Changes

April 2023 — minor update. Updated link to the contraception assessment topic. 

Update

Goals

To support primary healthcare professionals to: 

• Make a working diagnosis of uterine fibroids.
• Arrange appropriate investigations to confirm the diagnosis and exclude serious causes for symptoms.
• Arrange specialist referral for further assessment and management if needed.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

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

QOF indicators

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

QIPP - Options for local implementation

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

NICE quality standards

The following NICE quality standards are relevant for this CKS topic:

• Statement 1. Women presenting with symptoms related to heavy menstrual bleeding have a focused history taken that includes the impact on their quality of life.
• Statement 2. Women with heavy menstrual bleeding and suspected submucosal fibroids, polyps or endometrial pathology are offered outpatient hysteroscopy.
• Statement 3. Women with heavy menstrual bleeding have a discussion with their healthcare professional about all their treatment options.

[NICE, 2020]

What is it?

• Uterine fibroids (leiomyomas) are benign tumours which are caused by proliferation of a mixture of smooth muscle cells and fibroblasts, which form hard, round, whorled tumours in the myometrium [Perez-Lopez, 2014; Lumsden, 2015].
  • They can be single, or multiple, and their size varies from a few millimetres to 30 cm or larger [Lumsden, 2015].
  • They typically develop in women of reproductive age, as their growth and maintenance is thought to be oestrogen- and progesterone-dependent [Perez-Lopez, 2014].
• Fibroids may develop anywhere within the myometrium. They may be defined as [Perez-Lopez, 2014; Lumsden, 2015]:
  • Subserosal
    • These develop near the outer serosal surface of the uterus and extend outside the uterus into the peritoneal cavity. They are commonly asymptomatic or minimally symptomatic even when relatively large. When they are sufficiently large they may cause symptoms due to pressure on adjacent structures.
  • Intramural
    • These develop within the myometrium without extending predominately into the uterine cavity or peritoneal cavity. They may cause heavy menstrual bleeding and dysmenorrhea by interfering with the constriction of blood vessels during menstruation.
  • Submucosal
    • These develop near the inner mucosal surface of the uterus and extend into the uterine cavity. Even relatively small submucosal fibroids may cause significant heavy menstrual bleeding, dysmenorrhea, or reduce fertility.

What are the risk factors?

• Risk factors associated with the development of fibroids include [Baird, 2003] [Perez-Lopez, 2014] [Lumsden, 2015] [de la Cruz, 2017] [Yang, 2022]:
  • Increasing age — risk increases with age during reproductive years until the menopause.
  • Early menarche — risk increased if menarche before age of 11 years.
  • Nulliparity.
  • Older age at first pregnancy — fibroids may enlarge during the first trimester of pregnancy, and tend to shrink post-partum.
  • Comorbidities — obesity (weight gain and central distribution of body fat); diabetes; hypertension.
  • Ethnicity — higher risk in black and Asian women compared with white women. In addition, fibroids are more likely to be symptomatic, occur at an earlier age, be larger, and multiple in these ethnic groups.
  • Family history — risk is higher in women who have an affected first-degree relative.

How common is it?

The true prevalence of fibroids is likely to be underestimated, as they are frequently asymptomatic and under- or unreported to healthcare professionals [Perez-Lopez, 2014] [Giuliani, 2020] [Yang, 2022].

• Fibroids are the most common benign uterine tumours in women of reproductive age [Perez-Lopez, 2014].
• The incidence of fibroids increases with age during the reproductive years, peaks in the perimenopausal years, and declines after menopause [Perez-Lopez, 2014; Lumsden, 2015].
• A review of epidemiological studies found the prevalence rates varied according to case definition [Wise, 2016]:
  • 12.8 per 1000 person-years for cases diagnosed by pelvic examination, ultrasound, or hysterectomy.
  • 2 per 1000 person-years for hysterectomy-confirmed cases alone.
• An American ultrasound-based screening study of randomly selected women aged 35–49 years (n = 1364) found [Baird, 2003]:
  • 51% of pre-menopausal women with no previous diagnosis had ultrasound evidence of fibroids, and the proportion was higher for Black women (59%) compared with white women (43%).
  • The estimated cumulative incidence of fibroids by the age of 50 years was more than 80% for Black women and nearly 70% for white women.

What are the complications?

Possible complications of fibroids include [Perez-Lopez, 2014] [Lumsden, 2015] [de la Cruz, 2017] [El Mahdi, 2019] [Giuliani, 2020] [Yang, 2022]:

• Iron deficiency anaemia.
  • Heavy or abnormal uterine bleeding may occur due to distortion of the endometrial lining by fibroids, leading to endometrial and vascular dysfunction. See the CKS topic on Anaemia - iron deficiency for more information.
• Compression of adjacent organs by large fibroids, which may cause:
  • Recurrent urinary tract infection (UTI) — if pressure on the bladder. See the CKS topic on Urinary tract infection (lower) - women for more information on assessment and management.
  • Urinary retention — if pressure on the bladder.
  • Hydronephrosis — rare, due to a large fibroid causing ureteric compression which may affect renal function. See the CKS topics on Acute kidney injury and Chronic kidney disease for more information.
• Subfertility or infertility (rare).
  • Submucosal or deep intramural fibroids may distort the uterine cavity and interfere with implantation and live birth rates. The risk increases with age. See the CKS topic on Infertility for more information.
• Complications during pregnancy (rare). 
  • Miscarriage — submucosal or deep intramural fibroids may distort the uterine cavity and interfere with pregnancy outcome. See the CKS topic on Miscarriage for more information.
  • Fibroid vascular infarction ('red degeneration') — may cause acute pain due to degenerative changes when rapid growth of a fibroid, promoted by high levels of sex hormones, causes it to outgrow its blood supply.
  • Possible higher rates of caesarean instrumental delivery.
  • Fetal malpresentation.
  • Pre-term delivery.
• Torsion of a pedunculated fibroid (rare).
  • This can affect subserosal and submucosal fibroids, if they are attached to the myometrium by a pedicle containing their blood supply, and may present with acute pelvic or abdominal pain.
  • Occasionally, fibroid regression may occur when the blood supply is cut off due to torsion.
• Haemoperitoneum (rare).
  • This may result from spontaneous rupture or avulsion of fibroids, or rupture of an overlying blood vessel.

