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What causes
irregular
bleeding?
Assessing
irregular vaginal
bleeding
Management and
referral
Case studies
The authors
DR CHRISTINE READ,
medical director,
Family Planning NSW.
IRREGULAR
vaginal bleeding
DR TANIA MAY,
senior clinician and educator in
sexual and reproductive health,
Family Planning NSW.
Background
IN this article, irregular bleeding is
defined as bleeding that occurs outside of the normal menstrual pattern. A normal menstrual pattern is
taken to be a ‘monthly bleed’. The
cycle length can vary, with a generally accepted normal range of 2135 days and a bleeding duration of
4-7 days.
Irregular bleeding can consist of
intermenstrual bleeding with a flow
similar to that of a menstrual
period. It can be ‘spotting’ that is
noted as stains on the underwear or
after toileting. It also includes postcoital bleeding and postmenopausal
bleeding.
Amenorrhoea and menorrhagia
may occur as part of the irregular
menstrual pattern, but a full discussion of these topics is not covered in
this article.
The physiology of menstruation
A regular menstrual pattern depends
on the presence of a functioning
reproductive hormone feedback
system including the hypothalamus,
anterior pituitary gland and ovaries,
as well as normal uterine and vaginal anatomy.
The menstrual cycle is ‘switched
on’ at puberty when the hypothalamus secretes gonadotrophin-releasing hormone (GnRH). Pulses of this
hormone cause the release of follicle-stimulating hormone (FSH) from
the anterior pituitary.
FSH in turn stimulates the growth
of a cohort of ovarian follicles, the
granulosa cells of which produce
increased amounts of the hormone
oestradiol, which in turn triggers a
surge of luteinising hormone (LH)
that causes the dominant follicle to
ovulate.
As a result of stimulation by
oestradiol, the endometrium thickens in preparation for implantation
of an embryo, should fertilisation
and pregnancy occur. The dominant
DR MARGARET
STELLINGWERFF,
medical officer,
Family Planning NSW.
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How to treat – irregular vaginal bleeding
from previous page
follicle resolves to become the
corpus luteum, which then
produces the hormone progesterone as well as oestradiol.
If a pregnancy does not
eventuate, the corpus luteum
becomes non-functional and
stops producing hormones,
causing the breakdown of
the endometrium and menstrual bleeding starts.
Irregular bleeding —
what can be normal?
It is important to understand
that menstrual patterns that
do not conform to the regular cycling discussed above
can be a normal occurrence.
The age of the woman is a
critical factor in assessing the
need to investigate or
manage an irregular menstrual pattern.
During puberty and the
perimenopause — the
extremes of reproductive life
— regular menstruation may
not be recognisable. In both
these transitional phases
anovulatory cycles occur,
leading to failure to establish a distinct ‘withdrawal’
menstrual bleed. With continued endometrial stimulation there is often an irregular and sometimes heavy and
prolonged breakdown of the
endometrial lining.
In periovulatory bleeding,
bleeding or spotting can
occur at ovulation, about 14
days before the following
menstrual period.
If there is a luteal phase
defect, spotting can occur
premenstrually each month,
said to be due to a lack of
progesterone. However,
endometriosis is a more
common diagnosis for
episodes of spotting or
bleeding that occur in the
days leading up to menstruation.
How common is irregular
vaginal bleeding?
Women commonly present
to their doctor for bleeding
problems. One study in the
US found menstrual disor-
ders were the reason for
19.1% of gynaecological
consultations over a twoyear period and that 25% of
gynaecological surgery
involved abnormal uterine
1
bleeding.
However, the incidence of
irregular bleeding is low overall, and the incidence of significant pathology is also low,
making the issue a difficult
one in terms of how much
investigation is warranted.
In a study of menstruation
in 621 normal women over
20,672 cycles, intermenstrual bleeding was reported
in 100 cycles (39 women;
6.3% of the women studied
2
and 0.5% of cycles studied).
These women were all investigated and no pathology
was found.
A study looking at referrals to a gynaecology department for postcoital bleeding
reviewed the records of 248
women referred over a fiveyear period and found that
benign polyps (including
endometrial polyps) were
found in 20% of cases, 25%
had a cervical ectropion,
while cervical intraepithelial
neoplasia was detected in
3
6.8% of cases.
Intermenstrual or postcoital bleeding has been
reported in 13% of women
diagnosed with chlamydial
cervicitis.
What causes irregular bleeding?
IT is beyond the scope of this article to give an exhaustive coverage
of all the causes of abnormal bleeding. We have attempted to highlight causes that are relatively
common and straightforward to
manage, as well as illustrating the
more serious conditions that may
present as irregular bleeding.
Of the causative factors listed in
table 1, the most common are use
of hormones, either as contraception or menopausal hormone therapy, pregnancy, endometrial
hyperplasia, cervical ectropion and
cervicitis. The causes of irregular
bleeding tend to be related to age
and stage of reproductive life (table
2).
Figure 1: Endometrial hyperplasia and carcinoma.
(Image courtesy of Dr Glenn McNally of Warren and McNally Ultrasound, Sydney.)
Figure 2: Cervical cancer.
Exogenous hormones and
menstruation
The physiological menstrual cycle
is particularly dependent on the
pattern of hormonal biofeedback
systems that connect the functioning of the hypothalamus, pituitary
and ovary.
Exogenous hormones, particularly in the form of steroidal contraceptives or menopausal hormone therapy, are a potent
influence on this system, and an
ensuing irregular cycle is not necessarily a sign of abnormality. It is
therefore important to know the
menstrual changes expected with
the administration of steroidal contraceptives and HRT (table 3).
