The Pharmaceutical Journal 71
CPD
Menorrhagia and its management
Over-the-counter tranexamic acid is likely to become available from some
pharmacies in the next month, so pharmacists are more likely to be asked about
heavy menstrual bleeding. Sally Haynes gives an overview of menorrhagia
The absence of pregnancy during a menstrual
cycle and the associated changes in hormonal
activity result in menstruation, the sloughing
o of the lining of blood and tissue
(endometrium) that has built up in the uterus
in preparation for an embryo to implant. A
typical menstrual cycle will last between 21
and 35 days with menstruation lasting
between three and eight days. Epidemiological
studies show that, up until perimenopause,
cycle length and duration of menstruation
tend to decrease with age, and cycle regularity
tends to improve. Other factors that can aect
the menstrual cycle include rapid weight
change, emotional stress and illness.
Menorrhagia and what is normal
Women cope with menstruation in dierent
ways. Some, for example, may view period
pains (dysmenorrhoea) as part and parcel of
their monthly cycle. However, menorrhagia
(excessive and prolonged uterine bleeding
occurring at the regular intervals of
menstruation) is one of the most common
complaints aecting women of childbearing
age.
Thirty per cent of women complain about
heavy menstrual bleeding and 5 per cent of
women aged from 29 to 44 years will consult
their GP about heavy periods. Studies indicate
Roger Harris/Science Photo Library
that bleeding increases with age. Menorrhagia
can also be a problem for peri-menopausal
women.
Generally, total menstrual blood loss is
between 35ml and 80ml. Losses over 80ml
have been dened as heavy but in extreme
cases, blood loss can be up to 500ml.
However, it should be noted that heavy loss is
subjective and, in practice, it should be
dened by the womans assessment, as has
been recommended by the National Institute
for Health and Clinical Excellence 2007
clinical guideline on heavy menstrual
bleeding.1
Some women might describe having to use
tampons with sanitary towels, or having to
change sanitary towels at least every two
hours. They might complain of having large
clots of menstrual blood or of prevention of
normal daily activities, such as sport or going
out, and they might also talk about feeling
The author
Sally Haynes, BSc, MRPharmS, is a self
employed locum pharmacist and formerly
lead pharmacist at Birmingham Womens
Hospital
Reflect
Evaluate Plan
Act
REFLECT
1 What are the causes of menorrhagia?
2 What medicines can be used to treat
menorrhagia?
3 What are the options if drug treatment fails?
Before reading on, think about how this article
may help you to do your job better.
tired or appearing pale. Menorrhagia can also
adversely aect sex life and lead to
depression.
Mechanisms, causes and risk factors
The normal control of the endometrium, and
thus the volume of menstrual loss, is complex.
The endometrium undergoes a process of
vascular and glandular proliferation,
dierentiation and regeneration with each
menstrual cycle. Clearly, anything that
increases the thickening of the endometrium,
vascularisation or blood ow can potentially
cause menorrhagia.
The thickness of the endometrium is
controlled by oestrogen, which is released
during the rst half of the menstrual cycle.
Vascular endothelial growth factor (VEGF),
an endothelial cell-specic protein, is an
oestrogen-responsive factor for angiogenesis
that is also involved.
The endometrium produces and responds
to prostaglandins. (The rst prostaglandin
identied was found in menstrual ow by an
enthusiastic researcher who kept his
daughters sanitary towels for research.) The
fundamental actions of these prostaglandins
are to inhibit or stimulate smooth muscle
contraction, and to inhibit the release of
noradrenaline. They aect both uterine and
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72 The Pharmaceutical Journal
Learning & development
No suspected structural or
histological abnormality
Drug treatment
Drug
treatment
fails
Consider physical examination
Consider
alternative drug
Women with severe
impact of quality of
life and no wish to
conceive and a
normal uterus with or
without fibroids <3cm
Endometrial ablation
Care pathway for a woman presenting with heavy periods (adapted from NICE guidelines)
vascular smooth muscle and the net eect can
be either an increase or decrease in blood loss,
depending on the muscles aected.
(Menorrhagia that is linked to prostaglandins
is likely to be accompanied by period pains
because of eects on muscle.) Inhibition of
noradrenaline release will cause an increase in
blood loss.
