MenorrhagiaLast revised in August 2012

Changes

Last revised in August 2012February 2013 — minor update. The 2013 QIPP options for local implementation have been added to thistopic [NICE, 2013 (/menorrhagia#!references/A72185)].

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to thistopic [NPC, 2012 (/menorrhagia#!references/A69139)].

September 2012 — minor update. Black triangle removed from Qlaira tablets.

August 2012 — reviewed. A literature search was conducted in July 2012 to identify evidence­basedguidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Nochanges to clinical recommendations have been made.

Previous changes

May 2011 — information on Qlaira , a quadraphasic combined oral contraceptive pill, was added toprescribing information (/menorrhagia#!prescribinginfosub:15). Issued in June 2011.

May 2011 — the 2010/2011 QIPP options for local implementation have been added to this topic [NPC,2011 (/menorrhagia#!references/A67819)]. Issued in June 2011.

January 2011 — correction to the dosage and usage instructions for tranexamic acid(/menorrhagia#!prescribinginfosub:7). Prescription also corrected. Issued in January 2011.

October 2010 — topic structure revised to ensure consistency across CKS topics — no changes to clinicalrecommendations have been made.

September 2010 — minor update. A prescription for Rigevidon , another new ethinylestradiol pluslevonorgestrel combined oral contraceptive pill, has been added. Issued in September 2010.

June 2010 — minor update. A prescription for Levest , a new ethinylestradiol plus levonorgestrel combinedoral contraceptive pill, has been added. Issued in June 2010.

NICE (http://www.nice.org.uk)

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February 2009 — minor update to the combined oral contraceptive pill prescriptions. The upper age limit foruse has been reduced to 50 years. Issued in March 2009.

June to September 2007 — converted from CKS guidance to CKS topic structure. The evidence­base hasbeen reviewed in detail, and recommendations are more clearly justified and transparently linked to thesupporting evidence.

The most important change to the recommendations is that the levonorgestrel­releasing intrauterine systemis now recommended first­line for most women with heavy menstrual bleeding.

October 2005 — minor technical update. Issued in November 2005.

July 2005 — updated to incorporate the Referral guidelines for suspected cancer published by the NationalInstitute for Health and Care Excellence. Issued in July 2005.

February 2005 — updated to include prescribing advice from the Committee on Safety of Medicines on theeffect of depot medroxyprogesterone acetate contraception on bones. Issued in February 2005.

May 2004 — reviewed. Validated in September 2004 and issued in November 2004.

March 2002 — updated to incorporate referral advice from the National Institute for Health and CareExcellence. Issued in April 2002.

June 2001 — reviewed. Validated in July 2001 and issued in October 2001.

October 1998 — written.

Update

New evidence

Evidence­based guidelinesNo new evidence­based guidelines since 1 July 2012.

HTAs (Health Technology Assessments)No new HTAs since 1 July 2012.

Economic appraisalsNo new economic appraisals relevant to England since 1 July 2012.

Systematic reviews and meta­analysesSystematic reviews published since the last revision of this topic:

Matteson, K.A., Rahn, D.D., Wheeler, T.L., et al. (2013) Nonsurgical management of heavy menstrualbleeding: a systematic review. Obstetrics and Gynecology 121(3), 632­643. [Abstract(http://www.ncbi.nlm.nih.gov/pubmed/23635628 )]

Primary evidence

Primary evidenceRandomized controlled trials published since the last revision of this topic:

Gupta, J., Kai, J., Middleton, L., et al. (2013) Levonorgestrel intrauterine system versus medical therapyfor menorrhagia. New England Journal of Medicine 368(2), 128­137. [Abstract(http://www.ncbi.nlm.nih.gov/pubmed/23301731)]

New policies

No new national policies or guidelines since 1 July 2012.

New safety alerts

No new safety alerts since 1 July 2012.

Changes in product availability

No changes in product availability since 1 July 2012.

Goals

To reduce or stop excessive menstrual bleedingTo prevent or correct iron deficiency anaemia due to heavy menstrual bleedingTo refer women who may benefit from surgical treatmentsTo improve the quality of life of women with heavy menstrual bleeding

Outcome measures

For full audit criteria on Heavy menstrual bleeding published by the National Institute for Health and CareExcellence, see www.nice.org.uk (http://www.nice.org.uk/guidance/index.jsp?action=download&r=true&o=30412) [NICE, 2007 (/menorrhagia#!references/A29468)].

QIPP — Options for local implementation

Non­steroidal anti­inflammatory drugs (NSAIDs)Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in peoplewho are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality(e.g. older patients).If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg perday or less).Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to

Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing toibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRAadvice and the NICE clinical guideline on osteoarthritis [CSM, 2005(/menorrhagia#!references/A13561); NICE, 2008 (/menorrhagia#!references/A66197)].Co­prescribe a proton pump inhibitor (PPI) with NSAIDs for people with osteoarthritis, rheumatoidarthritis, or low back pain (for people over 45 years) in accordance with NICE guidance [NICE, 2008(/menorrhagia#!references/A66197); NICE, 2009a (/menorrhagia#!references/A49561); NICE, 2009b(/menorrhagia#!references/A52598)].Take account of drug interactions when co­prescribing NSAIDs with other medicines (see Summariesof Product Characteristics). For example, co­prescribing NSAIDs with ACE inhibitors or angiotensinreceptor blockers (ARBs) may pose particular risks to renal function; this combination should beespecially carefully considered and regularly monitored if continued.

[NICE, 2013 (/menorrhagia#!references/A72185)]

DefinitionWhat is it?

Menorrhagia is excessive (heavy) menstrual blood loss over several consecutive cycles whichinterferes with a woman's physical, emotional, social, and material quality of life. Menorrhagia can occuralone or in combination with other symptoms [Duckitt and Collins, 2006(/menorrhagia#!references/A29873); National Collaborating Centre for Women's and Children's Health,2007 (/menorrhagia#!references/A26790)].For the purposes of this CKS topic, the terms menorrhagia and heavy menstrual bleeding are usedinterchangeably.

In research, it is usually defined as an objectively measured blood loss of 60–80 mL or more permenstruation (the average blood loss is 30–40 mL, and 90% of women have losses less than 80 mL)[Apgar et al, 2007 (/menorrhagia#!references/A29077)].However, objective measurements of menstrual blood loss are not practical in the clinical setting, andthey correlate poorly with a woman's subjective assessment of blood loss and its impact on quality oflife [Warner et al, 2004 (/menorrhagia#!references/A29076); National Collaborating Centre forWomen's and Children's Health, 2007 (/menorrhagia#!references/A26790)].

PrevalenceHow common is it?

Studies vary in their reporting of how common heavy menstrual bleeding is:About one third of women describe their periods as heavy [Lethaby and Farquhar, 2003(/menorrhagia#!references/A29074)].A prospective cohort study of a general practice with 10,000 registered patients found a 25% 12­monthcumulative incidence of menorrhagia symptoms in menstruating women [Shapley et al, 2004(/menorrhagia#!references/A29075)].

One in 20 women aged 30–49 years consult their GP each year for heavy menstruation [Vessey et al,1992 (/menorrhagia#!references/A30995)].Menstrual disorders are the second most common gynaecological conditions resulting in hospital referraland 12% of all gynaecological referrals [NHS CRD, 1995 (/menorrhagia#!references/A2580)].

Causes of menorrhagia

Causes of menorrhagiaWhat are the causes of menorrhagia?

In 40–60% of women with menorrhagia, no underlying cause is found. These women are said tohave dysfunctional uterine bleeding (unexplained menorrhagia) [Hickey et al, 2007(/menorrhagia#!references/A8059)].Causes of menorrhagia include:

Uterine and ovarian pathologies:Uterine fibroids (dysmenorrhoea, pelvic pain).Endometriosis and adenomyosis (dysmenorrhoea, dyspareunia, pelvic pain, difficulty conceiving).See the CKS topic on Endometriosis (/endometriosis).Pelvic inflammatory disease and pelvic infection (for example chlamydia — may also present withvaginal discharge, pelvic pain, intermenstrual and postcoital bleeding, and fever). See the CKStopic on Pelvic inflammatory disease (/pelvic­inflammatory­disease).Endometrial polyps (intermenstrual bleeding).Endometrial hyperplasia or carcinoma (postcoital bleeding, intermenstrual bleeding, pelvic pain).Polycystic ovary syndrome (causing anovulatory menorrhagia and irregular bleeding). See the CKStopic on Polycystic ovary syndrome (/polycystic­ovary­syndrome).

Systemic diseases and disorders:Coagulation disorders (for example von Willebrand disease).Hypothyroidism (which may also present with fatigue, constipation, intolerance of cold, and hair andskin changes). See the CKS topic on Hypothyroidism (/hypothyroidism).Liver or renal disease.

Iatrogenic causes:Anticoagulant treatment.Chemotherapy.Intrauterine contraceptive device (blood loss may be increased by 40–50% over 6–12 monthscompared with pre­insertion values) [RCOG, 1998 (/menorrhagia#!references/A3714)].Tubal sterilization (evidence is conflicting) [Wilcox et al, 1992 (/menorrhagia#!references/A29447);Gentile et al, 1998 (/menorrhagia#!references/A29446); Basgul et al, 2007(/menorrhagia#!references/A29445)].

[NHS CRD, 1995 (/menorrhagia#!references/A2580); Shah and Grainger, 1996(/menorrhagia#!references/A8079); Kadir et al, 1998 (/menorrhagia#!references/A2834)]

Complications

Heavy menstrual bleeding may negatively affect quality of life by limiting normal activities, social life,and work [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

In three qualitative studies, women described mood changes and becoming self­conscious as keyconcerns.A woman's sex life may also be negatively affected.

Iron deficiency anaemia occurs in about two thirds of women with heavy menstrual bleeding [Lethabyand Farquhar, 2003 (/menorrhagia#!references/A29074); Duckitt and Collins, 2006(/menorrhagia#!references/A29873)].

Diagnosis

DiagnosisHow should I diagnose menorrhagia?

Menorrhagia is diagnosed when both the woman and clinician agree menstrual bleeding is heavy after ahistory has been taken.It is not necessary to measure blood loss to diagnose menorrhagia.

Basis for recommendation

These recommendations are consistent with clinical guidelines on Heavy menstrual bleeding, published bythe National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's andChildren's Health, 2007 (/menorrhagia#!references/A26790)].

HistoryWhat should I ask about when taking the history?

The history should set out to define the nature of the bleeding; identify potential underlying causes; andaddress the woman's ideas, concerns, expectations, and needs.

Ask the woman her age at menarche and for details about her menstrual cycle, for example length ofcycle, the number of days of menstruation, for how long she has considered her periods to be heavy,what her periods were like previously, and the impact on her quality of life.Enquire about symptoms that suggest an underlying pathology (/menorrhagia#!diagnosisadditional),particularly 'red flag' symptoms (for example persistent intermenstrual or postcoital bleeding).Consider the possibility of an underlying systemic disease, such as hypothyroidism or a coagulationdisorder (for example von Willebrand disease).Take a family history, and in particular ask about endometriosis and coagulation disorders that may havea hereditary component.Check the woman's smear status.Ask about current contraceptive use, contraceptive plans, and future plans for a family.