Because irregular vaginal bleeding in women using hormonal contraception or other hormonal therapies is common (usually known
as break-through bleeding), it is
obviously impractical, unreasonably worrying and inappropriate
to refer every case for immediate
investigation.
It may be appropriate to stop the
hormonal medication for 2-3
months, making sure that if contraception is needed another
method, such as condoms, is used
during this time. If the bleeding
problem persists, it should be investigated.
While the rate of significant
pathology (particularly malignancy
in the reproductive age group) is
low, there are good reasons to consider serious causes when irregular
bleeding is a presenting symptom.
The age of the woman is an important factor in assessing her risk (see
table 4).
Genital tract malignancy is an
28
| Australian Doctor | 18 May 2007
Table 1: Causes of irregular
bleeding
General
■ Contraceptives — hormonal
contraceptive methods and
intrauterine devices
■ Menopausal hormone therapy,
including with tibolone, in a
woman with an intact uterus
■ Endometriosis — may cause
pre- and postmenstrual spotting.
Generally presents with
dysmenorrhoea, which
worsens with time
Uterine
■ Endometrial polyps
■ Endometrial hyperplasia
■ Fibroids — generally cause
menorrhagia but can present with
intermenstrual bleeding
■ Pregnancy — ectopic, early
pregnancy loss
■ Endometritis — postnatal and
postsurgical
■ Endometrial/myometrial
malignancy
Lower genital tract
■ Cervical ectropion
■ Cervical polyps
■ Cervicitis
■ Cervical malignancy
Cervical cancer: a
cautionary tale
A 22-YEAR-old woman presented
to a gynaecologist with breakthrough bleeding while using the
combined OCP. A Pap test was
done and reported as normal.
Several times over the following
year the patient presented to a GP,
with a history of intermittent breakthrough bleeding and postcoital
bleeding while taking the pill. A
repeat Pap test reported monilia
and mild squamous atypia,
possibly due to inflammation, with
a recommendation to repeat in 3-6
months.
The patient continued to note
variable postcoital bleeding and
presented to another GP. She was
then referred to a gynaecologist.
The gynaecologist found an eroded
and friable cervix with contact
bleeding. Biopsy confirmed
malignancy.
Review of the previous Pap test
indicated abnormal cells, including
CIN 3. The patient went on to have
a radical hysterectomy for stage 1b
carcinoma of the cervix. Despite
further surgery, radiotherapy and
chemotherapy over several years,
she died of metastatic disease.
uncommon cause of bleeding at
any age and is rare in younger
women.
Endometrial hyperplasia and
carcinoma
This is the most common invasive
gynaecological cancer in Australia
(figure 1), ranking sixth in terms
of incident cancers in women. It
results in about 1400 new cases
and 260 deaths every year. Risk
increases with age. It is most commonly diagnosed in women aged
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Table 2: Relation of age to common causes of irregular bleeding
Age group
15-20
20-30
30-45
45-55
55+
STIs: cervicitis (especially chlamydia)
HRT
Cervical ectropion
Endometrial cancer
Endometrial polyps
Endometrial hyperplasia
Uterine fibroids
Intrauterine devices
Pregnancy and complications: miscarriage/ectopic pregnancy
Contraceptive steroids (especially progestogens)
Endometriosis
Trauma/surgery
Table 3: Changes to bleeding pattern with use of steroidal
hormones
Steroidal hormone
Bleeding problem
Combined oestrogen and
Break-through bleeding may happen:
progestogen contraceptives ■ In the first 3-4 months of use
(pills and vaginal ring)
■ After missed pills or delay in inserting rings
■ After episodes of vomiting or diarrhoea
■ With concomitant use with
liver-enzyme-inducing drugs*
Progestogen-only
All associated with irregular bleeding patterns,
contraceptives (pills,
which may include episodes of amenorrhoea,
injectable depot
spot bleeding and prolonged, frequent bleeding.
medroxyprogesterone
Note that the effect of DMPA may persist for
acetate [DMPA], implant
up to 12 months
[Implanon] and
levonorgestrel IUD [Mirena])
HRT — cyclical
Expect a monthly bleed, but women may
experience breakthrough of their natural cycle in
the perimenopause
HRT — continuous
Designed to be ‘bleed free’, but women may
(including tibolone)
have break-through bleeding in the
perimenopause (for this reason it is not indicated
for use 12-18 months after menopause)
*Carbamazepine, oxcarbamazepine, phenobarbital, phenytoin, primidone, topiramate
rifampicin and rifabutin protease inhibitors, non-nucleoside reverse-transcriptase
inhibitors, griseofulvin and St John’s wort may interfere with drug metabolism in the liver
Table 4: Important ‘not to miss’ causes of irregular bleeding
15-20
20-30
30-45
45-55
55+ (Years)
Chlamydia/PID
Endometrial/ovarian cancer
Pregnancy and pregnancy complications
Endometrial polyps
Endometrial hyperplasia
Cervical cancer
50-70 and is rare in those under
40.
Risk factors include age >40,
weight >90kg, prolonged exposure
to endogenous or exogenous unopposed oestrogen.
Cervical cancer
The incidence of cervical cancer
(figure 2) in Australia has been
dramatically reduced as a result
of the cervical screening program.
The incidence in 2002 was 6.9 per
100,000 women, with a mortality
of 1.7 per 100,000 women.
While the occurrence of intermenstrual or postcoital bleeding as
a presenting symptom in cervical
cancer is low, it should not be
ignored. The case study above left
provides a cautionary tale for GPs
and led to the development of the
Guidelines for Referral for Investigation of Intermenstrual and Postcoital Bleeding, by the Royal Australian and New Zealand College
of Obstetricians and Gynaecolo4
gists (RANZCOG).
