Abnormal uterine ∖bleeding

Introduction to abnormal uterine bleeding

Menstruation is a unique physiological event, occurring approxi­mately once each month for the major part of a woman's reproductive phase of life.

An understanding of normal menstruation and the normal men­strual cycle and the various factors which can influence them is critical to determining whether a woman is experiencing abnormal uterine bleeding (AUB) at any one point in time. The patterns of normal menstrual bleeding vary greatly from menarche to meno­pause, with considerable irregularity and intermittent long cycles being common within the first 2-5 years after menarche and the last 2-5 years before menopause. The menopause is defined as the last natural menstrual period that a woman experiences, a point which can only be determined 1 year later, when no further menstruation has occurred. It needs to be emphasized that there is great variability in normality of menstrual cycles between women, and in some in­dividual women from one phase of their lifetime to another (1). Variability tends to be greater at the extremes of reproductive life.

FIGO recommendations on menstrual terminologies and definitions

Fifteen years ago, understanding of the clinical field of AUB was confused and poorly defined (2).

The three main terms recommended for exclusion from further international use were ‘menorrhagia', ‘metrorrhagia' (terms of Greek and Latin origin used in the English language without clear defin­ition) and ‘dysfunctional uterine bleeding' (a term from the 1930s which was never clearly defined and was an admission of ignorance, which can now be replaced by a much more precise description of three defined underlying causes). These three abandoned terms have all been used in the past to describe both the symptoms and under­lying causes of AUB, a very confusing situation! The list of archaic and abandoned terms is included in Box 41.1.

Responsibility for the veracity and the educational promotion of this major exercise in revising definitions, terminologies, and causes of abnormal bleeding was accepted by the International Federation of Gynecology and Obstetrics (Federation Internationale de Gynecologie et d'Obstetrique (FIGO)) (3, 4), and this flexible system has been re­viewed and revised on a triennial basis by FIGO since its introduction (known as the FIGO AUB System 1 (description of symptoms)).

The components of normal and abnormal menstrual cycles and menstruation can be clearly defined by a group of four criteria (Box 41.3): these criteria all relate to the varied symptoms of normal and AUB (Box 41.2):

1.

2. Frequency of successive episodes of menstruation.

3. Duration of each bleeding episode.

4. Volume of bleeding, as perceived by the woman on different days of her menstruation.

The limits of each of these parameters in ‘normal' menstrual cycles have been clearly defined, based on 5th and 95th percentiles

Box 41.1 Menstrual terminologies which are now obsolete and should no longer be used

They have never been well defined and were used in a very confused manner:

• Menorrhagia (including combination terminology, such as essen­tial menorrhagia, idiopathic menorrhagia, primary menorrhagia, functional menorrhagia, ovulatory menorrhagia, and anovulatory menorrhagia)

• Hypermenorrhoea

• Uterine haemorrhage

• Metropathia haemorrhagica

• Metrorrhagia

• Hypomenorrhoea

• Menometrorrhagia

• Polymenorrhoea

• Polymenorrhagia

• Epimenorrhoea

• Epimenorrhagia

• Functional uterine bleeding

• Dysfunctional uterine bleeding

from population studies (Box 41.3). These ‘normal limits' have thus allowed the definition of specific abnormalities of uterine bleeding. The Washington experts determined that the overarching term to describe any abnormality of the symptoms of uterine bleeding should be AUB.

Patterns of abnormal uterine bleeding

The most troublesome and frequent patterns of AUB are:

• heavy menstrual bleeding (HMB)

• irregular menstrual bleeding

• prolonged menstrual bleeding

• intermenstrual bleeding

• infrequent or absent menstrual bleeding.

These bleeding patterns are also the commonest departures from the normal limits defined in Box 41.3. Sometimes these patterns combine together to provide a more problematic symptom complex. For example, heavy and prolonged episodes of bleeding are often seen in the same woman. Complaints of HMB with or without pro­longed bleeding are about ten times more common than complaints of prolonged bleeding on its own.

Box 41.2 Modern descriptive terminologies around menstruation

Box 41.3 Parameters of normal menstruation and the menstrual cycle

• Regularity of successive episodes of menstruation; variation of less than 7 to 9 days difference between the shortest and longest cycles.