Increased menstrual loss can be a
symptom of disease, but often there is no
known cause. The presumption then is that
the problem lies in chemical or hormonal
control of the menstrual cycle.
In the absence of any underlying disease,
heavy menstrual bleeding is called
dysfunctional uterine bleeding (DUB) and,
as Panel 1 shows, most women with
menorrhagia fall into this category.
A pathological cause (eg, a uterine
tumour) requires treatment outside the scope
of this article and Panel 2 lists symptoms
suggestive of underlying disease that may
require urgent referral.
Fibroids are benign tumours of the uterus
associated with menorrhagia and are often
treated by hysterectomy. Incidence increases
with age (until menopause) and they are more
common in black women than white women.
Age and race are also related to risk of
menorrhagia.
Drug treatment
Drug treatment should be the rst-line option
for women with menorrhagia and no
symptoms suggestive of underlying disease. In
general, a drug treatment should be given a
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Take history and full blood count
No abnormality or
fibroids <3cm
No
abnormality
or fibroids
<3cm
Consider imaging (ie, ultrasound)
Provide information and discuss options
Women in whom other
treatments have failed (or
have been
contraindicated or
declined), who wish for
amenorrhea or have no
desire to retain a uterus
or fertility
Hysterectomy
three-month trial before changing to another
or looking at non-pharmaceutical options.
In some cases, multiple treatments may be
required since, as well as trying to nd a long-
term solution, it may be necessary to deal rst
with heavy bleeding that cannot be contained
by normal sanitary protection (ooding).
The Figure above gives an overview of a
care pathway for a woman presenting with
heavy periods, as described by NICE.
There is a wide range of drug treatments
for DUB. The main groupings are
haemostatic agents (eg, tranexamic acid),
non-steroidal inammatory drugs (eg,
mefenamic acid) and hormonal treatments.
Haemostatic agents The antibrinolytic
tranexamic acid has been shown to reduce
menstrual blood loss by up to 58 per cent. It
works by inhibiting plasminogen activators in
the endometrium levels of these enzymes,
which change plasminogen to plasmin, are
raised in menorrhagia. Plasmin dissolves brin
clots. It is thought that the dissolution of clots
adds to menstrual ow so tranexamic acid
reduces menstrual blood loss.2,3
The normal dose is 1g three times a day
for up to four days during menstruation. The
maximum daily dose is 4g.
The main adverse eects of tranexamic
acid are nausea, vomiting and diarrhoea.
Thromboembolic events are rarely reported
(but see below). More rarely, patients may
report disturbances in colour vision
and this is an indication to discontinue
treatment.
Possible structural or
histological abnormality
Physical examination
Palpable Consider endometrial
uterus or biopsy for persistent
pelvic mass intermenstrual bleeding and
in women over 45 years or
treatment failure
Women with severe
impact on quality of
life and fibroids >3cm
Fibroidectomy Uterine artery embolisation
The Medicines and Healthcare Products
Regulatory Agency permitted reclassication
of tranexamic acid as a pharmacy-only
medicine in March 2010 and in the next few
weeks Cyclo-F (500mg tranexamic acid
tablets) will become available to the public.
Points to note from this products summary of
product characteristics are listed in Panel 3.
Tranexamic acid has been available over the
counter in Sweden since 1997. According to
the MHRA reclassication assessment,4 the
drug is not thrombogenic and does not induce
a general prothrombotic state. (Swedish
studies indicate that incidence of thrombosis is
comparable to frequency of spontaneous
thrombosis in the general population.) It
points out that a Royal College of
Obstetricians and Gynaecologists guideline
recommends that before treatment a history of
heavy clinical menstrual blood loss should be
obtained, an abdominal and pelvic
examination should be performed, and a full
blood count should be obtained but recognises
the argument that most GPs do not carry out
a pelvic examination or full blood count in
patients presenting with menorrhagia. In
addition, it is sub-mucous broids that are
assumed to cause menorrhagia, and these can
only be detected by ultrasound scan and/or
hysteroscopy; therefore the benet of vaginal
examination by GPs is said to be
questionable, it adds.
The haemostatic drug etamsylate
(Dicynene) is also licensed for use in
menorrhagia. It is thought to act by increasing
capillary vascular wall resistance and platelet
 The Pharmaceutical Journal 73