AD_HTT_027_034___MAY18_07 11/5/07 4:01 PM Page 29
Assessing irregular vaginal bleeding
History
IMPORTANT signposts in
history taking include:
■ The woman’s age and stage
of reproductive life.
■ History of bleeding (how
often, what time of the
month, postcoital, etc).
■ Risk of pregnancy/recent
delivery/recent gynaecological surgery or instrumentation.
■ Use of hormonal therapy
and contraceptive history.
■ Previous abnormal Pap
tests.
■ Sexual history, including
risk for sexually transmissible infections, and relevant partner history.
■ Previous history of STIs.
Figure 3 presents a flow
chart for investigating intermenstrual and postcoital
bleeding.
Examination
Conduct a speculum examination with a good light and
look for:
■ Ectropion and contact
bleeding on the cervix.
■ Friability of tissue or ulceration of the cervix.
■ Presence of cervical polyps.
■ Other possible sites of
bleeding.
■ Signs of vaginal discharge,
foreign body or IUD tail.
■ If pregnant, whether the cervical os is open or closed.
Perform an abdominal
and bimanual pelvic examination, assessing:
■ Tenderness on rocking the
cervix.
■ Size of the uterus.
■ Adnexal masses/tenderness.
Investigations for
intermenstrual and
postcoital bleeding
The information presented
in this section is adapted
from the RANZCOG guide4
lines:
■ If the patient has not had a
Pap smear within the previous three months, take a
Pap smear using the speculum carefully so as not to
provoke further bleeding.
These diagnostic (rather
than screening) Pap smears
should be sent to laboratories using appropriate qual-
Figure 3: Algorithm for investigating intermenstrual and postcoital bleeding.
Investigating intermenstrual or postcoital bleeding
Is the patient pregnant?
YES
NO
Exclude ectopic pregnancy and manage any
complications of uterine pregnancy
Is there a iatrogenic cause, eg,
combined OCP, recent colposcopy
YES
Check Pap test up to date
■ Screen for chlamydia if ≤25 and risk factors
■ Discuss and cease or modify medication
NO
Look for pathological cause
■
If bleeding persists
? Cervix
Speculum exam
Pap test
Swabs
Speculum exam looking for:
■ Ectropion
■ Endocervical polyp
■ Cervicitis
■ IUD tail
Non-screening Pap
test looking for:
■ Cervical dysplasia
Swabs for infection
(especially think of
chlamydia PCR)
■
Important practice points
Intermenstrual bleeding and postcoital bleeding are by nature intermittent, and duration, volume
and frequency need to be taken into account in determining whether symptoms are ‘persistent’. It
is not possible to give a simple and all-encompassing definition of ‘persistent’ but, for example,
several minor episodes over a three-month period, or two episodes of heavy bleeding, should
generally prompt referral. If there is uncertainty, it may be useful to ask a woman to keep a
menstrual diary so that you can make an assessment of the frequency and timing of her bleeding.
■ Cervical ectopy (ectropion) is a common finding in premenopausal women, especially in
combined OCP users and pregnant women. Contact bleeding or ectopy should not prompt
referral unless other features are present or intermenstrual or postcoital bleeding have been
persistent.
■ In women with intermenstrual or postcoital bleeding, a negative smear does not rule out the
possibility of pathology.
■ The Pap smear is a screening test, not a diagnostic test, and is only 80-90% sensitive and may
therefore not detect underlying pathology in 10-20% of affected women.
■ Practitioners should always bear in mind the need to re-examine the woman if bleeding recurs.
■ Pregnancy testing in women of childbearing age is important to exclude pregnancy complications
as a cause of irregular bleeding.
■ In some instances high-resolution transvaginal ultrasound scanning may provide additional
information, and saline infusion sonohysterography may also be useful (see right)
■ It is important to keep adequate documentation in the clinical notes on the type of abnormal
bleeding, any hormonal therapy being used, any past history of bleeding and previous
investigations, the date and report of the last Pap smear, examination findings, action taken for
investigation and treatment, and the follow-up recommended.
■
ity control procedures.
Contact bleeding from the
cervix is relatively common
when taking a smear, particularly from the endocervix using a cytobrush. A
ThinPrep sample should
Endometriosis
Laparoscopy
also be sent if bleeding is
likely to obscure the cells
on the slide. The occurrence
of contact bleeding or
abnormal bleeding in the
case history should be
noted on the request form.
Cervical swabs should be
taken for Chlamydia trachomatis if appropriate.
Ultrasound imaging
High-resolution transvaginal
ultrasound can be a useful
additional test in investigating
abnormal bleeding when an
endometrial cause is suspected. It permits the endometrial texture to be assessed, as
well as the myometrium and
ovaries. The addition of
colour or power Doppler
assists in detecting vascular
abnormalities, including neovascularisation, which may be
associated with malignancy.
Focal thickening of the
endometrium can be suggestive of polyps, and submucosal fibroids may distort the
endometrial stripe, while
global thickening of the
endometrium can be indicative of hyperplasia, and gross
myometrial involvement is
suggestive of malignancy.
Unenhanced endovaginal
ultrasonography is non-invasive and convenient, but factors such as residual bladder
volume, the orientation of the
? Uterine
Bimanual pelvic
examination
Ultrasound
Hysteroscopy
Endometrial
sampling for
histopathology
uterus, uterine size and obesity can limit its sensitivity.
Saline infusion sonohysterography (SIS) can clarify
the contours, symmetry and
thickness of the endometrium.
A thin catheter is inserted
through the cervix and 20mL
of saline instilled, which distends the uterine cavity.
