Dr Rachel Brown explores updated NICE recommendations for the diagnosis and treatment of heavy menstrual bleeding

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Dr Rachel Brown

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Read this article to learn more about:

  • advances in techniques, medication, equipment, and software in the management of heavy menstrual bleeding (HMB)
  • when a physical examination and/or further investigation is needed
  • benefits of outpatient hysteroscopy for some causes of HMB.

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Heavy menstrual bleeding (HMB) or as it has been previously known, menorrhagia, is excessive menstrual blood loss that interferes with a woman’s physical, social, emotional, and/or material quality of life.1 It is one of the most common reasons for gynaecological consultations in both primary and secondary care; about 1 in 20 women (mostly aged 30–49 years) consult their GP each year because of heavy periods and these consultations lead to around 12% of all referrals to gynaecology services.1,2

NICE first published guidance on HMB more than 10 years ago. Since then, there have been many advances in techniques, medication, equipment, and software. To reflect these developments, NICE published NICE Guideline (NG) 88 on Heavy menstrual bleeding: assessment and management in March 2018, which updated and replaced NICE Clinical Guideline 44. NG88 was further updated in November 2018, following the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) review of ulipristal acetate.1

NICE Guideline 88 aims to help healthcare professionals advise each woman with HMB about the treatments that are right for her, with a clear focus on the woman’s choice. The priority should be that the woman herself decides which treatment is appropriate for her and whether a treatment has been successful, based on her symptoms and improvement in quality of life.1,3

NICE Guideline 88 includes care pathways for diagnosis4 (see Figure 1) and management5 (see Figure 2). A NICE Pathway on heavy menstrual bleeding is also available.

This article discusses the medical advances in HMB that provide the basis for NG88 and what the new recommendations mean for primary care.

Please note that not all of the treatments discussed in this article currently (January 2019) have UK marketing authorisation for the indications mentioned. The prescriber should follow relevant professional guidance, taking full responsibility for all clinical decisions. Informed consent should be obtained and documented. See the General Medical Council’s guidance on Good practice in prescribing and managing medicines and devices6 for further information.

Figure1_Heavy menstrual bleeding_diagnosis

Figure1: Heavy menstrual bleeding: diagnosis pathway4

© NICE 2018 Heavy menstrual bleeding: assessment and management. Tools and resources. Diagnosis care pathway. Available from: www.nice.org.uk/ng88 All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

HMB=heavy menstrual bleeding; TV=transvaginal; TA=transabdominal; MRI=magnetic resonance imaging 

* For example, women with persistent intermenstrual or persistent irregular bleeding and women with infrequent bleeding who are obese or havepolycystic ovary syndrome, women taking tamoxifen, women for whom treatment for HMB has been unsuccessful

If high risk for endometrial pathology (see *)

Figure2_Heavy menstrual bleeding_management

Figure 2: Heavy menstrual bleeding: management pathway5

© NICE 2018 Heavy menstrual bleeding: assessment and management. Tools and resources. Management care pathway. Available from: www.nice.org.uk/ng88 All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

LNG-IUS: levonorgestrel-releasing intrauterine system; TXA: tranexamic acid; NSAIDs: non-steroidal anti-inflammatory drugs; UAE: uterine artery embolisation; GnRHa=gonadotrophin-releasing hormone analogue.

* Ulipristal acetate is indicated for one course (up to 3 months) of preoperative treatment for moderate to severe symptoms of uterine fibroids and for intermittent treatment (up to four courses) of moderate to severe symptoms of uterine fibroids in women ineligible for surgery. See also the summary of product characteristics.

 

Medical advances in HMB

Transvaginal ultrasound definition and primary care access have vastly improved. Outpatient hysteroscopy has become more widely available, and is more acceptable to women due to the miniature hysteroscope. This has caused alterations in the relative clinical- and cost-effectiveness of diagnostic strategies.1,7

Some new treatments have become available, such as ulipristal acetate to shrink fibroids and reduce bleeding. In May 2018, the EMA PRAC carried out a review of ulipristal acetate following reports of serious liver injury, including liver failure leading to transplantation. The PRAC concluded that ulipristal acetate may have contributed to the development of some cases of serious liver injury, and recommended that use of the medicine should be restricted.8

Improvements in diagnostic imaging in recent years have resulted in an increase in the reported prevalence of adenomyosis, which was not included in CG44.1 However, this remains an area of debate in terms of symptoms, implications, and appropriate treatment options.9,10

Primary-care and outpatient management with a levonorgestrel-releasing intrauterine system (LNG-IUS) has increased in popularity in recent years, and this has led to a reduction in surgical procedures.1 Some endometrial ablation techniques (such as microwave endometrial ablation) are no longer available in the UK, and dilatation and curettage is used only in exceptional circumstances.1,7