• Frequency of successive episodes of menstruation (24-38 days).

• Duration of each bleeding episode (up to 8 days in a single period).

• Volume of each bleeding episode (as perceived by the woman on different days of menstruation); less than 80 mL.

• Variability of any of these parameters can be disturbing for many women.

• Any repeated departure outside these limits is known as abnormal uterine bleeding.

Heavy menstrual bleeding

This is one of the commonest and most troublesome complaints of AUB. It is a particularly difficult symptom to evaluate because the volume of menstrual bleeding is impossible to assess accurately without awkward laboratory research assays. In addition, women do not generally discuss details of their menstrual periods with each other, and therefore do not have any good framework of reference to assess their own experiences. On the other hand, this avoidance of discussing menstruation may now be changing with the in­tense modern focus on social media by young people. Many young women are now sharing information about themselves with their friends in a way that was almost unheard of a decade ago. In some countries, this is leading to a new social movement among educated young women for a ‘bleed-free' existence (through the use of tai­lored hormonal contraceptive regimens to cause pharmacological amenorrhoea) until they are ready to try for a pregnancy.

There are two definitions of HMB

See Box 41.4.

The research definition of HMB In the research situation, HMB is defined as a monthly blood loss of greater than 80 mL. This limit has been determined by population studies using objective labora­tory measurements of menstrual losses of carefully collected sani­tary pads and tampons in general female communities in Sweden and the United Kingdom (5, 6).

The routine clinical definition of HMB In the clinical situation, HMB should be defined as ‘excessive menstrual blood loss, which

• Abnormal uterine bleeding (AUB): the overarching symptom.

• Heavy menstrual bleeding (HMB) (replaces ‘menorrhagia' and 'hypermenorrhoea').

• Irregular menstrual bleeding (replaces 'metrorrhagia').

• Prolonged menstrual bleeding.

• Infrequent menstrual bleeding (replaces 'oligomenorrhoea').

• Amenorrhoea (absent menstrual bleeding; retained).

• Inter-menstrual bleeding (bleeding in between periods; retained).

• Dysfunctional uterine bleeding is replaced by better defined under­lying causes: AUB-C, AUB-O, and AUB-E.

Box 41.4 Definitions of heavy menstrual bleeding

• Research definition of heavy menstrual bleeding: in most menstrual cycles the measured menstrual blood loss should exceed 80 mL.

• Clinical definition of heavy menstrual bleeding: 'Excessive menstrual blood loss, which interferes with the woman's physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms.'

• Any intervention should improve quality of life. interferes with the woman's physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms'. Any interventions should therefore aim to improve quality of life measures (7). The woman with HMB presents with a complaint that reflects her perception of the abnormality of her menstrual flow, and as such, her clinical problem requires manage­ment. This is a valuable clinical definition, which provides a sound basis for therapy.

Some important clinical messages about HMB

• Composition of the menstrualflow: the total menstrual flow is com­posed of around 50% of venous (and some arteriolar) blood and 50% of an endometrial transudate, hence it is ‘very dilute blood'.

• Lack of awareness that periods are abnormally heavy: many women with HMB are unaware that their menstrual periods are abnor­mally heavy, and do not complain until they have a really excessive episode of loss.

• Complaint of HMB when periods are actually normal: by contrast, there are also many women who complain of heavy bleeding when their measured loss would be within the normal range. This indi­cates that they probably have experienced a change in their men­strual period, which needs assessment.

• Women with HMB and menstrual pain are more likely to com­plain: those women who have pelvic pain (or other perimenstrual symptoms) accompanying their heavy bleeding are more likely to complain of their HMB, suggesting that they have significantly greater difficulty coping with a combination of symptoms, rather than with the HMB on its own.

• Cultural differences: women from different cultures may view their menstrual experiences in different ways. In many countries, women regard a heavy red bleed as a ‘good thing’, reflecting a thorough ‘clean out' of body impurities, when in reality, this red bleed is more likely to signify a heavier period, which may be increasing a woman's risk of developing iron deficiency, especially if she comes from a back­ground of inadequate dietary iron intake. This same woman may find the brownish menstrual loss at the end of her period to be unhealthy looking and unpleasant (especially ifit is prolonged in any way), when it is actually a reflection of very light bleeding with healthy partial me­tabolism of haemoglobin before it reaches the vagina.

