence from quantitative studies and theexperience and opinion of the GC]

• If initial hormonal treatment for endometriosis is noteffective, not tolerated, or is contraindicated, refer thewoman to a gynaecology service (see box 2), specialistendometriosis service (endometriosis centres, box 2), orpaediatric and adolescent gynaecology service forinvestigation and treatment options. [Based on high to lowquality evidence from quantitative studies and theexperience and opinion of the GC]

When to refer women with suspected orconfirmed endometriosis?

•Consider referring women to a gynaecology service for anultrasound or gynaecology opinion if:–They have severe, persistent, or recurrent symptoms of

endometriosis–They have pelvic signs of endometriosis– Initial management is not effective, not tolerated, or is

contraindicated.[Based on the experience and opinion of the GC]

•Refer women to a specialist endometriosis service(endometriosis centre) if they have suspected or confirmeddeep endometriosis involving the bowel, bladder, or ureter.[Based on the experience and opinion of the GC]

Evidence suggests endometriosis is often not suspected in youngwomen6 and, because of this they are often not referred to theright services for endometriosis.

•Consider referring young women (aged ≤17 years) withsuspected or confirmed endometriosis to a paediatric andadolescent gynaecology service, gynaecology service, orspecialist endometriosis service (endometriosis centre)depending on local service provision. [Based on theexperience and opinion of the GC]

What are the surgical options?Discuss surgical management options with women withsuspected or confirmed endometriosis. In most cases surgicalmanagement would be considered after conservative treatmentshave been unsuccessful unless the woman shows signs of deependometriosis involving the bowel, bladder, or ureter.

•Discussions may include:–What a laparoscopy involves–That laparoscopy may include surgical treatment (with

prior patient consent)–How laparoscopic surgery could affect endometriosis

symptoms–The possible benefits, risks, and complications of

laparoscopic surgery–The possible need for further surgery (for example, for

recurrent endometriosis or if complications arise)–The possible need for further planned surgery for deep

endometriosis involving the bowel, bladder, or ureter.[Based on the experience and opinion of the GC]

Surgical management if fertility is a priorityThe management of endometriosis related subfertility shouldhave multidisciplinary team involvement with input from afertility specialist. This should include the recommendeddiagnostic fertility tests or preoperative tests, as well as otherrecommended fertility treatments such as assisted reproductionthat are included in the NICE guideline on fertility problems(www.nice.org.uk/guidance/cg156).

What information and support is available?The Guideline Committee acknowledged that for most womenthe healthcare professional is the first point of contact regardinginformation about their condition, and the GC highlighted thatthe information provided is often inadequate.8 It is importantfor women to understand the consequences of their choices (forexample, choosing hormone treatment that is contraceptive) andbe able to make an informed decision. However, the challengefor healthcare professionals is to tailor information to individualneeds, preferences, and circumstances while also allowing forflexibility, because information needs may change with time,if new symptoms develop, or if priorities change.The GC made the following recommendations:

•Be aware that endometriosis can be a long term condition,and can have a significant physical, sexual, psychological,and social impact. [Based on moderate to low qualityevidence from qualitative studies and the experience andopinion of the GC]

•Assess the individual information and support needs ofwomen with suspected or confirmed endometriosis, takinginto account their circumstances, symptoms, priorities,desire for fertility, aspects of daily living, work and study,cultural background, and their physical, psychosexual, andemotional needs. [Based on moderate to low qualityevidence from qualitative studies and the experience andopinion of the GC]

Organisation of careRecommendations on organisation of care are summarised inbox 2.

