Changes

July 2025 — minor update.  Added information regarding the management of women with endometriosis who may still require combined HRT following hysterectomy. 

Update

Goals

To support primary healthcare professionals to:

• Recognize the symptoms and signs of endometriosis.
• Assess a woman with suspected endometriosis.
• Offer appropriate treatment in primary care, or referral to secondary care if needed.

Outcome measures

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

• Women presenting with suspected endometriosis have an abdominal and, if appropriate, a pelvic examination.
• Women are referred to a gynaecology service if initial hormonal treatment for endometriosis is not effective, not tolerated, or contraindicated.
• Women with suspected or confirmed deep endometriosis involving the bowel, bladder, or ureter are referred to a specialist endometriosis service.

[NICE, 2018]

What is it?

• Endometriosis is a chronic inflammatory disease defined by the growth of endometrium-like tissue outside the uterus.
  • Endometriosis is hormone-mediated and is associated with menstruation. 
  • The main clinical consequences of endometriosis are chronic pain and impaired fertility.
  • Endometriotic deposits are most commonly distributed in the pelvis; on the ovaries, uterosacral ligaments, pouch of Douglas, rectum and sigmoid colon, bladder, and distal ureter. Extra-pelvic deposits, such as in the bowel, diaphragm, abdominal wall, umbilicus, pleural cavity, and central and peripheral nervous system are rare.
    • The more common pelvic or abdominal cavity endometriosis is divided into three subtypes: superficial peritoneal endometriosis, ovarian endometriosis (often called chocolate cysts or endometriomas), and deep endometriosis, although more than one subtype may be found in combination.

[ESHRE, 2022; Horne, 2022; Allaire, 2023; NICE, 2024]

What causes it?

• The exact cause of endometriosis is unknown [NICE, 2024]. Several theories have been proposed to explain the underlying mechanisms for the development and progression of the disease, but no single one can account for every case or manifestation. It is likely to be multifactorial in origin, and theories about mechanisms or factors involved include [Zondervan, 2020; Signorile, 2022; BMJ Best Practice, 2023; Lamceva, 2023]:
  • Retrograde menstruation — where endometrial cells flow backwards from the uterine cavity, through the fallopian tubes, and implant on pelvic organs, where they can seed and grow. Studies show, however, that most women (up to 90%) experience some form of retrograde menstruation, yet most do not develop endometriosis. This theory also does not explain why endometriosis occurs in some women after hysterectomy or, rarely, in some men following exposure to oestrogen through drug treatments. 
  • Lymphatic or circulatory dissemination — it has been suggested that endometriotic tissue may also be able to travel to distant sites (such as the lungs, eyes, and brain) through the lymphatic system or in the bloodstream.
  • Genetic predisposition — genetic predisposition to endometriosis has been well documented in family and twin-based studies, and heritability may be up to 50%, but no specific gene has been identified. There are currently no genetic tests available.
  • Müllerian remnants — it has been suggested that atypical migration or differentiation of Müllerian remnants may lead to endometriotic lesions once stimulated by oestrogen in puberty. Studies of female foetuses at autopsy have shown ectopic endometrium in pelvic structures in a proportion of cases.
  • Metaplasia — this describes a process by which cells in the pelvic and abdominal area, such as peritoneal mesothelium, transform into endometrial-type cells of the germinal epithelium. 
  • Environmental factors — this theory suggests that environmental toxins can affect the body, immune system, and reproductive system, and cause endometriosis. Factors that may be involved include tobacco use, caffeine, alcohol, diet, and organic pollutants produced by industrial processes (dioxins and polychlorinated biphenyls).
  • Immune dysfunction — many women with endometriosis appear to have reduced immunity to other conditions. Inflammation may be caused by immune dysregulation. It is not known whether this contributes to endometriosis or whether it is a result of endometriosis.

What are the risk factors?

• Risk factors for endometriosis include [Zondervan, 2020; Horne, 2022; Allaire, 2023; BMJ Best Practice, 2023]:
  • Low birth weight.
  • Early menarche.
  • Short menstrual cycles.
  • Increased menstrual flow.
  • Nulliparity.
  • Family history.
  • Vaginal outflow obstruction.
  • White ethnicity.
  • Low body mass index (BMI).
  • Autoimmune disease (an increased prevalence of autoimmune diseases has been noted in women with surgically confirmed endometriosis).

How common is it?