• Hazards of HMB: the hazards of HMB are mainly twofold. Firstly, a regular monthly loss of greater than 80 mL of ‘whole blood' signifi­cantly increases that woman's risk of developing iron deficiency (a reduction in circulating levels of serum ferritin—the best reflection of body iron stores) (Box 41.5) and a reduction of serum transferrin saturation—the best reflection of circulating ‘available’ iron, which is in a form immediately accessible by cells in need). Iron deficiency is probably a much greater problem for quality of life than widely rec­ognized, because of the additional troublesome symptoms which it brings. Secondly, other quality of life measures are disturbed by the overlapping symptoms both from HMB and iron deficiency, and by the social problem of ‘containment' of the excessive flow.

Box 41.5 Definitions and assessment of iron deficiency

• Haemoglobin (to assess anaemia in a non-pregnant woman; should be 30 ng/mL; a measure of bleeding in women in the reproductive years)

The FIGO system of classification of underlying causes of AUB is simply based on dividing the major causes into two groups: the ‘structural’ causes, where pathology can be imaged by pelvic ultra­sound, magnetic resonance imaging (MRI), or direct visualization, and the ‘non-structural’ causes, which cannot be ‘imaged’. These causes are illustrated by the mnemonic PALM-COEIN (Box 41.6).

‘Structural’ lesions (PALM):

• AUB-P: endometrial or endocervical polyps, which typically cause intermenstrual bleeding and sometimes HMB.

• AUB-A: adenomyosis, which commonly coexists with other causes and may sometimes cause HMB and pelvic pain.

• AUB-L: leiomyomas, a very common cause of the heaviest daily bleeding during a period.

Box 41.6 The PALM-COEIN system: underlying causes of abnormal uterine bleeding in women in the reproductive years

Structural causes

• AUB-P: endometrial or endocervical polyps

• AUB-A: adenomyosis

• AUB-L: leiomyoma

• AUB-M: malignancy or endometrial hyperplasia

Non-structural causes

• AUB-C: coagulopathy

• AUB-O: ovulatory disturbances

• AUB-E: primary endometrial disturbances

• AUB-I: iatrogenic

• AUB-N: not otherwise classified

• AUB-M: endometrial hyperplasia or malignancy can cause erratic light or heavy bleeding.

Non-structural molecular causes (COEIN):

• AUB-C: coagulopathies can be genetically linked causes of very heavy bleeding, but von Willebrand disease can be a common cause of moderate HMB.

• AUB-O: ovulatory disturbances are a common cause of disturbed bleeding (light or heavy), particularly in adolescence and in the perimenopausal period.

• AUB-E: primary endometrial causes are mainly local disturbances of molecular pathways or a reflection of low-grade, chronic infec­tion (such as chlamydia). Most of the research studies of ‘HMB’ have been done on women with AUB-E.

• AUB-I: iatrogenic causes of AUB include a wide range of drugs causing irregular, light, heavy, or prolonged bleeding. Ceasing the drug therapy will usually correct the AUB rapidly. This section in­cludes intrauterine contraceptive devices.

• AUB-N: not otherwise classified is a group of rarities or unusual causes which have not yet been defined or do not easily fit into the other categories. This includes rarities such as arteriovenous mal­formations in the uterus.

Flexibility of the PALM-COEIN classification allows for the de­velopment of subclassifications where needed. This is particularly the case with AUB-L where fibroids in different parts of the uterus and with differing relationships to the endometrium may have very different effects on symptoms and management. This system also al­lows for more than one cause to be recognized and graded in the same patient. The system also allows for modification of each com­ponent with new research, and has an inbuilt requirement for review every 3 years.