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PRACTICE

Box 2: Organisation of care of women with suspected or confirmed endometriosis• Community, gynaecology, and specialist endometriosis services (endometriosis centres) should:

– Provide coordinated care for women with suspected or confirmed endometriosis– Have processes in place for prompt diagnosis and treatment of endometriosis, because delays can affect quality of life and result

in disease progression

• Gynaecology services for women with suspected or confirmed endometriosis should have access to:– A gynaecologist with expertise in diagnosing and managing endometriosis, including training and skills in laparoscopic surgery– A gynaecology specialist nurse with expertise in endometriosis– A multidisciplinary pain management service– A healthcare professional with an interest in gynaecological imaging– Fertility services

• Specialist endometriosis services (endometriosis centres) should have access to:– Gynaecologists with expertise in diagnosing and managing endometriosis, including advanced laparoscopic surgical skills– A colorectal surgeon with an interest in endometriosis– A urologist with an interest in endometriosis– An endometriosis specialist nurse– A multidisciplinary pain management service with expertise in pelvic pain– A healthcare professional with specialist expertise in gynaecological imaging of endometriosis– Advanced diagnostic facilities (for example, radiology and histopathology)– Fertility services

[Based on the experience and opinion of the GC]

ImplementationThere are challenges to delivering high quality care to womenwith endometriosis. Women typically present to communityservices including general practitioners, practice nurses, schoolnurses, and sexual health services, and the information in thisguideline will help diagnosis and guide referral. There arecurrently geographical inequalities in access to specialist care.The recommendations related to organisation of care willimprove access to gynaecology specialist nurses with expertisein endometriosis. Implementation related to surgery ingynaecological and specialist endometriosis services can alsobe improved by providing clearer guidance on consent fordiagnostic laparoscopy, since it often serves a dual purpose ofdiagnosis as well as management. New guidance on this fromthe Royal College of Obstetricians and Gynaecologists couldfacilitate this process.9

To help women make choices in the management of theircondition, a patient decision aid for hormonal treatment is indevelopment and will be published alongside the guideline.

The members of the Guideline Committee were (shown alphabetically):Rachel Brown, Dominic Byrne, Natasha Curran, Alfred Cutner, CathyDean, Lynda Harrison, Jed Hawe, Lyndsey Hogg, Andrew Horne, JaneHudson-Jones, Wendy-Rae Mitchel, Caroline Overton (chair), and CarolPearson. Co-opted members: Moji Balogun, Christian Becker,Mohammed Belal, Natalie Lane, Sanjiv Manek, and Tim Rockall.The members of the National Guideline Alliance technical team were(shown alphabetically): Alexander Bates, Zosia Beckles, ShonaBurman-Roy, Anne Carty, Melanie Davies, Katharina Dworzynski,Annabel Flint, Maryam Gholitabar, Elise Hasler, Sadia Janjua, LauraKuznetsov, Sabrina Naqvi, Amir Omidvari, Hugo Pedder, and FerruccioPelone.

Contributors All authors contributed to the initial draft of this article,helped revise the manuscript, and approved the final version forpublication.Funding The National Guideline Alliance was commissioned and fundedby the National Institute for Health and Care Excellence to develop thisguideline and write this BMJ summary.Competing interests: We declare the following interests based on NICE'spolicy on conflicts of interests (available at http://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/code-of-practice-for-declaring-and-managing-conflicts-of-interest.pdf): MD and CO haveprivate practice that may include treating women with endometriosis.These authors’ full statements can be viewed at www.bmj.com/content/bmj/358/bmj.j3935/related#datasupp.

1 Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am1997;358:235-58. doi:10.1016/S0889-8545(05)70302-8 pmid:9163765.

2 Hudelist G, Fritzer N, Thomas A, et al. Diagnostic delay for endometriosis in Austria andGermany: causes and possible consequences. Hum Reprod 2012;358:3412-6. doi:10.1093/humrep/des316 pmid:22990516.

3 Ballard K, Lowton K, Wright J. What’s the delay? A qualitative study of women’sexperiences of reaching a diagnosis of endometriosis. Fertil Steril 2006;358:1296-301.doi:10.1016/j.fertnstert.2006.04.054 pmid:17070183.

4 Nnoaham KE, Hummelshoj L, Webster P, et al. World Endometriosis Research FoundationGlobal Study of Women’s Health consortium. Impact of endometriosis on quality of lifeand work productivity: a multicenter study across ten countries. Fertil Steril2011;358:366-373.e8. doi:10.1016/j.fertnstert.2011.05.090 pmid:21718982.

