Reviews in Gynaecological Practice 3 (2003) 81–84

Review
Medical management of dysfunctional uterine bleeding
Alison Porteous a , Andrew Prentice b,∗
a The Rosie Hospital, Box 224, Robinson Way, Cambridge CB2 2SW, UK
b University Department of Obstetrics and Gynaecology, The Rosie Hospital, Box 223, Robinson Way, Cambridge CB2 2SW, UK
Received 28 February 2003; accepted 3 March 2003

Abstract

Dysfunctional uterine bleeding is the diagnosis in the majority of cases of menorrhagia. The symptom of menorrhagia accounts for a
significant proportion of referrals to gynaecologists. There is no hormonal defect in dysfunctional uterine bleeding, however, disturbances
in endometrial mediators have been noted. The majority of cases are associated with ovulatory cycles, when cycle control is not an issue,
and can thus be treated with non-hormonal methods such as prostaglandin synthetase inhibitors and antifibrinolytics. Those patients with
anovulatory cycles may benefit from exogenous control of the pattern of bleeding with hormonal preparations. When effective contraception
is also required the use of either the combined oral contraceptive or the levonorgestrel releasing intrauterine system (IUS) are suitable
choices. National guidelines exist for the management of menorrhagia. If appropriate attention is made to such guidelines, in addition to
the individuals’ symptoms and requirements, then the avoidance of inappropriate investigations, referrals and treatments may be achieved.
The medical management of dysfunctional bleeding should ideally be based in the community. Referral to hospital being reserved for those
cases where menorrhagia is thought to de due to underlying pathology or when initial treatment appears to fail.
© 2003 Elsevier Science B.V. All rights reserved.

Keywords: Dysfunctional uterine bleeding; Menorrhagia; Medical therapy

1. Introduction
Dysfunctional uterine bleeding is the commonest cause
of menorrhagia and it is a diagnosis of exclusion made
in the absence of underlying medical, haematological or
pelvic pathology. Menorrhagia is defined as a menstrual
blood loss of greater than 80 ml per month. Discrepancies
between subjective impressions of menstrual loss and objec-
tive measurements may in part be accounted for by the fact
that much of the fluid volume of menstruation may be from
other sources than blood [1]. In addition, the perception of
loss is affected by social and psychological factors such as
emotional upset, marital problems and fear of cancer. It is
the subjective perception of menstrual loss rather than the
objective loss that is important in determining requests for
consultation and treatment.
As many as 20% of women may be affected by exces-
sive menstrual loss during their reproductive years [2]. Of
all gynaecological referrals from general practice, menstrual
disorders accounts for up to 21%, and of these menorrhagia
is the main symptom [3]. The rate of referral varies consid-
∗ Corresponding author. Tel.: +44-1223-336876;
fax: +44-1223-215327.
E-mail address: ap128@cam.ac.uk (A. Prentice).
erably between different practices and there has been wide
variation in the management of dysfunctional uterine bleed-
ing. Evidence-based guidelines have been produced with
the aim providing recommendations for the management of
menorrhagia [4].
2. Pathophysiology
Dysfunctional uterine bleeding can be classified as ei-
ther ovulatory or anovulatory. The distinction between these
types is critical in the rational management of this condition.
Ovulatory dysfunctional uterine bleeding is the more
common diagnosis. With ovulatory dysfunctional bleed-
ing there is regular ovulation and heavy regular menstrual
loss with maintenance of hormonal cyclicity. Alterations in
the production of prostaglandins (PG) and in fibrinolytic
activity have been noted in the endometrium of women
experiencing menorrhagia and these are thought to play a
role in this condition.
A shift in endometrial synthesis of PG, toward more
PGE2 and less PGF2␣, in women with menorrhagia
was first suggested by Smith in 1981 [5]. PGE2 has
vasodilatation and antiplatelet aggregation effects whereas
PGF2␣ produce vasoconstriction and platelet aggregation,

1471-7697/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S1471-7697(03)00018-2
82 A. Porteous, A. Prentice / Reviews in Gynaecological Practice 3 (2003) 81–84
thus prostaglandins are thought to be mediators in the reg-
ulation of menstrual loss. Increased fibrinolytic activity
has been demonstrated in the endometrium of women with
increased menstrual loss [6].