SIS is particularly valuable
in detecting endometrial
polyps that are not apparent
on a standard ultrasound
and it more clearly delineates
areas of endometrial thickening and irregularity.
The sensitivity of SIS can
be similar to that of hysteroscopy. In experienced
hands it has been found to
have a sensitivity of 80100% and a specificity of
76-96% for detecting
intrauterine pathology.
A more recent technique
is hysterosalpingo-contrastsonography (hy-co-sy). This
technique, using a special
occlusive catheter and either
ultrasonic contrast agent or
a mix of air and saline, is
also capable of assessing
tubal patency.
Management and referral
Persistent intermenstrual
and/or postcoital bleeding
without any unusual features
WOMEN with persistent bleeding
— even if Pap smears and other
tests are normal and regardless of
whether or not an ectropion is present — should be referred for specialist opinion.
In general, a hysteroscopy/D&C
by a specialist should be the primary
procedure in women with persistent
intermenstrual bleeding, while colposcopy should be the primary procedure with persistent postcoital
bleeding or if a suspicious lesion is
present on the cervix. Both investigations may be required.
Women with a friable cervix
The smear report suggests the
presence of CIN-1 (low-grade
squamous intraepithelial lesion
[LSIL]) or a higher grade abnormality or the presence of any glandular abnormality.
■ On repeated diagnostic Pap smear
testing 2-3 times over a 12-month
period, the smear contains cells
suggestive of an underlying squamous lesion of lower grade than
CIN-1 (possible LSIL).
However, if bleeding is persistent, immediate referral is
needed, as per the first guideline
above.
Practitioners in remote areas
should consider telephone consul■
When this is causing persistent
symptoms, women should be
referred for assessment and possible treatment. After careful exclusion of significant pathology by
colposcopy, a variety of ablative
methods may be used. Generally
the problem will resolve without
treatment.
Intermenstrual or
postcoital bleeding and an
abnormal Pap smear
Even if these women have minor
intermittent episodes of bleeding
(ie, not ‘persistent’) they should be
referred for colposcopy if:
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tation with a specialist if the circumstances are unclear.
Women using hormonal therapy
Women with intermenstrual
bleeding who are on the
progestogen-only minipill or in
the first six months of DepoProvera treatment (often called
break-through bleeding) should
generally not be referred in the
first instance unless bleeding is
excessively frequent or prolonged, and provided Pap smears
are normal and up to date.
Low-oestrogen-dose combined
pills and IUDs are also frequent
cont’d next page
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How to treat – irregular vaginal bleeding
from previous page
Figure 4: Transformation zone of the cervix.
causes of intermenstrual
bleeding, especially in the
first few months of use.
Time period
Columnar cells
Postmenopausal bleeding
When a woman presents
with a history of postmenopausal bleeding (more
than 12 months since
menopause), referral should
be made for transvaginal
ultrasound. If the ultrasound
reveals that the endometrial
stripe is homogenous and
uniformly 5mm or less, no
further evaluation is generally required. The likelihood
of missing a significant
endometrial abnormality is
very low (0.1% in HRT
users and 1% in non-users).
Tamoxifen can increase
the risk of endometrial
cancer. When a woman
taking tamoxifen presents
with postmenopausal bleeding, prompt referral should
be made for transvaginal
ultrasound, as above.
Recurrent postmenopausal
bleeding
A postmenopausal woman
with a normal transvaginal
ultrasound report and persistent bleeding should be
further investigated by hysteroscopy/D&C/endometrial
biopsy.
Area of metaplasia
(transformation zone)
During puberty,
pregnancy and when
on the OCP when
oestrogen levels are
high
Original squamocolumnar junction
Squamous cells
Transformation zone
Position of the
transformation zone,
endocervical canal and
cervix
Cells lining
endocervical
canal
During reproductive
life
Cells on
ectocervix
When oestrogen
levels are low,
eg, menopause,
breastfeeding
Is your patient pregnant?
Ectopic pregnancy or
miscarriage
Pregnancy should be
excluded when a woman of
childbearing age at risk of
pregnancy presents with
irregular bleeding and/or
abdominal pain. A simple
qualitative urine dipstick test
for human chorionic gonadotrophin is quick, easy
and sensitive.
Even if a woman reports
a normal period within the
last four weeks, a negative
urine pregnancy test will
exclude a clinically significant ectopic pregnancy.
Serum pregnancy testing
offers little advantage over
these sensitive urine tests.
In modern practice, transvaginal ultrasonography is
the diagnostic tool of choice
for detecting an intrauterine
or ectopic pregnancy in the
presence of a positive pregnancy test.
A single progesterone level
can be helpful in predicting
pregnancy outcome in the
first eight weeks of gestation
and may be useful in women
who have a positive pregnancy test and no uterine sac
on ultrasound.
A level <20nmol/L is likely
to be associated with a poor
pregnancy outcome (eg,
spontaneous abortion or
ectopic pregnancy), while a
level >60nmol/L is associated
with a probable viable pregnancy (based on levels used
by the Early Pregnancy
Assessment Service, Royal
Prince Alfred Hospital,
Sydney, NSW).
Early diagnosis and referral
to an early pregnancy unit
where possible allows the clinician to consider conservative
management options such as
methotrexate, or an expectant
approach for ectopic pregnancy.
External appearance of the
cervix when viewed with a
speculum
Sampling
External os of
endocervical
canal
Cervix sampler
(or spatula
alone)
External os of
endocervical
canal
Cervix sampler
(or spatula
alone)
External os of
endocervical
canal
Cervix sampler
(or spatula) and
cytobrush
The diagnosis of a threatened miscarriage does not
always require hospital
admission and raises the
question of whether GPs
should consider the prophylactic use of RhD immunoglobulin in this circumstance.