What is the prognosis?

Fibroids can develop at any time between puberty and the menopause.

• The natural history of fibroids is unpredictable and varies depending on the woman's age and reproductive status [Perez-Lopez, 2014].
  • Expert opinion in a review article states that about 3–7% of untreated fibroids in premenopausal women regress over six months to three years [de la Cruz, 2017].
• Once formed, fibroids tend to persist until the menopause when they usually shrink [Perez-Lopez, 2014].
  • Shrinkage may be limited by calcification or delayed by taking hormone replacement therapy (HRT). See the CKS topic on Menopause for more information [Perez-Lopez, 2014; Moro, 2019].
  • Occasionally, fibroids may degenerate before the onset of menopause [Perez-Lopez, 2014].

When should I suspect a diagnosis of fibroids?

Fibroids are commonly asymptomatic and may be identified incidentally during a routine pregnancy assessment or gynaecology assessment for a different condition.

• Typical symptoms may include:
  • Heavy menstrual bleeding and/or dysmenorrhoea. See the CKS topics on Menorrhagia and Dysmenorrhoea for more information.
  • Pelvic pain, pressure, or discomfort; dyspareunia.
  • Abdominal discomfort or bloating; back pain.
  • Urinary symptoms, such as frequency, urgency, urinary incontinence, or retention; and increased risk of urinary tract infections (particularly if a large fibroid is causing pressure on the bladder). See the CKS topics on Incontinence - urinary, in women and Urinary tract infection (lower) - women for more information.
  • Bowel symptoms, such as bloating, constipation, and/or painful defecation (particularly if a large fibroid is causing pressure on the bowel). See the CKS topic on Constipation for more information.
  • Subfertility or infertility (particularly if there are submucosal fibroids). See the CKS topic on Infertility for more information.
• On abdominal and pelvic examination there may be:
  • Typically a firm, enlarged, and irregularly shaped non-tender uterus on pelvic examination.
  • A central irregular abdominal mass (if a large fibroid).
• Pelvic or renal tract ultrasound may show:
  • Classical appearance of uterine fibroid(s).
  • Evidence of a complication such as hydronephrosis if a large fibroid causes ureteric compression.

How should I assess a woman with suspected or confirmed fibroids?

If a woman has suspected or confirmed fibroids (for example on pelvic ultrasound scan): 

• Ask about:
  • Any symptoms, their severity, duration, and impact on daily functioning and quality of life.
  • Any clinical features which may suggest an additional or alternative diagnosis.
  • Any previous fertility issues and hopes for future fertility. See the CKS topic on Infertility for more information.
  • Any risk factors, including family history.
  • History of cervical screening and results. See the CKS topic on Cervical screening for more information.
  • Any previous treatments for heavy menstrual bleeding and/or fibroids. See the CKS topic on Menorrhagia for more information.
• Examine the woman:
  • Perform an abdominal and bimanual pelvic examination to assess for the presence of pelvic tenderness and any mass(es).
• Arrange a routine pelvic ultrasound scan (transabdominal and transvaginal, if needed) to determine the number, size, and location of fibroid(s), particularly if there are any of the following:
  • The uterus is palpable abdominally.
  • History or examination suggests a pelvic mass.
  • Examination is inconclusive or difficult, for example, if a woman is obese.
• Consider arranging additional investigations, depending on clinical judgement.
  • Check a full blood count to assess for iron deficiency anaemia if there is a history of heavy menstrual bleeding and/or symptoms of anaemia. See the CKS topic on Anaemia - iron deficiency for more information.

What else might it be?

Alternative conditions which may present with a pelvic mass or symptoms similar to uterine fibroids include:

• Malignant causes
  • Ovarian cancer. See the CKS topic on Ovarian cancer for more information.
  • Endometrial cancer. See the CKS topic on Gynaecological cancers - recognition and referral for more information.
    • Very rarely a pelvic mass may be due to a leiomyosarcoma which typically presents with rapid or unexpected growth after menopause. It can only be reliably diagnosed by histopathology. It is uncertain whether leiomyosarcoma is due to de novo growth or malignant transformation of a benign uterine fibroid.
  • Gastrointestinal malignancy. See the CKS topics on Gastrointestinal tract (lower) cancers - recognition and referral and Gastrointestinal tract (upper) cancers - recognition and referral for more information.
  • Urinary tract malignancy. See the CKS topic on Urological cancers - recognition and referral for more information.
• Benign causes
  • Endometrial polyp or hyperplasia.
  • Adenomyosis or endometriosis. See the CKS topic on Endometriosis for more information.
  • Urinary retention.
  • Pregnancy including ectopic pregnancy. See the CKS topic on Ectopic pregnancy for more information.

Scenario: Management of fibroids

From age 16 years onwards (Female).

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of fibroids.

Search dates

June 2017 - June 2022

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp Leiomyoma/, fibroid$.tw., $myoma.tw.

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.