Anda di halaman 1dari 6

How to Treat

PULL-OUT SECTION

www.australiandoctor.com.au

Complete How to Treat quizzes online


www.australiandoctor.com.au/cpd to earn CPD or PDP points.

INSIDE
Aetiology
Structural causes
Systemic or
iatrogenic causes
Assessment
Management

the authors

Dr Alejandra Izurieta
director, Alana Healthcare for
women, Randwick; and specialist,
IVFAustralia, Sydney, NSW.

Premenopausal
abnormal uterine
bleeding

Associate Professor
Jason Abbott
associate professor of
gynaecological surgery,
University of NSW; and director of
gynaecology, Royal Hospital for
Women and Alana Healthcare for
Women, Randwick, NSW.

Background
course; cyclic; or erratic with no patcal interventions and day-stay surgiABNORMAL uterine bleeding in
tern.
cal procedures to extirpative surgery,
premenopausal women is a common
Conditions causing the underlywith the aims of reducing the symppresentation to the GP, with 20-25%
ing bleeding may be acute or chronic;
toms and in the case of surgical treatof women in their reproductive years
associated with changes in bowel or
ments obtaining tissue for diagnostic
experiencing some form of the conbladder habits; may or may not be
purposes.
dition. In fact, 25% of gynaecologiaccompanied by pain; have an associChanges in menstrual flow frecal surgery is performed as a direct
ated discharge; or be associated with
quency, duration or heaviness tend
result of this presentation. While most
fertility concerns. Abnormal uterine
to dominate presentation to the GP.
causes are benign, the symptoms may
bleeding (the previous used term dysIn addition to menstrual bleeding dissubstantially impact on a womans
BI GP
7 4 Management
8 _ A D _ B options
1 2 turbances,
0 1 4 - 0 abnormal
7 - 3 0 Tbleeding
1 1 : 1 may
2 : 3be4 + functional
1 0 : 0 0 uterine bleeding is now
quality
of8 life.
obsolete) is a diagnosis of exclusion.
intermenstrual; associated with interare varied, ranging from simple medi-

Pathological conditions may be local,


systemic or iatrogenic; and pregnancy
must always be considered and appropriately excluded before management
is initiated.
This article will concentrate on
bleeding occurring in women of
reproductive age, being mindful that
any presentation of premenarchal or
postmenopausal bleeding is abnormal and always requires review.
contd next page

Copyright 2014
Australian Doctor
All rights reserved. No part of this
publication may be reproduced,
distributed, or transmitted in any
form or by any means without
the prior written permission of
the publisher.
For permission requests, email:
howtotreat@cirrusmedia.com.au

PALEXIA SR is now PBS listed


Please see the primary advertisement for PBS Information and Product Information.
Further information is available on request from bioCSL.
PALEXIA SR is a registered trademark of Grunenthal Pty Ltd. PALEXIA SR is distributed by bioCSL (Australia) Pty Ltd under licence from Grunenthal Pty Ltd. bioCSL (Australia) Pty Ltd, ABN 66 120 398 067,
63 Poplar Road, Parkville, Victoria 3052. Medical Information: 1800 642 865. bioCSL is a registered trademark of CSL Limited. DC 6553. BIGP8748/AD/B. August 2014.

www.australiandoctor.com.au

22 August 2014 | Australian Doctor |

19

How To Treat Premenopausal abnormal uterine bleeding


Aetiology
The physiology of menstruation
IN order to appropriately manage abnormal uterine bleeding, an
understanding of the menstrual
cycle is warranted. The menstrual
cycle may be divided into three
phases: the follicular or proliferative phase, ovulation, and the
luteal or secretory phase.
In the follicular phase, FSH is
secreted by the pituitary and signals the ovary to commence the
maturation of a cohort of follicles
ultimately resulting in the emergence of a dominant follicle. This
dominant follicle is responsible for
the surge in oestradiol in the first
half of the cycle that feeds back
to the pituitary to cause a surge in
LH and subsequent ovulation.
This surge in oestrogen also
stimulates endometrial proliferation and growth in the uterus during this phase. Once ovulation
has occurred, luteinisation of the
follicle to form the corpus luteum
allows production and release of
progesterone that stabilises the
endometrium as it enters the secretory phase. The proliferation of
the endometrium ends, and its differentiation begins. In the absence
of pregnancy, menstruation occurs
when the corpus luteum ceases
production of progesterone and
shedding of the endometrium
ensues. A normal cycle is considered to be within the range of
21-35 days and have less than
three days of variance between
each cycle. Bleeding lasting less
than two or more than seven days
is considered abnormal.

The pathophysiology of
abnormal uterine bleeding
Abnormal uterine bleeding may
be either ovulatory or anovulatory. Anovulation is more com-

Differential diagnoses of
abnormal uterine bleeding
Structural PALM
Polyps
Adenomyosis and endometriosis
Leiomyoma (fibroid or myoma)
Malignancy
As well as localised lesions or
infections
Non-structural - COIEN
Coagulation disorders
Ovulatory dysfunction (anovulation,
perimenopause, perimenarche,
PCOS/androgen excess, thyroid
disorders, excess prolactin)
Iatrogenic
Endometrium
Not yet classified

Table 1: Terms used to describe abnormal uterine bleeding


Term

Definition

Amenorrhoea

No menses for >90 days

Oligomenorrhoea

Bleeding intervals >35 days


(mainly due to a prolonged follicular phase)