Diagnosis

In the past, HMB was quantified as blood loss equal to or greater than 80 ml per month during a period.11 However, it is now generally agreed that HMB should be diagnosed based on the impact of the woman’s symptoms and not in terms of blood volume, so intervention should focus on reducing the impact on quality of life rather than on blood loss.1

There is often no cause found for HMB,12,13 although it can be caused by specific pathology and can occur in combination with other symptoms. NG88 focuses on HMB that is not caused by other diseases but it can be due to hypothyroidism (which should be considered if the patient has relevant symptoms),14 polycystic ovary syndrome (PCOS),15 sexually transmitted diseases (for example, chlamydia),16 clotting disorders,17 and may also be due to other medication, for example chemotherapy,18 anticoagulants,19 and the intrauterine device (IUD).20

History

There needs to be a detailed discussion with the woman to assess her periods, including:1

  • the nature of the bleeding, i.e. frequency, regularity, chronicity
  • any related symptoms such as persistent intermenstrual bleeding, pelvic pain or pressure symptoms that might suggest uterine cavity abnormality (e.g. polyp, histological abnormality, fibroids, or adenomyosis)
  • the impact it is having on her quality of life (e.g. time off work, having to get up at night, embarrassing flooding, fatigue due to anaemia)
  • other factors such as co-morbidities or previous treatment.

It is important to be aware that there is a huge range and natural variability in menstrual cycles and blood loss even within the course of one woman’s life. What one woman will consider normal, another will find significantly impacts her life.1

If the woman’s history suggests HMB without other related symptoms, then oral pharmacological treatment can be used without carrying out a physical examination. If the treatment chosen is LNG-IUS, then a bimanual vaginal examination would form part of the fitting procedure.1

If the woman’s history includes other symptoms such as intermenstrual bleeding, pelvic pain and/or pressure symptoms, then a physical examination1 and/or other investigations should be carried out.

Physical examination

Palpation of the abdomen should exclude any abdominal or pelvic masses. A speculum examination should then be done to assess the vagina and cervix, looking for polyps or any other abnormality, followed by a bimanual vaginal examination to assess the size and position of the uterus and presence of possible fibroids. It is also useful to assess any pain or tenderness or other symptoms.

If the examination is normal or small fibroids (less than 3 cm in diameter) or adenomyosis are suspected, then a LNG-IUS can be considered as first-line treatment.

If large fibroids, adenomyosis, or other pathology is suspected, then further investigations should be considered.1

Laboratory tests

A full blood count should be done to check for anaemia, but there is no evidence for routinely checking ferritin, or for hormone or thyroid function tests (TFTs), unless there are other symptoms. Testing for coagulation disorders (for example, von Willebrand’s disease) should only be done for women who have had HMB since their periods started and who have a personal or family history suggesting a coagulation disorder.1

Investigations

If cancer is suspected because of persistent, heavy intermenstrual bleeding or an abnormal examination, then an urgent cancer referral should be made.1,21

If the woman’s history and/or examination suggests a low risk of uterine cavity or histological abnormality or adenomyosis, then starting pharmacological treatment for HMB can be considered immediately without investigations.1

Suspected submucosal fibroids, polyps, or endometrial pathology—outpatient hysteroscopy

If the history or examination suggests polyps, submucosal fibroids, or endometrial pathology because there are symptoms such as persistent intermenstrual bleeding, or if the patient has risk factors for endometrial pathology (for example, obesity, PCOS, tamoxifen use, previous failed treatment for HMB), then first-line investigation should be an outpatient hysteroscopy in preference to pelvic ultrasound.1

It is recognised that outpatient hysteroscopy is not widely available but it is more accurate in identifying uterine cavity causes of HMB than pelvic ultrasound.1 This is a significant change to current practice as direct access booking will be needed for hysteroscopy services, which will ideally need to be delivered in community clinics.1 A hysteroscopy under anaesthesia might be an option for women who are not keen on the procedure as an outpatient. An endometrial biopsy can be performed at the time of hysteroscopy and often the cause of the HMB may be treated.1,22

Palpable uterus, suspected pelvic mass, significant dysmenorrhoea—ultrasound

A transvaginal ultrasound scan (TVS) is the investigation of choice if the woman has a palpable uterus, or a history or examination that suggests a pelvic mass, or significant dysmenorrhoea; also if the examination is inconclusive or difficult due to obesity, or she declines a hysteroscopy.1 It is now recognised that ultrasound is not as accurate at detecting uterine cavity causes of HMB as outpatient hysteroscopy, and hysteroscopy is not able to detect abnormalities outside the uterine cavity (for example, subserous or intramural fibroids, or adenomyosis).1,23

