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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-
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19
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
Definition
Amenorrhoea
Oligomenorrhoea
Polymenorrhoea
Menorrhagia
Metrorrhagia
Intermenstrual bleeding
Menometrorrhagia
Mid-cycle spotting
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.
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.
20
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.
Figure 2:
A uterus with
adenomyosis
and a fibroid.
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
Figure 3:
Location of
fibroids within
the uterus.
Up to 70% of women
in the reproductive
years have a uterine
myoma, of which half
will present clinically.
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).
Ovulatory disorders
There are several conditions that
22
perimenopause, postmenopause,
PCOS/androgen excess (such as in
adrenal hyperplasia and Cushings
disease), thyroid disease, hyperprolactinaemia,
hypothalamic
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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.
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
Examination
Sexual history
Age of at first intercourse
Number of sexual partners in the last 12 months
STIs
Pap smears
Contraception
Pap smear
Number of pregnancies/complications
Biochemical
Associated symptoms
A
naemia: lethargy, shortness of breath, palpitations
beta-hCG
T
hyroid dysfunction: changes in weight, cold intolerance, fatigue,
constipation
FBC
Other investigations to include:
Coagulation profile
LH/FSH
TSH
Day 21 progesterone
Fe studies
AMH
Medical history
Prolactin
Medications
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
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.
24
Dose
Treatment goal
Combined oral
contraceptive pills
Cycle regulation/control
Contraception
Prevention of endometrial hyperplasia
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
Cycle regulation
5mg tds
Levonorgestrel
intrauterine system
Etonogestrel
Initial release rate 60g daily
subcutaneous implant (Release rate is reduced by 50% by the end
of two years)
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
Nonhormonal
Hormonal
PO
Combined
hormones
(oral, vaginal,
transdermal)
Local (LNGIUS)
Surgical
Medical
Progestogens
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
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
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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
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 |
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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
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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
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