Not all genital tract bleeding is uterine

The previous discussion has related specifically to ‘uterine’ bleeding since this is the commonest and potentially the most complicated aspect of genital tract bleeding. However, it is not uncommon to en­counter abnormalities of bleeding arising from the vulva, vagina, or cervix, and these should generally be excluded during history taking and pelvic examination. The possibility of a pelvic malig­nancy should not be overlooked. Abnormal bleeding from an un­diagnosed early pregnancy should also be excluded as a potential cause of symptoms mimicking AUB.

Box 41.7 Potential investigations for abnormal uterine bleeding

• Full blood count, including haemoglobin, film.

• Iron studies (ferritin; transferrin saturation).

• Pap smear.

• High vaginal swab/chlamydia and gonorrhoea polymerase chain reaction.

• Pelvic/transvaginal ultrasound (becoming routine).

• Magnetic resonance imaging (rarely needed).

• Hysteroscopy with or without excision.

• Diagnostic laparoscopy with or without excision.

Investigations

For most of these patients, there is little need for extensive investiga­tion. The key to good management is usually a ‘good clinical history' defining the characteristics of the menstrual pattern and relevant lifestyle features (such as cigarette smoking or risk factors for cer­vical infection), and a clinical examination, including bimanual pelvic and speculum examinations. Specific investigations should include the following (Box 41.7):

1. Full blood count, primarily to assess anaemia and platelet count.

2. Blood film, to assess the possible presence of hypochromia and microcytosis of the red blood cells, and reticulocytes.

3. Iron studies, including serum ferritin and serum transferrin sat­uration (see Box 41.5 to assess iron deficiency). We believe that iron deficiency is underdiagnosed in most countries.

4. The pelvic examination should allow collection of a Pap smear, if not up to date with routine collection. Pelvic examination al­lows assessment of palpable or visible lesions on the vulva, va­gina, or ectocervix, and provides information on the presence of tenderness.

5. Transvaginal ultrasound scan has become a technique of cen­tral importance in the assessment of AUB. Pelvic scanning has become a complex technology and ideally needs to be car­ried out by an expert. A good-quality scan carried out with modern equipment and assessed by an expert in pelvic scan­ning can yield surprising details of the presence and structure of pelvic lesions, and may render other types of scanning or endoscopy unnecessary. Basic ultrasound scanning can be sup­plemented by the instillation of saline into the uterine cavity (sonohysterography) to outline the endometrial surface and encroaching lesions with much greater clarity. Colour Doppler scanning can provide evidence of the vascularity of endometrial polyps, fibroids, or other structures, and may highlight a rare arteriovenous malformation.

Basic transvaginal scanning has a relatively high level of error in assessing endometrial polyps and should be supplemented by sonohysterography when polyps may be present, unless a clear feeder vessel is seen in the polyp on colour Doppler.

6. MRI provides very clear images of most pelvic structures and may provide clearer assessments of structural lesions such as fibroids or endometriosis/adenomyosis than ultrasound. However, it is costly and can be difficult to access, and is un­necessary in straightforward cases of menstrual dysfunction.

7. Diagnostic hysteroscopy is an important tool for visualizing le­sions encroaching into the uterine cavity, and allows excision

Box 41.8 A simple screening questionnaire to determine the likelihood that a woman with a complaint of heavy menstrual bleeding will have an underlying coagulopathy

A positive screen comprises any of the following

• HMB from the time of menarche onwards.

• One of the following:

— Postpartum haemorrhage

— Excessive bleeding during surgery

— Bleeding with dental work.

• Two or more of the following symptoms:

— Significant bruising one or two times per month

— Epistaxis one or two times per month

— Frequent bleeding from the gums

— Family history of bleeding symptoms.

• Patients with a positive screen should be assessed further by a haematologist.

Source data from Kouides PA, Conard J, Peyvandi F, Kadir R. Hemostasis and menstru­ation: appropriate investigation for underlying disorders of haemostasis in women with excessive menstrual bleeding. Fertil Steril 2005;84:1345-49.

or biopsy for assessment of the pathology of the visible lesion. Hysteroscopy can be carried out without local or general anaes­thesia in an outpatient clinic situation if the premises and equip­ment are suitable.

8. Other possible investigations include an initial screening for coagulopathy, if the clinical picture contains suggestive features. A simple, specific, three-question questionnaire will usually give a strong indication whether definitive coagulopathy laboratory investigations are indicated (Box 41.8).