It is important to ascertain the woman's need for contraception as this may impact on the choice oftreatment. For more information, see Advice and counselling(/menorrhagia#!scenariorecommendation).

Symptoms suggesting an underlying pathology

Underlying pathologies that might be found in women with heavy menstrual bleeding include pelvicinflammatory disease, endometriosis, and endometrial carcinoma. For further information, see Causes ofmenorrhagia (/menorrhagia#!backgroundsub:2).Symptoms that may indicate an underlying pathology include:

Persistent postcoital bleeding.Persistent intermenstrual bleeding.Dyspareunia.Dysmenorrhoea.Pelvic pain and/or pressure symptoms.Vaginal discharge.

Vaginal discharge.

Basis for recommendation

These recommendations are consistent with clinical guidelines on Heavy menstrual bleeding, published bythe National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's andChildren's Health, 2007 (/menorrhagia#!references/A26790)].

ExaminationWhen and how should I examine the woman?

Consider abdominal and pelvic examination in the following women:Women with symptoms suggestive of underlying abnormalities, before further investigations arearranged.Those in whom initial treatment has proved ineffective.Those for whom the levonorgestrel­releasing intrauterine system is being considered.

A pelvic examination should include:Vulval examination for evidence of external bleeding and signs of infection (for example vaginaldischarge).Speculum examination of vagina and cervix. High vaginal, endocervical, and chlamydia swabs shouldbe obtained if infection is suspected.Bimanual palpation to identify uterine or adnexal enlargement or tenderness.

In addition to an abdominal and pelvic examination, look for systemic signs of underlying disease:Endocrine disease: hirsutism, striae, thyroid enlargement or nodularity, or changes in skinpigmentation.Coagulation disorders: bruises or petechiae.

If a woman refuses an examination, refer her directly for investigations (/menorrhagia#!diagnosissub:3)as appropriate.If a woman has fibroids that are palpable abdominally, offer immediate referral(/menorrhagia#!scenariorecommendation:5) or sent her for an ultrasound.

Basis for recommendation

These recommendations are consistent with clinical guidelines on Heavy menstrual bleeding, published bythe National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's andChildren's Health, 2007 (/menorrhagia#!references/A26790)], and are based on consensus opinion ratherthan primary evidence.

InvestigationsWhat investigations should I carry out?

Menstrual blood loss does not have to be measured accurately, and objective measurement is impractical.

Take a full blood count in all women to rule out iron deficiency anaemia.

Iron deficiency anaemia is a strong indicator of excessive menstrual bleeding (see the CKS topic onAnaemia ­ iron deficiency (/anaemia­iron­deficiency)).

Other blood tests and endocrine investigations are not routinely indicated.Thyroid function tests should only be carried out if the woman has other symptoms or signs suggestiveof thyroid disease (for more information on hypothyroidism, see the CKS topic on Hypothyroidism(/hypothyroidism)).Tests for bleeding disorders (for example von Willebrand disease) should be performed if there aresuggestive features in the history or on examination. Investigations should be arranged in conjunctionwith the local haematology department as many of the tests are not routine. Women who may requirescreening include:

Those who have had heavy menstrual bleeding since menarche, or a history of excessive bleedingafter tooth extraction, operations, or childbirth.Those with a family history of a coagulation disorder.

Consider opportunistic cervical screening, if appropriate, in line with national recommendations.Consider arranging for a trans­vaginal pelvic ultrasound to identify structural abnormalities, if the womanhas symptoms suggesting an underlying cause for heavy menstrual bleeding, or if she:

Has a uterus that is palpable abdominally.Has a pelvic mass of uncertain origin on vaginal examination (although also consider urgent referral).Has had treatment that has proved ineffective.

If a suspicious mass is detected, consider urgent referral (/menorrhagia#!scenariorecommendation:5) toa specialist (rather than referral for ultrasound).Investigations that may be used in secondary care include hysteroscopy and tissue biopsy forendometrial cancer; for further information, see Management in secondary care(/menorrhagia#!scenariorecommendation:6).

Basis for recommendation

These recommendations are consistent with clinical guidelines on Heavy menstrual bleeding, published bythe National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's andChildren's Health, 2007 (/menorrhagia#!references/A26790)].

Although there is evidence from diagnostic studies to support objective measurements to determinemenstrual blood loss, this is generally felt to be impractical in most clinical situations and is unlikely toguide clinical management.

Direct objective measurement of menstrual blood loss includes the alkaline haematin technique.The pictorial blood loss assessment chart is an indirect measure.

Results from epidemiological studies have found that:Thyroid disease is not associated with menstrual disorders and therefore should not be routinelytested for.Coagulation disorders, such as von Willebrand disease, are an identifiable risk factor in women whohave experienced heavy bleeding since the menarche.

Scenario: ManagementScenario: Management of menorrhagia (heavy menstrual bleeding)

Age from 12 years onwards (Female)

Advice and counselling

Advice and counsellingWhat advice and counselling should I give to a woman with menorrhagia?

Discuss the natural variability and range of menstrual blood loss. For some women, reassurance may beall that is required, and treatment may not be needed.If reassurance alone is not appropriate, discuss the different treatment options for heavy menstrualbleeding, covering issues such as:

Effectiveness of treatments.Acceptability of treatments, including likelihood of adverse effects.The need for contraception.Implications of treatment on fertility.

Give written information such as patient information leaflets, to explain the condition and treatmentoptions, where appropriate.

Patient information covering heavy menstrual bleeding is published by the National Institute for Healthand Care Excellence (NICE) and can be found at www.nice.org.uk (pdf)(http://www.nice.org.uk/nicemedia/live/11002/30406/30406.pdf).If asked, advise that no specific lifestyle changes benefit menorrhagia.

If the woman and clinician cannot agree on the most appropriate treatment option, she should be offeredthe option of a second opinion.

Basis for recommendation

These recommendations are based on clinical guidelines on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

NICE could find no evidence from controlled trials or other types of study that showed any benefit oflifestyle changes (for example diet or exercise). Some studies have identified risk factors (for examplesmoking and obesity), but these are not currently seen as planned interventions, but as general health­promotion issues.

Prescribing drug treatmentWhen should I prescribe pharmaceutical treatment in women presenting with menorrhagia?

Pharmaceutical treatment is recommended first­line for woman with menorrhagia who:Have no symptoms suggestive of underlying pathology including postcoital bleeding, intermenstrualbleeding, dyspareunia, dysmenorrhoea, vaginal discharge, and pelvic pain and/or pressure (thesesymptoms may indicate pelvic inflammatory disease, endometriosis, or endometrial carcinoma). SeeHistory (/menorrhagia#!diagnosissub:1).Are awaiting the results of investigations.

Basis for recommendation

This recommendation is based on clinical guidelines on Heavy menstrual bleeding, published by the

National Institute for Health and Care Excellence [National Collaborating Centre for Women's and Children'sHealth, 2007 (/menorrhagia#!references/A26790)].

Once major structural or histological abnormalities have been excluded, the cause of menorrhagia islikely to be idiopathic with no obvious underlying pathology. In most cases, this will respond tosymptomatic treatment.

Which drug treatment to prescribeWhich pharmaceutical treatment should I prescribe in a woman with menorrhagia?

The levonorgestrel­releasing intrauterine system (LNG­IUS) (Mirena ) is the preferred first­choice forthe treatment of menorrhagia, provided that long­term contraception with an intrauterine device isacceptable (anticipated minimum use of 12 months).Tranexamic acid, nonsteroidal anti­inflammatory drugs (NSAIDs), or the combined oralcontraceptive pill (COC) should be considered as second choice treatment, if LNG­IUS is unsuitable.

Tranexamic acid and NSAIDs are suitable if contraception is not desired and are first­choice drugswhile investigations or definitive treatment is being organized.

If dysmenorrhoea is present, NSAIDs may be preferred, as they provide relief of menstrual pain.If an NSAID is to be used, mefenamic acid, naproxen, or ibuprofen should be prescribed.

The COC offers more readily reversible contraception than the LNG­IUS. It also has the benefit ofregulating cycles and reducing dysmenorrhoea.

Oral norethisterone or long­acting progestogens should be considered as third choice if the othertreatments are unsuitable.

Oral norethisterone should be taken during the follicular and luteal phases (days 5 to 26). It is not aneffective form of contraception. However, a dose that is effective in decreasing menstrual blood loss isalso likely to inhibit ovulation, and so its use is not appropriate in women wishing to conceive.Depot medroxyprogesterone acetate (Depo­Provera ) is the recommended long­acting progestogen.It is taken as an intramuscular injection once every 12 weeks.

Danazol, gestrinone, and etamsylate are not recommended for the treatment of menorrhagia.Gonadotropin­releasing hormone analogues (for example leuprorelin or buserelin) are not recommendedfor use in primary care, but are an option in secondary care. For more information, see Management insecondary care (/menorrhagia#!scenariorecommendation:6).

For more information on prescribing drugs to treat menorrhagia, see the Prescribing information(/menorrhagia#!prescribinginfo) sections on Levonorgestrel­releasing intrauterine system(/menorrhagia#!prescribinginfosub:1), Tranexamic acid (/menorrhagia#!prescribinginfosub:5), Nonsteroidalanti­inflammatory drugs (/menorrhagia#!prescribinginfosub:9), Combined oral contraceptives(/menorrhagia#!prescribinginfosub:13), Oral norethisterone (/menorrhagia#!prescribinginfosub:17), andLong­acting progestogens (/menorrhagia#!prescribinginfosub:21).

Basis for recommendation

These recommendations are based on clinical guidelines on Heavy menstrual bleeding, published by theNational Institute for Health and Care Excellence (NICE) [National Collaborating Centre for Women's andChildren's Health, 2007 (/menorrhagia#!references/A26790)].

The order of treatment recommended by NICE is based on the clinical effectiveness and cost­effectiveness of the available pharmaceutical interventions for menorrhagia. For details of the evidence

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effectiveness of the available pharmaceutical interventions for menorrhagia. For details of the evidencefrom controlled trials on menorrhagia treatment, see individual sections of Supporting evidence(/menorrhagia#!supportingevidence) on:

Levonorgestrel­releasing intrauterine system (/menorrhagia#!supportingevidence1:2)Tranexamic acid (/menorrhagia#!supportingevidence1:3)Nonsteroidal anti­inflammatory drugs (/menorrhagia#!supportingevidence1:4) (NSAIDs)Combined oral contraceptives (/menorrhagia#!supportingevidence1:5)Oral norethisterone (/menorrhagia#!supportingevidence1:6)Danazol and etamsylate (not recommended) (/menorrhagia#!supportingevidence1:8)

CKS recommends mefenamic acid, naproxen, and ibuprofen as the NSAIDs of choice because:They have been shown to be effective in controlled trials.They are all licensed for dysmenorrhoea. However, only mefenamic acid is specifically licensed formenorrhagia.

Initial treatment ineffectiveWhat should I do if initial drug treatment is ineffective in a woman with menorrhagia?