A transabdominal ultrasound or magnetic resonance imaging (MRI) can be considered, although both these techniques have significant limitations. It is not advised to use saline infusion sonography, MRI, or dilatation and curettage as first-line diagnostic tools.1

Referral for suspected endometriosis

Pain associated with HMB may be caused by endometriosis rather than adenomyosis.1,9 This should be considered as a diagnosis if the woman also experiences associated dyspareunia or bowel and urinary symptoms and therefore a referral for laparoscopy might be needed.9

Information for women with HMB

It is very important that the patient should be at the centre of the decision-making process for her treatment options. She should be provided with information about all possible treatment options and discussions should cover the benefits and risks of the various options and suitable treatments. Her options will be influenced if she is trying to conceive and if she wants to retain her fertility and/or her uterus.1

If she chooses an LNG-IUS then it is important to have a detailed discussion about possible changes in bleeding pattern, which are likely to last for 4 months but can sometimes continue for longer than 6 months. It is advisable to encourage women to wait for at least six cycles to see the benefits of the treatment, though this can sometimes be problematic for those women experiencing persistent bleeding.1

It is also important to discuss the impact that any planned surgery or uterine artery embolisation (UAE) may have on fertility. Uterine artery embolisation or myomectomy might allow the woman to retain her fertility. However, after endometrial ablation, women should avoid subsequent pregnancy and use effective contraception until menopause.1

If hysterectomy is being considered, then advice about the implications of surgery should include:1

  • sexual feelings
  • impact on fertility
  • bladder function
  • need for further treatment
  • treatment complications
  • her expectations
  • alternative surgery
  • psychological impact.

There is an increased risk of serious complications (such as intraoperative haemorrhage or damage to other abdominal organs) associated with hysterectomy when uterine fibroids are present.1

Women also need to know about the risk of possible loss of ovarian function and its consequences, even if their ovaries are retained during hysterectomy.1

Treatment

It is important to take into account a number of issues including: the woman’s preferences, any co-morbidity, the presence or absence of polyps, fibroids (including size, number, and location), endometrial pathology or adenomyosis, other symptoms such as pressure and pain.1

The LNG-IUS is the first-line treatment for HMB for women with:1

  • no identified pathology or
  • small fibroids (less than 3 cm in diameter which are causing no distortion of the uterine cavity) or
  • suspected or diagnosed adenomyosis.

Some women may also need oral pharmacological treatments in addition, for example, tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs), combined hormonal contraception, or cyclical oral progestogens.1

If treatment is unsuccessful, or if it is the woman’s preference, or her symptoms are severe, then referral to secondary care should be offered for investigations to diagnose the cause of HMB.1

If women have submucosal fibroids, then hysteroscopic removal might be an option.1

Women with large fibroids (that is, fibroids that are 3 cm or more in diameter) should be referred to secondary care for investigations and discussion of treatment options. While investigations and definitive treatment are being organised, tranexamic acid and/or NSAIDs, or oral hormonal options can be used,1 though these treatments are of limited effectiveness in these women.1 Ulipristal acetate, however, is showing some good results, notwithstanding the recent MHRA safety concerns.24,25  Ulipristal acetate is mostly prescribed in secondary care at present but is also sometimes prescribed in primary care.

Women taking ulipristal acetate should be monitored with monthly liver function tests (LFTs) prior to, during, and after treatment and need to be advised of the risk of severe liver injury. Ulipristal should not be started if alanine aminotransferase (ALT) or aspartate aminotransferase (AST) are more than 2 times the upper limit of normal (ULN) and should be stopped if ALT or AST are more than 3 times ULN. Patients should be advised about the signs and symptoms of liver injury and treatment should be stopped and investigations should be done immediately if any symptoms develop.26,27

More than one treatment course of ulipristal acetate is now authorised only in women who are not eligible for surgery (for example, where the risks of surgery outweigh the benefits or where the woman declines surgical treatment).27 Ulipristal can also be used as a pre-operative treatment for moderate-to-severe symptoms of uterine fibroids (this is initiated by a specialist). NICE recommends that when ulipristal acetate is used for intermittent treatment in women who are not eligible for surgery:1

  • offer ulipristal acetate 5 mg once daily for 3 months (up to four courses after a break of at least two menstrual periods between each course)27 to women with heavy menstrual bleeding and fibroids of 3 cm or more in diameter, and a haemoglobin level of 102 g per litre or below
  • consider ulipristal acetate 5 mg (up to four courses after a break of at least two menstrual periods between each course)27 for women with heavy menstrual bleeding and fibroids of 3 cm or more in diameter, and a haemoglobin level above 102 g per litre.