9. A small number of centres have extended the availability of these tests so that they can be offered to new patients as a ‘one- stop shop', where all necessary investigations can be completed at the first visit and a clear management strategy expeditiously initiated.

Management of abnormal uterine bleeding

Aims of therapy

The acute and severe (or ‘acute on chronic') presentations of HMB symptoms and the commoner chronic and less severe HMB symp­toms require quite different approaches for initial management.

Management of acute and severe presentations of HMB

Women presenting with acute and severe genital tract blood loss need an urgent history and pelvic examination, aligned with urgent measures to limit further blood loss and stabilize the cardiovascular system (Boxes 41.9 and 41.10) and consideration of the principles of ‘patient blood management' (see ‘Management of chronic presenta­tions of HMB').

Management of chronic presentations of HMB

In most Western societies, ‘chronic' presentations are much com­moner than ‘acute and severe'. An ideal approach to management requires the sequence of menstrual and medical case history, pelvic and speculum examination, and relevant investigations.

Medical therapies for chronic presentations of HMB have been well studied over the past two decades:

Box 41.9 Principles for urgent management of acute and severe heavy menstrual bleeding

1 Insert intravenous line.

2 Take blood for full blood count, biochemistry, and crossmatching.

3 Assess and stabilize cardiovascular status.

4 Assess continuing rate and extent of vaginal blood loss.

5 Complete menstrual, 'HMB', and medical history.

6 Consider transvaginal ultrasound scan.

7 Assessment of patient blood management principles.

8 Plan the best approach to minimizing active blood loss.

9 Consider iron infusion.

1. The most effective medical therapy for HMB is the Ievonorgestrel- releasing intrauterine system (LNG-IUS; marketed as Mirena by the Bayer Healthcare, Berlin). This system reduces menstrual blood loss by around 90%, and is designed to last for up to 5 years. Other LNG-IUS systems are beginning to come onto the market but these have not yet been adequately studied for HMB treatment. It is recommended by all modern guidelines that the LNG-IUS should be offered as first choice unless the woman has contraindications or has other personal preferences.

There is good evidence that the LNG-IUS can have a strong beneficial effect on reducing menstrual blood loss no matter what is the underlying cause of the HMB. It has highly bene­ficial effects on HMB in AUB-A, AUB-C, AUB-O, AUB-E, and AUB-M (endometrial hyperplasia; but is not recommended when there is any suspicion of endometrial cancer). It also works well for most cases of AUB-L, provided that the fibroids are not submucous. It appears to be effective in preventing recurrences of endometrial polyps, but when a polyp is present (AUB-P) the usual recommendation is surgical removal.

The commonest side effect of the LNG-IUS is erratic and ‘nuisance-value’ light bleeding, sometimes prolonged. This tends to reduce with time, but does sometimes lead to a need for

Box 41.10 Specific active therapies to stop acute and severe HMB

1 Consider uterine balloon tamponade.

2 Consider antifibrinolytic therapy (tranexamic acid)—intravenous or oral.

3 Start hormonal therapies to reduce bleeding and control future bleeding episodes:

a Many anecdotal regimens.

b Intravenous conjugated equine oestrogens in countries where this is still available.

c Oral medroxyprogesterone acetate in moderate dose (10-20 mg three times a day for 7-10 days).

d Oral norethisterone acetate in moderate dose (5-10 mg three times a day for 7-10 days).

e Consider intramuscular medroxyprogesterone acetate.

f Suitable 30 mcg combined oral contraceptive.

g Plan future hormonal control with LNG-IUS or a suitable oral contraceptive.