Anovulatory bleeding accounts for approximately 10% of
cases where women complain of excess menstrual loss [7].
In this situation, irregular bleeding occurs and cycle control
is an additional problem. Anovulatory problems are more
common at the extremes of reproductive life. Normal men-
strual bleeding is in response to withdrawal of progesterone
and oestradiol. Failure of ovulation results in an absence of
progesterone and consequently lack of secretory change in
the endometrium. Unopposed oestrogen causes persistent or
proliferative or hyperplastic endometrium followed by oe-
strogen withdrawal bleeds. Bleeding of this type is often
heavy or prolonged.
3. Clinical assessment
When assessing a patient who is complaining of heavy
menstrual loss, it is important to ascertain the nature of her
complaint and the impact it is having on her. In the man-
agement of dysfunctional bleeding, the management of the
illness is as important as the management of the disease. It
must be remembered that dysfunctional uterine bleeding is
a diagnosis of exclusion, thus attempts should be made to
detect any obvious underlying pathological cause for men-
orrhagia before concluding that this is the diagnosis.
3.1. History and examination
Within the history, it is important to clarify the pattern,
duration and severity of her bleeding. The patients’ percep-
tion of the heaviness of her menstrual loss and the effect
on her quality of life are important. Associated gynaecolog-
ical symptoms may indicate relevant underlying pathology.
A general enquiry should reveal any symptoms of anaemia,
medical disorders or bleeding diathesis in addition to any
factors that would contraindicate specific treatments.
A general, abdominal and pelvic examination should be
performed [4] to detect any signs of anaemia and exclude
any obvious underlying pathology.
3.2. Investigation
Prior to requesting any investigation, it is a basic princi-
ple of good practice to decide if the result would alter the
management of the patient. The aim of investigation with
regard to this situation is to assess the physical effect of
excess menstrual loss on the patient and to exclude other
conditions. A full blood count is the only investigation that
should be routinely requested [4]; it will give a reflection
of the actual blood loss by identifying if there is iron defi-
ciency anaemia. Blood loss in excess of 80 ml per month is
often associated with anaemia.
4. Treatment of dysfunctional uterine bleeding
The various aims of treatment of dysfunctional uterine
bleeding are listed below:
• Reduction in heaviness of menstrual loss.
• Reduction in irregularity of menstrual loss.
• Reduction of anaemia.
• Improvement in quality of life.
• Avoidance of unnecessary anxiety.
In considering which management option is appropriate
for an individual, it is important to consider various aspects
including their concerns regarding their symptoms and their
expectations of management. It is helpful to define what is
the problem of most importance to them, is it the heaviness
or the irregularity of bleeding that concerns them? What are
their contraceptive or fertility requirements? There is great
importance in adequate counselling of a patient regarding
any treatment as this should lead to increased adherence to
therapy. In some cases, reassurance that there is no signif-
icant underlying pathology or that the loss is not excessive
may be all that is required.
Prior to commencing any medication, it is important to
consider the rational behind its use, contraindications and
possible adverse effects. In addition, other potential bene-
ficial effects and cost will have an influence on choice of
treatment. The various medical treatments commonly used
are listed below:
• Iron (to treat secondary anaemia).
• Non-hormonal medication:
◦ Prostaglandin synthetase inhibitors.
◦ Antifibrinolytics.
• Hormonal medication:
◦ Combined oral contraceptive pill.
◦ Oral progestogens.
◦ Levonorgestrel releasing intrauterine system.
◦ Danazol.
4.1. Non-hormonal treatments
In the majority of cases of menorrhagia, there is no
hormonal abnormality and thus no rational for hormonal
therapy. Non-hormonal medications are thus the first line
of therapy and are taken during menstruation rather than
throughout cycle. Thus, adherence to therapy is likely to be
good. Such medication is appropriate for those planning to
conceive, as it is not contraceptive.
Non-steroidal anti-inflammatory drugs (NSAIDs) reduce
prostaglandin levels and are thus a rational therapy. The
ability of mefenamic acid to reduce excessive menstrual
bleeding was first described by Anderson et al. in 1976 [8].