CPD

PANEL 1: CAUSES AND PANEL 3: POINTS TO CONSIDER IF SUPPLYING CYCLO-F OTC*

OCCURRENCE
No known cause (ie, dysfunctional uterine
bleeding) >60 per cent of cases
Gynaecological (eg, endometrial cancer,
ovarian tumours, endometriosis, fibroids or
polyps, chronic pelvic inflammatory disease)
>30 per cent of cases
Endocrine and haematological (eg, thyroid
disorders, clotting abnormalities, platelet
disorders) <5 per cent of cases
PANEL 2: SYMPTOMS THAT
NEED TO BE REFERRED
The woman must have regular (no more than three days variation
in cycle duration) 21 to 35 day cycles and be 18 years or over.
Use can continue as long as periods remain heavy and regular
but women who do not experience reduced bleeding within three
menstrual cycles should consult their GP.
Contraindications include irregular menstrual bleeding, kidney
problems (higher risk of blood clots), thromboembolic disease
(including family history), use of anticoagulants, haematuria, use
of oral contraceptives, pregnancy and breastfeeding (tranexamic
acid crosses the placenta and is present in breastmilk).
Cautions include women over 45 years, those who are obese and
diabetic (they may be at greater risk of endometrial cancer and Dreamstime.com
thromboembolic disease), those who have polycystic ovary
syndrome or history of endometrial cancer (in a first degree relative) and those taking tamoxifen
(increased risk of endometrial cancer) or unopposed oestrogen therapy (these women should not
be having periods). These women should consult their GP before starting treatment.
* Adapted from Cyklo-F summary of product characteristics

Irregular bleeding
An increase in blood loss that is different
from what is normal for the woman (unless
due to an intrauterine contraceptive device)
Intermenstrual bleeding
Postcoital bleeding
Pain during intercourse (dyspareunia)
Pelvic pain
Premenstrual pain (eg, headache, backache,
joint and muscle pain)
adhesiveness. However it has not been shown
to produce signicant reductions in menstrual
loss and is not recommended for use.1
NSAIDS Both prostaglandin E2 synthesis and
prostaglandin E binding sites are known to be
increased in women who suer from
menorrhagia. This makes NSAIDS a logical
treatment choice due to their inhibition of
cyclo-oxygenases that play an important part
in prostaglandin production. In addition, they
are useful when dysmenorrhoea co-exists.
NSAIDS have been shown to reduce blood
loss by 2050 per cent but mefenamic acid is
the only one licensed for treating
menorrhagia. Mefenamic acid remains the
most eective choice because it has a dual
action, both reducing prostaglandin synthesis
and inhibiting binding of prostaglandin E2 to
its receptor. The normal dose is 500mg three
times a day, starting on the rst day of heavy
bleeding. Although its summary of product
characteristics states that it can impair female
fertility, this should not be an issue for short-
term use in menorrhagia.
Mefenamic acid can be combined with
tranexamic acid if menstrual bleeding and
dysmenorrhoea are problematic5 but the
combined dosage schedule may make this
option unacceptable to many women,
especially with the need to time medication
with food.
Ibuprofen and naproxen are licensed for
use in dysmenorrhoea but not in menorrhagia.
However each has been shown to reduce
blood loss. There is also evidence for the