4 May need to consider surgery for non-responsive, continuing blood loss.

removal. Amenorrhoea is very common, is reversible following removal of the device unless the woman is perimenopausal, and is usually recognized as a beneficial end-point of the therapy

2. Second-line medical therapies include the following:

a. Combined oral contraceptives:

i. All modern combined hormonal contraceptives con­taining ethinyl oestradiol (including vaginal ring and transdermal systems) are effective in reducing menstrual blood loss by an average of 30-50%.

ii. Oral contraceptives based on oestradiol-17-beta as the oestrogen component seem to be more effective in redu­cing menstrual blood loss (by 70-80%).

b. Tranexamic acid is a lysine analogue, which has major antifibrinolytic properties by inhibiting the action of plasmin. Hence, it counteracts the breakdown of fibrin by the plasmin system within the endometrium, a tissue which has a very ac­tive fibrinolytic system in women with HMB. This drug does not increase the risk of venous thrombosis in large vessels. It works by inhibiting tissue plasminogen activator solely within the tissues. It is highly effective in reducing menstrual blood loss, by around 50%. The drug needs to be taken each month as soon as menstrual bleeding starts, in an oral dosage of 1.0 g three times daily for 3-4 days. Tranexamic acid has a fairly low bioactivity and therefore needs to be taken in this apparently ‘high dosage’ to maintain its antifibrinolytic effect. This dosage has a low incidence of side effects, mainly mild gastrointestinal symptoms which settle with time. This is a valuable non-steroidal therapy, which only needs to be taken during the heaviest days of menstruation itself. The extensive Scandinavian experience suggests that it can be safely taken on a monthly basis for many years.

c. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat HMB, although they are generally less ef­fective in reducing the actual blood loss (by around 30%) than other therapies. However, they are often effective in reducing menstrual pain, which is a common accompani­ment of HMB. The drugs which have been most thoroughly studied are mefenamic acid, naproxen, and flurbiprofen. These are taken during the time of heavy bleeding, gener­ally in a dosage of 500 mg three times daily. They should not be taken on an empty stomach because they may occasion­ally cause epithelial erosion within the gastrointestinal tract. Food inhibits this.

3. A new therapy for HMB associated with uterine fibroids is the oral progesterone receptor modulator, ulipristal acetate (Esmya). This novel therapy is beginning to establish its place for long­term management of uterine fibroids, and shows great promise in reducing fibroid size and greatly reducing menstrual blood loss (Box 41.11).

4. Third-line medical therapies (oral danazol and gonadotrophin­releasing hormone (GnRH) analogues) are no longer recom­mended for treatment of HMB (mainly because of side effects), except in special extenuating circumstances.

5. Iron therapy is a critical part of the medical management of HMB, and should be initiated at the same time as the chosen therapy aimed at stopping the heavy bleeding.

Box 41.11 Use of ulipristal acetate for uterine fibroids

• Confirm diagnosis of leiomyomas (uterine fibroids).

• Establish subclassification of fibroid positioning within the uterus.

• Use of ulipristal acetate contraindicated with genital bleeding of un­known origin.

• Each course lasts 3 months (5 mg daily for 84 days; 7-day break be­fore further courses).

• Produces significant reduction in menstrual blood loss.

• Produces significant reduction in individual fibroid size.

Recent research has demonstrated that it takes the average woman with HMB 1 year to recharge her iron stores to normal levels after starting use of a LNG-IUS or having a hysterectomy, unless her iron deficiency is deliberately and adequately treated. Iron therapy can either be with standard oral formulations or, increasingly, with a loading dose of a modern rapid impact intra­venous preparation with a low incidence of side effects, such as ferric carboxymaltose.

Patient blood management is a recent concept focusing man­agement strategies for bleeding symptoms around the best health needs of the patient. It can be defined as: ‘The timely application of evidence-based medical and surgical concepts designed to maintain haemoglobin concentration, optimize haemostasis, and minimize blood loss in an effort to improve patient outcome' (9, 10). This concept developed along with increasing awareness of the serious hazards and questionable efficacy of allogeneic blood transfusion. Allogeneic blood transfusions are risky, costly, in limited supply and are linked to worsening of patient outcomes. In addition, blood transfusion is a demanding and expensive service to maintain.

Patient blood management has become a multimodal approach to minimize perioperative use of blood products, based on the triad of detection and treatment of preoperative iron deficiency and an­aemia, reduction of perioperative blood loss, and harnessing and optimizing patient-specific factors such as inflammation-related hepcidin release.

It is now becoming recognized that menstruating women are at particular risk of the symptoms and complications of iron deficiency and that those with HMB have a condition akin to major surgical blood loss once a month (when they menstruate).

