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Philippine Obstetrical and Gynecological


Society (Foundation), Inc. (POGS)

CLINICAL

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PRACTICE
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GUIDELINES

ABNORMAL
UTERINE
BLEEDING
Second Edition,
November
2009
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November 2009
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Technical Working Group for the Clinical Practice Guidelines


On Abnormal Uterine Bleeding

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Philippine Obstetrical and Gynecological


Society (Foundation), Inc (POGS)

CLINICAL PRACTICE GUIDELINES


on
ABNORMAL UTERINE BLEEDING

November 2009!

Technical Working Group for the Clinical Practice Guidelines


On Abnormal Uterine Bleeding

FOREWORD"
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LOURDES B. CAPITO, MD
President
Philippine Obstetrical and Gynecological Society (Foundation), Inc. (POGS), 2009
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INTRODUCTION"

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EFREN J. DOMINGO, MD, PhD
Chair, AdHoc Committee on the Clinical Practice Guidelines, 2009

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BOARD OF TRUSTEES 2009


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ABNORMAL UTERINE BLEEDING
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I. DEFINITION OF TERMS
Statement 1
Abnormal uterine bleeding (AUB) encompasses any significant deviation from
normal frequency, regularity, heaviness (volume or amount) and duration of
menstrual bleeding. It is used to describe all abnormal menstrual signs and
symptoms arising from the uterine corpus. (III, C)
Reference:
1. Fraser IS (2007) What do we mean by abnormal uterine bleeding and dysfunctional uterine
bleeding? Gynecol Forum 12:2, 3-5.

Statement 2
The normal limits for the four main clinical dimensions of menstruation and the
menstrual cycle (regularity, frequency, duration and volume or amount) are
outlined below. Based on these limits, AUB may include short or long (but
regular) menstrual cycles, irregular menstrual cycles, heavy or light menstrual
periods, intermenstrual bleeding, premenarcheal or postmenopausal bleeding,
with or without any recognizable pathology.
Normal limits for menstrual parameters in the mid-reproductive years (III, C)
(Modified from the Consensus Meeting of Clinicians and Scientists (2007) by Frasier IS, Critchley
HOD, Munro MG, Broder M. Hum Reprod, 1-9.)

Clinical Dimensions of Menstruation Descriptive


and Menstrual Cycle
Terms
Frequency of menses (days)
Frequent
Normal
Infrequent
Regularity of menses (cycle to cycle Absent
variation over 12 months; in days)
Regular
Irregular
Duration of flow (days)
Prolonged
Normal
Shortened
Volume of monthly blood loss (ml)
Heavy
Normal
Light

Normal Limits
(5th-95th percentiles)
< 24
24-38
> 38
Variation of 2 to 20 days
Variation > 20 days
> 8.0
4.5-8.0
< 4.5
> 80
5-80
<5

Supporting Statements:
Suggested normal limits for the four main clinical dimensions of menstruation and the
menstrual cycle (regularity, frequency, duration and flow) are set on the basis of
medians and 95% confidence intervals. These have been developed following the
consensus meeting of clinicians and scientists in Washington1, based primarily on the
independent WHO analysis2, and also on other published population data3-6.

References:

d"

1. Frasier IS, Critchley HOD, Munro MG, Broder M (2007) Can we achieve international
agreement on terminologies and definitions used to describe abnormalities of menstrual
bleeding? Hum Reprod, 1-9.
2. Belsey EM and Pinol AP, World Health Organization Task Force on Long-Acting Systemic
Agents for Fertility Regulation (1997) Menstrual bleeding patterns in untreated women.
Contraception 55, 57-65.
3. Hallberg L, Hogdahl AM, Nilsson L and Rybo G (1966) Menstrual blood loss: a population
study. Acta Obstet Gynecol Scand 45, 320-351.
4. Treloar AE, Boynton RE, Behn BG and Brown BW (1967) Variation of the human menstrual
cycle through reproductive life. Int J Fertil 12, 77-126.
5. Snowden R and Christian B (eds) (1983) Patterns and Perceptions of Menstruation (A World
Health Organization international study). Croom Helm, London, p.339.
6. Fraser IS and Inceboz US (2000) Defining disturbances of the menstrual cycle. In: OBrien
PMS, Cameron IT and Maclean AB (eds). Disorders of the menstrual cycle. London: RCOG
Press, 141-52.

Statement 3
It is recommended that the term menorrhagia be discarded and replaced by the
term heavy menstrual bleeding. (III, C)
Supporting Statements:
The most common clinically significant disturbance in uterine bleeding is abnormally
heavy bleeding. The term menorrhagia is used to describe such heavy bleeding, but its
exact use is variable. It is usually used to describe a symptom, but some clinicians use
it as a diagnosis. Thus, it is recommended that this term, along with other terms such
as hypermenorrhea, metrorrhagia and menometrorrhagia, be abandoned1-2. The
current popular term for heavy menstruation is heavy menstrual bleeding3.
References:
1. Fraser IS and Inceboz US (2000) Defining disturbances of the menstrual cycle. In: OBrien
PMS, Cameron IT and Maclean AB (eds). Disorders of the menstrual cycle. London: RCOG
Press, 141-52.
2. Frasier IS, Critchley HOD, Munro MG, Broder M (2007) Can we achieve international
agreement on terminologies and definitions used to describe abnormalities of menstrual
bleeding? Hum Reprod, 1-9.
3. National Institute for Health and Clinical Excellence (NICE). Heavy menstrual bleeding
(2007).

Statement 4
Dysfunctional uterine bleeding (DUB) is defined as excessive bleeding of uterine
origin that is not due to complications of pregnancy or to any systemic or local
pelvic pathology. It has been used as a diagnosis of exclusion. Ovulatory DUB is
described as having regular cycles with heavy bleeding. On the other hand,
anovulatory DUB is characterized by irregular, prolonged and/or heavy
bleeding. (GPP)
Supporting Statements:
DUB is commonly used to describe abnormally heavy or irregular bleeding without
recognizable organic pathology1-2. In Europe, DUB is further differentiated into
ovulatory and anovulatory DUB; while in USA, DUB usually connotes anovulatory
cycles. It is a term used when the disorder involves primarily the endometrial
molecular mechanisms (ovulatory DUB) or the hypothalamic-pituitary-ovarian axis
(anovulatory DUB).3
e"

The recent FIGO 2009 Congress recommended that the term DUB should be
discarded. The justifications for abolishing the term DUB are as follows4:
A diagnosis of exclusion and admission of our ignorance about local
mechanisms
Terminology used very differently in different countries (symptoms, signs,
diagnoses)
old DUB includes the following coagulopathies (congenital and acquired),
ovulatory disorders and endometrial dysfunction (infection, disturbances of
local hemostasis, inflammation, vasoactive regulators)
The Technical Working Group for the POGS 2009 Clinical Practice Guidelines on
Abnormal Uterine Bleeding concurs with the FIGO recommendation.
References:
1. Fraser IS (1985) The dysfunctional uterus- dysmenorrhea and dysfunctional uterine bleeding.
In: Shearman RP, ed. Textbook of clinical reproductive endocrinology. Edinburgh: Churchill
Livingstone, 578-98.
2. Crosignani PG and Rubin B (1990) Dysfunctional uterine bleeding. Hum Reprod 5: 637-8.
3. Fraser IS (2007) What do we mean by abnormal uterine bleeding and dysfunctional uterine
bleeding? Gynecol Forum 12:2, 3-5.
4. Fraser IS et al. FIGO 2009 Congress Interactive Session on AUB, Cape Town International
Convention Center, South Africa. 6 October 2009.

Statement 5
AUB includes both DUB and bleeding from organic causes. (III, C)
Supporting Statements:
When AUB is due to systemic causes or disorders of the reproductive tract, the
etiology is described as organic. The absence of organic pathology makes the cause of
bleeding as dysfunctional1-2.
References:
1. Lindeque BG (2007) Clinical approach to a patient with abnormal uterine bleeding. SA Fam
Pract 49(8): 32-33.
2. Ely JW, Kennedy CM, Clark EC and Bowdler NC (2006) Abnormal uterine bleeding: a
management algorithm. J Am Board Fam Med; 19: 590-602.