If initial treatment fails to produce an adequate reduction in menstrual bleeding (and treatment wascomplied with), consider three options:

Switch to an alternative pharmaceutical treatment. Oral norethisterone or depot medroxyprogesteroneare often suitable if initial treatment was ineffective.Add on an additional drug. Typically, tranexamic acid can be combined with a nonsteroidal anti­inflammatory drug (NSAID), or an NSAID can be combined with the combined oral contraceptive.Refer (/menorrhagia#!scenariorecommendation:5) to a specialist.

Basis for recommendation

These are pragmatic recommendations by CKS, based on standard clinical practice. They are consistentwith the clinical guideline on Heavy menstrual bleeding, published by the National Institute for Health andClinical Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

NICE recommends on the basis of consensus opinion, that 'when a first pharmaceutical treatment hasproved ineffective, a second pharmaceutical treatment can be considered rather than immediate referralto surgery'.NICE does not make any recommendations on combining treatments, nor is there evidence fromcontrolled trials on the effectiveness of combining treatments. Nevertheless, this is often done in practiceand anecdotal evidence suggests that it can be beneficial. For further information on which treatmentscan be combined, see When to combine treatment (/menorrhagia#!prescribinginfosub:25).Further treatment options, including referral, are available from specialist management in secondary care.

Rapidly stopping heavy bleeding

How can I rapidly stop heavy bleeding, if necessary?

Consider stopping heavy menstrual bleeding by prescribing oral norethisterone.Oral norethisterone, 5 mg three times daily for 10 days, usually stops bleeding within one to threedays. Inform the woman that a withdrawal bleed will occur two to four days after stopping treatment.If bleeding is exceptionally heavy ('flooding'), 10 mg three times daily (off­label dose) may providebetter results (get informed consent). This should then be tapered down to 5 mg three times daily forabout a week once bleeding has stopped.

Basis for recommendation

These recommendations are mainly pragmatic and are based on the British National Formulary [BNF 63,2012 (/menorrhagia#!references/A68735)], manufacturer's Summary of Product Characteristics [ABPIMedicines Compendium, 2010 (/menorrhagia#!references/A69110)], the available medical literature [Rees,2003 (/menorrhagia#!references/A15334)], and expert opinion [Rees, Personal Communication, 2007(/menorrhagia#!references/A12623)].

There is no strict definition on what constitutes very heavy bleeding. It ranges from prolonged, heavymenstruation to acute periods of exceptionally heavy bleeding that is difficult to control using sanitaryproducts. In these cases, the woman may desire acute treatment to rapidly stop the bleeding.CKS could not find any controlled trials that investigated the use of drugs to stop acute and exceptionallyheavy menstrual bleeding, but oral progestogens are usually used for this purpose.

The licensed dose of norethisterone to arrest dysfunctional uterine bleeding is 10–15 mg per day[ABPI Medicines Compendium, 2010 (/menorrhagia#!references/A69110); BNF 63, 2012(/menorrhagia#!references/A68735)]. This should be adequate in most cases; if the higher doseregimen of oral norethisterone (i.e. 30 mg per day, off­label) is considered necessary, informedconsent should be sought before starting treatment.

When to referWhen should I refer?

Refer the woman to a specialist if:There are alarm symptoms (/menorrhagia#!scenarioclarification) suggesting a possible malignancy.Urgent referral is required (within 2 weeks).Heavy bleeding persists that negatively affects the woman's quality of life, despite adequate trials ofpharmaceutical treatment. A routine referral should be made according to local protocols.The woman wishes to consider surgery rather than persist with medical treatment. A routine referralshould be made according to local protocols.The woman has iron deficiency anaemia that has failed to respond to treatment, and other causeshave been excluded. The timing of referral should reflect clinical judgement.

Alarm symptoms

Alarm symptoms or signs suggestive of gynaecological cancer include:Persistent intermenstrual or postcoital bleeding.An unexplained vulval lump or vulval bleeding due to ulceration.A palpable abdominal mass that is not obviously uterine fibroids.

A palpable abdominal mass that is not obviously uterine fibroids.If there are clinical features of cervical cancer, an urgent referral (within 2 weeks) should be made withoutthe need for a smear test, and regardless of previous smear results.For further information on when to refer to a specialist when a gynaecological cancer is suspected, seethe CKS topic on Gynaecological cancer ­ suspected (/gynaecological­cancer­suspected).

Basis for recommendation

These referral recommendations are based on Referral Advice: A guide to appropriate referral from generalto specialist services [NICE, 2001 (/menorrhagia#!references/A1784)] and Referral guidelines for suspectedcancer: quick reference guide [NICE, 2005a (/menorrhagia#!references/A14250)], both published by theNational Institute for Health and Care Excellence.

Specialist services are in a position to:Confirm, establish, or exclude a diagnosis. Investigations in secondary care include endometrialbiopsy, hysteroscopy, and/or pelvic ultrasound.Advise women on, and oversee where necessary, drug management.Discuss and undertake surgical operations, such as endometrial ablation and hysterectomy.

For more information on treatments that may be undertaken in secondary care, see Management insecondary care (/menorrhagia#!scenariorecommendation:6).

Secondary careWhat management is available in secondary care?

Secondary care investigationsWhat investigations can be carried out in secondary care?

An endometrial biopsy for histological examination should be taken to exclude endometrial cancer oratypical hyperplasia, if appropriate, for example in women:

With persistent intermenstrual bleeding.Aged 45 years and over.Whose treatment has failed or is ineffective.

Hysteroscopy allows direct visualisation of the uterine cavity and the opportunity to take an endometrialbiopsy. It is used as a diagnostic tool when ultrasound results are inconclusive, to determine the exactlocation of a fibroid or the exact nature of an abnormality.Dilatation and curettage (D and C) is no longer recommended as a diagnostic tool for heavy menstrualbleeding.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Secondary care drug treatments

Secondary care drug treatmentsWhat drug treatments are available in secondary care?

CKS recommends that therapy with gonadotrophin­releasing hormone (GnRH) analogues (for exampleleuprorelin and buserelin) should not be initiated in primary care.

They produce a profound hypogonadal effect through downregulation, resulting in no ovulation and nomenses.They may be used under specialist supervision before surgery or when all other treatment options foruterine fibroids, including surgery or uterine artery embolization, are contraindicated. They may also beused to produce temporary endometrial thinning and relief of bleeding before fibroid surgery.

GnRH analogues are effective at treating menorrhagia. Evidence from two randomized controlled trialshas shown that:

They are effective at reducing menstrual blood loss (RR 1.39, 95% CI 1.12 to 1.72).They cause amenorrhoea in most women (89%).

GnRH analogues can cause significant adverse effects that often limit their use. These are principallyperimenopausal in nature, including hot flushes, increased sweating, and vaginal dryness (due tooestrogen deficiency).GnRH analogues are given by subcutaneous or intramuscular injection, or intranasally, and they areusually used for less than 6 months. If treatment with these drugs is required for more than 6 months or ifadverse affects are experienced, 'add­back' treatment with supplemental oestrogens and progestogens isrecommended.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Secondary care surgical treatmentsWhat surgical treatments are available in secondary care?

Surgical treatments are almost always used as second­line options in the treatment of menorrhagia,despite the long­term effectiveness (and irreversible nature) of surgery. A systematic review found thatsurgery improved control of bleeding compared with pharmaceutical treatments after 5 years (OR 1.99,95% CI 0.84 to 4.73). However, this does not take into account the reversibility of pharmaceuticaltreatments and other risks with surgery.Surgery should be reserved for:

Use on the woman's request (following full counselling on the advantages and disadvantages).Difficult­to­treat cases where pharmaceutical treatment has failed to be sufficiently effective or iscontraindicated.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Endometrial ablation

Endometrial ablation involves destroying the endometrium (lining) and the superficial myometrium(muscle) of the uterus. The process also prevents the woman from having children in the future. The

technique was first developed in the mid­1990s, and has since evolved.First generation techniques consisted of transcervical resection with an electrosurgical loop to destroy

First generation techniques consisted of transcervical resection with an electrosurgical loop to destroytissue or the use of a heated rollerball. These require highly­trained surgeons and are nowrecommended only where hysteroscopic myomectomy is needed.Second generation techniques were developed to be simpler to use, and are now recommended asstandard. These include methods using thermal balloons, microwaves, radiowaves, and cryotherapy.

There is good evidence from controlled trials that endometrial ablation techniques lead to clinicallysignificant improvements in menstrual blood loss as well as improvements in quality of life. Endometrialablation is generally preferred to hysterectomy in most women, as it is a less drastic option. It isrecommended by the National Institute for Health and Care Excellence, provided:

Bleeding is having a severe negative impact on the woman's quality of life.Pharmaceutical treatment has been tried but was ineffective, or was not suitable, and a surgicalsolution is appropriate.The woman does not want to conceive in the future (although contraception may still be needed).The uterus is normal or has fibroids less than 3 cm in diameter, or is no bigger than a 10 weekpregnancy.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Hysterectomy

Hysterectomy is the surgical removal of the uterus and may also involve removal of the cervix, fallopiantubes, and/or ovaries (oophorectomy). It is a major surgical procedure with a risk of seriouscomplications. It requires weeks of physical recovery post­operatively and may have psychologicalcomplications.Hysterectomy was considered the only viable surgical treatment until the mid­1990s; however, sincethen, other effective techniques have become available. This is reflected in the numbers ofhysterectomies performed in the UK: 24,355 in 1993 compared with 10,559 in 2002 (most of thisreduction will have been due to alternative surgical treatments and improved pharmaceutical treatmentsfor menorrhagia).In general, other less invasive techniques are preferred to hysterectomy for the surgical treatment ofmenorrhagia, as it is beneficial for most women to retain their uterus. The National Institute for Health andClinical Excellence recommends that, after a thorough discussion with the woman about the benefits anddisadvantages of hysterectomy, it should be considered when:

The woman requests it.Other treatment options have failed, are contraindicated, or are declined by the woman.There is a wish for amenorrhoea, and the woman no longer wishes to retain her uterus or fertility.

Removal of the ovaries (oophorectomy) at the same time as hysterectomy is not recommended unless:There is a family history of breast or ovarian cancer (refer for genetic counselling first).There are symptoms related to ovarian dysfunction such as premenstrual syndrome (a trial ofpharmaceutical ovarian suppression should be used first).The woman expressly requests it (after appropriate counselling).

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Uterine artery embolization/myomectomy

Uterine artery embolization and myomectomy

Uterine artery embolization and myomectomy are both techniques primarily aimed at reducing the size of,or removing, uterine fibroids, but both have benefits in reducing menstrual blood loss. Previously,hysterectomy was seen as the only viable surgical option for these women.

Uterine artery embolization involves blocking the uterine arteries by injection of particles from acatheter inserted into the femoral artery, causing fibroids to shrink.Myomectomy is the surgical removal of fibroids through laparotomy, laparoscopically, orhysteroscopically. Its main disadvantage is that uterine fibroids can grow back, requiring furthersurgery.