Polymenorrhoea

Bleeding intervals <21 days


(mainly due to a luteal phase defect)

Menorrhagia

Excessive or prolonged but regular bleeding

Metrorrhagia

Irregular intervals between bleeding

Intermenstrual bleeding

Irregular bleeding occurring between cycles

Menometrorrhagia

Excessive or prolonged bleeding at irregular


non-cyclical intervals

Mid-cycle spotting

Spotting occurring just before ovulation


(mainly due to a decline in the estrogen levels)

mon, with abnormal bleeding


resulting from unopposed oestrogen stimulation of the endometrium leading to its proliferation
and hyperplasia. In the absence
of progesterone, the endometrium does not differentiate nor
stabilise. This leads to increasing
sloughing of the endometrium,

manifesting as polymenorrhoea
(shortened cycles <21 days), oligomenorrhoea (lengthened cycles
>35 days), intermenstrual spotting or menorrhagia (>80mL per
cycle, estimated from clinical history). Ovulatory forms of abnormal uterine bleeding may lead to
aberrations in both the follicular

In the assessment of a
patient, it is imperative
that pregnancy and
pathology are excluded
prior to instituting any
management.

and luteal phase. Table 1 outlines


the terms used to describe abnormal uterine bleeding.

Causes
In the assessment of a patient, it
is imperative that pregnancy and
pathology are excluded prior to
instituting any management.

Other causes
Other causes are mostly rare.
Include trauma, and endocrine and
hepatic disorders

Pregnancy
All menstruating women who
are sexually active are pregnant
and have an ectopic until proven
otherwise.
Do you recall your medical school
days when this mantra was drilled
in at every lecture on abnormal
bleeding? This still holds true, since
ectopic pregnancy is a life-threatening condition and should always
be excluded as a cause of abnormal
uterine bleeding.
Pathology
The pathological causes of abnormal
uterine bleeding are broadly defined
as being either structural or nonstructural. The differential diagnoses
are commonly then further classified
using the acronym PALM COIEN
(see box above).

Structural causes
Polyps

Figure 1:
Endometrial
pedunculated
polyp.

ABOUT 25% of women who


experience
abnormal
uterine
bleeding have polyps. Polyps are
outgrowths of endometrial tissue
that may either have a flat base
(sessile) or have a stalk (pedunculated) (figure 1). They contain
blood vessels, glandular epithelium and stromal tissue and are
therefore responsive to hormonal
changes. Endometrial polyps are
largely benign, with only 0.5-3%
malignant (commonly adenocarcinoma), with risk factors for malignancy including size >2.5cm and
multiplicity.
Clinical presentation
The tissue of a polyp is fragile
and susceptible to erosion which
is the primary reason for bleeding
and clinical presentation. Rarely,
endometrial polyps will cause
crampy pelvic pain.
Diagnosis and management
Imaging by 2D grey-scale ultrasonography is the most frequently
used modality for diagnosis, with
contrast sonohysterography used
on occasion. Hysteroscopy is the
definitive diagnostic tool that also
enables surgical removal and his-

20

| Australian Doctor | 22 August 2014

tological assessment.
Spontaneous regression of small
endometrial polyps (<0.8cm)
occurs in about 25% of women
particularly those who are asymptomatic. Conservative management is a suitable option for
women with polyps under 0.8cm
who are asymptomatic.
The risk of malignancy and the
relative ease of treatment with
low-invasive means in a day-stay
setting are the primary indications
for removal of this type of pathology.

Adenomyosis and endometriosis


Endometriosis is the presence of
ectopic endometrial tissue (both
glands and stroma) in the pelvis,
abdomen or even more remote
organs. Adenomyosis may be considered to be on the spectrum of
endometriosis in that the ectopic
endometrial tissue occurs in the
myometrium (figure 2). It can cause
abnormal uterine bleeding owing to
a combination of possible pathologies. Adenomyosis may induce
hyperplasia and hypertrophy of
the myometrium, both enlarging
www.australiandoctor.com.au

Figure 2:
A uterus with
adenomyosis
and a fibroid.

the uterus and increasing the endometrial surface area. In addition,


changes in the vasculature may also
contribute to the aberrant bleeding.
Clinical presentation
Women with adenomyosis and
endometriosis may present with
abnormal uterine bleeding, such
as menorrhagia and premenstrual
spotting. Pain is a common presenting symptom, including pelvic
and low back pain, dysmenorrhoea, dyspareunia and dyschezia.
Infertility may also be a symptom

of adenomyosis or endometriosis.
Diagnosis and management
While adenomyosis and endometriosis may be diagnosed on ultrasound, a normal scan result does
not rule out the conditions. MRI
may also confirm the diagnosis,
however the cost is prohibitive
and this modality is rarely used.
Laparoscopy is the gold standard
for diagnosis.
Management may be medical,
which is mainly in the form of horcontd page 22

How To Treat Premenopausal abnormal uterine bleeding


from page 20
monal treatment to achieve endometrial suppression. Options include
local or systemic hormonal treatments, including the levonorgestrel
IUD (Mirena) or the combined oral
contraceptive pill. Non-hormonal
options includes NSAIDs (eg, ibuprofen, naproxen, mefenamic acid),
or tranexamic acid (1g qid on day
1-3 of the cycle)
Surgical options vary from ablative treatments, such as endometrial ablation and laparoscopic
resection, to hysterectomy.

Figure 3:
Location of
fibroids within
the uterus.