Statement 6
Acute AUB is characterized by significant blood loss that results in hypovolemia
(hypotension or tachycardia) or shock. (GPP)
Supporting Statements:
Acute uterine bleeding ranges from modestly heavy menstrual bleeding to excessively
heavy bleeding associated with hypovolemic shock.1,2,5 It occurs more frequently in
anovulatory women.3,4 Acute uterine bleeding requires urgent or emergent medical
intervention that more often leads to frequent use of urgent care, emergency and
operating room resources.
References:
1. Munro MG. Acute uterine bleeding unrelated to pregnancy. Gynaecol Forum 2007; 12(2): 1114.

f"

2.
3.
4.
5.

Speroff L, Glass RH, Kase NG. Clinical gynecologic endocrinology and infertility. 6th ed.
Baltimore: Lippincott Williams & Wilkins 1999; 21-38,499,575-9.
Word RA, Kamm KE, Casey ML. Contractile effects of prostaglandins, oxytocin, and
endothelin-1 in human myometrium in vitro: refractoriness of myometrial tissue of pregnant
women to prostaglandins E2 and F2 alpha. J Clin Endocrinol Metab 1992; 75: 127-32.
Livingston M, Fraser IS. Mechanisms of abnormal uterine bleeding. Hum Reprod Update
2002; 8: 60-7.
Fraser IS et al. FIGO 2009 Congress Interactive Session on AUB, Cape Town International
Convention Center, South Africa. 6 October 2009.

Statement 7
Chronic AUB is bleeding from the uterine corpus, that is abnormal in duration,
volume, regularity, and/or frequency and has been present for the majority of
the last six (6) months. (GPP)
References:
1. Fraser IS et al. FIGO 2009 Congress Interactive Session on AUB, Cape Town International
Convention Center, South Africa. 6 October 2009.

II. PATHOPHYSIOLOGY
A. Normal Menstruation:

Factors that come into play for hemostasis:


1) a higher thromboxane level (PGF2) in relation to prostacyclin (PGE2 )
2) fibrin clot formation, and
3) stabilization of the hemostatic platelet plug.
The absence of any, or all of these factors may result in heavier
menstruation.

B. Abnormal Uterine Bleeding (AUB)


Etiology of Abnormal Uterine Bleeding
1. Organic Causes
a. Reproductive Tract Disease
i. Pregnancy related complication

Pregnancy is the first consideration in women of reproductive age who


present with AUB. Potential causes of pregnancy-related bleeding include:
o spontaneous pregnancy loss
o ectopic pregnancy
o placenta previa
o abruptio placentae
o hydatidiform mole
o choriocarcinoma

ii. Non-pregnancy related genital lesions (benign or malignant pelvic


lesions)
M"

W!"

Non-pregnancy related genital causes include:


o Myomas
o Endometrial carcinoma, polyps or hyperplasia
o Chronic cervicitis
o Cervical polyps & carcinomas
o Vaginal carcinoma
o Functional ovarian cysts or neoplasms

Bleeding from a secretory endometrium, which indicates ovulation,


usually implies an anatomic lesion rather than an endocrine disorder,
although ovulatory bleeding may occasionally produce minimal midcyclic
bleeding in the absence of an organic lesion.

Myomas and polyps are widely recognized structural abnormalities


causing abnormal uterine bleeding, but the precise mechanisms by which
they increase bleeding are poorly understood.

The abnormal bleeding associated with submucous myomas typically


begins as prolonged menses, which may be sufficiently severe to cause
anemia. It has been suggested that myoma-related AUB may result from:
o an increased surface area of the endometrium due to mechanical
distortion
o ulceration and hemorrhage of endometrium overlying the
submucous fibroids
o interference by the myomas with normal uterine hemostasis
o mechanical compression of the venous drainage by the myomas at
any site, and
o dilatation of the venous plexuses draining the endometrium

Submucous myomas are highly vascularized, with large, fragile vessels on


their surfaces. Bleeding from these large-caliber vessels during
menstruation cannot be stopped promptly by myometrial contractions
because of their intracavitary position.

The association of adenomyosis with AUB is controversial and remains


unclear. However, several hypotheses have been introduced and these
include:
o an increased endometrial surface
o altered PGE/PGF ! balance
o hampered myometrial contractility
o abnormal myometrial angionesis associated with fragile blood
vessels.

Endometrial polyps are found in all age groups, but mostly in older
women, and may also present as heavy menstrual, intermenstrual, or
postmenopausal bleeding and may be associated with dysmenorrhea.

Arteriovenous malformations, despite their rare occurrence, contribute to


the problem of AUB and should therefore be included in the differential
diagnosis of women with acute, heavy menstrual bleeding.

Genital tract infections, particularly Chlamydia trachomatis infection


should likewise be considered among women who presents with irregular
bleeding and post-coital spotting.

b. Systemic Disease

Non-pregnancy-related systemic disorders (i.e. neoplasms, metabolic,


organic, and other anatomic causes must be ruled out):
o Blood dyscrasias
o Thrombocytopenia
o Deficient clotting factors
o Thyroid dysfunction
o Hepatic dysfunction
o Renal dysfunction

AUB, particularly in premenarcheal girls, may be suggestive of an


inherited systemic disorder of hemostasis. A meta-analysis of high-quality
epidemiological prevalence studies indicated a 13% prevalence rate of the
biochemical markers of von Willebrand disease among women with heavy
menstruation.

AUB is likewise associated with hypothyroidism. Hyperthyroidism,


hypothalamic dysfunction, hyperprolactinemia, premature ovarian failure,
and primary pituitary disease are, most often than not, associated with
amenorrhea and rarely result in heavy bleeding.

Diabetes mellitus can be associated with anovulation, obesity, insulin


resistance, and androgen excess, and increases the likelihood of abnormal
uterine bleeding.

Renal or liver diseases may also result in abnormal uterine bleeding.


Women with liver disease may have higher circulating levels of estrogen
due to hepatic dysfunction and an inability to metabolize estrogen.
Coagulopathies also may occur with liver disease, while renal failure is
associated with irregularities of the HPO axis due to gonadal resistance to
hormones, platelet dysfunction, and abnormal factor VIII activity.

c. Iatrogenic

AUB among women on contraceptive hormones are usually manifested as


irregular bleeding, and may result from an inconsistent use, or, more
commonly, as a breakthrough bleeding especially during the first few
months of hormonal contraceptive use. However, not all bleeding that
occurs in this group of women can be attributed to hormonal contraceptive
use.

Women on chronic use of steroids, anticoagulants, tranquilizers, digitalis,


dilantin and/or IUD may manifest with AUB.

2. Dysfunctional (or Endocrinologic) Causes (anovulatory or ovulatory


dysfunctional uterine bleeding)
WW"

Dysfunctional uterine bleeding (DUB) is usually anovulatory and is


associated with a non-secretory endometrium. It is most common after the
menarche or just before the menopause, but it may occur at other times as
well.

In puberty, the HPO axis has not yet developed the necessary hormonal
feedback to sustain the endometrium.

In perimenopause, the decline of inhibin and rise in follicle-stimulating


hormone (FSH) levels reflect the loss of follicular activity and
competence.

Prolonged DUB may result from a persistent graafian follicle. In such


cases, withdrawal of estrogen leads to a delayed endometrial shedding and
irregular bleeding. The bleeding is caused by estrogenic overstimulation
followed by withdrawal or diminution of estrogen, unopposed by
progesterone.

High sustained levels of estrogen result in episodes of amenorrhea


followed by acute heavy bleeding. Healing within the endometrium is
irregular and dyssynchronous.

Abnormal uterine bleeding may reflect a disordered regulation of


endometrial gene expression.

Despite a wealth of studies on this very common clinical entity,


explanations on many of the cellular and molecular alterations in
endometrial pathologies remain to be elusive and have yet to be fully
elucidated.

References:
1.
2.
3.
4.
5.
6.

Albers JR, Huli SK, Wesley MA. Abnormal Uterine Bleeding. Am Fam Physician 2004;
69:1915-26; 1931-2.
Berek JS. Berek & Novaks Gynecology. 14th ed. Philadelphia, PA: Lippincott Williams &
Wilkins, 2007.
Garefalakis M, Hickey M. Present understanding of abnormal uterine bleeding mechanisms.
Gynaecology Forum 2007 Vol. 12, No. 2: 6-8.
Lukes AS. The role of disorders of hemostasis and abnormal uterine bleeding. Gynaecology
Forum 2007 Vol. 12, No. 2: 14-19.
Munro MG. Acute uterine bleeding unrelated to pregnancy. Gynaecology Forum 2007 Vol.
12, No. 2: 11-14.
Wynn RM. Obstetrics and Gynecology the clinical core. 5th ed. Philadelphia, PA: Lea &
Febiger, 1992.