Liver function tests should be performed before each new treatment course and 2–4 weeks after the end of each treatment course, and when clinically indicated.27

Second-generation endometrial ablation is an option for women with HMB and fibroids of 3 cm or more in diameter. However, they need to meet the criteria specified in the manufacturers’ instructions, which differ among the different techniques.1

If treatment is unsuccessful then uterine artery embolisation, myomectomy, or hysterectomy may need to be considered.1

Pre-treatment with a gonadotrophin-releasing hormone analogue or ulipristal acetate (one course [up to 3 months]; see precautions and advice above) before hysterectomy and myomectomy should be considered if uterine fibroids are causing an enlarged or distorted uterus.1

If a woman decides on a hysterectomy, then it is important to discuss the route (laparoscopy, laparotomy, or vaginal) with the woman. Discuss the options of total hysterectomy (removal of the uterus and the cervix), subtotal hysterectomy (removal of the uterus and retention of the cervix), and also oophorectomy with the woman.1

Key priorities for primary care

LNG-IUS should be available to all women presenting to primary care with uncomplicated HMB. GPs need to feel comfortable about when they can treat without further investigation without concern that they are missing pathology.

Practitioners should feel confident in prescribing ulipristal in appropriate patients once the safety concerns have been addressed.

Practitioners should be able to decide which women need a hysteroscopy and this should be easily accessible.

Summary

NICE Guideline 88 aims to direct the focus of care for women with HMB on to the woman and her quality of life, thereby ensuring that she receives prompt, effective treatment in primary care, without investigation if appropriate. Those who cannot be managed in primary care should be given prompt supportive treatment and referral. Ulipristal acetate should be considered where appropriate.

Dr Rachel Brown

GP, Bristol; Member of the guideline development group for NICE NG88

Key points

  • Diagnosis of HMB should be based purely on the woman’s symptoms
  • If the woman’s symptoms consist just of heavy regular periods, with no intermenstrual bleeding or pain, then treatment can be given without investigation
  • Thyroid function tests and clotting studies should only be requested if, from the history, they are likely to be abnormal
  • LNG-IUS is recommended with or without oral non-hormonal treatment
  • If the woman has pain, then a TVS should be undertaken to consider adenomyosis
  • If the woman has intermenstrual bleeding, then she should have a hysteroscopy
  • Ulipristal acetate is a useful option for cases where surgery is not suitable, or prior to surgery to reduce symptoms
    • monitoring regarding possible liver side-effects is essential, before, during, and after treatment
  • Consider the woman’s ongoing need for fertility
  • Do not deny the woman a hysterectomy if she has exhausted all other options.

LNG-IUS= levonorgestrel-releasing intrauterine system; TVS=transvaginal ultrasound

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Agree and establish a multi-professional review group to explore how compliant local services are with this guidance
  • Define access to, and indications for, outpatient hysteroscopy as a superior diagnostic to ultrasound in many cases of HMB
  • Publish a care pathway for HMB that details recommended interventions for primary care clinicians and clear guidance for referral for diagnostics and/or specialist opinion
  • Ensure that access to IUS fitting is available to all women in the community though GP surgeries, local clinics family planning, or sexual health clinics
  • Indicate through local formularies appropriate pharmacotherapies for HMB with recommendations for who initiates these (especially ulipristal acetate).

STP=sustainability and transformation partnership; ICS=integrated care system; HMB=heavy menstrual bleeding; IUS=intrauterine system