Leiomyoma (fibroid or myoma)


Up to 70% of women in the
reproductive years have a uterine
myoma, of which half will present clinically. These are benign
smooth muscle tumours of the
uterus (figure 2). Fibroids tend to
have an unpredictable growth pattern and are not always responsive
to increases in hormones such
as oestrogen and are not considered premalignant. Like polyps
they may be sessile or pedunculated. Fibroids are described
depending on their location within
the uterus (figure 3), as follows:
Submucosal: Underneath the
endometrial layer.
Intramural (myometrial): Within
the myometrium.
Subserosal: Underneath the serosal layer.
Clinical presentation
Depending on the size and location
of the fibroid, clinical presentations
may vary. Symptoms may include
abnormal uterine bleeding such as
intermenstrual spotting, menorrhagia or menorrhagia. Pelvic and
low back pain, dysmenorrhoea and
dyspareunia may occur. Fibroids
may cause urinary symptoms, such
as incontinence, incomplete bladder emptying and urgency, as well
as symptoms from bowel pressure
effects. Infertility may also be a presenting complaint.

Up to 70% of women
in the reproductive
years have a uterine
myoma, of which half
will present clinically.

Diagnosis and management


Although clinical palpation is possible when fibroids are large, diagnosis
is best achieved with imaging such as
2D ultrasonography. Management
depends on the presentation and

symptomatology. Medical options


include local or systemic hormonal
treatments, such as the levonorgestrel IUD (Mirena) and the combined pill. The effectiveness of either
oral or local uterine hormonal treatments will depend on the size of the
fibroid, its position and the desired
outcome. Obviously such hormonal
treatments are not an option if fertility is the primary goal.
Non-hormonal treatments include
NSAIDs and tranexamic acid (1g
qid on day 1-3 of the cycle) that
are intended to reduce bleeding and
pain, particularly in the first few
days of the cycle.
Surgical treatments vary from
local removal (myomectomy via
hysteroscopic, laparoscopic or laparotomy approach) to more radical
surgery (hysterectomy).
Radiological intervention by uterine artery embolisation (where the
myoma is devascularised through
vascular occlusion using an intravascular approach) has been demonstrated to be effective and provides
an alternative to surgery. Magnetic
resonance-guided focused ultrasound (MRgFUS) is a new technique that uses ultrasonic energy to
destroy the myoma. It has not been
as fully evaluated for uterine artery
embolisation and is not widely avail-

able in Australia at this time.

once childbearing is complete.

Malignancy

Cervical
Cervical cancer has a similar presentation with cycle irregularity,
post-coital
and
intermenstrual
bleeding. The average age of diagnosis is around 50 years, when
many women are still having menstrual cycles. Cervical screening has
decreased the incidence of cervical
cancer over the years and a further
decline is expected with following
the introduction of routine HPV
vaccination.
Currently, women younger than
30 years with low-grade squamous intraepithelial lesions (LSIL)
should have a repeat Pap smear at
12 months and referred for colposcopy if the repeat smear shows LSIL
again. Women aged 30 years or
more with LSIL without a normal
Pap result in the preceding 2-3 years
should be offered either colposcopy
or a repeat Pap smear at six months.
Women with high-grade squamous
intraepithelial lesions (HSIL) should
be given an early referral for colposcopic assessment and management. Lesions that are confirmed to
be high-grade lesions on biopsy are
treated with an excisional or laser
method to eradicate abnormal cells.
Early cervical cancers are generally
managed surgically in conjunction
with a gynaecological oncologist,
with radiation therapy for laterstage cancers.

Endometrial
Endometrial hyperplasia or malignancy commonly presents with
abnormal vaginal bleeding. Endometrial cancer is more likely in
postmenopausal than premenopausal women with >90% of cases
diagnosed over the age of 50.
Endometrial cancer in adolescent
girls is extremely rare but the risk
increases with age.
Hyper-oestrogenism
will
increase a womans risk for hyperplasia and malignant endometrial
changes. Risk factors include a
history of PCOS, obesity, early
menarche and/or late menopause,
a history of infertility, nulliparity
and tamoxifen use.
The premenopausal woman
with endometrial malignancy may
present with intermenstrual bleeding, cycle irregularity or menorrhagia. Clinical presentation, risk
assessment and the use of ultrasound to triage woman into high
or low risk will aid in the decision
for referral. Once referred, diagnosis is confirmed with endometrial
biopsy that may be done in an
ambulatory setting using an endometrial sampler (such as a pipelle)
or in a day-stay surgical setting by
hysteroscopy and directed endometrial biopsy.
Once diagnosed, management
will usually involve a gynaecological oncologist. Total hysterectomy
with bilateral salpingo-oopherectomy with or without pelvic and
para-aortic lymphadenectomy is
the primary surgical treatment
for endometrial cancer. Fertilitysparing non-surgical options may
be considered when fertility is
desired. Management in cases of
complex hyperplasia may involve
high-dose progestogens administered either orally or locally, monitored frequently with biopsy, but
definitive surgery is recommended

Localised causes
Bleeding anywhere from the genital tract and surrounding anatomy
should be excluded. Local and
genital tract pathology that may
cause abnormal uterine bleeding
includes: inflammation, infections (STIs, PID endometritis,
cervicitis), benign anatomical
abnormalities (eg, cervical polyps, haemorrhoids), premalignant
lesions (cervical dysplasias) and
trauma (eg, foreign bodies, abrasions, lacerations).