III. EPIDEMIOLOGY

WL"

Abnormalities in menstruation are a common cause of general practice


consultations with considerable health-service resources devoted to their
management.1

W]"

Women who report one or more menstrual symptoms have significantly


lower health status and quality of life compared with women reporting no
menstrual symptoms.3

Women with heavier periods are 72% as likely to be working as women


who have normal flow. Menstrual abnormalities, especially heavy periods,
have significant economic implications, and work loss secondary to heavy
periods has been estimated to cost $1692 per woman annually.4

The 12-month cumulative incidence of AUB are as follows5:


o Menorrhagia 25% (95% CI 2229%)
o Metrorrhagia 29% (95% CI 2632%)
o Oligomenorrhea 15% (95% CI 1318%)
o Intermenstrual bleeding 17% (95% CI 1419%)
o Postcoital bleeding 6% (95% CI 58%)

The modern-day definition of menorrhagia is a blood loss of > 80 ml but it


is of limited clinical usefulness since the diagnosis and treatment of
patients appears to be unrelated to the volume of blood loss. Subjective
judgment of the volume lost in combination with clinical features can
predict a loss of > 80 ml.6,7

Menstrual problems are common during adolescence due to a relatively


immature hypothalamo-pituitary-ovarian (HPO) axis leading to
anovulation.8

Anovulation (46%) was the predominant cause of admission for adolescent


menorrhagia, followed by hematological disease (33%) and unfortunately,
nearly 63% of adolescents required blood transfusion in view of severe
anemia.9

A Nepal survey of 96 school girls with an age range of 1117 years,


menorrhagia was identified in 6.2% of girls. Nearly 10% of girls gave a
history of hypomenorrhea and 6.9% had oligomenorrhiec cycles.10

A population-based survey of 1019 Swedish girls with a mean age of 16.7


years found that nearly 37% of girls experienced menorrhagia and onefifth of them were being treated with drugs for this condition. A family
history of menorrhagia was documented in 38% of girls and more than
50% of them suffered from heavy periods themselves.11

A postal survey of 4610 women (aged 2544 years) in Scotland found that
3035% of women reported menorrhagia.12

In a cross-sectional survey of 2262 women of reproductive age (1845


years), moderate-to-severe dysmenorrhea was reported in 33.4% of
participants (95% CI 31.435.4%) with the incidence of dysmenorrhea
being 1.92 times higher in women with menorrhagia (95% CI 1.42.6).13

Menstrual irregularities are more common in female athletes and in those


who begin training prior to menarche (43%). AUB in athletes has

significant associations with low body fat and weight and the stress of
sports activity. Ball-game players (35%) and distance runners (51%) most
commonly experience oligomenorrhea or amenorrhea, whereas swimmers
(37%) and sprinters (41%) experience dysmenorrhea and menorrhagia.14
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.

Coulter A, McPherson K & Vessey M. Do British women undergo too many or too few
hysterectomies? Soc Sci Med 1988; 27: 987994.
Barnard K, Frayne SM, Skinner KM et al. Health status among women with menstrual
symptoms. J Womens Health (Larchmt) 2003; 12: 911919.
Cote I, Jacobs P & Cumming D. Work loss associated with increased menstrual loss in the
United States. Obstet Gynecol 2002; 100: 683687.
Shapley M, Jordan K & Croft PR. An epidemiological survey of symptoms of menstrual loss in
the community. Br J Gen Pract 2004; 54: 359363.
Warner PE, Critchley HO, Lumsden MA et al. Menorrhagia I: measured blood loss, clinical
features, and outcome in women with heavy periods: a survey with follow-up data. Am J
Obstet Gynecol 2004; 190: 12161223.
Warner PE, Critchley HO, Lumsden MA et al. Menorrhagia II: is the 80-mL blood loss
criterion useful in management of complaint of menorrhagia? Am J Obstet Gynecol 2004;
190: 12241229.
Quint EH & Smith YR. Abnormal uterine bleeding in adolescents. J Midwifery Womens
Health 2003; 48:186191.
Smith YR, Quint EH & Hertzberg RB. Menorrhagia in adolescents requiring hospitalization. J
Pediatr Adolesc Gynecol 1998; 11: 1315.
Sharma M & Gupta S. Menstrual pattern and abnormalities in the high school girls of
Dharan: a cross sectional study in two boarding schools. Nepal Med Coll J 2003; 5: 3436.
Friberg B, Orno AK, Lindgren A et al. Bleeding disorders among young women: a
population-based prevalence study. Acta Obstet Gynecol Scand 2006; 85: 200206.
Santer M, Warner P & Wyke S. A Scottish postal survey suggested that the prevailing clinical
preoccupation with heavy periods does not reflect the epidemiology of reported symptoms and
problems. J Clin Epidemiol 2005; 58: 12061210.
Patel V, Tanksale V, Sahasrabhojanee M et al. The burden and determinants of
dysmenorrhoea: a population-based survey of 2262 women in Goa, India. Br J Obstet
Gynaecol 2006; 113: 453463.
Toriola AL & Mathur DN. Menstrual dysfunction in Nigerian athletes. Br J Obstet Gynaecol
1986; 93: 979985.

IV. DIAGNOSIS
Diagnosis of Heavy Menstrual Bleeding
1. History
2. Physical Examination
3. Blood Tests
4. Imaging Procedures
Statement 1
Wa"

A detailed history should be obtained, which should include inquiry into the
character and nature of bleeding, related symptoms that may implicate a
structural or histologic abnormality, family history, contraceptive history, as
well as presence of co-morbid factors. (III, C)
Supporting Statements:
The clinical history should focus on the probable causes of abnormal menstrual
bleeding by determining the interval, amount, frequency, and duration of bleeding.
Pregnancy must always be excluded. Symptoms such as intermenstrual or postcoital
bleeding, pelvic pain and/or pressure symptoms, suggest structural or histologic
abnormality.1 Risk factors for endometrial carcinoma should be sought. Family
history should investigate risks for cancer, coagulopathies, and other medical
conditions that can cause abnormal uterine bleeding.2
References
1. Penny GC. The investigation of menorrhagia. In: Disorders of the Menstrual Cycle. London:
RCOG press, 2000. Chapter 16.
2. Higham JM, Page LM, Mohan S. How do we assess abnormal uterine bleeding?
Gynaecology Forum 2007; 12(2): 8-10.

Statement 2
Physical examination should be performed to identify any structural pathology
or systemic disease as the etiology for abnormal uterine bleeding. (III, C)
Supporting Statements:
General survey should include assessment for anemia, thyroid disease and
coagulopathies. Abdominal palpation may detect an enlarged uterus.1 Pelvic
examination to inspect the vulva, vagina and cervix is essential to exclude any gross
pathology. Bimanual examination will allow assessment of the uterine size, pelvic
tenderness and adnexal masses.
References
1. National Collaborating Centre for Womens and Childrens Health; National Institute for
Health and Clinical Excellence. Heavy menstrual bleeding. Clinical guideline. 24 January
2007. London: RCOG Press, 2007.

Statement 3
A complete blood count should be obtained from all women with abnormal
uterine bleeding. (III, C)
Supporting Statements:
A full blood count should be obtained to identify women with anemia. Five
epidemiological studies showed that anemia is an associated problem for women with
HMB.1-5 These studies show that MBL and iron-deficiency anemia are linked, with
iron deficiency becoming a clinical problem at a menstrual blood loss of 6080 ml.
Iron supplements should be prescribed as needed.6 Serum ferritin level may be useful
if there is any doubt on iron deficiency,7 but should not be part of routine
investigation.8
References

Wg"

1.
2.
3.
4.
5.
6.
7.
8.

Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United
States. JAMA: the journal of the American Medical Association 1997;277(12):9736.
Hallberg L, Hogdahl AM, Nilsson L, et al. Menstrual blood loss--a population study.
Variation at different ages and attempts to define normality. Acta Obstetricia et Gynecologica
Scandinavica 1966;45(3):32051.
Andrade AT, Souza JP, Shaw ST Jr, et al. Menstrual blood loss and body iron stores in
Brazilian women. Contraception 1991; 43(3):2419.
Janssen CA, Scholten PC, Heintz AP. Reconsidering menorrhagia in gynecological practice.
Is a 30-year-old definition still valid? European Journal of Obstetrics, Gynecology, and
Reproductive Biology 1998;78(1):6972.
Gao J, Zeng S, Sun BL, et al. Menstrual blood loss and hematologic indices in healthy
Chinese women. Journal of Reproductive Medicine 1987;32(11):8226.
Royal College of Obstetricians and Gynaecologists. The Management of Menorrhagia in
Secondary Care. National Evidence Based Clinical Guideline No 5. London: RCOG, 1999.
Fraser IS. Menorrhagia a pragmatic approach to the understanding of causes and the need
for investigations. Br J Obstet Gynaecol 1994; 101(supplement 11): 37.
National Collaborating Centre for Womens and Childrens Health; National Institute for
Health and Clinical Excellence. Heavy menstrual bleeding. Clinical guideline. 24 January
2007. London: RCOG Press, 2007.

Statement 4
Coagulation tests may be considered only in women with HMB at an early age
(since menarche), and have personal or family history suggestive of a
coagulopathy. (III, C)
Supporting Statements:
Universal screening for coagulation disorders in women with HMB is not costeffective. A review of 11 studies (988 women) on the prevalence of Von Willebrand
disease in women with HMB showed that the prevalence in individual studies ranged
from 5% to 24%, with an overall prevalence rate of 13% (95% CI 11.0-15.6).1 A
personal and family history of bleeding symptoms is a valid reason for investigation.
Any one of the following aspects in the history taking should prompt the clinician to
work-up the woman for a coagulation disorder: HMB since menarche, postpartum
hemorrhage, surgery-related bleeding, and/or bleeding associated with dental work.2
References
1. Shankar M, Lee CA, Sabin CA, et al. Von Willebrand disease in women with menorrhagia: a
systematic review. Br J Obstet Gynaecol 2004; 111: 734-40.
2. Kouides PA, Conard J, Peyvandi F, et al. Hemostasis and menstruation: appropriate
investigation for underlying disorders of hemostasis in women with excessive menstrual
bleeding. Fertil Steril 2005; 84: 1345-51.

Statement 5
Female hormone testing (estradiol, progesterone, LH, FSH) should not be
routinely done on women with HMB. Thyroid screening should only be obtained
in the presence of signs and/or symptoms of thyroid disease. 3 III, C
Supporting Statements:
Epidemiological studies have found no link between hormone levels and heavy
menstrual bleeding.1-2 One casecontrol study (n = 428) found no link between
thyroid disorders and menstrual disturbances. Of the 214 women with thyroid
disorders, 168 (78.5%) had regular menstrual cycles and 46 (21.5%) had irregular
cycles. Out of 214 normal controls, matched for age and weight, 196 (91.6%) had
normal menstruation and 18 (8.4%) had irregular cycles.3
Wd"

References
1. Eldred JM, Thomas EJ. Pituitary and ovarian hormone levels in unexplained menorrhagia.
Obstetrics and Gynecology 1994;84(5): 7758.
2. Haynes PJ, Anderson ABM, Turnbull AC. Patterns of menstrual blood loss in menorrhagia.
Research and Clinical Forums 1979;1(2): 738.
3. Krassas GE, Pontikides N, Kaltsas T, et al. Menstrual disturbances in thyrotoxicosis. Clinical
Endocrinology 1994;40(5):6414.

Statement 6
Pregnancy test should be done in women of reproductive-age group. (III, C)
Supporting Statements:
Pregnancy is the primary consideration of abnormal uterine bleeding in women of
childbearing age.1 Possible causes of pregnancy-related bleeding include abortion,
ectopic pregnancy, placenta previa, abruptio placenta, and trophoblastic disease.2 A
bimanual pelvic exam (to assess uterine size), beta-hCG test and pelvic ultrasound are
useful in ruling out pregnancy-related causes.
References
1. Shwayder JM. Pathophysiology of abnormal uterine bleeding. Obstet Gynecol Clin North Am
2000;27:219-34.
2. Albers JR, Hull SK, Wesley RM. Abnorma uterine bleeding. Am Acad Fam Physician 2004.

Statement 7
Ultrasound is the first-line diagnostic tool
abnormalities. (I, A)

for identifying

structural

Supporting Statements:
Transvaginal ultrasound (TVUS) may reveal myomas, endometrial thickening, or
focal masses. It is highly sensitive for detecting endometrial carcinoma (96%) and
endometrial abnormality (92%).1 TVUS is most sensitive in detecting disease in
women with postmenopausal bleeding, since a cutoff of 5 mm or less reliably
excludes endometrial cancer. Evidence suggests that measurement of endometrial
thickness via TVUS can accurately discriminate between women at high and low risk
of endometrial cancer. In a meta-analysis of > 6,000 women with postmenopausal
bleeding, the use of a 5 mm cut-off to define abnormal endometrium identified 96%
of women with endometrial cancer and 92% of women with any endometrial
pathology with a false-positive rate of 39% and 10%, respectively.2
In premenopausal women, endometrial thickness varies between the proliferative
phase (4 to 8 mm) and the secretory phase (8 to 14 mm), and TVUS should be
scheduled between days 4 to 6 of the menstrual cycle, when the endometrium is the
thinnest. Transvaginal ultrasound allows rapid assessment of size, position, and
presence of uterine fibroids. The texture of the endometrium can be evaluated for
homogeneity or heterogeneity. Adnexal pathology and pelvic tenderness can be
assessed. Measurement of the endometrial echo in postmenopausal women is helpful
in determining whether endometrial biopsy or further imaging studies are necessary.
Normally, the endometrial echo measures less than 5 mm. Increased endometrial
thickness is associated with intrauterine synechiae, endometrial hyperplasia,
endometrial polyps, fibroids, and endometrial cancer. When the endometrium is
We"

greater than 5 mm, cannot be visualized completely, is indistinct or indeterminate, an


enhanced view is required with saline infusion sonography (SIS) or hysteroscopy. An
endometrial echo of less than 5 mm is associated with malignancy in less than 0.5%
of cases.3
A systematic review studied the use of ultrasound, sonohysteroscopy and
hysteroscopy in an AUB population. The review showed a wide range in variation of
results. For identification of any intrauterine pathology, transvaginal ultrasound (TVS)
(10 studies) had a sensitivity range of 48100% and specificity of 12100%. For
sonohysteroscopy (11 studies) the range of sensitivity was 85100% and for
specificity it was 50100%. For hysteroscopy (3 studies) the range of sensitivity was
9097% and for specificity it was 6293%. The review concluded that all three
methods were at least moderately accurate at identifying uterine pathology.4 A second
review also showed a range of results for the various investigations.5
References
1. Tabor A, Watt HC, Wald NJ. Endometrial thickness as a test for endometrial cancer in women
with post menopausal vaginal bleeding. Obstet Gynecol 2002;99:663-70.
2. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al: Endovaginal ultrasound to exclude
endometrial cancer and other endometrial abnormalities. JAMA 1998;20:15101517.
3. Weber A, Belinson JL, Bradley LD, et al: Vaginal ultrasonography versus endometrial biopsy
in women with postmenopausal bleeding. Am J Obstet Gynecol. 1997;177:924929.
4. Farquhar C, Ekeroma A, Furness S, et al. A systematic review of transvaginal
ultrasonography, sonohysterography and hysteroscopy for the investigation of abnormal
uterine bleeding in premenopausal women. Acta Obstetricia et Gynecologica Scandinavica
2003;82(6):493504.
5. Dueholm M, Lundorf E, Olesen F. Imaging techniques for evaluation of the uterine cavity and
endometrium in premenopausal patients before minimally invasive surgery. Obstetrical and
Gynecological Survey 2002;57(6):389403.

Statement 8
Saline-infusion sonography should not be used as first-line diagnostic tool, but
may be useful in providing a more accurate evaluation of the uterus with
intracavitary lesions. (I, A)
Supporting Statements:
Saline infusion sonography infuses saline into the endometrial cavity during TVUS to
enhance the image. Confirmation of an intracavitary mass (submucous fibroid or
polyp) is improved substantially with SIS.1-2 A meta-analysis involving 16 studies on
saline contrast hysterosonography for AUB showed pooled sensitivity of 95% and
specificity of 88%. The review concluded that saline infusion sonography was an
accurate method for investigation of uterine pathology.3 However, it should not be
used as first-line in the investigation of AUB.4
References
1. Justin Clark T. Outpatient hysteroscopy and ultrasonography in the management of
endometrial disease. Curr Opin Obstet Gynecol 2004; 16: 305311.
2. Widrich T, Bradley L, Mitchinson AR, et al: Comparison of saline infusion sonography with
office hysteroscopy for the evaluation of the endometrium. Am J Obstet Gynecol
1996;174:13271334.
3. De Kroon CD, de Bock GH, Dieben SW, et al. Saline contrast hysterosonography in abnormal
uterine bleeding: a systematic review and meta-analysis. BJOG: an International Journal of
Obstetrics and Gynaecology 2003; 110:(10)93847.