Non-steroidal anti-inflammatory drugs act mainly by inhibit-
ing the cyclooxygenase system a controlling step in the pro-
duction of cyclic endoperoxidases from arachidonic acid. In
addition, fenmates, which is the group of NSAIDs to which
 A. Porteous, A. Prentice / Reviews in Gynaecological Practice 3 (2003) 81–84
mefenamic acid belongs, have an additional inhibitory ef-
fect by binding to prostaglandin receptors [9]. Mefenamic
acid may also act through improvement in platelet aggre-
gation and degranulation and through vasoconstriction [10].
Non-steroidal anti-inflammatory drugs are more effective
than placebo at reducing heavy menstrual bleeding, but less
effective than either tranexamic acid or danazol [11]. Gas-
trointestinal effects are less likely with mefenamic acid than
naproxen [11]. NSAIDs reduce menstrual loss by approxi-
mately a third.
Tranexamic acid is an inhibitor of fibrinolysis, its effect
on menstrual loss was initially reported in 1967 [12]. For
the treatment of menorrhagia, it is given at a dose of 1–1.5 g
three to four times daily for 3–4 days and the only contraindi-
cation to its use is thrombo-embolic disease. Anxieties that
tranexamic acid might cause thrombo-embolism have been
unfounded. It has been shown to reduce menstrual loss by
approximately 50% [13].
4.2. Hormonal medications
Hormonal medications are useful in that they can exert an
exogenous control of the menstrual cycle.
A non-contraceptive benefit noted in women taking the
combined oral contraceptive pill is that it reduces blood loss
[14]. The combined oral contraceptive pill taken in a cycli-
cal manner leads to the regular shedding of a thinner en-
dometrium. Unfortunately there is lack of sufficient data to
confirm this effect of the pill [15] although a wealth of anec-
dotal experience is testimony to its effectiveness. One small
study [16] has shown an overall reduction of menstrual blood
loss of 43% in women taking the combined oral contracep-
tive pill and no significant difference in loss between groups
treated with combined oral contraceptive, mefenamic acid,
low dose danazol or naproxen. A more recent trial [17] has
looked at third generation contraceptives, it found them to
be effective in between 80 and 93% of cases of heavy men-
struation with average reduction of menstrual blood loss of
up to 69%.
The provision of good cycle control and in addition
contraception makes the combined oral contraceptive pill
an acceptable long-term therapy for many women. There
is, however, a reluctance to use the pill in the age group
most commonly most affected by dysfunctional uterine
bleeding.
4.3. Oral progestogens
The first subjective study using progestogens for the treat-
ment of menorrhagia was published in 1960 [18]. Of the
various medical treatments for menorrhagia, oral progesto-
gens have been the most widely prescribed in many western
countries. There is little objective evidence to support the
use of oral progestogens, especially in women with ovula-
tory menstruation. Only high dose progestogens used in a
cyclical manner are effective (3 out of 4 weeks). They are
83
useful in the anovulatory patient to co-ordinate and regulate
bleeding.
In a Cochrane systematic review [19], norethisterone was
the only oral progestogen assessed and there were no studies
identified as comparing progestogens with placebo. Most
data is in relation to the use of progestogen during luteal
phase and this shows that there is no benefit compared with
other medical treatment and in fact significantly less effect
than antifibrinolytics and danazol. One trial [20] has com-
pared norethisterone given from days 5 to 26 with the lev-
onorgestrel releasing intrauterine system (IUS). This showed
significant reduction in blood loss but less effect and lower
patient acceptability than when the intrauterine system was
used. Side effects of prolonged use of high dose progesto-
gens may include: fatigue mood changes, weight gain, nau-
sea, bloating, oedema, headaches, depression, loss of libido,
irregular bleeding and atherogenic changes on lipid profile.
4.4. Progesterone/progestogen releasing intrauterine
systems
Intrauterine devices were primarily devised for use as con-
traceptives. The addition of progesterone/progestogens was
initially in an attempt to reduce the chance of expulsion of
the devices. Progestasert was the first hormonally impreg-
nated intrauterine device; from it, there is release of 65 ␮g
of progesterone per day, re-insertion of this device being re-
quired every 18 months. This device is no longer available.