The National Institute for Health and Care Excellence recommends that [National Collaborating Centrefor Women's and Children's Health, 2007 (/menorrhagia#!references/A26790)]:

Uterine artery embolization, myomectomy, or hysterectomy, should be considered when the womanhas large fibroids and heavy menstrual bleeding with other accompanying symptoms, such asdysmenorrhoea or pressure symptoms; or the woman has large fibroids that are causing bleeding thatis having a severe impact on the woman's quality of life.Myomectomy should be considered for women who want to retain their uterus.Uterine artery embolization is recommended for women who want to retain their uterus and avoidinvasive surgery.

Primary care treatments for menorrhagiaSummary of primary care treatments for menorrhagia

Table 1 (/menorrhagia#!prescribinginfosub/A­467850:1) shows the characteristics of pharmacologicalinterventions used to treat menorrhagia in primary care.

Table 1 . Drug treatments for menorrhagia in primary care.

Treatment Regimen, duration When toconsider?*

Contraceptive? Comment

Levonorgestrel­releasing intrauterinesystem

Intrauterine device,used for a minimum of6 months and replacedafter 5 years

Preferredchoice

Yes Requires fitting by aqualified practitioner Themost effectivepharmacologicaltreatment for reducingblood loss available inprimary care

Tranexamic acid Tablet taken for 3–4 days after start ofbleeding

Secondchoice

No Effective at reducingbleeding Can becombined with an NSAID

Nonsteroidal anti­

inflammatory drugs

Tablet taken for

duration of bleeding (orstarted just before)

Second

choice

No Reduces blood loss and

menstrual painMefenamic acid,

†

†

naproxen, or ibuprofenare recommended

Combined oralcontraceptive

Regular tablet takenthroughout cycle(except during the pill­free interval)

Secondchoice

Yes Reduces blood loss,regulates cycles, andreduces dysmenorrhoeaNumerous otheradvantages anddisadvantages

Oral norethisterone(high dose)

Tablet taken from days5–26 of the cycle

Thirdchoice

No Unpleasant adverseeffects, may not betolerated by somewomen

Depotmedroxyprogesteroneacetate

Intramuscular injection;lasts 12 weeks

Thirdchoice

Yes Likely to causeamenorrhoea

NSAID = nonsteroidal anti­inflammatory drug. * Depending on the individual wishes and characteristics ofthe woman. † First choice if the woman is awaiting investigation or if contraception is not desired. ‡ High­dose oral norethisterone is also useful to arrest exceptionally heavy bleeding ('flooding').

Data from: [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Levonorgestrel­releasing intrauterine system

For more information on the use of the levonorgestrel­releasing intrauterine system, see Scenario:Intrauterine system (/contraception­iusiud#!scenario) in the CKS topic on Contraception ­ IUS/IUD(/contraception­iusiud). This gives comprehensive information on the device, based on guidelines publishedby the National Institute for Health and Care Excellence [National Collaborating Centre for Women's andChildren's Health, 2005 (/menorrhagia#!references/A24606)], and the Faculty of Sexual and ReproductiveHealthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC)[FFPRHC, 2004 (/menorrhagia#!references/A12005)].

Who it is suitable forWhich women with menorrhagia is the levonorgestrel­releasing intrauterine system suitable for?

The levonorgestrel­releasing intrauterine system is regarded as the first­choice treatment formenorrhagia.It is a long­acting treatment, and the woman should be advised that it is intended for use for a minimumof 12 months.

Basis for recommendation

This information is taken from the clinical guideline on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007

‡

(/menorrhagia#!references/A26790)].

How it is usedHow is the levonorgestrel­releasing intrauterine system used in women with menorrhagia?

The levonorgestrel­releasing system (LNG­IUS) is marketed as Mirena in the UK and providescontraception as well as being an effective treatment for menorrhagia.The LNG­IUS should only be fitted by a suitably qualified practitioner after a full history and physicalexamination has been undertaken, to ascertain any contraindications that may make it unsuitable. If theexpertise is not available to fit the LNG­IUS, the woman should be referred to a family planning clinic fortreatment.The woman should be fully informed about the disadvantages as well as the benefits of the device.Consent (preferably written) should be obtained from the woman before fitting the device.Mirena is effective for 5 years, after which time it should be removed or replaced.

Basis for recommendationThis information is taken from the clinical guidelines The levonorgestrel–releasing intrauterine system incontraceptive and reproductive health and Intrauterine contraception issued by the Faculty of Sexual andReproductive Healthcare, formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC)[FFPRHC, 2004 (/menorrhagia#!references/A12005); FSRH, 2007 (/menorrhagia#!references/A37957)], andthe manufacturer's Summary of Product Characteristics [ABPI Medicines Compendium, 2012a(/menorrhagia#!references/A27362)].

Adverse effectsWhat are the adverse effects of the levonorgestrel­releasing intrauterine system?

The main initial adverse effect of the levonorgestrel­releasing intrauterine system (IUS) is a change inbleeding pattern, which may become irregular or heavy at first. Women should be advised to perseverewith treatment for a minimum of six cycles, as the benefit of treatment may not be seen until this point.Progestogenic adverse effects, such as breast tenderness and mood changes, are not usually markedwith the levonorgestrel­releasing IUS, because only small amounts of hormone are released directly totheir target of action (i.e. cervical mucous and endometrium). Functional ovarian cysts have occasionallybeen reported and normally resolve once treatment is stopped (ultrasound monitoring is recommended).Other adverse effects reported include abdominal pain, peripheral oedema, pelvic pain, back pain, and,rarely, hirsutism or hair loss, migraine, rash, or itching.

Basis for recommendationThis information is taken from the clinical guideline on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)] and the British National Formulary [BNF 63, 2012(/menorrhagia#!references/A68735)].

Tranexamic acid

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Who it is suitable forWhich women is tranexamic acid suitable for?

Tranexamic acid is suitable for women who:Do not want hormonal treatment (i.e. contraception), long­acting treatment, or invasive treatment.Do not have significant dysmenorrhoea.Are awaiting investigation or definitive treatment.

Women should be advised that tranexamic acid is a symptomatic treatment — it will reduce blood lossbut will not affect the underlying cause or directly benefit other symptoms, such as menstrual pain.Tranexamic acid is not suitable for the following groups of women [ABPI Medicines Compendium, 2011(/menorrhagia#!references/A69109)]:

Women with:A history of (or active) thromboembolic disease.Severe renal impairment (risk of accumulation).History of convulsions.Fibrinolytic conditions following consumption coagulopathy.

Women taking medication that can affect blood clotting (including the combined oral contraceptive).

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

How to prescribeHow should I prescribe tranexamic acid?

Treatment with tranexamic acid should only be started once heavy bleeding has started, whereupon two500 mg tablets should be taken three times a day, for up to 4 days. For very heavy menstrual bleeding,dose may be increased to a maximum of 4 g (8 tablets) daily [ABPI Medicines Compendium, 2011(/menorrhagia#!references/A69109)].The dose of tranexamic acid should be reduced in moderate renal insufficiency, and it should be avoidedin more severe disease. For more information, consult the Summary of Product Characteristics.Tranexamic acid can be used for an indefinite number of cycles as long as it is relieving heavy blood loss.However, if it is found to be ineffective, treatment should be stopped after 3 months.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

Adverse effectsWhat are the adverse effects of tranexamic acid?

Tranexamic acid is generally well tolerated, and adverse effects do not usually interfere with compliance,as the drug is taken only for a short duration each month.

Gastrointestinal effects, such as indigestion and diarrhoea, and headache are most common but affectless than 1% of women.Visual disturbances or thromboembolic events are very rare and require immediate cessation oftreatment.

treatment.

Basis for recommendationThis information is taken from the clinical guideline on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)] and the manufacturer's Summary of Product Characteristics [ABPIMedicines Compendium, 2011 (/menorrhagia#!references/A69109)].

Nonsteroidal anti­inflammatory drugs

A full discussion of the contraindications, adverse effects, monitoring issues, and interactions of nonsteroidalanti­inflammatory drugs (NSAIDs) is beyond the scope of this guidance. However, a summary of these aregiven in the following sections. For further information on prescribing mefenamic acid, naproxen oribuprofen, see the CKS topic on NSAIDs ­ prescribing issues (/nsaids­prescribing­issues).

Who it is suitable forWhich women are nonsteroidal anti­inflammatory drugs suitable for?

Nonsteroidal anti­inflammatory drugs (NSAIDs) are suitable for women who:Do not want hormonal treatment (i.e. contraception), long­acting treatment, or invasive treatment.Are awaiting investigation or definitive treatment.Have dysmenorrhoea.

Women should be advised that NSAIDs are a symptomatic treatment — they will reduce blood loss andmenstrual pain (dysmenorrhea) but will not affect the underlying cause.NSAIDs should be avoided or carefully monitored in women who:

Have previously experienced bronchospasm, urticaria, angioedema, rhinitis, or a severe skin reactionwith aspirin or an NSAID.Have a history of peptic ulceration or gastrointestinal bleeding, or are at risk of these conditions.Have asthma, hypertension, renal impairment, or heart failure.Are receiving low­dose aspirin.Are pregnant.

Basis for recommendationThis information is taken from the clinical guideline on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)] and the British National Formulary [BNF 63, 2012(/menorrhagia#!references/A68735)].

Choice of regimenWhich regimen of nonsteroidal anti­inflammatory drugs should I prescribe?

Mefenamic acid, naproxen, and ibuprofen are the recommended nonsteroidal anti­inflammatory drugs(NSAIDs) because:

They have been shown to be effective in controlled trials.They are all licensed for dysmenorrhoea. However, only mefenamic acid is specifically licensed formenorrhagia.

menorrhagia.Advise the woman to start the NSAID on the first day of bleeding and to continue until bleeding stops orreduces to satisfactory levels. The following doses are recommended:

Mefenamic acid — 500 mg three times daily.Naproxen — 500 mg as the first dose, then 250 mg every 6–8 hours.Ibuprofen — 400 mg three or four daily.

NSAIDs can be used for an indefinite number of cycles as long as they are relieving heavy blood loss andnot causing significant adverse effects. If they are found to be ineffective, treatment should be stoppedafter 3 months.

Basis for recommendationThe information on doses of NSAIDs is taken from the British National Formulary [BNF 63, 2012(/menorrhagia#!references/A68735)].The recommendation that NSAIDs can be used indefinitely if effective, but stopped after 3 months ifineffective, is based on the clinical guideline on Heavy menstrual bleeding, published by NICE [NationalCollaborating Centre for Women's and Children's Health, 2007 (/menorrhagia#!references/A26790)].

Adverse effectsWhat are the adverse effects of nonsteroidal anti­inflammatory drugs?

Generally speaking, the risk of severe adverse effects (gastrointestinal or cardiovascular) fromnonsteroidal anti­inflammatory drugs (NSAIDs) are reduced in people younger than 65 years of age whoare taking NSAIDs for short periods. Women receiving NSAIDs to reduce the symptoms of menorrhagiaon a monthly basis are unlikely to experience severe or life­threatening adverse effects.