Wf"

4.

National Collaborating Centre for Womens and Childrens Health; National Institute for
Health and Clinical Excellence. Heavy menstrual bleeding. Clinical guideline. 24 January
2007. London: RCOG Press, 2007.

Statement 9
Hysteroscopy should be used as a diagnostic tool only when ultrasound results
are inconclusive, e.g. to determine the exact location of a fibroid or the exact
nature of an abnormality. (I, A)
Supporting Statements:
Modern hysteroscopes combine miniaturization with excellent image resolution and
visualization.1 It is better at identifying polyps than ultrasound.2 Hysteroscopy allows
direct visualization of the endometrial cavity and, importantly, targeted endometrial
sampling of any suspicious areas. A review of 65 papers on the use of hysteroscopy in
endometrial disease found that hysteroscopy is accurate at identifying endometrial
cancer (sensitivity = 86.4%, specificity = 99.2%), but less so at identifying
endometrial disease (sensitivity = 78%, specificity = 95.8%).3
References
1. Fraser IS. Menorrhagia a pragmatic approach to the understanding of causes and the need
for investigations. Br J Obstet Gynaecol 1994; 101(supplement 11): 37.
2. National Collaborating Centre for Womens and Childrens Health; National Institute for
Health and Clinical Excellence. Heavy menstrual bleeding. Clinical guideline. 24 January
2007. London: RCOG Press, 2007.
3. Clark TJ, Voit D, Gupta JK, et al. Accuracy of hysteroscopy in the diagnosis of endometrial
cancer and hyperplasia: a systematic quantitative review. JAMA: the Journal of the American
Medical Association 2002;288(13):161021.

Statement 10
Endometrial biopsy may be performed in symptomatic women who are at high
risk for the disease. Endometrial sampling is recommended for: 1
1. Any postmenopausal woman with bleeding or premenopausal woman
with heavy and/ or irregular vaginal bleeding;
2. Postmenopausal women with endometrial cells seen on pap smear or
premenopausal women with atypical glandular cells on pap smear;
3. Breast cancer patients on Tamoxifen who complain of abnormal vaginal
bleeding; and
4. Women who are still menstruating after 52 years of age
Reference
1. Society of Gynecologic Oncologists of the Philippines. General Guidelines for the General
Obstetrician and Gynecologist: SGOP, 2003.

V. MANAGEMENT
A. Medical Management of Acute Heavy Menstrual Bleeding
1. High dose estrogen
2. High dose combined oral contraceptives
3. Progestins
4. Tranexamic acid
WM"

Statement 1
Medical management of non-gestational acute AUB should be considered before
any surgical procedure, unless bleeding is suspected to be due to intrauterine
lesions (i.e. submucous myoma).1 (III, C)
Reference
1. Munro MG. Acute uterine bleeding unrelated to pregnancy. Gynaecol Forum 2007;12 (2):1114.

Statement 2
High dose conjugated equine estrogen is effective in treating acute severe
abnormal uterine bleeding. (I, A)
Supporting Statements:
One randomized trial showed that intravenous conjugated equine estrogen (CEE) was
effective in treating non-pregnant acute uterine bleeding.1 In this study, 25 mg
intravenous CEE every 4 hours stopped the bleeding within 5 hours in 72% of the
treatment group versus 38% of the placebo group. In another review, oral CEE 2.5 mg
every 6 hours was recommended as outpatient management of severe acute bleeding
in the non-pregnant woman.2 Promethazine was given as needed for nausea. Such
regimen is continued for 24 hours, to achieve hemodynamic stability.
References
1. DeVore GR, Owens O, Kase N. Use of intravenous Premarin in the treatment of dysfunctional
uterine bleeding- a double-blind randomized control study. Obstet Gynecol 1982;59:285-91.
2. Ely JW, et al. Abnormal uterine bleeding: a management algorithm. J Am Board Fam Med
2006;19:590-602.

Statement 3
Combined oral contraceptive pills may be used to treat acute AUB. (I, B)
Supporting Statements:
Combined oral contraceptives (COCs) are frequently used in treating acute AUB
despite the relative lack of evidence. In a modest-sized randomized controlled trial,
COC containing 35 ug ethinylestradiol and 1 mg norethisterone was equivalent to a
progesterone-only regimen; bleeding stopped within 3 days when the COC was given
3 times a day for a week and then tapered to once a day for 3 weeks.1 In the algorithm
for treating acute AUB, a tapering schedule of COCs was recommended.2 The
regimen is 30 ug ethinylestradiol/norgestrel 0.3 mg 1 active pill 4 times a day for 4
days, followed by 3 times daily for 3 days, then 2 times a day for 2 days, then once
daily for 3 weeks.
References
1. Munro MG, Mainor N, Basu R, et al. Oral medroxyprogesterone acetate and combination
oral contraceptives for acute uterine bleeding: a randomized trial. Obstet Gynecol
2006;108:924-9.
2. Ely JW, et al. Abnormal uterine bleeding: a management algorithm. J Am Board Fam Med
2006;19:590-602.

Statement 4
There is limited evidence that oral progestogens are effective in treating acute,
L!"

heavy menstrual bleeding. (II, B)


Supporting Statements:
In one study (24 adolescents hospitalized for excessive bleeding and anemia), oral
medroxyprogesterone acetate (MPA) was given at a dose of 60-100 mg for the first
day and 20 mg/day for the next 10 days.1 This resulted to a reduction in blood loss in
all patients (25% stopped bleeding within 24 hours, the rest by the fourth day). In an
RCT, 60 mg /day for a week, followed by 20 mg/day, stopped bleeding on average on
day 3 of the regimen.2 Norethisterone acetate (5-15 mg/day) daily until cessation of
bleeding for at least 2 days, followed by 5-10 mg/day for 3-6 weeks, is another
alterntive.3
References
1. Aksu F, Madazli R, Budak E, et al. High-dose medroxyprogesterone acetate for the treatment
of dysfunctional uterine bleeding in 24 adolescents. Aust NZ J Obstet Gynaecol 1997;37:22831.
2. Munro MG, Mainor N, Basu R, et al. Oral medroxyprogesterone acetate and combination
oral contraceptives for acute uterine bleeding: a randomized trial. Obstet Gynecol
2006;108:924-9.
3. Munro MG. Acute uterine bleeding unrelated to pregnancy. Gynaecol Forum 2007;12 (2):1114.

Statement 5
Tranexamic acid may be used to treat of acute AUB. (I, A)
Supporting Statements:
In one study, menorrhagia treatment for five days from day 1 of menses during three
consecutive menstrual periods was done on 76 patients. Twenty-seven (27) patients
were randomised to take ethamsylate 500 mg six hourly, 23 patients to take
mefenamic acid 500 mg eight hourly, and 26 patients to take tranexamic acid 1 g six
hourly. Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic
acid reduced blood loss by 20% (mean blood loss 186 ml before treatment, 148 ml
during treatment) and tranexamic acid reduced blood loss by 54% (mean blood loss
164 ml before treatment, 75 ml during treatment). Sanitary towel usage was
significantly reduced in patients treated with mefenamic acid and tranexamic acid.
Tranexamic acid given during menstruation is a safe and highly effective treatment for
excessive bleeding.
Reference
1. Bonnar J & Sheppard BL. Treatment of menorrhagia during menstruation: randomised
controlled trial of ethamsylate, mefenamic acid and tranexamic acid. BMJ 1996;313:579-582.