Mirena is an IUS that releases 20 ␮g of levonorgestrel
each day. It was first licensed for use in the UK in 1995
and in 12 other countries by 1998. Replacement of the de-
vice is required every 5 years. Endometrial proliferation is
prevented and consequently there is a reduction in duration
and quantity of menstrual loss. Despite being a relatively
new intervention, use of the IUS has been rapidly adopted
for treatment of menorrhagia based mainly on reports from
case series rather than full evaluation in randomised con-
trolled trials. One study [21] looked at 50 women and found
that menstrual loss was reduced in 74% of them within 3
months, 82% within 9 months, and that the additional ben-
efit of reduced dysmenorrhoea occurred in 80%.
In a Cochrane systematic review [22], there were no trials
identified comparing such devices with either placebo or no
treatment. There were only five trials that met the criteria of
that review, the majority looking at the levonorgestrel sys-
tem. Studies have shown up to a 90% reduction in menstrual
loss from women treated with levonorgestrel intrauterine
system [22]. Additional benefits of this method are its
contraceptive effect, reduction in dysmenorrhoea and a
possible reduction in the incidence of pelvic inflammatory
disease. Disadvantages of the IUS is that insertion may
be regarded as invasive by some and in addition may re-
quire local anaesthesia and dilatation, in nulliparous and
perimenopausal women. Frequent intermenstrual bleeding
and spotting is likely during the first few months. Use of
this method is expensive if it is discontinued prior to the 5
84 A. Porteous, A. Prentice / Reviews in Gynaecological Practice 3 (2003) 81–84
years but much cheaper than the surgical alternatives it may
prevent.
4.5. Danazol
Danazol was first used in the treatment of dysfunctional
uterine bleeding in 1979 [23]. It is a synthetic steroid with
weak androgenic properties in addition to antioestrogenic
and antiprogestogenic activity. Its action results in endome-
trial atrophy and consequently reduced menstrual loss and
leads to amenorrhoea in many women [24]. Danazol at a
dose of 200 mg per day has been shown to reduce menstrual
blood loss by 60 % [25]. Due to the androgenic properties
danazol may cause acne, seborrhoea and hirsutism. Other
side effects include weight gain, irritability, musculoskeletal
pains, hot flushes and breast atrophy. Long-term treatment
may affect the liver and may cause benign hepatic adenomas.
A systematic review of the use of danazol [26] identified
nine randomised controlled trials, however, many had small
sample sizes. From this review, danazol appears to be more
effective than placebo, progestogens, NSAIDs and contra-
ceptive pill at reducing menstrual blood loss. Danazol re-
duces the duration of menstruation compared with NSAIDs
and intrauterine system. However, danazol caused more ad-
verse events than NSAIDs and progestogens. The use of
danazol may be limited by its side effects, unacceptability
to many women and the need for continuation of therapy.
5. Conclusions
The majority of cases of dysfunctional uterine bleeding
can be adequately managed within the community setting.
Benefits of treatment within primary care include: continu-
ity of care, avoidance of delay in commencing treatment,
and avoidance of unnecessary investigations and procedures.
In addition, hospital resources can then be concentrated on
those cases in which more intervention is required. Medi-
cal management of dysfunctional bleeding is appropriate if
a rational approach to this problem is followed as outlined
in national guidelines. Optimal care will have considerable
impact on physical, psychological and economic functions
of the individual and society.
References
[1] Frazer IS, McCarron G, Markham R, Resta T. Blood and total fluid
content of menstrual discharge. Obstet Gynaecol 1985;65:194–8.
[2] Jacobs A, Butler EB. Menstrual blood loss in iron-deficiency
anaemia. Lancet 1965;II:407–9.
[3] Coulter A, Bradlow J, Agass M, Mertin-Bates C, Tulloch A. Out-
comes of referrals to gynaecology outpatient clinics for menstrual
problems: an audit of general practice records. Br J Obstet Gynaecol
1991;98:789–98.
[4] Royal College of Obstetricians and Gynaecologists. The initial man-
agement of menorrhagia. Evidence-based clinical guidelines. No. 1.
London: RCOG; 1998.
[5] Smith SK, Abel MH, Kelly RW, Baird DT. Prostaglandin synthesis
in the endometrium of women with ovular dysfunctional bleeding.
Br J Obstet Gynaecol 1981;88:434–42.