The lowest dose and duration of NSAID therapy that adequately controls symptoms should be used.The most common adverse effects are indigestion or diarrhoea, which are rarely a cause for concern.Peptic ulceration is a rarer but more severe adverse effect. Women should be advised to stopmedication and seek advice if symptoms suggestive of a serious condition develop (for examplesevere gastric discomfort or blood in stools).

Basis for recommendationThis information is taken from the clinical guideline on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)] and Reminder: gastrointestinal toxicity and NSAIDs, published by theMedicines and Healthcare products Regulatory Agency (MHRA), formerly the Committee on Safety ofMedicines [CSM, 2003 (/menorrhagia#!references/A1882)].

Combined oral contraceptives

For more information on prescribing the combined oral contraceptive pill (COC), including details on theadvantages and disadvantages of the COC, and contraindications and adverse effects, see the Scenario:Combined oral contraceptive pill (/contraception­combined­hormonal­methods#!scenario) in the CKS topicon Contraception ­ combined hormonal methods (/contraception­combined­hormonal­methods). This givescomprehensive information on the COC, based on guidelines published by the National Institute for Healthand Care Excellence [National Collaborating Centre for Women's and Children's Health, 2005(/menorrhagia#!references/A24606)], and the Faculty of Sexual and Reproductive Healthcare [FSRH, 2011(/menorrhagia#!references/A68645)].

(/menorrhagia#!references/A68645)].

Who it is suitable forWhich women is the combined oral contraceptive suitable for?

The combined oral contraceptive (COC) is suitable for women who:Do not want to conceive, but do not desire long­term or invasive treatment.Desire improved cycle control.Have dysmenorrhoea but do not want to, or cannot, take nonsteroidal anti­inflammatory drugs.

Advise the woman that the COC has many benefits but also has some risks and disadvantages.See the section on advantages, disadvantages, and risks (/contraception­combined­hormonal­methods#!scenariorecommendation:22) in the CKS topic on Contraception ­ combined hormonalmethods (/contraception­combined­hormonal­methods) for detailed information on the advantages,disadvantages, and risks of combined oral contraceptives.

Basis for recommendationThis information is taken from the clinical guideline on Heavy menstrual bleeding, published by NICE[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

Prescribing choiceWhich combined oral contraceptive pill should I prescribe?

A monophasic combined oral contraceptive (COC) with 30­35 micrograms ethinylestradiol combinedwith norethisterone or levonorgestrel is recommended for women with menorrhagia [FSRH, 2011(/menorrhagia#!references/A68645)].

Norethisterone­ and levonorgestrel­containing COCs may have a lower relative risk ofthromboembolism than those containing desogestrel or gestodene, although the absolute risk is verysmall for all COCs (especially in younger women who do not smoke).There is no evidence from controlled trials about the effectiveness of COCs containing lessethinylestradiol (i.e. 20 micrograms) [National Collaborating Centre for Women's and Children'sHealth, 2007 (/menorrhagia#!references/A26790)]. However, although contraceptive efficacy is similarwith both doses, breakthrough bleeding is more common with the lower dose.There is no evidence to support the use of biphasic or triphasic over monophasic preparations.Qlaira is a quadraphasic combined oral contraceptive pill licensed for the treatment of heavymenstrual bleeding in women without organic pathology who desire oral contraception [ABPIMedicines Compendium, 2012b (/menorrhagia#!references/A67866)]. CKS found no studiescomparing its efficacy with other combined oral contraceptives.

How to prescribeHow should I prescribe the combined oral contraceptive pill?

Before prescribing the combined oral contraceptive (COC), blood pressure and body mass index shouldbe measured, and a full history should be taken, encompassing [FFPRHC, 2007(/menorrhagia#!references/A25332)]:

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(/menorrhagia#!references/A25332)]:General information on previous and existing medical conditions, and relevant family history.Specific questions about migraine, hyperlipidaemia, blood clotting disorders, hypertension, andsmoking status.Concomitant drug use, including non­prescription and herbal remedies.

Note: CKS does not recommend the use of the COC in girls aged less than 13 years, even if it is notbeing used as a contraceptive (see the section on Scenario: Prescribing to young people (/contraception­assessment#!scenario:3) in the CKS topic on Contraception ­ assessment (/contraception­assessment)).In practice, heavy menstrual bleeding is rare in this age group. If there is insufficient response totranexamic acid or nonsteroidal anti­inflammatory drugs, seek specialist advice.

Oral norethisterone

Who it is suitable forWhich women is oral norethisterone suitable for?

Oral norethisterone is regarded as a third­choice treatment by the National Institute for Health and CareExcellence. It is suitable for women in whom:

Other treatments (i.e. the levonorgestrel­releasing intrauterine system, tranexamic acid, nonsteroidalanti­inflammatory drugs, or combined oral contraceptives) are unsuitable or not wanted.Other treatments have been tried but are ineffective.

Advise the woman that the use of oral norethisterone to treat menorrhagia is not an effective method ofcontraception.Oral norethisterone can also quickly arrest severe acute menstrual bleeding ('flooding(/menorrhagia#!scenariorecommendation:4)').Oral norethisterone should be used with caution in women who have conditions that will worsen with fluidretention, including epilepsy, hypertension, migraine, and asthma. It should not be used in women with[ABPI Medicines Compendium, 2010 (/menorrhagia#!references/A69110); BNF 63, 2012(/menorrhagia#!references/A68735)]:

A history of, or predisposition to, thromboembolism.Liver cancer.Genital or breast cancer (unless progestogens are being used in the management of theseconditions).Severe arterial disease.Undiagnosed vaginal bleeding.Acute porphyria.A history during pregnancy of idiopathic jaundice, severe pruritus, or pemphigoid gestationis.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

How to prescribeHow should I prescribe oral norethisterone?

Prescribe a relatively high dose of oral norethisterone (5 mg three times daily) from days 5–26 of themenstrual cycle (the follicular and luteal phases). This is not a licensed regimen and requires informedconsent.

The licensed regimen of oral norethisterone, used only during the luteal phase (days 19–26) [ABPIMedicines Compendium, 2010 (/menorrhagia#!references/A69110)], is no longer recommended andshould be avoided, as it is ineffective.An extended trial of treatment with norethisterone is recommended, although there is no information onthe ideal duration of the course (but probably lasting several months).Higher doses are recommended if the woman has severe acute menstrual bleeding that requiresimmediate arresting; for more information, see Rapidly stopping heavy bleeding(/menorrhagia#!scenariorecommendation:4).

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Adverse effectsWhat are the adverse effects of oral norethisterone?

The most common adverse effects of oral norethisterone (affecting more than 1% of women) are weightgain, bloating, breast tenderness, headaches, and acne. These are usually transient and mild, but theyare unpleasant enough to be an important factor when choosing treatment.Depression is a rare adverse effect (affecting fewer than 1 in 10,000 women).

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

Long­acting progestogens

For more information on prescribing long­acting progestogens, see the section on Progestogen–onlyinjectable (/contraception­progestogen­only­methods#!scenario:2) in the CKS topic on Contraception ­progestogen­only methods (/contraception­progestogen­only­methods). This gives comprehensiveinformation based on guidelines published by the National Institute for Health and Care Excellence [NationalCollaborating Centre for Women's and Children's Health, 2005 (/menorrhagia#!references/A24606)] and theFaculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning andReproductive Healthcare (FFPRHC) [FSRH, 2009 (/menorrhagia#!references/A58153)].

Who it is suitable forWhich women is a long­acting progestogen suitable for?

A long­acting progestogen is regarded as a third­choice treatment by the National Institute for Health andCare Excellence. It is suitable for women in whom:

Treatment with other drugs (i.e. the levonorgestrel­releasing intrauterine system, tranexamic acid,nonsteroidal anti­inflammatory drugs, or combined oral contraceptives) is unsuitable or not wanted.Other treatments have been tried but are ineffective.Long­term contraception is desired, with the possibility of amenorrhoea.

Prescribing choiceWhich long­acting progestogen should I prescribe?

Medroxyprogesterone acetate (Depo­Provera ) is the recommended long­acting progestogen. It is givenas an intramuscular injection and provides treatment of menorrhagia and contraception for 12 weeks:

No long­acting progestogens are licensed for the treatment of menorrhagia, and informed consentshould be sought before proceeding with treatment.

Two other options are available, but they have not been specifically recommended by the NationalInstitute for Health and Care Excellence:

A depot injection of 200 mg norethisterone enantate (Noristerat ) provides 8 weeks of contraceptivecover.A subdermal implant of etonogestrel (Implanon ) provides up to 3 years of contraceptive cover.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

How to prescribeHow should I prescribe depot medroxyprogesterone acetate?

Before administering depot medroxyprogesterone acetate (Depo­Provera ), take a full history to excludepregnancy and comorbid conditions which preclude use of the drug. The woman should be fully informedabout the advantages and disadvantages of treatment.

Other than being effective at reducing menorrhagia, long­acting progestogens are also very effectivecontraceptives which are usually well tolerated.A major disadvantage is that it may take up to 1 year for fertility to return after stopping treatment. Inaddition, not all women desire amenorrhoea.Other possible adverse effects include weight gain, erratic menstrual bleeding for the first few months,and bone thinning.

[National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

When to combine treatmentWhen should treatment be combined in women with menorrhagia?

Treatment can be combined when initiating pharmaceutical therapy, or an additional drug can be addedto the initial treatment if improvement in symptoms is not satisfactory.

Tranexamic can be combined with a nonsteroidal anti­inflammatory drug (NSAID) if menstrualbleeding and dysmenorrhoea are problematic.An NSAID may be used with a combined oral contraceptive (COC), especially if dysmenorrhoea isproblematic.

Do not combine tranexamic acid with the COC or the levonorgestrel intrauterine system (LNG­IUS).There are no recommendations on whether an NSAID may be combined with the LNG­IUS, although inpractice this is probably acceptable.If combined medication is being considered because bleeding or pain is very severe, reconsider thecause, and consider referral (/menorrhagia#!scenariorecommendation:5).

Basis for recommendationThese are pragmatic recommendations from CKS, and are based on standard practice in response to

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These are pragmatic recommendations from CKS, and are based on standard practice in response tocommon clinical situations, taking into account documented contraindications and drug interactions. Theyare consistent with the clinical guideline Heavy menstrual bleeding published by the National Institute forHealth and Care Excellence [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)].

CKS could find no guidelines, reviews, or controlled trials on the safety or effectiveness of combiningdrugs to treat menorrhagia.Tranexamic acid is at least as effective as NSAIDs at reducing blood loss, but does not relieve menstrualpain. Therefore, a practical approach is to combine both treatments when bleeding is substantial and thewoman has dysmenorrhea.

CKS did not find any evidence that these drugs interact.Tranexamic acid is limited to a (maximum) four­day regimen. Therefore it is practical to use an NSAIDif additional coverage is needed.Some clinicians will start with an NSAID and only add in tranexamic acid if bleeding remainsproblematic.

Tranexamic acid should not be combined with the COC, as theoretically there is an increased risk ofthrombosis, although this has not been reported in practice [ABPI Medicines Compendium, 2011(/menorrhagia#!references/A69109)].There is no advice on what additional treatment may be used in conjunction with the LNG­IUS.