eectiveness of indometacin and urbiprofen
in reducing blood loss. There is no evidence to
support the use of cyclo-oxygenase 2
inhibitors and none is licensed for this
indication.
The side eects of NSAIDS are well
known but in a predominantly young
population and with intermittent use they
should not be a problem.
Hormonal treatment If the woman requires
contraception, hormonal treatments are an
option.
Intrauterine levonorgestrel The
levonorgestrel intrauterine system (LNG-
IUS) reduces blood loss by up to 95 per cent.
It also relieves dysmenorrhoea, and provides
reliable contraception. It is especially useful if
long-term contraception (anticipate at least 12
months) is required and the combined oral
contraceptive is contraindicated. It can be kept
in place for ve years. The LNG-IUS has
been shown to be superior to other drugs in
randomised controlled trials.
The LNG-IUS is generally well tolerated
but signicant side eects can develop,
including oedema, weight gain, headache,
depressive mood, abdominal and pelvic pain,
acne, dysmenorrhoea and vaginal discharge.
In addition, any intrauterine device can cause
an increase in menstrual loss and spotting.
Insertion of the device can cause pain,
which normally responds to NSAIDs. Uterine
perforation is also a risk during insertion.
Once in situ there is a risk of infection of
between 1:100 and 1:1,000.
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Combined oral contraceptive The
combined oral contraceptive pill is accepted as
the rst-line treatment when relatively short-
term contraception is required (see later). This
is thought to work by inducing regular
shedding of a thinner endometrium. It will
also reduce associated dysmenorrhoea and
regulate menstrual cycles. However there is
little trial data to support use for its
menorrhagia a Cochrane review was
unable to achieve its object because of the
paucity of data.6 Also the data that do exist
involve higher dose preparations containing
50mg ethinylestradiol. A small study found no
signicant dierence between groups treated
with a combined oral contraceptive,
mefenamic acid, low dose danazol or
naproxen but, overall, the evidence from this
one study is not sucient to assess ecacy.
In terms of combined treatments, an
NSAID may be used with a combined oral
contraceptive where dysmenorrhoea is
problematic but Clinical Knowledge
Summaries advises against the prescribing of
tranexamic acid with a combined oral
contraceptive or the LNG-IUS.5
Progestogen-only treatment
Norethisterone is recommended for 21 days
each cycle, starting from day 5, to cover the
follicular and luteal phases. The dose
(unlicensed) is relatively high, at 5mg tds.5
According to CKS and NICE, the licensed
regimen of oral norethisterone for DUB, 5mg
two to three times a day used only during the
luteal phase (ie, from day 19 to day 26 of the
cycle) is no longer recommended because it is
ineective.1,5 [The British National Formulary
includes a licensed dose of norethisterone for
menorrhagia, 5mg twice daily from day 19 to
day 26 of the menstrual cycle, but
acknowledges the relative ineectiveness of
this regimen compared with other treatments
(BNF 60, section 6.4.1.2, Progestogens).]
High dose norethisterone (eg, 30mg a day
[unlicensed] until bleeding stops, then reduce
the dose by 5mg a day) has been used to stop