Systemic or iatrogenic causes


Coagulopathy
UP to 18% of women with abnormal uterine bleeding may have an
underlying inherited coagulopathy.
Von Willebrands disease is the most
common inherited bleeding disorder
in women who present with abnormal uterine bleeding. The qualitative or quantitative dysfunction or
deficiency in von Willebrands factor, which is required for platelet
adhesion, commonly manifests as
heavy menstrual bleeding, bleeding
at childbirth or nosebleeds. Both
inherited and acquired forms of this
disease exist, the latter predominating in patients with a predisposition
for developing autoantibodies. The
recommended primary investigations if there is suspicion of the disease are vWF testing in addition to
FBC, coagulation studies, platelet
function tests and iron studies are.
Desmopressin (DDAVP) is the main
treatment, however tranexamic acid
is a useful adjunct for women experiencing abnormal uterine bleeding.
Referral to a haematologist is warranted.

Ovulatory disorders
There are several conditions that

22

| Australian Doctor | 22 August 2014

suppression (such as with stress,


weight loss, excessive exercise)
and renal disease.
Post menarche and perimenopause
Hormonal irregularities secondary
to altered GnRH pulsatility either
because of immaturity in the HPO
axis (pubertal), or failing ovarian
response, (perimenopausal) may
result in menstrual cycle irregularities and abnormal uterine bleeding.

interfere with the hypothalamic


pituitaryovarian (HPO) axis,
whether age-related or pathological, causing disruption to ovulation. These include post-menarche,

perimenopause, postmenopause,
PCOS/androgen excess (such as in
adrenal hyperplasia and Cushings
disease), thyroid disease, hyperprolactinaemia,
hypothalamic
www.australiandoctor.com.au

PCOS/androgen excess
Polycystic
ovarian
syndrome
(PCOS) or elevated androgen levels may impair ovulatory function
and cause anovulation that presents with abnormal uterine bleeding. Hormonal changes in these
and associated conditions such
as hyperinsulinaemia act both
directly and indirectly to cause
menstrual cycle irregularity and
irregular bleeding. Ovulatory dysfunction manifests in PCOS as a
result of anovulation and absence
of the LH surge but also as a direct
result of insulin acting centrally at
the level of the hypothalamus and
pituitary and locally at the ovarian
insulin receptors.

Thyroid disease and


hyperprolactinaemia
Both conditions cause ovulatory
dysfunction as a result of numerous interactions of the hormones
with the female reproductive system. Menstrual irregularities arise
secondary to an alteration in TRH
production and GnRH pulsatile
secretion leading to a delay in the
LH response and inadequate corpus luteum formation. Both hypothyroidism and hyperthyroidism
have been associated with menstrual irregularities and changes in
menstrual flow. Checking thyroid
function tests and an early morning prolactin are recommended.

Iatrogenic
Iatrogenic causes of abnormal
uterine bleeding need exploration.
Medications that may induce bleeding include anticoagulants, antipsychotics, corticosteroids, herbal and
other supplements (such as ginseng,
ginkgo, soy), all hormone treatments
(including HRT, the combined pill
and progestogen-only contraceptives), IUDs, SSRIs, tamoxifen and
thyroid replacement therapy.
contd page 24

How To Treat Premenopausal abnormal uterine bleeding


Assessment
History
DIRECTING the assessment based
on the age and concern of the
patient is a good starting point. A
detailed history will provide clues
in the direction of the cause and
some guidance to investigations.
Questions to consider asking when
history-taking in a presentation
of abnormal uterine bleeding are
listed in the box, right.

Questions to consider when taking a history in


abnormal uterine bleeding
Menstrual history
Menarche
Cycle regularity
Volume and nature of flow/clots (number, frequency of tampon/pad use)
Intermenstrual bleeding
Post-coital bleeding
Premenstrual spotting

Examination

Associated symptoms: pelvic pain, dysuria, urgency, dyschezia

Examination may often reveal


pathology, with structural pathology palpated (fibroids, nodular
endometriosis, ovarian cysts) or
even visualised (cervical polyps,
warts or cancers). In addition to
aiding the diagnosis, a genital tract
examination will also facilitate primary investigations. Do not omit
the general examination that may
provide clues for systemic causes of
abnormal bleeding.
Examination should include:
Weight, height and BMI.
Blood pressure and heart rate.
Assessment for bruising and jaundice.
Thyroid examination for thyroid
size and nodularity.
Abdominal examination for
hepato/splenomegaly, masses and
tenderness.
Assessment of the external genitalia, perineum, anal opening and
urethral meatus.
Vaginal examination, assessing
uterine size and mobility, adnexal
masses and tenderness.
Speculum examination for visualisation of any lesion or abnormality both in the vagina and cervix
and for swabs and cervical smears
to be obtained as indicated.
Directed systems examinations
should then be guided by the clinical presentation.