It is important to monitor the effectiveness of the LNG­IUS, especially during the first 6 months. Thereis a risk that tranexamic acid or an NSAID could mask a poor response to treatment with LNG­IUS.In practice, many women will use an NSAID for associated dysmenorrhoea, especially ibuprofen,which is available over­the­counter.

Supporting evidence

Comparison of drugs that reduce blood lossComparative efficacy of drugs in primary care at reducing blood loss

Table 1 (/menorrhagia#!supportingevidence1/A­282451:1) shows the relative effectiveness ofpharmacological treatments in reducing menstrual blood loss.

Table 1 . Summary of evidence base for pharmacological interventions in menorrhagia.

Treatment Reductionin bloodloss (%)

Source ofevidence

Additional comment

Levonorgestrel­releasingintrauterine system

71–90 Several high­quailty RCTs

Compared favourably with other treatments in head­to­head trials in terms of effectiveness and patientsatisfaction

Tranexamic acid 29–58 Several high­quality RCTs

No long­term outcomes have been reported

Nonsteroidal anti­

inflammatory drugs

20–49 Several high­

quality RCTs

Mefenamic acid most effective, ibuprofen significantly

less effective Also effective treatment for menstrualpain

Combined oral 43 One small Other benefits including regulation of cycles and

Combined oralcontraceptive

43 One smallRCT (n = 45)

Other benefits including regulation of cycles andreduction in breast pain

High­dose oralprogestogen*

83 One smallRCT (n = 44)

Not as effective or preferred as the levonorgestrel­releasing intrauterine system Requires long­term use

Long­actingprogestogen

22–47 No directevidencefrom RCTs

Data extrapolated from large trials of womenrequiring long­term contraception

Danazol About 50 Several high­quality RCTs

Use limited by frequent, clinically significant adverseeffects

Etamsylate About 13 Several high­quality RCTs

Least effective treatment for menorrhagia

RCT = randomized controlled trial * Use in both the follicular and luteal phases. Use in the luteal phaseonly is ineffective. † Figure relates to the proportion of women with amenorrhoea after 1–2 years of usewith depot medroxyprogesterone acetate.

Data from: [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]

Drugs to treat menorrhagiaEvidence on individual drugs to treat menorrhagia

The supporting evidence in this section is based mainly on the evidence reviews and statements from theclinical guidelines on Heavy menstrual bleeding, published by the National Institute for Health and CareExcellence [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]. For details of the primary studies and systematic reviews that NICEused to make their recommendations and a full bibliography, see their full guideline at www.nice.org.uk(http://www.nice.org.uk/guidance/CG44/guidance/pdf/English).

Subsequent to the publication of the NICE clinical guidelines on Heavy menstrual bleeding, CKSidentified other studies conducted on drugs to treat menorrhagia. These studies have been incorporatedinto the relevant evidence sections.

Levonorgestrel­releasing intrauterine systemEvidence on the levonorgestrel­releasing intrauterine system

The LNG­IUS has local and systemic hormonal effects, and inhibits endometrial proliferation, thickens thecervical mucous, and, in a small proportion of women, inhibits ovulation.The system is most useful in women seeking contraception over longer time frames (it is licensed for5 years).

The LNG­IUS has been shown to be effective by several randomized controlled trials (RCTs) and byuncontrolled case series. The National Institute for Health and Clinical Excellence identified twosystematic reviews and a subsequent RCT.

One systematic review combined RCTs in a meta­analysis and found LNG­IUS compared favourably

†

One systematic review combined RCTs in a meta­analysis and found LNG­IUS compared favourablyto other forms of pharmaceutical interventions.

Amenorrhoea was greater after 3 months (OR 8.67, 95% CI 1.52 to 49.35) compared with all othertreatments.The proportion of woman unwilling to continue treatment was lower (OR 0.27, 95% CI 0.10 to 0.67)compared with all other treatments.

One systematic review and a subsequent RCT did not combine data in a meta­analysis, but reportedreductions in mean blood loss by LNG­IUS ranging from 71–96% in various RCTs.For a comparison with other pharmacological treatments, see Drugs in reducing blood loss(/menorrhagia#!supportingevidence1).

Subsequent to NICE, CKS identified three systematic reviews and one RCT on the use of the LNG­IUSfor treating heavy menstrual bleeding.

One systematic review analyzed the available literature for economic and health­related quality of lifeoutcome data associated with the use of the LNG­IUS in the management of heavy menstrualbleeding. The authors reported that treating heavy menstrual bleeding with the LNG­IUS was cost­effective, and that irrespective of the measuring instrument used, health­related quality­of­lifeoutcomes were found to be improved to a degree similar to (or in some cases more than) thatachieved with a hysterectomy or endometrial ablation [Blumenthal et al, 2011(/menorrhagia#!references/A68919)].Another systematic review analyzed five trials investigating the effect of the LNG­IUS on idiopathicmenorrhagia in 230 women. Results showed that after year 2 and year 5, the decrease in menstrualblood loss was greater than 96%. Also, haemoglobin and serum ferritin levels increased significantly[Endrikat et al, 2012 (/menorrhagia#!references/A68916)].The third systematic review analyzed the available evidence on the risks and benefits of using theLNG­IUS in the treatment of heavy menstrual bleeding, compared with other medical treatments,including combined oral contraceptives, oral progestogens, tranexamic acid, mefenamic acid, andendometrial ablation. Results showed that the LNG­IUS reduced menstrual blood loss to a greaterextent than other medical treatments except endometrial ablation (menstrual blood loss was reducedto a similar extent). The authors concluded that the LNG­IUS was an effective option for treating heavymenstrual bleeding, even for women with underlying pathology or bleeding disorders [Kaunitz and Inki,2012 (/menorrhagia#!references/A68910)].The RCT (n = 165) compared the efficacy and safety of the LNG­IUS with oral medroxyprogesteroneacetate in the treatment of idiopathic heavy menstrual bleeding. The results showed that the LNG­IUSreduced menstrual blood loss more effectively (–128.8 mL, range –393.6 to +1242.2 mL) than oralmedroxyprogesterone acetate (–17.8 mL, range –271.5 to +78.6mL, p < 0.001). The LNG­IUS alsohad a higher likelihood of treatment success (84.8%) compared with oral medroxyprogesteroneacetate (22.2%, p < 0.001) [Kaunitz et al, 2010 (/menorrhagia#!references/A68926)].

Tranexamic acidEvidence on tranexamic acid

Tranexamic acid is an antifibrinolytic agent which affects uterine haemostasis and reduces bleeding. Itdoes not alter the underlying pathology of the condition or reduce symptoms other than blood loss.There is good evidence from randomized controlled trials (RCTs) that tranexamic acid is effective atreducing blood loss. The National Institute for Health and Care Excellence identified three systematicreviews. Although each review had different methodologies and inclusion criteria (some included womenwith intrauterine devices), all concurred that tranexamic acid offered a clinically significant benefit in

with intrauterine devices), all concurred that tranexamic acid offered a clinically significant benefit inreducing blood loss.

Overall, tranexamic acid, taken at a dose of 2.0 to 4.5 grams per day, for 3–5 days, reduced blood lossby 29 to 58%.However, there were no long­term studies on effectiveness.For a comparison with other pharmacological treatments, see Drugs in reducing blood loss(/menorrhagia#!supportingevidence1).

Subsequent to NICE, CKS identified two systematic reviews and two RCTs on the use of tranexamic acidfor treating heavy menstrual bleeding.

One systematic review looked at the use of tranexamic acid in the treatment of heavy menstrualbleeding and concluded that tranexamic acid is well tolerated, cost effective, and reduces menstrualblood loss by 34 to 59%. It improves health­related quality of life in women with heavy menstrualbleeding, and is especially useful in women who do not wish to take (or cannot take) hormonalcontraception [Lumsden and Wedisinghe, 2011 (/menorrhagia#!references/A68917)].The second systematic review [Naoulou and Tsai, 2012 (/menorrhagia#!references/A68915)]assessed the efficacy of tranexamic acid in the treatment of idiopathic and non­functional heavymenstrual bleeding, compared with other medical treatments. The evidence showed that tranexamicacid resulted in:

A 34–54% reduction in menstrual blood loss.A 46–83% improvement in the measured quality­of­life parameters, compared with 15–45% for oralnorethisterone treatment.A 70% decrease in blood loss compared with placebo (p < 0.001).A potential benefit in fibroid patients with menorrhagia (limited evidence, further studies areneeded).

One RCT (n = 189) assessed the efficacy and safety of tranexamic acid in the treatment of heavymenstrual bleeding compared with placebo [Lukes et al, 2010 (/menorrhagia#!references/A68925)].Results showed that:

The women in the tranexamic acid group had a significantly greater reduction in menstrual bloodloss of 69.6 mL (40.4%) compared with 12.6 mL (8.2%) in the placebo group (p < 0.001).Compared with the placebo group, the tranexamic acid group experienced significant improvementsin limitations in social or leisure and physical activities (p < 0.005), and self­perceived menstrualblood loss (p < 0.01).Most of the adverse effects reported were mild to moderate in severity, and the incidence ofgastrointestinal adverse events was comparable with placebo.

One RCT (a multicentre, long­term, open­label study) assessed the long­term safety of tranexamicacid [Muse et al, 2011 (/menorrhagia#!references/A68923)]. Safety was assessed by treatment­emergent adverse event monitoring, physical examinations, laboratory results, ophthalmologicexaminations, and electrocardiography. Results showed that:

The majority of the treatment­emergent adverse events were mild to moderate in severity and werelargely considered unrelated to study treatment. The most commonly reported treatment­emergentadverse events among women in the intent­to­treat population (n = 723) were headache, menstrualdiscomfort, and back pain.Long term treatment with tranexamic acid was well tolerated and improved measures of health­related quality of life in women with cyclic heavy menstrual bleeding.

Nonsteroidal anti­inflammatory drugsEvidence on nonsteroidal anti­inflammatory drugs

It is probable that the mechanism of action of NSAIDs in menorrhagia is due to their inhibition ofcyclooxygenase, an enzyme involved in prostaglandin synthesis. Prostaglandins are implicated ininflammatory response, pain pathways, uterine bleeding, and uterine cramps.There is evidence from two systematic reviews identified by the National Institute for Health and CareExcellence (NICE) that NSAIDs are effective at reducing blood loss in women with menorrhagia. Bothreviews concluded that NSAIDs produced a clinically significant reduction in blood loss, varying between20–49%, depending on the study.

NSAIDs were not found to be as effective as tranexamic acid or the synthetic steroid danazol.However, they were found to be as well tolerated as tranexamic acid and better tolerated thandanazol.For a comparison with other pharmacological treatments, see Drugs in reducing blood loss(/menorrhagia#!supportingevidence1).

The choice of NSAID for the treatment of menorrhagia with associated menstrual pain is based onevidence from one of the systematic reviews identified by NICE.