A dose of 250IU (50µg)
RhD immunoglobulin (anti-D)
should be offered to every
RhD-negative woman with no
preformed anti-D to ensure
adequate protection against
immunisation for the following indications, up to and
including 12 weeks’ gestation:
■ Miscarriage.
■ Termination of pregnancy.
Ectopic pregnancy.
Chorionic villus sampling.
Beyond 12 weeks, a higher
dose of RhD immunoglobulin
is used.
There is insufficient evidence
to support the use of RhD
immunoglobulin for bleeding
before 12 weeks’ gestation in
an ongoing pregnancy.
For successful immunoprophylaxis, RhD immunoglobulin should be administered as soon as possible
after the sensitising event,
but always within 72 hours.
If RhD immunoglobulin has
not been offered within 72
hours, a dose within 9-10
■
■
Confidence
†1 patient-year of experience = 1 patient on LIPITOR therapy for 1 year. LIPITOR is indicated as an adjunct to diet for the treatment of patients with hypercholesterolaemia. Also indicated in hypertensive
patients with risk factors for heart disease to reduce risk of non-fatal myocardial infarction and non-fatal stroke. Refer to Product Information before prescribing. The full disclosure Product Information
is available on request from Pfizer Australia Pty Ltd. LIPITOR (atorvastatin calcium). Supplier: Pfizer Australia Pty Ltd, ABN 50 008 422 348, 38–42 Wharf Road, West Ryde NSW 2114. Pfizer Medical Affairs 1800 675 229. Dosage and administration:
10–80mg/day as a single daily dose. LIPITOR can be taken at any time of the day, with or without food. Contraindications: Hypersensitivity to any component of this medication; active liver disease or unexplained persistent elevations of serum transaminases;
pregnancy and lactation. Women of child-bearing potential, unless on an effective contraceptive and highly unlikely to conceive. Precautions: Patients who consume substantial quantities of alcohol and/or have a history of liver disease; Myopathy (monitor CK); Risk
factors predisposing to development of renal failure secondary to rhabdomyolysis; Use of concomitant medication that may reduce activity/ levels of steroid hormones (ketoconazole, spironolactone and cimetidine); Interactions with other medicines: inhibitors of
30
| Australian Doctor | 18 May 2007
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AD_HTT_027_034___MAY18_07 11/5/07 4:01 PM Page 31
days may offer some protection.
always postcoital, the bleeding is most likely due to the
ectropion.
However, if there is any
doubt about the ectropion
being responsible for the
bleeding, it is preferable to
refer for further investigation. In any case if the bleeding is regularly present after
intercourse (ie, persistent),
referral is appropriate as per
the guidelines above.
Figure 5: Cervicitis.
Cervical ectropion
In the past, cervical ectopy,
or cervical ectropion, was
known as cervical erosion. It
is the transformation zone of
the cervix (figure 4), visible
on the ectocervix. It is seen
when, due to hormonal
changes, the columnar
epithelium moves onto the
vaginal portion of the cervix.
A cervical ectropion looks
red and may appear
inflamed because the columnar epithelium is thinner
than the squamous epithelium, making the underlying
blood vessels more apparent.
The columnar epithelium
may also secrete more
mucus, which sometimes
causes a vaginal discharge
This is a normal finding in
high-oestrogen states, such
as being young, during pregnancy and in women using
oestrogen therapy, including
the combined OCP.
Contact bleeding is
common with this condition,
as the ectropion can bleed
easily with minimal trauma
such as penetrative sexual
intercourse, inserting a
speculum or taking a Pap
test. The condition regresses
with age.
Cervicitis
It is not easy to determine
whether an ectropion found
on clinical examination can
be attributed as the cause of
intermenstrual or postcoital
bleeding. If an ectropion
bleeds easily on a Pap test or
by brushing over it with a
swab and the bleeding is
OVER
Inflammation of the cervix,
or cervicitis (figure 5), may
be responsible for postcoital
or intermenstrual bleeding.
Depending on the cause of
the inflammation there may
be associated symptoms such
as vaginal discharge, pain
with intercourse or odour.
The most common sexually transmissible infection
causing cervicitis is chlamydia, and this should be
actively searched for. Gonorrhoea, trichomonas and
genital herpes are other
possible causes. Cervicitis
may also be due to allergic
reactions and to bacterial
vaginosos.
Chlamydia
Chlamydiae are specialised,
intracellular Gram-negative
bacteria. Chlamydia tra-
chomatis is the most
common sexually transmissible bacterial pathogen in
Australia. There were
36,100 notifications in Australia in 2004.
Between 10% and 40% of
chlamydial infections in
women can lead to pelvic
inflammatory disease (PID)
if left untreated; of those
with PID, up to 20% may
become infertile.
Indications for testing for
chlamydia include:
■ Mucopurulent discharge
from the cervix.
■ An inflamed friable ectropion with contact bleeding.
■ Suspected PID.
■ Sterile pyuria.
In the absence of national
guidelines, opportunistic
testing has been recommended for all sexually
active women aged 25 or
younger, pregnant, or who
report a new sexual partner
within the past 12 months
and are not using condoms
5,6
all the time.
Treatment options for
chlamydial cervicitis and
urethritis include:
■ Azithromycin 1g orally
once (preferred treatment).
It is important that the partner takes the treatment at
the same time. Azithromycin may be taken during
pregnancy. (NB: azithromycin is indicated only for
cervicitis and is not at present indicated for the management of PID).
■ Doxycycline 100mg twice
daily for 10 days. Alert
patients to the risk of photosensitivity. Doxycycline is
contraindicated during
pregnancy and/or breastfeeding (discoloration of
permanent teeth).