Sexual history
Age of at first intercourse
Number of sexual partners in the last 12 months
STIs
Pap smears

Investigations for abnormal uterine bleeding

Contraception

Obtained in conjunction with the examination

Fertility and pregnancy

Pap smear

Number of pregnancies/complications

Endocervical swabs/Microbial swabs/first pass urine for STIs

Any fertility concerns

Biochemical

Associated symptoms

For all women:

A
 naemia: lethargy, shortness of breath, palpitations

beta-hCG

T
 hyroid dysfunction: changes in weight, cold intolerance, fatigue,
constipation

FBC
Other investigations to include:

Androgen excess: acne, hirsutism

Coagulation profile

Pituitary adenomas/prolactinomas: galactorrhoea, headache, visual field


disturbances

LH/FSH
TSH

Bleeding disorders: easy bruising

Day 21 progesterone

Hypothalamic suppression: weight loss, excessive exercise, stress

Fe studies

Malignancy: bloating, unexplained weight loss

AMH

Medical history

Prolactin

Medications

Sex hormone-binding globulin, free androgen index, testosterone

Family history

Investigations
Only a few investigations are
required to aid the diagnosis of
abnormal uterine bleeding in
women of reproductive age. These
should be targeted according to the
likely differential diagnoses. Investigations for consideration are noted

in the box (right).


Further investigations would
require a referral to a gynaecologist.
These may include hysteroscopy,
endometrial biopsy or curettage and
laparoscopy (which may be used for
both confirming a suspected diagnosis and as a management tool).

LFTs
Dehydroepiandrosterone sulfate
17-OHP
75g oral glucose tolerance test
Imaging
Pelvic ultrasound
Hysterosalpingo-contrast-sonography/Sonohystography

Management
OPTIONS will depend on any
underlying pathology, a womans
symptoms and desired outcome.
Once specific pathology is ruled
out and abnormal uterine bleeding
is diagnosed either as ovulatory or
anovulatory, the chosen management may be initiated. It is important to ensure whatever treatment
is instituted that a comprehensive
discussion about options is undertaken with the woman and appropriate follow-up is arranged. It is
also worth remembering that conservative management may be a
suitable initial option, since most
medical and surgical options come
with potential side effects or complications.

Anovulatory abnormal uterine


bleeding
Age, fertility considerations and
a womans preference will guide
management choice. Medical
treatments are generally hormonal
and therefore contraceptive (see
table 2). The aim of treatment is
to provide a balance to unopposed
oestrogen stimulation on the endometrium, thereby decreasing risks
of endometrial hyperplasia and
cancer.
Use of the combined oral contra-

24

| Australian Doctor | 22 August 2014

Table 2: Medical management of anovulatory abnormal uterine bleeding


Medication

Dose

Treatment goal

Combined oral
contraceptive pills

20-35g ethinyl estradiol plus progestin


(monophasic) taken daily

Cycle regulation/control
Contraception
Prevention of endometrial hyperplasia

35g ethinyl estradiol plus progestin


taken bd-qid for 5-7 days until menses stops,
taper to daily pill for completion of 28-day
pack, then continue with continuous COCP
for 3-6 months

Management of non-emergency heavy


bleeding

Ovulatory abnormal uterine


bleeding

Progestogens
Medroxyprogesterone 5-10mg bd for 21 days of the month
acetate
10mg tds until menses stops then taper every
three days

Cycle regulation

Norethisterone

5mg daily for 21 days of the month

Cycle regulation

5mg tds

Management of non-emergency heavy


bleeding

Initial release rate 20g daily


(Release rate is reduced by 50% by five
years)

Management of non-emergency heavy


bleeding
Prevention of endometrial hyperplasia

Levonorgestrel
intrauterine system

Etonogestrel
Initial release rate 60g daily
subcutaneous implant (Release rate is reduced by 50% by the end
of two years)

Management of non-emergency heavy


bleeding

Management of non-emergency heavy


bleeding
Prevention of endometrial hyperplasia

Adapted with permission from Albers JR, et al.1

ceptive pill is the mainstay of treatment but progestogen-only pills


(given for 21 days of the menstrual
cycle) or local devices such as the

levonorgestrel intrauterine system


(LNG-IUS or Mirena) or etonorgestrel implant (Implanon) can be
used. Progestogens may be first line
www.australiandoctor.com.au

Surgical options may be offered


to those women who have completed their childbearing or where
fertility is not desired. Ablation
and hysterectomy are generally
offered when hormonal options
have failed but may be first line
for a woman who requests this
and who has been appropriately
counselled.

in women for whom oestrogen is


contraindicated, such as in heavy
smokers and those at risk of thromboembolic disease.

Medical treatment may be both hormonal and non-hormonal. Hormonal options include the combined
pill, the choice of which will be
dictated by the presentation. If the
patients presents with heavy flow,
then a combined pill containing a
stronger progestogen (eg, norethisterone) will be most effective. If the
woman experiences intermenstrual
bleeding in the proliferative or secretory phase, higher-dose oestrogencontaining pills will address issues
pertaining to pre-ovulatory spotting,
whereas stronger progestogens may
assist in secretory phase bleeding
problems.
Women who have been on the
combined pill for some time and
present with new-onset intermenstrual spotting may benefit from

changes in, or a break from, the pill


depending on whether the bleeding
occurs in the first or second half of
the cycle.
GnRH agonists such as goserelin
(Zoladex) used monthly for 3-6
months or nafarelin (Synarel) are
an option for women experiencing
severe bleeding, mostly associated
with pain, uncontrolled by other
hormonal treatments. The aim is
for complete suppression of ovar-

taken regularly in the first few


days of the menstrual cycle will
benefit women who also have
dysmenorrhoea. Tranexamic acid
used on the heaviest days of the
cycle (generally prescribed as 1g
qid) may reduce menstrual volume
by up to 80%.
The potential for thromboembolism with tranexamic acid and the
aforementioned hormonal options
for treating ovulatory abnormal

ian function. These are generally


used as an interim measure, before
definitive treatment is instituted.
Local devices such as the LNGIUS or implant may cause further
breakthrough bleeding, so assessment and appropriate counselling
regarding the possible side effects
are important.
Non-hormonal options may
have both anti-inflammatory and
antifibrinolytic effects. NSAIDs

Abnormal uterine bleeding

Nonhormonal

Hormonal

PO

Combined
hormones
(oral, vaginal,
transdermal)

Local (LNGIUS)

Figure 4: Management options for


women of reproductive age with
abnormal uterine bleeding.
Radiological

Surgical

Medical

Progestogens

uterine bleeding need to be discussed with the patient.