[6] Gleeson N, Devitt M, Sheppard BL, Bonnar J. Endometrial fibri-
nolytic enzymes in women with normal menstruation and dysfunc-
tional uterine bleeding. Br J Obstet Gynaecol 1993;100:768–71.
[7] Cameron IT, Haining R, Lumsden MA. The effects of mefenamic
acid and norethisterone on measured menstrual blood. Obstet Gynecol
1990;76:85–8.
[8] Anderson ABM, Haynes PJ, Guillebaud J, Turnbull AC. Reduction of
menstrual blood loss by prostaglandin-synthetase inhibitors. Lancet
1976;I:774–6.
[9] Rees MCP. Effects of fenmates on PG binding. Lancet 1988;II:541–2.
[10] van Eijkeran MA, Christiaens GCML, Geuze HJ, Haspels AA, Sixma
JJ. Effects of mefenamic acid on menstrual hemostasis in essential
menorrhagia. Am J Obstet Gynecol 1992;166:1419–28.
[11] Lethaby A, Augood C, Duckitt K. Non-steroidal anti-inflammatory
drugs for heavy menstrual bleeding (Cochrane review). In: The
Cochrane library, issue 3. Oxford: Update Software; 2002.
[12] Nilsson IM, Rybo G. Acta Obstet Gynaecol 1967;90:78–83.
[13] Preston J, Cameron IT, Adams EJ, Smith SK. Comparative study
of tranexamic acid and norethisterone in the treatment of ovulatory
menorrhagia. Br J Obstet Gynaecol 1995;102:401–6.
[14] Mishell DR. Non-contraceptive health benefits of oral steroidal con-
traceptives. Am J Obstet Gynecol 1982;142:809–16.
[15] Iyer V, Farquhar C, Jepson R. Oral contraceptive pills for heavy
menstrual bleeding (Cochrane review). In: The Cochrane library,
issue 4. Oxford: Update Software; 2002.
[16] Fraser IS, McCarron G. Randomised controlled trial of two hormonal
and two prostaglandin inhibiting agents in women with a complaint
of menorrhagia. Aust N Z J Obstet Gynaecol 1991;31:66–70.
[17] Agarwal N, Kripilani A. Medical management of dysfunctional uter-
ine bleeding. Int J Gynaecol Obstet 2001;75(2):199–201.
[18] Bishop PMF, Cabral de Almedia JC. Treatment of functional men-
strual disorders with norethisterone. Br Med J 1960;I:1103–10.
[19] Lethaby A, Irvine GA, Cameron IT. Cyclical progestogens for heavy
menstrual bleeding (Cochrane review). In: The Cochrane library,
issue 3. Oxford: Update Software; 2002.
[20] Irvine GA, Cambell-Brown MB, Lumseden MA, Heikkaila A, Walker
JJ, Cameron IT. Randomised comparative trial of the levonorgestrel
intrauterine system and norethisterone for treatment of idiopathic
menorrhagia. Br J Obstet Gynaecol 1988;105(6):592–8.
[21] Barrington JW, Bowen-Simpkins P. The levonorgestrel intrauterine
system in the management of menorrhagia. Br J Obstet Gynaecol
1997;104:614–6.
[22] Lethaby A, Cooke I, Rees M. Progesterone/progestogen releasing
intrauterine system for heavy menstrual bleeding (Cochrane review).
In: The Cochrane library, issue 4. Oxford: Update Software; 2002.
[23] Chimbira TH, Anderson ABM, Bolton FG. The effect of danazol on
menorrhagia, coagulation mechanisms, haematological indices and
body weight. Br J Obstet Gynaecol 1979;86:46–50.
[24] Chimbira TH, Anderson ABM, Naish C, et al. Reduction of men-
strual loss by danazol in unexplained menorrhagia: lack of effect by
placebo. Br J Obstet Gynaecol 1980;87:1152–8.
[25] Dockeray CJ, Sheppard BL, Bonnar J. Comparison between mefe-
namic acid and danazol in the treatment of established menorrhagia.
Br J Obstet Gynaecol 1989;96:840–4.
[26] Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for heavy
menstrual bleeding (Cochrane review). In: The Cochrane library,
issue 3. Oxford: Update Software; 2002.