■ Roxithromycin 150mg bd
or 300mg daily as a single
dose for 10 days.
In pregnant women erythromycin should be used in
place of doxycycline at a
dose of 800mg bd for 10
days. If this dose is not tolerated, 250mg qid for 10
days can be used. Alternatively, give roxithromycin
150mg bd or 300mg daily
for 10 days.
General advice includes:
■ Limit or stop alcohol consumption while on medication.
■ Partners should be given
treatment regardless of
whether or not they show
infection on testing.
■ Advise abstinence from
sexual intercourse until
seven days after both partners have completed their
treatments, even if taken at
the same time.
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patient - years of experience
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18 May 2007 | Australian Doctor |
31
AD_HTT_027_034___MAY18_07 11/5/07 4:01 PM Page 32
How to treat – irregular vaginal bleeding
Authors’ case studies
References
1. Nicholson WK, et al.
Patterns of ambulatory care
use for gynecologic conditions:
a national study. American
Journal of Obstetrics and
Gynecology 2001; 184:52330.
2. Vollman RF. The Menstrual
Cycle. WB Saunders,
Philadelphia, 1977.
3. Selo-Ojeme D, et al. A
clinico-pathological study of
postcoital bleeding. Archives of
Gynecology and Obstetrics
2004; 270:34-36.
4. The Royal Australian &
New Zealand College of
Obstetricians &
Gynaecologists. College
statement C-Gyn 6. Guidelines
for Referral for Investigation of
Intermenstrual and Postcoital
Bleeding. July 2004 [cited 7
February 2007]. Available
from: www.ranzcog.edu.au/
publications/statements/
C-gyn6.pdf
5. Chen YM, Donovan B.
Genital Chlamydia trachomatis
infection in Australia:
epidemiology and clinical
implications. Sexual Health
2004; 1:189-96.
6. Harris M, et al (editors).
Guidelines for preventive
activities in general practice.
6th edn. Royal Australian
College of General
Practitioners, Melbourne,
2005.
7. Federal Health Department.
National Sexually
Transmissible Infections
Strategy 2005-2008. Federal
Health Department, Canberra,
2005.
Online resources
Guidelines for the use of Rh
D Immunoglobulin (Anti-D)
in Obstetrics in Australia,
College Statement C-Obs 6
RANZCOG March 2006:
www.ranzcog.edu.au
■ National library for health
clinical knowledge
summaries:
www.cks.library.nhs.uk/
clinical_knowledge
■ Royal College of
Obstetricians and
Gynaecologists. National
Evidence-Based Clinical
Guidelines: The Initial
Management of
Menorrhagia, 2006:
www.rcog.org.uk/index.asp?
PageID=698.
■ New Zealand Guidelines
Group. Heavy Menstrual
Bleeding. www.nzgg.org.nz
■ Royal College of
Obstetricians and
Gynaecologists. National
Evidence-Based Clinical
Guidelines. The Management
of Menorrhagia in Secondary
Care; The Initial
Management of
Menorrhagia.
www.rcog.org.uk/index.
asp?PageID=1046
■ Royal Women’s Hospital.
Women’s Health Nurse
Practitioner Assessment
Clinical Practice Guidelines.
Abnormal Vaginal Bleeding.
www.rwh.org.au/rwhcpg/
womenshealth.cfm?doc_id=
6068
■
32
Intermenstrual bleeding
in a young woman
SARAH, 15, presents
because she is concerned she
is pregnant. She had previously been on the OCP but
had run out four months
previously. She had been in a
new sexual relationship for
one month and was only
using condoms some of the
time.
Her last menstrual period
had been three weeks previously, her last episode of
unprotected sex two weeks
previously, and she had had
two days of spotting one
week before her presentation. She had had a urine
pregnancy test, which was
negative, and a urine sent off
for a chlamydia PCR.
Sarah’s chlamydia test
came back positive. She was
recalled for treatment with
azithromycin 1g stat and
advised to tell her current
partner so he could be tested
and treated as well.
Intermenstrual bleeding
in a middle-aged woman
Mary, 39, presented with a
small amount of bleeding
lasting one day, occurring
about a week before her
period. Her vaginal discharge was different —
“vinegary”. She had been in
the same monogamous relationship for 14 years. She
had no postcoital bleeding.
Many years earlier she
had had two atypical Pap
smears, which had needed
no treatment, and all biennial Pap smears since then
had been negative. Mary
had experienced minor
amounts of pre- and postmenstrual spotting close to
her period, but this most
recent intermenstrual bleeding was different.
Physical examination was
normal. The cervix appeared
healthy and the vaginal discharge was normal. A nonscreening Pap smear was
taken and a high-resolution
ultrasound requested. A highvaginal swab for microscopy
and culture and a cervical
swab for chlamydia PCR was
taken although Mary was at a
very low risk of an infection.
The ultrasound did not
reveal any focal abnormality that could account for
the bleeding, and vaginal
and cervical swabs were negative, as expected. However,
the Pap smear detected a
high-grade epithelial abnormality (CIN3).
Mary was referred for colposcopy. Macroscopically
the cervix was normal but
application of acetic acid
showed dense aceto-white
areas with punctation and
mosaic change consistent
with high-grade dysplasia.
Biopsy revealed extensive
adenocarcinoma in situ, with
features suggestive of early
invasion. Histopathology on
core biopsy confirmed early
| Australian Doctor | 18 May 2007
Figure 6: Endometrial fibroid and polyp.
(Image courtesy of Dr Glenn McNally of Warren and McNally Ultrasound, Sydney.)