References

  1. NICE. Heavy menstrual bleeding: assessment and management. NICE Guideline 88. NICE, March 2018 (updated November 2018). Available at: www.nice.org.uk/ng88
  2. Philipp C, Faiz A, Dowling N et al. Age and the prevalence of bleeding disorders in women with menorrhagia. Obstet Gynecol 2005; 105 (1): 61–66.
  3. NICE. Patient experience in adult NHS services: improving the experience of care for people using adult NHS services. NICE Clinical Guideline 138. NICE, 2012. Available at: www.nice.org.uk/cg138
  4. NICE. Heavy menstrual bleeding: assessment and management. Tools and resources. Diagnosis care pathway. NICE Guideline 88. NICE, 2018. Available at: www.nice.org.uk/guidance/ng88/resources/diagnosis-care-pathway-pdf-4783791277
  5. NICE. Heavy menstrual bleeding: assessment and management. Tools and resources. Management care pathway. NICE Guideline 88. NICE, 2018 Available at: www.nice.org.uk/guidance/ng88/resources/management-care-pathway-pdf-4783791278
  6. General Medical Council. Good practice in prescribing and managing medicines and devices. GMC, 2013. Available at: www.gmc-uk.org/Prescribing_guidance.pdf_59055247.pdf
  7. Cooper N, Barton P, Breijer M et al. Cost-effectiveness of diagnostic strategies for the management of abnormal uterine bleeding (heavy menstrual bleeding and post-menopausal bleeding): a decision analysis. Health Technol Assess 2014; 18 (24): 1–201.
  8. European Medicines Agency. 26/07/2018 Esmya: new measures to minimise risk of rare but serious liver injury EMA concludes review of medicine for uterine fibroids. 26 July 2018. EMA/482522/2018. Available at: www.ema.europa.eu/documents/referral/esmya-article-20-procedure-esmya-new-measures-minimise-risk-rare-serious-liver-injury_en-0.pdf
  9. NICE. Endometriosis: diagnosis and management. NICE Guideline 73. NICE, 2017. Available at: www.nice.org.uk/ng73
  10. Kennedy S, Bergqvist A, Chapron C et al on behalf of the ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group. ESHRE guideline for the diagnosis and treatment of endometriosis. Human Reproduction 2005; 20 (10): 2698–2704.
  11. Oehler M, Rees M. Menorrhagia: an update. Acta Obstet Gynecol Scand 2003; 82 (5): 405–422.
  12. Maresh M, Metcalfe M, McPherson K et al. The VALUE national hysterectomy study: description of the patients and their surgery. BJOG 2002; 109 (3): 302–312.
  13. Speroff L, Fritz M. Dysfunctional uterine bleeding. In: Speroff L, Fritz M, editors. Clinical gynecologic endocrinology and infertility—7th edition. Philadelphia: Lippincott Williams and Wilkins, 2005: 547–571.
  14. Weeks A. Menorrhagia and hypothyroidism. BMJ 2000; 320 (7235): 649.
  15. Hapangama D, Bulmer J. Pathophysiology of heavy menstrual bleeding. Womens Health (Lond) 2016; 12 (1): 3—13.
  16. Sriprasert I, Pakrashi T, Kimble T, Archer D. Heavy menstrual bleeding diagnosis and medical management. Contracept Reprod Med 2017; 2: 20.
  17. James A, Kouides P, Abdul-Kadir R et al. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol 2009; 201 (1): 12.e1–12.e8.
  18. Milbourne A. Up to date website. Heavy or irregular uterine bleeding during chemotherapy. www.uptodate.com/contents/heavy-or-irregular-uterine-bleeding-during-chemotherapy (accessed 15 January 2019).
  19. Boonyawat K, O’Brien S, Bates S. How I treat heavy menstrual bleeding associated with anticoagulants. Blood 2017; 130: 2603–2609.
  20. American College of Obstetricians and Gynaecologists. Frequently asked questions: gynecologic problems. Heavy menstrual bleeding.www.acog.org/Patients/FAQs/Heavy-Menstrual-Bleeding?IsMobileSet=false (accessed 15 January 2019).
  21. NICE. Suspected cancer: recognition and referral. NICE Guideline 12. NICE, 2017. Available at: www.nice.org.uk/ng12
  22. Dakhly D, Abdel Moety G, Saber W et al. Accuracy of hysteroscopic endomyometrial biopsy in diagnosis of adenomyosis. J Minim Invasive Gynecol 2016; 23 (3): 364–371.
  23. Royal College of Obstetricians and Gynaecologists (RCOG), British Society for Gynaecological Endoscopy. Management of endometrial hyperplasia. RCOG Green-top Guideline 67. RCOG, 2016. Available at: www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_67_endometrial_hyperplasia.pdf
  24. Medicines and Healthcare products Regulatory Agency (MHRA). Esmya: no new treatment courses prescribed until further notice. MHRA, 2018. Available at: www.gov.uk/government/news/esmya-no-new-treatment-courses-prescribed-until-further-notice (accessed 15 January 2019).
  25. Murji A, Whitaker L, Chow T, Sobel M. Selective progesterone receptor modulators (SPRMs) for uterine fibroids. Cochrane Database Syst Rev 2017; (1): CD010770.
  26. Electronic Medicines Compendium. Esmya 5 mg tablets (ulipristal acetate)—summary of product characteristics. 28 July 2018. www.medicines.org.uk/emc/product/3951/smpc (accessed 15 January 2019).
  27. NICE website. BNF. Ulipristal acetate. bnf.nice.org.uk/drug/ulipristal-acetate.html (accessed 15 January 2019).