Surgical management is appropriate if fertility is not a concern or
option, since these operations are
demonstrated to be more effective
management options for abnormal uterine bleeding than medical
treatments. Figure 4 is a flow diagram of the various management
options for women with abnormal
uterine bleeding.

GnRHa

NSAIDs

Localised
removal
(laparoscopy,
hysteroscopy,
open)

Endometrial
Hysterectomy
ablation

Uterine artery
embolisation

Magnetic
resonanceguided focused
ultrasound
(MRgFUS)

References
1. A
 lbers JR, et al. Abnormal uterine
bleeding. American Family Physician 2004; 69:1915-26.

Further reading
Journal of the American Association
of Gynecological Laparoscopists
2003; 10:49195.
Australian Institute of Health and
Welfare, Australasian Association of Cancer Registries. Cancer
in Australia: An Overview, 2012.
Cancer series no. 74. Cat. no. CAN
70. AIHW, Canberra, 2012.
Endocrine Reviews 2012; 33:9811030.
Fertility and Sterility 2000; 74:
1063-70.
Clinical Endocrinology 2007;
66:309-21.
Journal of Minimally Invasive
Gynecology 2011; 18:569-81.
Obstetrics and Gynecology Clinics
of North America 2000; 27: 219-34.

Tranexamic
acid

Implants/
Injectables

Case studies
abdomen and chin, which she treats
with laser. Her family has a strong
history of type 2 diabetes and hypothyroidism. Kylie is up-to-date with
her Pap smears and only stopped the
pill 18 months ago in an attempt to
give her body a break. Her cycles
have now ranged from 23-60 days
and are heavy, requiring hourly
changes of sanitary protection on
her heaviest days. Her last menstrual
period was eight weeks ago. There is
no other history of note.

Case 1
SOPHIE, a 23-year-old woman,
presents with new-onset intermenstrual bleeding. She has been sexually active for seven years and has
recently entered into a new relationship. Sophie has been using the combined oral contraceptive pill for eight
months and is happy with her contraception but is embarrassed about
the continuous per vaginal spotting.
History
A gynaecological history reveals
menarche at the age of 12, with a
regular cycle establishing soon after
that. Sophie denies concerns with
pelvic pain (dysmenorrhoea) but
does experience occasional heavy
menstrual flow (menorrhagia). She
commenced the combined pill after
a pregnancy scare but has never had
a positive pregnancy test.
Sophie has never had a Pap smear
and although she completed her
Gardasil vaccinations at school, she
had become sexually active prior to
the course being given. Her current
relationship started eight weeks ago
and up until one month ago she had
no concerns with her bleeding pattern while on the pill. She admits her
dosing compliance was not strong.
Examination
On examination there is little to find
on abdominal palpation. A speculum examination reveals a small
amount of white cloudy discharge
with a mildly erythematous vaginal mucosa and a normal cervix on
visual inspection. A Pap smear and
endocervical and high vaginal swab
were taken.
Investigations
Suspecting a STI, Sophies GP

treats her condition empirically


with azithromycin 1g stat and
arranges for some basic investigations while awaiting the Pap smear
results. Beta-hCG, FBC and pelvic
ultrasound scan are ordered. She
returns in one week to discuss her
results.
Diagnosis and management
At her next consultation, Sophie
describes a settling of her bleeding over the past three days. Her
GP reveals chlamydia was found
on her swab and a low-grade
squamous intraepithelial lesion
was noted on her Pap smear. He
takes the opportunity to discuss
the ramifications of STIs their
immediate effects and implications
for future pregnancy; follow-up
for an abnormal Pap smear result
and the importance of safe sex
practices. A more reliable longeracting method of contraception is
recommended, given her non-compliance with the combined pill.

Case 2
A 35-year-old woman, Kylie, presents with a history of increasingly irregular cycles. She has
two children who were conceived
unplanned in her early 20s and is
not wanting any more. Kylie lives
with her new partner of the past
two years.
History
A gynaecological history reveals
menarche at the age of 14. Cycles
were always irregular and there
was significant menorrhagia with
iron deficiency that prompted the
commencement of the combined
pill at age 17. Kylies dosing compliance was poor and subsequently
she had two unplanned pregnancies. During her pregnancies she
developed gestational diabetes and
required small doses of insulin. She
had acne during her teenage years
that settled after starting the combined pill. She also struggled with
an increased amount of hair on her
www.australiandoctor.com.au