B. Medical Management of Chronic Heavy Menstrual Bleeding


1. Levonorgestrel-releasing intrauterine system (LNG-IUS)
2. Antifibrinolytic agents (AFA)
3. Nonsteroidal anti-inflammatory drugs (NSAIDs)
4. Combined oral contraceptives
5. Cyclic progestogen
6. Danazol

LW"

Statement 1
The Levonorgestrel-releasing intrauterine system (LNG IUS) is a highly effective
treatment for heavy menstrual bleeding, with the additional benefit of relieving
dysmenorrhea. (I, A)
Supporting Statements:
The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective,
reversible contraceptive with the additional benefits of reducing blood loss and
dysmenorrhea. The LNG-IUS reduces endometrial thickness and vascularity, leading
to a marked reduction in blood loss. Recent evidence shows that LNG-IUS normalizes
blood flow in women with heavy menstrual bleeding, with 35% being amenorrheic at
2 years (Busfield et al, 2006). A meta-analysis of 9 RCTs comparing progesterone
releasing IUS with cyclic oral norethisterone (days 5-26 of cycle) showed that the IUS
was significantly more effective in reducing blood loss. Women with an LNG IUS are
more satisfied and willing to continue with treatment but experience more side effects,
such as intermenstrual bleeding and breast tenderness. When compared with
endometrial ablation, the LNG IUS results in a lesser reduction in menstrual blood
loss but there is no evidence of a difference in the rate of satisfaction with treatment.
In one trial of women awaiting hysterectomy, where the LNG IUS was compared
with a control group taking their existing medical therapy, a higher proportion of the
women in the intrauterine device group cancelled their planned surgery after six
months of treatment.
References:
1. Busfield RA, Farquhar CM, Sowter MC, et al. A randomized trial comparing the levonorgestel
intrauterine system and thermal balloon ablation for heavy menstrual bleeding. Br J Obstet
Gynaecol 2006; 113:257-63.
2. Lethaby A, Cooke I, Rees MC. Progesterone or progestogen-releasing intrauterine systems for
heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2005, Issue 4.

Statement 2
Antifibrinolytic therapy causes a greater reduction in heavy menstrual bleeding
when compared with placebo or other medical treatments (NSAIDs, oral luteal
progestogens and ethamsylate). This treatment is not associated with an increase
in side effects compared to placebo or other medical therapies (NSAIDs, oral
luteal progestogens, ethamsylate). (I, A)
Supporting Statements:
Antifibrinolytic agents inhibit plasminogen activation and subsequently fibrinolysis.
An increase in the levels of plasminogen activators has been found in the
endometrium of women with heavy menstrual bleeding compared with those with
normal menstrual loss. A meta-analysis of four randomized controlled trials compared
antifibrinolytic agents versus placebo or other medical therapies (NSAIDs, oral luteal
progestogen and ethamsylate). Results showed a significant reduction in mean blood
loss with antifibrinolytic therapy compared to placebo (WMD -94.0, 95% CI -151.4 to
-36.5). In all studies comparing antifibrinolytics with mefenamic acid, luteal
norethisterone and ethamsylate, results showed a significant reduction in mean blood
LL"

loss (WMD -73.0, 95% CI -123.4 to -22.6; WMD -111.0, 95% CI -178.5 to -43.5; and
WMD -100, 95% CI -143.9 to -56.1, respectively) and a strong, although nonsignificant trend in favor of tranexamic acid in the participants perception of an
improvement in menstrual blood loss. Moreover, there was no associated increase in
side effects compared to placebo and other medical therapies.
Reference:
1. Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane
Database of Systematic Reviews 2000, Issue 4.

Statement 3
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce heavy menstrual
bleeding when compared with placebo, but are less effective than tranexamic
acid, danazol, or levonorgestrel-releasing intrauterine system (LNG-IUS).
Limited evidence shows no significant difference in efficacy between NSAIDs
and oral luteal progestogen, ethamsylate, or oral contraceptive pill. (I, A)
Supporting Statements:
A rationale for the use of nonsteroidal anti-inflammatory drugs is due to an
accumulation of data suggesting a role for prostaglandins in the pathogenesis of HMB
(Hagenfeldt 1987). The endometrium of women with excessive menstrual bleeding
has been found to have higher levels of prostaglandin E2 and prostaglandin F2a when
compared with women with normal menses; using an NSAID may reduce
prostaglandin production by inhibiting the enzyme cyclo-oxygenase.
In the latest Cochrane review of nonsteroidal anti-inflammatory drugs for heavy
menstrual bleeding, seventeen randomized controlled trials comparing individual
NSAIDs with each other, placebo or other medical treatments in women with heavy
menstrual bleeding were analyzed. Seven crossover trials were also described.
Results showed that NSAIDs were more effective than placebo, but less effective than
tranexamic acid, danazol, LNG-IUS, in reducing heavy menstrual bleeding. In a
limited number of studies with small sample sizes, there were no statistically
significant differences between NSAIDs and other medical treatments like oral luteal
progestogen, ethamsylate, and oral contraceptive. Lastly, there was no difference in
efficacy between different NSAIDs (naproxen and mefenamic acid) in reducing heavy
menstrual bleeding.
References:
1. Hagenfeldt K. The role of prostaglandins and allied substances in uterine haemostasis.
Contraception 1987;36(1):2335.
2. Lethaby A, Augood C, Duckitt K, Farquhar C. Nonsteroidal anti-inflammatory drugs for heavy
menstrual bleeding. Cochrane Database of Systematic Reviews 2007, Issue 4.

Statement 4
Combined oral contraceptives may be an alternative in the medical management
of heavy menstrual bleeding. There was no significant difference in menstrual
blood loss (MBL) between treatments with OCP, danazol, and NSAIDs. (I, B)
Supporting Statements:
A Cochrane database systematic review found only one small (45 patients)
randomized, cross-over trial investigating the combined oral contraceptive in the
L]"

treatment of heavy menstrual bleeding (Frasier 1991). Treatments given were


mefenamic acid, naproxen, low dose danazol and a combined oral monophasic
contraceptive pill. There was no significant difference in menstrual blood loss
reduction between those patients treated with the OCP and danazol, mefenamic acid
or naproxen.
References:
1. Iyer V, Farquhar C, Jepson RG. Oral contraceptive pills for heavy menstrual bleeding.
Cochrane Database of Systematic Reviews 1997, Issue 2.
2. Frasier IS, McCarron G. Randomized trial of 2 hormonal and 2 prostaglandin inhibiting agents
in women with a complaint of menorrhagia. Aust NZ J Obstet Gynaecol 1991; 31: 66-70.

Statement 5
Cyclic progestogen given for twenty one (21) days for ovulatory bleeding results
in a significant reduction in blood loss, although it has no advantage over other
medical therapies (NSAIDs, tranexamic acid, danazol, and IUS). (I, A)
Supporting Statements:
A meta-analysis of seven randomized controlled trials compared cyclic progestogen
with other medical therapies such as danazol, tranexamic acid, non-steroidal antiinflammatory drugs (NSAIDs) and the IUS. Progestogens administered from day 15
or 19 to day 26 of the cycle offer no advantage over other medical therapies in the
treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for
21 days of the cycle results in a significant reduction in menstrual blood loss, although
women found the treatment less acceptable than intrauterine levonorgestrel. This
regimen of progestogen may have a role in the short-term treatment of menorrhagia.
Reference:
1. Lethaby A, Irvine GA, Cameron IT. Cyclical progestogens for heavy menstrual bleeding.
Cochrane Database of Systematic Reviews 2008, Issue 1.

Statement 6
Danazol appears to be an effective treatment for heavy menstrual bleeding
compared to other medical treatments. However, danazol use may be limited by
its side effect profile, its acceptability to women and the need for continuing
treatment. (I, A)
Supporting Statements:
Danazol appears to be more effective than placebo, progestogens, NSAIDs and the
OCP at reducing MBL. This is based on nine randomized controlled trials (353
women), but majority of which are unsuitable for meta-analysis. Results are based on
a small number of trials, all of which are underpowered, and with wide confidence
intervals. Treatment with Danazol caused more adverse events than NSAIDs (OR 7.0;
95% CI 1.7 to 28.2) and progestogens (OR 4.05, 95% CI 1.6 to10.2). The small
number of trials, and the small sample sizes of the included trials limit the
recommendations for clinical care. Further studies are unlikely in the future and this
review will not be updated unless further studies are identified.
Reference:
1. Beaumont HH, Augood C, Duckitt K, Lethaby A. Danazol for heavy menstrual bleeding.
Cochrane Database of Systematic Reviews 2007, Issue 3.