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74 The Pharmaceutical Journal

Learning & development

PANEL 4: SUMMARY OF DRUG TREATMENTS FOR MENORRHAGIA IN PRIMARY CARE*

Treatment Reduction of bleeding Common side effects
Levonorgestrel Up to 95% (full effect can take six months) Irregular bleeding, breast tenderness, acne, headache
Tranexamic acid Up to 58% Gastrointestinal discomfort
NSAIDs Up to 49% Indigestion, diarrhoea
Combined oral contraceptive 43% Mood changes, headaches, nausea, fluid retention,
breast tenderness
Norethisterone Up to 83% Weight gain, bloating, breast tenderness, headaches,
acne (all transient)
Medroxyprogesterone Amenorrhoea likely Weight gain, irregular bleeding, premenstrual-like syndrome

*Adapted from NICE clinical guidelines

ooding but there are no supporting trial Anaemia Complementary therapies

data.7 Bleeding can recur when treatment is
stopped. CKS suggests norethisterone 5mg
tds (which should stop bleeding within 48
hours) or, in severe cases, 10mg (unlicensed)
tds, tapering to 5mg tds for a further week.
Medroxyprogesterone acetate exerts anti-
androgenic and antigonadotrophic eects and
has been used (unlicensed indication) for
menorrhagia. A depot injection of 150mg will
provide contraception (12 weeks) and
complete amenorrhoea. It should be used with
caution in younger women because of its
potential for reducing bone density but,
according to the SPC for Depo-provera, bone
mineral density appears to increase after the
drug is stopped there is no evidence that its
use in young women increases the risk of
osteoporosis or fractures in later life.
Danazol Danazol is a synthetic steroid with
weak androgenic actions but it has
antiandrogenic, progestogenic,
antiprogestogenic, oestrogenic and
antioestrogenic actions. It has been prescribed
in menorrhagia and reduces blood loss by up
to 80 per cent but use is limited by a side-
eect prole that includes hirsutism and
deepening of the voice, and its many
interactions. It is not recommended for
routine use in menorrhagia.1
Choice CKS recommends the following
prescribing hierarchy in primary care:5
First line: levonorgestrel releasing
intrauterine systematic
Second line: tranexamic acid, an NSAID or
a combined oral contraceptive
Third line: norethisterone or
medroxyprogesterone acetate
However the nal choice will depend on
the womans fertility needs, the degree of any
accompanying dysmenorrhoea (when
NSAIDs are preferred over tranexamic acid1),
her attitude and motivations, and the type of
regimen best suited to her lifestyle. The
prospect of regular or cyclical medication may
not be acceptable to some women.
In secondary care, gonadotrophin-
releasing hormone (GnRH) analogues, such
as leuprorelin and buserelin, are options and
may be initiated under specialist supervision.
Pharmacists should remember that
menorrhagia is one of the main causes of iron
deciency anaemia, which can be treated with
oral iron. A CPD article on understanding
iron requirements (PJ, 12 July 2009,
pp4750) is available.
Other treatment options
Referral to a gynaecologist is recommended
when there is clear underlying disease that
will not respond to drug treatment. However,
women themselves can asked to be referred if
they believe pharmaceutical interventions are
not satisfactorily dealing with the problem.
If pharmaceutical options are deemed to
have failed, there are a number of surgical
options. Traditional hysterectomy is the
main choice. (Generally the ovaries are not
removed unless there is a clinical reason to do
so. If the ovaries are removed subsequent
menopausal symptoms can be severe and
rapid in onset.)
Thermal ablation of the endometrium is
also successful, as is endometrial cryopathy,
but a hysterectomy is the only permanent
solution because ablative treatment may need
to be repeated.
Although there are a large number of
interventions to choose from, menorrhagia is a
major cause of surgery because many women
referred to gynaecologists for menorrhagia
will have a hysterectomy.
PRACTICE POINTS
Reading is only one way to undertake CPD
and the regulator will expect to see various
approaches in a pharmacists CPD portfolio.
1 When women purchase over-the-counter
treatments for period pain, ask about any
symptoms of menorrhagia.
2 Ask about symptoms of anaemia when
supplying treatments for menorrhagia.
3 Make sure your staff are aware of the
availability of OTC tranexamic acid.
Consider making this activity one of your nine
CPD entries this year.
A large number of websites oer information
on complementary and alternative remedies
for menorrhagia. A lot of the advice seems to
be aimed at women experiencing problems
around the menopause when acute
menorrhagia can become a problem and there
is no clear evidence for the ecacy of any of
the recommended products. For example,
black cohosh has been used for menorrhagia
and is known to be safe but there is no good
evidence for its ecacy. Phyllanthus has also
been used.
Conclusion
With the availability of both tranexamic acid
and ibuprofen over the counter, pharmacists
now have eective products at their disposal
to help women with DUB. However, there is a
wide range of treatments for menorrhagia and
women need to be actively involved in all
treatment decisions and this requires that they
are given sucient information. Panel 4
presents a summary of ecacy and common
side eects.
References
1 National Institute for Health and Clinical
Excellence. Heavy menstrual bleeding.
Available at www.nice.org.uk (accessed on 13
January 2011).
2 Willacy H. Menorrhagia. Available at
www.patient.co.uk (accessed on 13 january
2011).
3 Meda Pharmaceuticals. Cyclo-F patient
information leaflet.
4 Medicines and Healthcare Products
Regulatory Agency. UK public assessment
report: Cyklo-F-500mg film-coated tablets
(tranexamic acid). Available at
www.mhra.gov.uk (accessed on 13 January
2011).
5 Clinical Knowledge Summaries. Menorrhagia
(heavy menstrual bleeding). Available at
www.cks.nhs.uk (accessed on 13 January
2011).
6 V Iyer, C Farquhar, R Jepson. Oral
contraceptive pills for heavy menstrual
bleeding. Cochrane Database of Systematic
Reviews 2007 Issue 2.
7 Rees M (2004) personal communication
Reader in reproductive medicine; honorary
consultant in medical gynaecology, Womens
Centre: John Radcliffe Hospital, Oxford.

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