Mefenamic acid is licensed for the treatment of menorrhagia and has been shown to be effective inrandomized controlled trials, reducing menstrual blood loss (MBL) by 29.0% (95% CI 27.9 to 30.2%).Naproxen and ibuprofen are not licensed for menorrhagia but are licensed for dysmenorrhoea.Naproxen has been shown to have similar effectiveness as mefenamic acid (reduction in MBL 26.4%,95% CI 24.6 to 28.3%). Ibuprofen is probably less effective (MBL 16.2%, 95% CI 13.6 to 18.7%).However, ibuprofen has a relatively good safety profile and can be considered an option if it is found tobe effective in the individual woman.Diclofenac was also found to be effective by two trials (reduction in MBL 26.9%, 95% CI 23.3 to30.6%). However, it is not licensed for the treatment of menorrhagia or dysmenorrhoea.

Combined oral contraceptivesEvidence on combined oral contraceptives

The combined oral contraceptive (COC) is believed to work by causing regular blood loss and a thinnerendometrium. The withdrawal bleed is thus less than that seen during a normal cycle.There is relatively little evidence from randomized controlled trials (RCTs) to verify the effectiveness oftreatment with COCs on blood loss, although the use of the COC in dysmenorrhoea is an acceptedclinical practice. The National Institute for Health and Care Excellence found two systematic reviews,which in turn identified a solitary RCT (n = 45) that compared use of the COC (ethinylestradiol, 30micrograms, combined with levonorgestrel, 150 micrograms) with naproxen, mefenamic acid, anddanazol.

The COC reduced mean blood loss by 43%, which was greater than naproxen, but less thanmefenamic acid or danazol.The dose of ethinylestradiol used is greater than some COCs available (no trials were found that usedthe 20 microgram dose).For a comparison with other pharmacological treatments, see Drugs in reducing blood loss(/menorrhagia#!supportingevidence1).

Subsequent to NICE, CKS identified two RCTs and a pooled analysis (of two RCTs) on the use ofcombined oral contraceptives for treating heavy menstrual bleeding.

One double­blind RCT (n = 231) investigated the efficacy and safety of estradiol valerate/dienogestcompared with placebo for the treatment of heavy idiopathic menstrual bleeding [Fraser et al, 2011a(/menorrhagia#!references/A68922)]. The primary end­point was the proportion of women with a return

(/menorrhagia#!references/A68922)]. The primary end­point was the proportion of women with a returnto 'menstrual normality' during a 90­day efficacy phase. Secondary end­points included changes inmenstrual blood loss, and iron metabolism parameters.

The mean reduction in menstrual blood loss in the estradiol valerate/dienogest group was 69.4%(median 79.2%) compared with 5.8% (median 7.4%) in the placebo group.The mean adjusted between­treatment difference in the menstrual blood loss volume was 373 ml infavour of estradiol valerate/dienogest (95% confidence interval 490, 255 ml; p < 0.0001).There were significant improvements in iron metabolism with estradiol valerate/dienogest but notwith placebo.Serious adverse events occurred in both the groups (each n = 2). A total of 14 women (9.7%) in theestradiol valerate/dienogest group and 5 women (6.2%) in the placebo group prematurelydiscontinued treatment due to adverse events, headache being the most prevalent.

Another double­blind RCT investigated the efficacy of an estradiol valerate/dienogest oralcontraceptive regimen in women with heavy and/or prolonged menstrual bleeding without organicpathology (the regimen was designed to deliver oestrogen in a step­down and progestogen in a step­up manner through each 28–day treatment cycle) [Jensen et al, 2011(/menorrhagia#!references/A68909)]. The study randomized women aged 18 years or older withprolonged, frequent, or heavy menstrual bleeding to treatment with estradiol valerate/dienogest orplacebo (ratio 2:1 respectively) for 196 days. The primary variable was complete resolution ofqualifying abnormal menstrual symptoms, including a 50% or greater reduction in pretreatmentmenstrual blood loss volume in women with heavy menstrual bleeding.

There were no marked differences in the characteristics of estradiol valerate/dienogest (n = 120)and placebo (n = 70) recipients.The proportion of complete responders was significantly higher in the estradiol valerate/dienogestgroup (35/120; 29.2%) compared with the placebo group (2/70, 2.9%, p < 0.001) in the intention totreat population. This was also the case when results were analyzed in the population ofparticipants with evaluable data (35/80; 43.8%) compared with the placebo group (2/48, 4.2%,p < 0.001).The mean reduction in menstrual blood loss in the estradiol valerate/dienogest group from the run­in phase to the efficacy phase was substantial (­353 mL [309 mL]; mean ­64.2%; median ­70.6%)and significantly greater than that in the placebo group (­130 mL [338 mL]; mean ­7.8%; median­18.7%; p < 0.001).Significant improvements in haemoglobin, haematocrit, and ferritin were seen with estradiolvalerate/dienogest, but not with placebo.

The pooled analysis assessed the efficacy of estradiol valerate/dienogest for the treatment of heavyand/or prolonged menstrual bleeding without organic pathology based on the analysis of data from twoidentically designed double­blind RCTs [Fraser et al, 2011b (/menorrhagia#!references/A69220)].Women aged 18 years and over with heavy and/or prolonged menstrual bleeding were randomized toestradiol valerate/dienogest (n = 269) or placebo (n = 152) for 196 days during which changes inmenstrual blood loss were assessed. The pooled analysis showed that:

Estradiol valerate/dienogest rapidly reduces blood loss in women with heavy and/or prolongedmenstrual bleeding. This effect is achieved at the first withdrawal bleed after treatment is initiatedand is sustained for the duration of the treatment.The reduction in menstrual blood loss was also associated with a decrease in the number ofsanitary protection items used and an improvement in iron metabolism parameters.

Both RCTs and the pooled analysis showed that estradiol valerate/dienogest is an effective treatmentin women with heavy and/or prolonged menstrual bleeding without organic pathology. However, furtherstudies are needed to compare estradiol valerate/dienogest with other medical treatments for heavymenstrual bleeding.

Oral norethisteroneEvidence on oral norethisterone

Progesterone is secreted in the luteal phase of the ovarian cycle and is responsible for the secretoryphase of the endometrium. Norethisterone is an analogue of progesterone (i.e. a progestogen). However,its mechanism of action in preventing menorrhagia is not fully understood.Evidence from randomized controlled trials (RCTs) to support the use of oral progestogens is limited. TheNational Institute for Health and Clinical Excellence identified two systematic reviews and an RCT thatinvestigated their efficacy.

The systematic reviews focussed on the use of progestogens used exclusively during the luteal phaseof the ovarian cycle. One review concluded that progestogens had no significant effect on blood loss.The other review found that all the active drugs norethisterone was compared with produced a greaterreduction in blood loss.One RCT investigated the long­term effect of norethisterone used during the follicular and luteal phasecompared with the levonorgestrel intrauterine system (LNG­IUS).

Norethisterone caused an 83% reduction in blood loss, which was less than that for LNG­IUS(94%).More women were satisfied with LNG­IUS (66%) than norethisterone (22%).

Progestogens other than norethisterone may also be effective in treating menorrhagia, but have not beenstudied. For a comparison of norethisterone with other pharmacological treatments, see Drugs inreducing blood loss (/menorrhagia#!supportingevidence1).

Long­acting progestogensEvidence on long­acting progestogens

Long­acting progestogens have an extended duration of action that allows for much less frequent dosing,which some women may prefer. Their prolonged duration of action often results in long­termamenorrhoea (absence of periods).The National Institute for Health and Care Excellence (NICE) did not find any direct evidence fromrandomized controlled trials (RCTs) on the use of long­acting progestogens in the treatment ofmenorrhagia. Instead, evidence was extrapolated from studies that used amenorrhoea as an outcome,taken from the NICE guideline Long­acting reversible contraception [NICE, 2005b(/menorrhagia#!references/A25640)].

One large RCT (n = 3172) found that medroxyprogesterone acetate caused amenorrhoea in 12% ofwomen within the first year of use, and 24% in the second year of use.In another large RCT (n = 1216) of women mainly from the developing world, 10% experiencedamenorrhoea after 3 months, increasing to 41–47% after 1 year.

For a comparison of the effectiveness of long­acting progestogens compared with other pharmacologicaltreatments, see Drugs in reducing blood loss (/menorrhagia#!supportingevidence1).

Danazol and etamsylate (not recommended)Evidence on danazol and etamsylate (not recommended)

Danazol is a synthetic androgenic steroid with anti­oestrogenic and anti­progestogenic properties. Itinhibits proliferation of the endometrium:

The National Institute for Health and Care Excellence (NICE) identified two systematic reviews and asubsequent primary study that showed danazol is an effective treatment in reducing blood loss.

Danazol was found to reduce blood loss by about 50%.Danazol was found to be more effective than nonsteroidal anti­inflammatory drugs (NSAIDs) orprogestogens. However, it also caused significantly more adverse effects than these drugs. Someof these adverse effects are severe enough to warrant stopping treatment (mainly androgenic­related adverse effects).

After analyzing the benefit–risk ratio and considering the availability of other treatments, NICEconcluded that danazol should not be recommended for the treatment of menorrhagia.

Etamsylate reduces capillary bleeding by correcting anomalies of platelet adhesion without undulyaffecting the fibrin cascade.

NICE identified three systematic reviews that assessed the use of etamsylate. Together, these foundthat:

Etamsylate reduced menstrual blood loss by an average of 13%.Etamsylate was not as effective as NSAIDs or antifibrinolytic drugs.

NICE concluded that, given the other drug treatments available, etamsylate was not effective enoughto be recommended.

For a comparison of the effectiveness of danazol and etamsylate with other pharmacological treatments,see Drugs in reducing blood loss (/menorrhagia#!supportingevidence1).

Search strategy

Scope of searchA literature search was conducted for guidelines, systematic reviews and randomized controlled trials onprimary care management of menorrhagia.

Search dates2007 ­ July 2012

Key search termsVarious combinations of searches were carried out. The terms listed below are the core search terms thatwere used for Medline.

exp Menorrhagia/, menorrhagia.tw., heavy menstrual bleeding.tw.

Table 1 . Key to search terms.