La"

!
C. Surgical Management of Heavy Menstrual Bleeding
1. Dilatation and curettage
2. Endometrial ablation
3. Hysterectomy
Statement 1
Dilatation and curettage should not be used as a therapeutic treatment. (III, C)
Supporting Statements:
The observational study (n = 22) showed that MBL was reduced for 1 month after
dilatation and curettage but then returned to previous levels.1 There were no
systematic reviews or RCTs.
Reference:
1. Haynes PJ, Hodgson H, Anderson AB, et al. Measurement of menstrual blood loss in patients
complaining of menorrhagia. British Journal of Obstetrics and Gynaecology 1977;
84(10):7638.

Statement 2
Dilatation and curettage may be performed for acute heavy mesntrual bleeding
unresponsive to initial medical management. (III, C)
Reference:
1. Ely JW. Journal of American Board of Family Medicine. 2007.

Statement 3
Endometrial ablation may be offered as an initial treatment for heavy menstrual
bleeding. It should be considered in women who have a normal uterus and also
those with small uterine fibroids (less than 3 cm in diameter). In women with
heavy menstrual bleeding alone, with uterus no bigger than a 10-week
pregnancy, endometrial ablation should be considered preferable to
hysterectomy. Second-generation ablation techniques should be used where no
structural or histological abnormality is present. [I, A]
Supporting Statements:
Three reviews and one RCT show that endometrial ablation and resection methods
produce clinically relevant reductions in MBL and are associated with improvements
in quality of life. Transcervical resection of the endometrium (TCRE), microwave
endometrial ablation (MEA), thermal balloon endometrial ablation (TBEA) and
rollerball endometrial ablation (REA) techniques appear to be largely equivalent to
one another in terms of clinical outcome, although one RCT found that MEA is
superior to TCRE in terms of satisfaction at 5 years follow-up. Endometrial ablation
and resection techniques are marginally less effective than hysterectomy at improving
MBL and quality of life. Inclusion criteria of RCTs showed that uterine fibroids < 3
cm in size were allowable.. When compared with hysterectomy, both TBEA and
Lg"

MEA are less costly, but result in slightly fewer QALYs. MEA performed in an
outpatient setting under local anaesthetic compares favourably in terms of cost with
standard MEA in a day-case setting after drug preparation of the endometrium.
Endometrial ablation versus other treatments
Hysterectomy was compared with endometrial ablation in a systematic review.
Hysterectomy provided greater reductions in MBL.(at 12 months (three studies, n =
440) OR 0.12 [95% CI 0.06 to 0.25]). More patients favored hysterectomy (at 12
months (three studies, n = 519) OR 0.46 [95% CI 0.24 to 0.88] and at 24 months
(three studies, n = 354) OR 0.31 [95% CI 0.16 to 0.59]). Quality of life measures SF36) showed no difference between groups. Endometrial ablation techniques required
less time to undertake ((five studies, n = 706) WMD = "23.06 [95% CI "23.80 to
"22.32] in favor of ablation/resection), shorter hospital stays ((five studies, n = 706)
WMD = "4.91 [95% CI "4.95 to "4.87]) and fewer adverse events. Of the 13 types of
adverse event reported, results favored ablation/resection over hysterectomy for eight
of these, and five were no different. However, more women in the endometrial
ablation groups required further surgery within 12 months ((five studies, n = 706) OR
7.33 [95% CI 4.18 to 12.86]). It was concluded that ablation/resection is an alternative
to hysterectomy. Ablation/resection is less effective at reducing MBL and improving
satisfaction. Ablation/resection, however, leads to shorter surgery, shorter hospital
stay and fewer complications.1
Endometrial ablation/resection
There is one systematic review which examined the effectiveness and safety of MEA
and TBEA for DUB. Amenorrhea rates at 12 months reported by seven trials ranged
from 36% to 40% for MEA and from 10% to 40% for TBEA. The review also
reported significant reductions in levels of MBL or reclassification of bleeding
patterns for both MEA and TBEA. There were high levels of satisfaction (> 75%) for
both MEA and TBEA. The review concluded that both MEA and TBEA were
equivalent to first-generation ablation techniques.2 A second systematic review (19
RCTs) compared the various ablation techniques with one another for treatment of
DUB. Only limited differences were found when comparing one ablation method with
another.3
Laser ablation versus TCRE
There were two RCTs (n = 388) were identified. There was no difference between
laser ablation and TRCE for amenorrhea rates, satisfaction, HRQoL or complications.
Vaporizing electrode ablation versus TCRE
One RCT (n = 91) was identified. There were no differences between methods for
amenorrhea rates, satisfaction or HRQoL.
REA versus TCRE
There was no difference between techniques in terms of future hysterectomy or resurgery at 2 and 5 years follow-up.
Thermal laser ablation versus TCRE
One RCT (n = 111) was identified. There were no differences between groups for
menorrhagia, re-surgery, complications or satisfaction.
Hydrothermablation versus REA
Ld"

One RCT (n = 269) was identified. Hydrothermablation patients were more likely to
have local than general anesthesia (OR 2.9 [95% CI = 1.6 to 5.1]) and were less likely
to experience hematometra (OR 0.18 [95% CI 0.03 to 0.93]) but were more likely to
have abdominal pain (OR 1.9 [95% CI 1.1 to 3.1]) and nausea (OR 3.7 [95% CI 1.5 to
9.0]).
Cryoablation versus REA
Two RCTs (n = 279) were identified. Women in the cryoablation group were less
likely to have amenorrhea at 1 year (OR 0.3 [95% CI 0.2 to 0.6]) but more likely to
have local than general anesthesia (OR 13.2 [95% CI 5.8 to 30.0]). There were no
differences in satisfaction rates, success rates (PBAC < 75), menorrhagia rates or
hysterectomy rates.
Electrode ablation (balloon or mesh) versus TCRE
Two RCTs (n = 520) were identified. The operation time with TCRE was longer
(WMD 18.7 minutes [95% CI 16.8 to 20.7]). The electrode group was more likely to
have local than general anesthesia (OR 15.9 [95% CI 10.1 to 25.1] and less likely to
have cervical tears or lacerations (OR 0.11 [95% CI "0.01 to 0.90]). There were no
differences between groups in amenorrhea rates, complications rates, 12 month
PBAC, satisfaction rates or need for hysterectomy.
MEA versus TCRE plus REA
One RCT (n = 322) was identified. At 2 years follow-up, microwave was more
satisfactory and acceptable than TCRE (OR 1.9 [95% CI 1.1 to 3.3] and OR 2.7 [1.1
to 6.8], respectively). At 5 years follow-up the difference was maintained (OR 2.3
[95% CI 1.2 to 4.3] and OR 3.7 [95% CI 1.3 to 10.1], respectively). The hysterectomy
rate was significantly lower (18% versus 28%) following MEA. In addition, odds of
hemorrhage were lower in the microwave group (OR 0.14 [95% CI 0.02 to 0.80]).
However, equipment failure rates (OR 4.07 [95% CI 1.1 to 15.0]), vomiting (OR 4.0
[95% CI 1.4 to 11.7] and uterine cramping (OR 1.7 [95% CI 1.1 to 2.8]) were greater
in the MEA group. There were no differences in other outcomes or in the same
outcomes at different time periods.
TBEA versus REA
One RCT (n = 239) was identified. Amenorrhea was less likely with TBEA at 12 and
36 months (OR 0.60 [95% CI 0.33 to 0.96] and OR 0.50 [95% CI 0.25 to 0.97],
respectively) but there were no differences at 24 months and 5 years. At 5 years, odds
of satisfaction with treatment were lower in the balloon group (OR 0.13 [95% CI 0.02
to 0.94]), and complications were more likely with TBEA than with REA. Duration of
surgery was lower in the balloon group (WMD 20.8 minutes [95% CI 19.2 to 22.5]).
Other outcomes showed no differences at 12, 24 and 36 months.
TBEA versus TCRE
One RCT (n = 82) was identified. TBEA was quicker (WMD 13 minutes [95% CI
10.8 to 15.2), mean intra-operative blood loss was lower (WMD "81.8 ml [95% CI
"70.3 to "93.3]) and satisfaction was greater at 24 months (OR 7.2 [95% CI 1.4 to
35.9]) when compared with TCRE.
TBEA versus laser ablation
One RCT (n = 70) was identified. Women having TBEA treatment had a significantly
greater pain score than women in the laser group (WMD 32.7 [95% CI 23.7 to 41.7]).
Le"

At 12 months follow up, women in the TBEA group had higher scores on the
Euroquol 5D VAS than women in the laser group (WMD 5.3 [95% CI 0.11 to 10.6]).
Bipolar radiofrequency endometrial ablation versus TBEA
One RCT (n = 126) was identified. Amenorrhea was more likely in the bipolar
radiofrequency group (OR 7.4 [95% CI 3.8 to 14.4]) and women in the bipolar
radiofrequency group were more likely to be satisfied with treatment outcome at 12
months (OR 3.0 [95% CI 1.3 to 7.0]).
References:
1. Lethaby A, Shepperd S, Cooke I, Farquhar C. Endometrial resection and ablation versus
hysterectomy for heavy menstrual bleeding.(Cochrane Review). In: Cochrane Database of
Systematic Reviews, Issue 2, 2004. Oxford: Update Software.
2. Garside R, Stein K, Wyatt K, et al. The effectiveness and cost-effectiveness of microwave and
thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and
economic modelling. Health Technology Assessment 2004;8(3):iii,1155.
3. Lethaby A, Hickey M. Endometrial destruction techniques for heavy menstrual bleeding.
(Cochrane Review). In: Cochrane Database of Systematic Reviews, Issue Oxford, 2005.
Oxford: Update Software.