Examination
On examination, her BMI is 27,
hair is noted on her face, abdomen
and upper thighs. Acanthosis nigricans is also evident. Both abdominal and vaginal examinations are
unremarkable.
Investigations
Kylies GP suspects PCOS and possible thyroid disease. She arranges
for a beta-hCG, FBC, TSH, 75g
oral glucose tolerance test, androgen
profile (testosterone, free androgen
index, sex hormone-binding globulin), dehydroepiandrosterone sulphate, iron studies, and prolactin.
She also requests a pelvic ultrasound
scan to check for uterine and ovarian
pathology.
Diagnosis and management
The pelvic ultrasound scan reveals
polycystic ovaries, but otherwise a
normal uterus. Her bloods show
evidence of increased androgens
and the glucose tolerance test shows
a response consistent with insulin
resistance. The remaining investigations were normal.
A long appointment is organised
to discuss the diagnosis of PCOS
with Kylie. Kylies previous use
of the combined pill substantially

decreased her risk of endometrial


hyperplasia because it acted to correct her hormonal imbalance. However when she stopped taking the
pill, the underlying pathological process resumed and manifested again
as abnormal uterine bleeding.
Given her age and increased
BMI, and no desire for fertility,
Kylies GP discusses hormonal
contraceptive options including
the combined pill and levonorgestrel IUD (Mirena). She opts for
the Mirena as she has never been
particularly good with the pill.
Kylie is at high risk of developing diabetes given her history of
gestational diabetes, family history
and PCOS. There is good evidence
for the use of metformin in combination with other treatments to
manage this risk. Her GP decides
to start an extended-release metformin (which has fewer gastrointestinal side effects). A dose of
850mg daily is recommended for
the first week, increasing the dose
to twice daily after one week if tolerated.

Case 3
SHARON, a 44-year-old woman
presents to her GP with an increase
in the frequency, irregularity and
heaviness of her menstrual cycles.
She has been in a stable relationship for 15 years and had two children with a tubal ligation at her
last delivery and wants to avoid
hormonal treatment because her
great aunt and close friend both
had breast cancer.
History
A gynaecological history reveals
a variable pattern of bleeding
throughout Sharons reproductive
contd next page
22 August 2014 | Australian Doctor |

25

How To Treat Premenopausal abnormal uterine bleeding


from previous page
life. Until her late 20s she had a
regular cycle with some dysmenorrhoea but no menorrhagia. It
took some months to conceive
her children but she never sought
medical intervention for infertility.
Sharon has always used condoms
and the Billings method to avoid
pregnancy. Her menstrual irregularities progressively started worsening three years ago with cycles
ranging now between 23-35 days.
Sharon is now passing clots, has
increasing lethargy, and is fearful of leaving the house when she
bleeds, since she has been embarrassed with flooding occurring in
her workplace recently. She has
just started bleeding again on the
day her GP sees her.
Examination
On examination, her GP finds
signs of anaemia, with pale conjunctiva and palmar creases. An
abdominal examination is unremarkable. A bimanual examination reveals a bulky uterus. The
vagina and cervix look normal on

speculum examination, and her


GP takes the opportunity to perform a Pap smear and high vaginal
swab.
Investigations
Investigations for the anaemia
and suspected uterine pathology are requested including betahCG, FBC, coagulation studies,
TSH and iron studies, and a pelvic
ultrasound scan.

Diagnosis and management


While waiting for the results of the
investigations, Sharons GP counsels her regarding the use of oral
progestogens which she declines,
given her concerns regarding cancer. Her GP then decides to commence tranexamic acid 1g qid for
the following 2-3 days to decrease
her immediate bleeding, and recommends NSAIDs in combination for
the next 2-3 days.

3. Which of the following TWO statements


about endometrial polyps are correct?
a) H
 alf of women with abnormal uterine bleeding
have polyps
b) Although most endometrial polyps are benign,
risk factors for malignancy include size over

DIAGNOSING abnormal uterine


bleeding can be complex, as there
are many different factors that
need to be considered in determining a cause. Such bleeding can
be ovulatory or anovulatory, and
structural or non-structural.
Heavy bleeding can be embarrassing and distressing for a
patient, who may be caught out
when it begins.
A gynaecological history is a
good starting point for a GP,
backed up by examination,
with pathology and imaging as
required.
Depending on the diagnosis,
the patient may require hormonal
treatment, NSAIDs or, in some
cases, surgery. Referral to a gynaecological oncologist will be necessary if a malignancy is revealed.

Complete this quiz online and fill in the GPevaluation form to earn 2 CPD or PDP points.
We no longer accept quizzes by post or fax.

Premenopausal abnormal uterine


bleeding 22 August 2014

2. Which of the following TWO statements


are correct regarding nomenclature in
abnormal uterine bleeding?
a) A
 menorrhoea is the absence of menses for six
months or more
b) Polymenorrhoea is bleeding that occurs at
intervals less than 21 days apart, usually due
to a luteal phase defect
c) M
 enometrorrhagia is excessive or prolonged
bleeding that occurs at irregular, non-cyclical
intervals
d) Intermenstrual bleeding describes the regular
spot bleeding some women experience just
prior to ovulation

Conclusion

Instructions

How to Treat Quiz


1. Which of the following TWO statements
regarding the pathophysiology of abnormal
uterine bleeding are correct?
a) A
 menstrual cycle is considered abnormal if
there are fewer than 20 or more than 30 days
between periods, and if the cycle length is not
the same each month
b) Abnormal uterine bleeding often indicates that
ovulation is not occurring
c) A
 novulation causes abnormal bleeding as a
result of unopposed oestrogen stimulation of
the endometrium
d) Ovulatory forms of abnormal uterine bleeding
are always associated with follicular phase
changes

On her return, her haemoglobin is


73g/dL with a ferritin level of 2ng/
mL; the remainder of the bloods
were normal. On ultrasound, a
small (1.2 0.8 0.5cm) intramural
fibroid is noted on the right cornua
but not impinging on the uterine
cavity. The myometrium is heterogeneous and reported as suspected
adenomyosis.
Iron supplementation and an
urgent referral to a gynaecologist
are arranged. The GP also discusses
with Sharon about the options and
necessity of surgical intervention if
she is adamant in avoiding hormonal treatment. Hysteroscopy with
endometrial biopsy is mandatory
as a preliminary investigation to
exclude endometrial hyperplasia
and cancer. After the investigation,
Sharon may consider hysterectomy, which is definitive. Endometrial ablation is an alternative and
only requires day surgical stays.
Endometrial ablation for suspected
adenomyosis has a higher failure
rate over five years (25% compared
with 10% for women without this
condition).