The concepts of patient blood management are reshaping trans­fusion medicine and the way that blood components are used. Emphasis is increasingly being placed on maximizing iron stores and circulating ‘available iron' prior to planned surgery, to min­imizing blood loss during surgery, to minimizing transfusion of blood products, and to maintaining iron stores and haemoglobin levels following surgery. There are now many effective oral and intravenous iron preparations that can initiate reasonably rapid restoration of iron stores and support steady replacement of haemoglobin and red blood cells. If the preoperative schedule al­lows for 3 months before elective surgery in ‘at-risk' patients, we tend to use oral iron polymaltose (100 mg twice daily, elemental iron), or if less than 4 weeks is available before urgent surgery, an intravenous total loading dose of ferric carboxymaltose (1000 mg). These preparations are well tolerated in the great majority of patients.

Box 41.12 Surgical procedures still used for management of some heavy menstrual bleeding cases of abnormal uterine bleeding

• Surgical procedures for benign gynaecology have greatly reduced (by around 50%) in most countries in the past two decades.

• Surgery is generally now restricted to the structural lesions (PALM).

• Hysterectomy is now usually carried out laparoscopically, unless the structural lesion is extensive.

• Uterine artery embolization is used in some centres for treatment of individual fibroids.

• Endometrial resection can be very effective for AUB-E and AUB-C.

• Modern laparoscopic surgery requires advanced endoscopic training.

Surgical and procedural approaches to management of AUB

Surgery is still required on a fairly frequent basis for managing the more difficult or persistent cases of HMB (Box 41.12). Structural causes of HMB, such as polyps, adenomyosis, uterine leiomyomas, and endometrial malignancy may all require surgery for man­agement. Surgery may sometimes involve hysteroscopic or lap­aroscopic resection of the whole lesion (e.g. endometrial polyps, solitary submucous myomas, or multiple myomas). Hysterectomy may still be necessary sometimes, especially if multiple fibroids, adenomyosis, or endometriosis are present. Demographic data from several European countries have demonstrated that the numbers of hysterectomies for benign gynaecological diseases have been re­duced by more than 50% in the past 20 years—since the LNG-IUS system has been introduced.

Alternative procedures of lesser degree than hysterectomy, which may effectively treat HMB, include endometrial ablation and uterine artery embolization for leiomyomas or adenomyosis. Endometrial ablation was designed to resect or coagulate the full depth of the endometrium and a small rim of underlying myometrium in those women who chose not to attempt future pregnancy. Overall, endo­metrial ablation has a similar degree of effectiveness as the LNG- IUS, but the potential disadvantages of being irreversible and not being ‘contraceptive'. Newer technologies have allowed modern ab­lation to be carried out using ‘high-tech' programmed devices as an office procedure.

Uterine artery embolization requires precise insertion of a uterine artery catheter under radiological guidance, with the tip being placed close to or in the largest feeder vessel of the targeted leiomyoma. Biodegradable microparticles of polyvinyl alcohol are injected to block the feeder vessels. The technique requires skilled interven­tional radiology and provides an effectiveness of greater than 90% in greatly reducing fibroid size, blood supply, and HMB symptoms. Side effects include ischaemic pain immediately postoperatively and a small risk of ischaemic damage to surrounding tissues, including ovary. This technique does not necessarily prevent the development of new fibroids in future.

Prognosis

The prognosis for patients with AUB or, more specifically HMB, is closely related to the nature and severity of the underlying cause of the bleeding (PALM-COEIN), and the effectiveness of any targeted therapy. Thus, the prognosis is specifically patient focused. If the un­derlying cause is not adequately treated, most patients will tend to have worsening symptoms and signs over a period of years, until the menopause.

Summary

This section has focused primarily on HMB since this is the com­monest and the most hazardous of the menstrual bleeding symp­toms, and is often accompanied by pelvic pain. The main hazard associated with HMB is the development of iron deficiency and iron deficiency anaemia. Many doctors are unaware that iron deficiency without anaemia is so common in menstruating women and that it is just as important in causing symptoms as when anaemia is also present. Hence, iron deficiency needs to be actively treated at the same time as giving therapy to reduce or stop the bleeding.