Statement 4
Hysterectomy should not be used as first-line treatment for heavy menstrual
bleeding. (I, C)
Supporting evidence:
In one systematic review (n = 821) in 2006, eight RCTs compared pharmaceutical
with surgical treatments for HMB. Two RCTs in the systematic review examined use
of pharmaceutical or surgical interventions on women with HMB in a secondary care
setting. The difference between pharmaceutical treatments and surgery diminished
over time. There was no statistical difference between the groups by the 5th year of
follow-up. Regarding control of bleeding, (cure or improvement): at 4 months (n =
186) OR 10.6 (95% CI 5.3 to 21.3) in favor of surgery, by 2 years (n = 173) OR 2.39
(95% CI 1.21 to 4.70) in favor of surgery, and by 5 years (n = 140) OR 1.99 [95% CI
0.84 to 4.73] There was no statistical difference between the groups. The figures for
patient satisfaction were: at 4 months (n = 183) OR 8.28 (95% CI 4.29 to 15.97) in
favor of surgery, by 2 years (n = 173) OR 2.83 [95% CI 1.46 to 5.50] in favor of
surgery, and by 5 years (n = 140) OR 1.69 (95% CI 0.77 to 3.70) with no statistical
difference between the groups. However, women in the pharmaceutical group were
more likely to undergo additional surgery: by 2 years follow-up (n = 236) OR 0.12
(95% CI 0.06 to 0.22) in favour of surgery and by 5 years follow-up (n = 140) OR
0.11 (95% CI 0.06 to 0.22) in favor of surgery.1
Six other RCTs compared LNG-IUS with surgery (hysterectomy, ablation) in
secondary care settings. These studies concluded that the treatments were equivalent.
The figures showed that objective measurement of MBL at 12 months was in favor of
surgery (one RCT, n = 223, OR 25.7 [95% CI 1.5 to 440.0]). Also, the subjective
measurement of MBL at 12 months was in favor of surgery (three RCTs, n = 189, OR
3.99 [95% CI 1.53 to 10.38]).However, results from health related quality of life
(HRQoL) measures were more mixed. There was no difference between groups on the
SF-36 (a short form with 36 questions, used in determining health status of patients)
scale for general health, physical function, mental health, vitality and physical role
limitation. There were statistically significant differences for emotional role (n = 269,
Lf"

WMD 9.67 [95% CI 1.65 to 17.69]), social function (n = 274, WMD 3.64 [95% CI
"1.14 to 8.43]) and bodily pain (n = 274, WMD 6.98[95% CI 1.68 to 12.29]) in favor
of surgery. Use of LNG-IUS was more likely to result in additional surgery at 12
months (n = 423, OR 0.11 [95% CI 0.04 to 0.30]) and were less likely to have
reported adverse effects (OR 0.24 [95% CI 0.11 to 0.49]).1
While surgery has an advantage over pharmaceutical treatment in terms of outcome,
this does not take into account the reversible nature of pharmaceutical treatment
compared with surgery.
The systematic review states that investigations for causes of HMB, attempts at
pharmaceutical treatment and provision of full information to the woman are required
prior to hysterectomy.2 A consensus statement highlights that hysterectomy for HMB
should only be undertaken after investigations to establish cause of HMB, failed
pharmaceutical treatment and full information provision to the woman.3 In addition,
hysterectomy is only indicated where HMB is causing anemia and/or serious HRQoL
impact. Patient preference studies show that women want certain outcomes for
treatment of HMB, but also often want to avoid hysterectomy in order to achieve
these outcomes.4-8
References
1. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual
bleeding. (Cochrane Review). In: Cochrane Database of Systematic Reviews, Issue 2, 2006.
Oxford: Update Software.
2. Lefebvre G, Allaire C, Jeffrey J, et al. SOGC clinical guidelines. Hysterectomy [French].
Journal of Obstetrics and Gynaecology Canada: JOGC 2002;24(1):3761.
3. Schilling J, Wyss P, Faisst K, et al. Swiss consensus guidelines for hysterectomy. Swiss
Society of Gynecology and Obstetrics, Switzerland. International Journal of Gynaecology and
Obstetrics 1999;64(3):297305.
4. Bourdrez P, Bongers MY, Mol BW. Treatment of dysfunctional uterine bleeding: patient
preferences for endometrial ablation, a levonorgestrel-releasing intrauterine device, or
hysterectomy. Fertility and Sterility 2004; 82(1):1606.
5. Nagele F, Rubinger T, Magos A. Why do women choose endometrial ablation rather than
hysterectomy? Fertility and Sterility 1998;69(6):10636.
6. Sculpher MJ, Dwyer N, Browning J, et al. A survey of womens preferences regarding
alternative surgical treatments for menorrhagia. Health Expectations 1998;1(2):96105.
7. Mingo C, Herman CJ, Jasperse M. Womens stories: Ethnic variations in womens attitudes
and experiences of menopause, hysterectomy, and hormone replacement therapy. Journal of
Womens Health and Gender-Based Medicine 2000;9(Suppl 2): S2738.
8. Nathorst-Boos J, Fuchs T, von Schoultz B. Consumers attitude to hysterectomy: The
experience of 678 women. Acta Obstetricia et Gynecologica Scandinavica 1992;71(3):2304.

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APPENDIX A
LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION
LEVEL
I
II-1
II-2
II-3
III
GRADE
A
B
C
D
E
GPP

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DEFINITION
Evidence obtained from at least one properly randomized controlled trial
Evidence obtained from well-designed controlled trials without
randomization
Evidence obtained from well-designed cohort or case-control analytic
studies, preferably from more than one center or research group
Evidence obtained from multiple time series with or without the
intervention.
Opinions of respected authorities, based on clinical experience; descriptive
studies and case reports or reports of expert committees.
DEFINITION
There is good evidence to support the recommendation of the practice in
abnormal uterine bleeding.
There is fair evidence to support the recommendation of the practice in
abnormal uterine bleeding.
There is insufficient evidence to recommend for or against the inclusion of
the practice in abnormal uterine bleeding.
There is fair evidence to support the recommendation that the practice be
excluded in abnormal uterine bleeding.
There is good evidence to support the recommendation that the practice be
excluded in abnormal uterine bleeding.
A good practice point (GPP) is a recommendation for best practice based
on the experience of the Technical Working Group.

APPENDIX B
DRUG DOSAGES
1. Levonorgestrel-releasing intrauterine system once every 5 years
2. Tranexamic acid 1 gram QID PO during heavy bleeding x 3 days
3. Ibuprofen 200 mg PO TID during heavy bleeding x 3 days
4. Mefenamic acid 500 mg PO TID during heavy bleeding x 3 days
5. Naproxen 550 mg LD, then 275 mg PO BID during heavy bleeding x 3 days
6. Medroxyprogesterone 10 mg PO OD on cycle days 16-25 for anovulatory
cycles
7. Medroxyprogesterone 10 mg PO TID on cycle days 5-26 for ovulatory cycles
8. Norethisterone acetate 5 mg PO TID on cycle days 16-25 for anovulatory cycles
9. Norethisterone acetate 5 mg PO TID on cycle days 5-26 for ovulatory cycles
10. Danazol 200-400 mg PO daily for progestin-resistant cases

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