Searchcommands

Explanation

/ indicates a MeSh subject heading with all subheadings selected

.tw indicates a search for a term in the title or abstract

exp indicates that the MeSH subject heading was exploded to include the narrower, morespecific terms beneath it in the MeSH tree

$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)

Sources of guidelinesNational Institute for Health and Care Excellence (NICE) (http://www.nice.org.uk)Scottish Intercollegiate Guidelines Network (SIGN) (http://www.sign.ac.uk)Royal College of Physicians (http://www.rcplondon.ac.uk/)Royal College of General Practitioners (http://www.rcgp.org.uk/)Royal College of Nursing (http://www.rcn.org.uk/development/practice/clinicalguidelines)NICE Evidence (https://www.evidence.nhs.uk/topics/)Health Protection Agency (http://www.hpa.org.uk)World Health Organization (http://www.who.int)National Guidelines Clearinghouse (http://www.guideline.gov)Guidelines International Network (http://www.g­i­n.net)TRIP database (http://www.tripdatabase.com)GAIN (http://www.gain­ni.org/index.php/audits/guidelines)NHS Scotland National Patient Pathways (http://www.pathways.scot.nhs.uk/)New Zealand Guidelines Group (http://www.nzgg.org.nz)Agency for Healthcare Research and Quality (http://www.ahrq.gov/)Institute for Clinical Systems Improvement (http://www.icsi.org)National Health and Medical Research Council (Australia)(http://www.nhmrc.gov.au/publications/index.htm)Royal Australian College of General Practitioners (http://www.racgp.org.au/your­practice/guidelines/)British Columbia Medical Association (http://www.health.gov.bc.ca/gpac/index.html)Canadian Medical Association (http://www.cma.ca/index.php/ci_id/54316/la_id/1.htm)Alberta Medical Association (http://www.topalbertadoctors.org/cpgs.php)University of Michigan Medical School (http://ocpd.med.umich.edu/cme/self­study/)Michigan Quality Improvement Consortium (http://mqic.org/guidelines.htm)Singapore Ministry of Health(http://www.moh.gov.sg/content/moh_web/home/Publications/guidelines/cpg.html)National Resource for Infection Control (http://www.nric.org.uk)Patient UK Guideline links (http://www.patient.co.uk/guidelines.asp)UK Ambulance Service Clinical Practice Guidelines(http://www2.warwick.ac.uk/fac/med/research/hsri/emergencycare/jrcalc_2006/guidelines/)RefHELP NHS Lothian Referral Guidelines (http://www.refhelp.scot.nhs.uk/index.php?option=com_content&task=view&id=490&Itemid=104)Medline (with guideline filter)Driver and Vehicle Licensing Agency (http://www.dft.gov.uk/dvla/medical/ataglance.aspx)NHS Health at Work (http://www.nhshealthatwork.co.uk/oh­guidelines.asp) (occupational health practice)

Sources of systematic reviews and meta­analysesThe Cochrane Library (http://www.thecochranelibrary.com) :

Systematic reviewsProtocolsDatabase of Abstracts of Reviews of Effects

Medline (with systematic review filter)EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisalsNIHR Health Technology Assessment programme (http://www.hta.ac.uk/)

NIHR Health Technology Assessment programme (http://www.hta.ac.uk/)The Cochrane Library (http://www.thecochranelibrary.com) :

NHS Economic EvaluationsHealth Technology Assessments

Canadian Agency for Drugs and Technologies in Health (http://www.cadth.ca)International Network of Agencies for Health Technology Assessment (http://www.inahta.org)

Sources of randomized controlled trialsThe Cochrane Library (http://www.thecochranelibrary.com) :

Central Register of Controlled TrialsMedline (with randomized controlled trial filter)EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summariesBandolier (http://www.medicine.ox.ac.uk/bandolier/)Drug & Therapeutics Bulletin (http://dtb.bmj.com/)TRIP database (http://www.tripdatabase.com)Central Services Agency COMPASS Therapeutic Notes (http://www.medicinesni.com/courses/type.asp?ID=CN)

Sources of national policyDepartment of Health (http://www.dh.gov.uk)Health Management Information Consortium (HMIC)

Patient experiencesHealthtalkonline (http://www.healthtalkonline.org/)BMJ ­ Patient Journeys (http://www.bmj.com/bmj­series/patient­journeys)Patient.co.uk ­ Patient Support Groups (http://www.patient.co.uk/selfhelp.asp)

Sources of medicines informationThe following sources are used by CKS pharmacists and are not necessarily searched by CKS informationspecialists for all topics. Some of these resources are not freely available and require subscriptions toaccess content.

British National Formulary (http://bnf.org/bnf/) (BNF)electronic Medicines Compendium (http://www.medicines.org.uk) (eMC)European Medicines Agency (http://www.ema.europa.eu/ema/) (EMEA)LactMed (http://toxnet.nlm.nih.gov/cgi­bin/sis/htmlgen?LACT)Medicines and Healthcare products Regulatory Agency (http://www.mhra.gov.uk/index.htm) (MHRA)REPROTOX (http://www.reprotox.org/Default.aspx)Scottish Medicines Consortium (http://www.scottishmedicines.org.uk/Home)Stockley's Drug Interactions (https://www.medicinescomplete.com/mc/stockley/current/login.htm?uri=http%3A%2F%2Fwww.medicinescomplete.com%2Fmc%2Fstockley%2Fcurrent%2F)TERIS (http://depts.washington.edu/terisweb/teris/)TOXBASE (http://www.toxbase.org/)Micromedex (http://www.micromedex.com/products/hcs/)UK Medicines Information (http://www.ukmi.nhs.uk/)

Menorrhagia ­ Summary

Menorrhagia is excessive (heavy) menstrual bleeding (periods) over several consecutive cycles thatinterferes with the woman's physical, emotional, social, and material quality of life.

interferes with the woman's physical, emotional, social, and material quality of life.About one third of women describe their periods as heavy, and 1 in 20 women aged 30–49 years consulttheir GP each year regarding heavy menstruation.In 40–60% of women with menorrhagia, no underlying cause is found (dysfunctional uterine bleeding).Underlying causes of menorrhagia include:

Uterine and ovarian pathologies such as uterine fibroids, endometriosis, and pelvic inflammatorydisease.Systemic diseases and disorders such as coagulation disorders, hypothyroidism, and liver or kidneydisease.Iatrogenic causes such as anticoagulant treatment or chemotherapy.

Menorrhagia may negatively affect quality of life by limiting normal activities, social life, and work. Sex­lifemay also be affected. Iron deficiency anaemia occurs in about two thirds of women with heavy menstrualbleeding.Menorrhagia is diagnosed when both the woman and the clinician agree that menstrual bleeding isheavy. Blood loss does not need to be measured accurately.

A full blood count should be performed in all women with suspected menorrhagia to rule out irondeficiency anaemia.Other investigations are not routinely indicated.

Red flag symptoms that suggest an underlying pathology (such as pelvic inflammatory disease,endometriosis, or endometrial cancer) include:

Persistent postcoital bleeding.Persistent intermenstrual bleeding.Dyspareunia.Dysmenorrhoea.Pelvic pain.Vaginal discharge.

The levonorgestrel­releasing intrauterine system (LNG­IUS) (Mirena®) is the preferred first­linemanagement. If this is unsuitable tranexamic acid, nonsteroidal anti­inflammatory drugs, or the combinedoral contraceptive should be considered.Referral for screening and pelvic examination may be necessary if:

There are alarm symptoms suggesting a possible malignancy.Initial treatment has proved ineffective.The woman wishes to consider surgical treatment.Iron deficiency anaemia has failed to respond to treatment.

Secondary care options for management include surgery (endometrial ablation, hysterectomy, uterineartery embolization and myomectomy) or drug treatment with gonadotrophin­releasing hormoneanalogues.

Have I got the right topic?

Age from 12 years onwards (Female)

This CKS topic covers the medical management of menorrhagia (heavy menstrual bleeding).

This CKS topic is based on the clinical guideline Heavy menstrual bleeding, developed by the NationalCollaborating Centre for Women's and Children's Health and published by the National Institute for Healthand Care Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2007(/menorrhagia#!references/A26790)]. Detailed information about contraceptives that are recommended forthe treatment of menorrhagia is available in the section on Menorrhagia, fibroids, previous ectopic

the treatment of menorrhagia is available in the section on Menorrhagia, fibroids, previous ectopicpregnancy (/contraception­assessment#!scenariorecommendation:13) in the CKS topic on Contraception ­assessment (/contraception­assessment).

This CKS topic does not cover the management of intermenstrual or irregular bleeding, postcoital bleeding,postmenopausal bleeding, or menopausal symptoms.

There are separate CKS topics on Amenorrhoea (/amenorrhoea), Anaemia ­ iron deficiency (/anaemia­iron­deficiency), Dysmenorrhoea (/dysmenorrhoea), Endometriosis (/endometriosis), Infertility (/infertility), andMenopause (/menopause); there is also a referral guideline, published by NICE, for Gynaecological cancer ­suspected (/gynaecological­cancer­suspected).

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, andproviding first contact or primary health care.

How up­to­date is this topic?

ChangesUpdate

Goals and outcome measures

GoalsOutcome measuresQIPP — Options for local implementation

Background information

DefinitionPrevalenceCauses of menorrhagiaComplications

Diagnosis and assessmentDiagnosis and assessment of menorrhagia (heavy menstrual bleeding)

DiagnosisHistoryExaminationInvestigations

Management

Scenario: Management (/menorrhagia#!scenario) : covers the primary care management ofmenorrhagia and criteria for referral to secondary care.

menorrhagia and criteria for referral to secondary care.

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this sectionspecifically for the drugs recommended in this CKS topic. For further information on contraindications,cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium(http://www.medicines.org.uk/emc) (eMC) (http://medicines.org.uk/emc), or the British National Formulary(http://www.bnf.org) (BNF) (www.bnf.org).

Evidence

Supporting evidenceSearch strategy

References

ABPI Medicines Compendium (2010) Summary of product characteristics for Norethisterone tablets.Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full­text(http://www.medicines.org.uk/emc/medicine/7257/SPC/Norethisterone+Tablets++%28Wockhardt+UK+Ltd%29)]

ABPI Medicines Compendium (2011) Summary of product characteristics for Tranexamic acid 500mgtablets. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [FreeFull­text (http://www.medicines.org.uk/EMC/medicine/24325/SPC/Tranexamic+Acid+500mg+Tablets/)]

ABPI Medicines Compendium (2012a) Summary of product characteristics for Mirena. Electronic MedicinesCompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full­text(http://www.medicines.org.uk/emc/medicine/1829/SPC/Mirena/)]

ABPI Medicines Compendium (2012b) Summary of product characteristics for Qlaira. Electronic MedicinesCompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full­text(http://www.medicines.org.uk/EMC/medicine/21700/SPC/Qlaira/)]

Apgar, B.S., Kaufman, A.H., George­Nwogu, U. and Kittendorf, A. (2007) Treatment of menorrhagia.American Family Physician 75(12), 1813­1819. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17619523)][Free Full­text (http://www.aafp.org/afp/2007/0615/p1813.html)]

Basgul, A., Uzuner, A., Kavak, Z.N. et al. (2007) Impact of tubal sterilization on women's health. Clinical andExperimental Obstetrics & Gynecology 34(1), 39­41. [Abstract(http://www.ncbi.nlm.nih.gov/pubmed/17447636)]

Blumenthal, P.D., Dawson, L. and Hurskainen, R. (2011) Cost­effectiveness and quality of life associatedwith heavy menstrual bleeding among women using the levonorgestrel­releasing intrauterine system.International Journal of Gynaecology and Obstetrics 112(3), 171­178. [Abstract(http://www.ncbi.nlm.nih.gov/pubmed/21269626)]

BNF 63 (2012) British National Formulary. 63rd edn. London: British Medical Association and RoyalPharmaceutical Society of Great Britain.

CSM (2003) Reminder: gastrointestinal toxicity and NSAIDs. Current Problems in Pharmacovigilance29(Sep), 8­9. [Free Full­text(http://www.mhra.gov.uk/Publications/Safetyguidance/CurrentProblemsinPharmacovigilance/CON007449)]

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