5 D’Hooghe TM, Debrock S. Endometriosis, retrograde menstruation and peritonealinflammation in women and in baboons. Hum Reprod Update 2002;358:84-8. doi:10.1093/humupd/8.1.84 pmid:11866244.

6 Greene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N. Diagnostic experience among4,334 women reporting surgically diagnosed endometriosis. Fertil Steril 2009;358:32-9.doi:10.1016/j.fertnstert.2007.11.020 pmid:18367178.

7 National Institute for Health and Care Excellence. Endometriosis: diagnosis andmanagement (NICE guideline 37). 2017. www.nice.org.uk/guidance/ng37.

8 Culley L, Hudson N, Mitchell H, Law C, Denny E, Raine-Fenning N. Endometriosis:improving the wellbeing of couples. Summary report and recommendations, 2013. www.dmu.ac.uk/documents/research-documents/health-and-life-sciences/reproduction-research/endopart/endopart-study-summary-report-and-recommendations.pdf.

9 Royal College of Obstetricians and Gynaecologists. Diagnostic laparoscopy (ConsentAdvice No 2). 2017. www.rcog.org.uk/guidelines-research-services/guidelines/consent-advice-2/.

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PRACTICE

Guidelines into practice• How might you use the information in this article to help achieve prompt investigation and diagnosis for women presenting with

symptoms suggestive of endometriosis?• Are you aware of how to refer to specialist services locally if you need support managing or diagnosing a patient with endometriosis?• What will you do differently as a result of reading this article?

Future researchThe GC prioritised the following research recommendations:

• What information and support interventions are effective to help women with endometriosis deal with their symptoms and improvetheir quality of life?

• Are specialist lifestyle interventions (diet and exercise) effective for women with endometriosis?• Are pain management programmes a clinically and cost effective intervention for women with endometriosis?• Is laparoscopic treatment (excision or ablation) of peritoneal disease in isolation effective for managing endometriosis related pain?

How patients were involved in the creation of this articleCommittee members involved in this guideline included two lay members with direct experience of endometriosis and one lay member froman organisation that represents women with endometriosis, who all contributed to the formulation of the recommendations summarised here.

MethodsThis guidance was developed by the National Guideline Alliance in accordance with NICE guideline development methods (www.nice.org.uk/media/default/about/what-we-do/our-programmes/developing-nice-guidelines-the-manual.pdf). A Guideline Committee (GC) was establishedby the National Guideline Alliance, chaired by a consultant gynaecologist, which comprised healthcare professionals (one general practitioner,one consultant in pain medicine, one consultant obstetrician and gynaecologist, one professor of gynaecology and reproductive science,two endometriosis clinical nurse specialists, and two consultant gynaecologists specialising in endometriosis), one clinical commissioner,and three lay members.The GC co-opted one consultant radiologist, one associate professor of gynaecology and reproductive medicine with a particular interestin adolescent care, one consultant urological surgeon, one consultant gynaecological pathologist, one clinical psychologist with a particularinterest in pelvic pain, and one consultant colorectal surgeon.The GC identified relevant clinical questions, collected and appraised clinical evidence, and evaluated the cost effectiveness of proposedinterventions where possible. Quality ratings of the evidence were based on GRADE methodology (www.gradeworkinggroup.org/). Theserelate to the quality of the available evidence for assessed outcomes rather than the quality of the study. The scope and the draft of theguideline went through a rigorous reviewing process, in which stakeholder organisations were invited to comment; the group took all commentsinto consideration when producing the final guideline. Two different versions of this guideline have been produced: a full version containingall the evidence, the process undertaken to develop the recommendations, and all the recommendations, known as the “full guideline”; anda short version containing a list of all the recommendations, known as the “short guideline.” Both versions are available from the NICEwebsite (www.nice.org.uk/guidance/ng37).A formal review of the need to update a guideline is usually undertaken by NICE three years after its publication. NICE will conduct a reviewto determine whether the evidence base has progressed significantly to alter the guideline recommendations and warrants an update.

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PRACTICE

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