• Endometriosis is one of the most common gynaecological disorders in women of reproductive age. 
  • Endometriosis is estimated to affect approximately 10% of women of reproductive age, translating to around 190 million women and girls globally [WHO, 2023].
  • True prevalence is difficult to determine because a definitive diagnosis requires direct visualization at laparoscopy [Zondervan, 2020]. In addition, its presentation is variable and delayed diagnosis common, and prevalence varies with the population studied [Horne, 2022; NICE, 2024].
  • It is most commonly diagnosed between the ages of 18 and 29 years, although it can present before menarche and in menopause [BMJ Best Practice, 2023].
  • Women with a first-degree relative with endometriosis have a 7 to 10-fold increased risk of developing the condition [BMJ Best Practice, 2023].

What is the prognosis?

• The prognosis of endometriosis is variable [Allaire, 2023; Tsamantioti, 2023; NICE, 2024]:
  • Endometriosis is usually a chronic disease, and in most affected people symptoms begin in adolescence and improve after menopause, although some continue to have pain after menopause.
  • It is not inevitably progressive, with studies showing regression of endometriotic lesions in up to a third of cases. Others remain stable or progress with time.
  • Medical and surgical treatments can often provide symptomatic relief but are not curative.
  • Some people with endometriosis develop more complex persistent pain syndromes, thought to be due to central sensitization, and this may be part of a cluster of overlapping comorbid pain syndromes, leading to complex needs and the need for long-term support.
  • Reported recurrence rates after surgery vary widely, between 6 and 67%.

What are the complications?

• Complications of endometriosis include [BMJ Best Practice, 2023; Tsamantioti, 2023; NICE, 2024]:
  • Endometriomas (ovarian cysts containing blood and endometriosis-like tissue) — if the ovaries are affected, endometriomas may develop. These may rupture and can affect fertility by distorting pelvic anatomy.
  • Fertility problems — endometriosis is commonly associated with infertility, with a prevalence of 25–40% in infertile women compared with 0.5–5% in fertile women. The mechanisms linking endometriosis and infertility are poorly understood, and causation is not established. Severe disease can lead to tubal adhesions (resulting in marked distortion of pelvic anatomy and pelvic pain), reduced ovarian reserve and oocyte and embryo quality, and poor implantation. Endometriosis can also impair fertility by disturbing the function of the fallopian tube, embryo transport, and the eutopic endometrium. Even mild endometriosis can impair fertility.
  • Adhesion formation — may occur due to the endometriosis, or secondary to surgery or infection, and may cause chronic pelvic pain.
  • Bowel obstruction — partial or complete bowel obstruction can occur due to adhesion formation or a circumferential endometriotic deposit. 
  • Chronic pain — in some people, pain from endometriosis may become chronic even when visible disease has been removed.
  • Reduced quality of life — symptomatic endometriosis can have a significant and sometimes severe impact on the person’s quality of life and activities of daily living, including relationships and sexuality, work productivity, fitness, and mental health.
  • Possible increased risk of ovarian cancer — systematic reviews and meta-analyses suggest that there is an almost two-fold increased risk of ovarian cancer in women with endometriosis, however, this represents a very small lifetime risk, and there are concerns regarding the limitations of this evidence [Kvaskoff, 2021; ESHRE, 2022; Horne, 2022; BMJ Best Practice, 2023; NICE, 2024]. There also appears to be an association with an increased risk of thyroid and breast cancers, although the absolute risk remains low [Kvaskoff, 2021; ESHRE, 2022].

When should I suspect endometriosis?

• Suspect endometriosis in women (including young women aged 17 years and younger) presenting with one or more of the following symptoms or signs:
  • Chronic pelvic pain (defined as a minimum of 6 months of cyclical or continuous 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.
• If endometriosis is suspected:
  • Take a detailed history. Ask questions about the symptoms and have a full discussion with women to:
    • Identify risk factors for endometriosis (such as history of endometriosis in first-degree relatives, early menarche, or nulliparity). 
    • Exclude differential diagnoses (such as irritable bowel syndrome or pelvic inflammatory disease).
    • Identify complications of endometriosis (such as fertility problems or depression).
  • Inform the woman that keeping a pain and symptom diary can aid assessment.
  • Examine the woman.
    • Offer an abdominal and pelvic examination to identify abdominal masses and pelvic signs, such as reduced organ mobility and enlargement, tender nodularity in the posterior vaginal fornix, and visible vaginal endometriotic lesions. An abdominal and pelvic examination may also help to exclude differential diagnoses (such as uterine fibroids).
    • If a pelvic examination is not appropriate, offer an abdominal examination to exclude abdominal masses.
  • Offer an ultrasound scan. See the management section for more information.
• Be aware that some women with endometriosis may be asymptomatic.
• Do not exclude the possibility of endometriosis if examination and/or ultrasound is normal.
  • If clinical suspicion remains or symptoms persist, consider referral for further assessment and investigation.

What else might it be?