Summary
Practice tips — bleeding while using hormonal contraception
■
Irregular vaginal bleeding
is commonly associated
with hormone-containing
medications.
■
Assess risk of chlamydia.
■
Look at the cervix for
signs of lesions that could
bleed.
Is the Pap test normal?
■
Increase the oestrogen dose if the patient is taking the combined OCP, or change the progestogen
to either a 1mg norethisterone combined OCP or a desogestrel- or gestodene-containing combined
OCP.
Ask the woman to keep a
menstrual diary for three
months and place her on a
recall system.
■
Progesterone-only OCP methods can cause irregular bleeding. In women who are not
contraindicated to using oestrogen, additional oestrogen for women using Depo Provera or Implanon
may help.
If irregular bleeding is
persistent, refer for
specialist assessment.
■
Bleeding that occurs more
than 12 months after the
menopause requires
investigation.
Exclude underlying causes: pregnancy, chlamydia, missed pills, vomiting or diarrhoea, concomitant
medications.
■
Is the Pap test normal?
■
■
Always exclude
pregnancy in a woman of
reproductive age.
■
■
■
■
Stopping the hormonal contraception for some months and using condoms will indicate whether the
bleeding is related to the hormonal contraceptive.
stromal invasion of <1mm.
Mary was advised to have a
hysterectomy, in view of the
nature of the lesion.
She had a radical, modified vaginal hysterectomy
without complications. No
residual carcinoma was identified in the cervix. There was
no obvious parametrial or
lymphatic spread. Mary will
continue to have annual vault
smears for 10 years for stage
1A carcinoma of the cervix.
Intermenstrual bleeding
persisting after stopping
a progesterone-only pill
Naomi was 41 when she
presented with an 18-month
history of abnormal vaginal
bleeding. She had been using
the progesterone-only pill for
contraception because she
was a smoker and unable to
take the combined OCP. She
had developed irregular
bleeding while using the
progesterone-only pill, which
persisted when she stopped.
Naomi was getting a
period every 21 days but
after the period finished she
was left with a smelly discharge and light spotting. A
pelvic ultrasound showed a
complex echogenic lesion in
the right fundal region. Hysteroscopy was recommended
to exclude sub-mucous
fibroid or endometrial polyp
(figure 6).
At hysteroscopy Naomi
was found to have a submucous fibroid with reasonably normal material around
it. A biopsy showed endome-
trial hyperplasia with mild
atypia.
Because Naomi was trying
to fall pregnant the decision
was made to allow her a
short period of time for this
to happen and then to repeat
her hysteroscopy. She failed
to fall pregnant and had a
repeat hysteroscopy eight
months later. This time a
repeat biopsy showed a
grade 1 well-differentiated
adenocarcinoma. She was
referred to a specialist
gynaeoncology unit.
At operation Naomi was
found to have stage 3C adenocarcinoma with involvement of the obturator and
para-aortic lymph nodes.
She had total abdominal
hysterectomy and bilateral
salpingo-oophorectomy as
well as adjuvant radiotherapy. She had no signs of
recurrence four years after
her surgery.
A 23-year-old on the
combined OCP with
intermenstrual bleeding
Mei had been taking Loette
for four months. She
reported that she has had
some bleeding each month
while taking the three weeks
of active hormone pills. She
had a withdrawal bleed each
month as well.
Before starting the pill Mei
was using condoms for contraception and did not have
any intermenstrual bleeding.
There had not been any
postcoital bleeding. A
screening Pap test was taken
www.australiandoctor.com.au
three months ago and this
was reported as normal. At
the time Mei started to use
the Loette she started a new
sexual relationship and said
she uses condoms inconsistently.
A speculum examination
reveals an ectropion but
there is no contact bleeding
or unusual features. The history of unprotected sex and
Mei’s age indicate the need
to exclude chlamydia. A cervical swab sent to pathology
for chlamydia PCR testing is
reported as negative.
A negative chlamydia test
and a screening Pap test that
was normal three months
ago, combined with a history of no bleeding until
starting to take Loette, indicate that the OCP may be
the cause of the bleeding.
Loette is a low-dose combined OCP containing 20µg
ethinyloestradiol and 100µg
levonorgestrel. The low dose
of oestrogen means cycle
control is very vulnerable to
any situations where pills are
missed, vomiting or diarrhoea occurs or concomitant
liver-enzyme-inducing drugs
are used.
However, Mei was sure
she was taking her pills properly, so it seemed useful to
try switching to a 30µg
ethinyloestradiol pill, such as
Microgynon 30 or Yasmin.
On review four months later,
Mei reported that, with the
change of pill, there had been
no irregular bleeding while
taking the active pills.
Guidelines
■
In women with
intermenstrual or
postcoital bleeding, a
negative smear does not
rule out the possibility of
pathology (RANZCOG
4
guidelines ).
■
It is important to exclude
chlamydia as a cause of
intermenstrual and postcoital bleeding, as it is
common, can lead to PID
if left untreated and, of
patients with PID, up to
20% may become infertile
(from National Sexually
Transmissible Infections
7
Strategy 2005-08 ).
■
Opportunistic testing for
chlamydia has been
recommended for all
sexually active women
≤25, or who are pregnant,
or who report a new
sexual partner within the
past 12 months and are
not using condoms all the
6
time (RACGP guidelines ).
■
Women with persistent
minor episodes of
bleeding over a
three-month period or
two episodes of heavy
bleeding should be
referred for investigation
4
(RANZCOG guidelines ).
■
Investigation of irregular
vaginal bleeding may
include transvaginal
ultrasound, colposcopy,
hysteroscopy and D&C.
4
(RANZCOG guidelines ).