2.5cm and the presence of multiple polyps


c) Most endometrial polyps cause pain as well
as bleeding
d) S
 mall endometrial polyps regress
spontaneously in about 25% of women,
especially those without symptoms
4. W
 hich of the following TWO statements
regarding adenomyosis and
endometriosis are correct?
a) Adenomyosis causes abnormal bleeding
by inducing myometrial hypertrophy, which
increases the endometrial surface area
b) W
 omen with abnormal uterine bleeding due
to adenomyosis and endometriosis will often
also report pain
c) Ultrasound is the most reliable way to
diagnose adenomyosis and endometriosis
as the cause of abnormal uterine bleeding
d) T
 he levonogestrel IUD is not a therapeutic
option for women with adenomyosis and
endometriosis, as medical management
aims to stimulate the endometrium
5. W
 hich of the following TWO statements
regarding fibroids are correct?
a) Up to 70% of women of reproductive age
have a uterine fibroid, of which half will be
symptomatic
b) F
 ibroids tend to grow predictably, usually in
response to hormone surges
c) Hormonal treatments for fibroids are
consistently effective, regardless of the size
and position of the fibroid
d) D
 evascularisation of a fibroid by guided
uterine artery embolisation is an effective
minimally invasive alternative to surgery for

The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.

GO ONLINE TO COMPLETE THE QUIZ

www.australiandoctor.com.au/education/how-to-treat
fibroids
6. Which of the following TWO statements
regarding abnormal uterine bleeding due
to malignancy are correct?
a) Endometrial cancer only causes abnormal
uterine bleeding in postmenopausal women
b) Risk factors for endometrial cancer include
a history of PCOS, nulliparity and tamoxifen
use
c) Complex endometrial hyperplasia may be
managed with high-dose progestogens
in women who wish to preserve their
childbearing capacity
d) Most women with cervical cancer are
diagnosed postmenopausally, around the
age of 70

examinations should be included in


your initial assessment of Sarah?
a) Weight, height and BMI
b) Thyroid examination
c) Speculum examination for visualisation
of the vagina and cervix and appropriate
sampling
d) PR examination

7. Which of the following TWO statements


regarding systemic causes of abnormal
uterine bleeding are correct?
a) About 1% of women with abnormal uterine
bleeding have an underlying coagulopathy,
usually haemophilia
b) Abnormal uterine bleeding may result from
physiological changes to GnRH pulsatility at
the extremes of reproductive life
c) PCOS leads to abnormal uterine bleeding
solely as a result of the effects of
anovulation
d) Abnormal uterine bleeding can be due to
either hypo- or hyperthyroidism

10. Sarahs abnormal uterine bleeding is


thought to be due to failing ovarian
reserve with perimenopause. Sarah tells
you she has completed her childbearing.
Which of the following TWO statements
are correct regarding the management
of Sarahs anovulatory abnormal uterine
bleeding?
a) The aim of treatment is to achieve a regular,
predictable bleeding pattern
b) The combined oral contraceptive pill is the
mainstay of medical treatment
c) There is no role for progestogen-only
hormonal contraceptives in the management
of anovulatory abnormal uterine bleeding
d) As Sarah has completed her childbearing,
she may wish to consider endometrial
ablation or hysterectomy, once she has
been fully informed about the medical
management options

8. Sarah is an overweight 47-year-old


mother of two who presents with
painless abnormal uterine bleeding.
She takes no regular medications.
Which of the following THREE

9. Which of the following THREE


investigations should form part of Sarahs
initial workup?
a) Beta-HCG
b) TSH
c) Free androgen index and testosterone
d) MSU culture

CPD QUIZ UPDATE


The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2014-16 triennium.
You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept
the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.

how to treat Editor: Dr Steve Liang


Email: steve.liang@cirrusmedia.com.au

Next week Fever in childhood is extremely common. Differentiating the causes of fever in a child may be challenging. Over the next two issues, How to Treat examines this topic. Part 1 discusses a
general approach to the febrile child, with a focus on areas of potential uncertainty in investigation and management. The authors are Dr Rebecca James , rheumatology fellow, Royal Childrens Hospital,
Parkville; Dr Peter Gowdie, paediatric rheumatologist and general paediatrician, department of paediatric rheumatology and department of general paediatrics, Monash Childrens Hospital, Monash
Medical Centre, Clayton; and Dr David Burgner, NHMRC senior research fellow Murdoch Childrens Research Institute, Parkville, professorial fellow, department of paediatrics, University of Melbourne,
Parkville, and consultant, paediatric infectious diseases, Monash Childrens Hospital, Clayton, Victoria..

26

| Australian Doctor | 22 August 2014

www.australiandoctor.com.au

Anda mungkin juga menyukai