Differential diagnoses of endometriosis include:

• Uterine conditions, such as: 
  • Adenomyosis or uterine fibroids — typically causes lower abdominal pain and heavy menstrual bleeding, and an enlarged uterus may be identified on pelvic examination. See the CKS topic on Fibroids for more information.
  • Primary dysmenorrhoea — painful cramping, usually in the lower abdomen, which occurs shortly before or during menstruation, or both. Primary dysmenorrhoea occurs in young females in the absence of any identifiable underlying pelvic pathology. See the CKS topic on Dysmenorrhoea for more information.
  • Uterine myoma — usually asymptomatic but often present with heavy and/or irregular menstrual bleeding. Pelvic examination may show an enlarged, nodular pelvic mass that can vary in size and shape.
• Other gynaecological conditions, such as:
  • Pelvic inflammatory disease (PID) — typically causes lower abdominal pain, dyspareunia, abnormal vaginal bleeding, and malodorous vaginal discharge, with fever and general malaise in acute infection. Chronic PID may be indistinguishable from endometriosis. See the CKS topic on Pelvic inflammatory disease for more information.
  • Benign ovarian cyst — may be asymptomatic with an incidental pelvic mass or present with acute rather than chronic pain, such as with haemorrhagic cysts.
  • Pelvic floor tension myalgia — may present similarly with chronic pelvic pain and dyspareunia. There may be focal spasm and tenderness on pelvic and rectovaginal examination, but there are no diagnostic tests and it tends to be a diagnosis of exclusion.
  • Obstructive lesions of the genital tract, including cervical stenosis — causing amenorrhoea and cyclical pain. For example: 
    • Following surgery to the cervix. 
    • Congenital anomalies of the reproductive tract, such as imperforate hemivagina or vaginal septum — a rare cause of dysmenorrhoea in adolescents.
  • Ovarian cancer — typical symptoms represent advanced-stage cancer, and include weight gain despite lack of appetite, increased abdominal girth, and altered bowel habits. See the CKS topic on Ovarian cancer for more information.
  • Pregnancy, including ectopic pregnancy — common symptoms and signs of ectopic pregnancy include abdominal or pelvic pain, amenorrhoea or missed period, vaginal bleeding, and pelvic, adnexal, and abdominal tenderness. See the CKS topic on Ectopic pregnancy for more information.
• Urological conditions, such as:
  • Interstitial cystitis — diffuse chronic pain and dyspareunia are common and often indistinguishable from endometriosis. Symptoms are primarily localized to the bladder, such as urinary frequency and urgency. The woman may complain of pain with a full bladder that is relieved upon voiding. 
  • Recurrent urinary tract infections (UTIs) — typical features of a UTI include dysuria, frequency, urgency, changes in urine appearance or consistency, nocturia, and suprapubic discomfort/tenderness. See the CKS topic on Urinary tract infection (lower) - women for more information.
• Gastrointestinal conditions, such as:
  • Irritable bowel syndrome, inflammatory bowel disease, or chronic constipation — typically cause lower abdominal or chronic pelvic pain associated with a range of bowel symptoms which may be cyclical. See the CKS topics on Irritable bowel syndrome, Ulcerative colitis, and Constipation for more information.
  • Appendicitis — classic symptoms are abdominal pain, anorexia, nausea, vomiting, and constipation. See the CKS topic on Appendicitis for more information.
  • Gastroenteritis — diarrhoea (loose or watery stools, usually at least three times in 24 hours) is the main symptom. Other symptoms may include nausea, sudden onset of vomiting, blood or mucus in stools, and systemic features (such as fever or malaise). See the CKS topic on Gastroenteritis for more information.
  • Coeliac disease — characterized by persistent, unexplained abdominal or gastrointestinal symptoms, such as indigestion, diarrhoea, abdominal bloating, and constipation. See the CKS topic on Coeliac disease for more information.
• Other conditions, such as:
  • Referred pain from degenerative disc disease — nerve entrapment pain is typically sharp, localised, or stabbing, and exacerbated by movement.
  • Other cancers, for example, cervical, uterine, rectal, or bladder. See the CKS topics on Cervical cancer and HPV, Gynaecological cancers - recognition and referral, Gastrointestinal tract (lower) cancers - recognition and referral, and Urological cancers - recognition and referral for more information.
  • Musculoskeletal pain. See the CKS topic on Sprains and strains for more information.

Scenario: Management of endometriosis

From age 16 years onwards (Female).

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of endometriosis.

Search dates

January 2020 - June 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 10th January 2020). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S3 S1 OR S2 
S2 AB endometriosis OR TI endometriosis 
S1 (MH "Endometriosis") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.