AD_HTT_027_034___MAY18_07 11/5/07 4:01 PM Page 34
How to treat – irregular vaginal bleeding
GP’s contribution
DR FIONA ROBINSON
Balmain, NSW
Case study
ESTELLE, 26, had recently
moved into the area and was
working in a local massage
parlour. She presented to me
because of postcoital bleeding,
worsening over the last few
months.
She had been a sex worker
for eight years, had a history
of abnormal Pap smears (CIN
1 and 2), numerous colposcopies and a cone biopsy.
Paps had been done irregularly, but the last one had
been reported as normal six
months ago.
Other history included
numerous sexually transmitted infections over the years
and three terminations. Her
current contraception was
Depo-Provera (which made
her amenorrhoeic) and she
used condoms — sometimes!
On examination, Estelle
had one (new) clitoral and
numerous labial piercings,
which looked red and
swollen. The cervix looked
angry and friable, with an
ectropion, and there was significant contact bleeding.
There was no cervical or
adnexal tenderness and no
palpable lymph nodes. I performed another Pap smear
(including ThinPrep), high
vaginal swabs, cervical swabs
and a test for chlamydial
PCR. A pregnancy test was
negative.
We discussed not working
until the results were known,
but she said this was not an
option. After a lengthy chat
about the importance of using
condoms, I did not feel confident this would happen.
Diagnosis of a chlamydial
infection prompted treatment
with azithromycin for Estelle,
but partner tracing was
impossible. Her Pap smear
revealed LSIL (CIN 1), so I
referred her for a colposcopy.
Questions for the authors
In high-risk patients, is there
any evidence to suggest prophylactic treatment against
chlamydia is beneficial, and
if so, what does it comprise?
There is no evidence for the
usefulness of prophylactic
treatment of chlamydia
except in cases of sexual
assault. However, in
resource-poor countries, a
syndromic approach is often
used to treat STIs, ie, treat-
ment after history-taking
and basic examination in the
absence of diagnostic testing,
with a combination of drugs
known to treat organisms
responsible for that syndrome, eg, vaginal discharge.
Despite your fear that
Estelle will not use condoms,
it is important that you continue to encourage their use.
The Sex Workers Outreach
Project (SWOP), funded by
NSW Health, provides a
range of health, safety, support and information services
for sex workers. They also
have counselling and referral
services. For more information visit www.swop.org.au
Outside of NSW the
national peak body is known
as the Scarlet Alliance; their
web site is www.scarlet
alliance.org.au
Should the local public health
unit become involved in this
type of situation?
Chlamydia is a notifiable
infection, so the pathology
laboratory will notify the
How to Treat Quiz
INSTRUCTIONS
Irregular vaginal bleeding
— 18 May 2007
FAX BACK
Photocopy form
and fax to
(02) 9422 2844
1. Which THREE statements about vaginal
bleeding are correct?
❏ a) The normal menstrual cycle length is
21-35 days
❏ b) During puberty, anovulation can cause
irregular and heavy bleeding
❏ c) All mid-cycle bleeding is abnormal
❏ d) Premenstrual spotting may be caused by
endometriosis
THREE elements of Stella’s history could
explain her bleeding?
❏ a) She has started taking St John’s wort for
mild depression
❏ b) She forgot a pill before the episode of
bleeding
❏ c) She also takes sodium valproate for
epilepsy
❏ d) She had an episode of gastroenteritis last
month
2. Which TWO statements about irregular
vaginal bleeding are correct?
❏ a) It is important to investigate all irregular
bleeding because a large proportion of
women with this symptom will have a serious
cause
❏ b) Endometrial cancer becomes a more likely
cause in women over 45
❏ c) Most women with chlamydial cervicitis will
report intermenstrual or postcoital bleeding
❏ d) Irregular bleeding is common during the
first few months of combined oral
contraceptive pill use
4. There are no obvious causes for
Stella’s bleeding on history or physical
examination. She keeps a bleeding diary
for two more months and reports that
bleeding is continuing to occur in the
second or third week of active pills. Which
TWO investigations would be most
appropriate?
❏ a) Saline infusion sonohysterogram
❏ b) Chlamydia PCR test
❏ c) Pap smear
❏ d) HPV DNA test
3. Stella, 22, has been taking Microgynon 20
for the past two months. She has had no
significant side effects from the pill except
for several days of light vaginal bleeding
noted last month during the third week of
active pills. She is in a stable relationship,
had previously used condoms for
contraception, had no irregular bleeding
before starting the Microgynon and had a
normal Pap smear 21 months ago. Which
5. Stella’s investigations return normal
results. Which TWO management options
would be appropriate at this stage?
❏ a) Immediate referral for colposcopy
❏ b) Changing her contraceptive pill to one
containing 30µg oestrogen
❏ c) Stopping the OCP and going back to
condom use for a few months to see if the
bleeding continues
❏ d) Change Stella’s pill to Loette
public health unit of the positive result. It is important that
we do have an epidemiological picture of this increasingly
common disease, so GPs
should be alert to the possibility of infection in young
sexually active people and
proactively offer chlamydia
PCR testing.
General questions for the
authors
In a patient with breakthrough bleeding on DepoProvera or Implanon, (when
pathology
has
been
excluded) would it be better
to give some supplemental
oestrogen or change the regimen completely?
A short-term prescription
of ethinyloestradiol can be
useful, such as three weeks’
treatment with any of the
active combined OCPs, to
settle bleeding (provided the
patient does not have a medical condition that contraindicates the use of
oestrogen). However, there
is no evidence that this treat-
ment makes any difference
to long-term management of
bleeding problems with
either Depo Provera or
Implanon.
When a Pap smear is performed (and reported
normal) but in the presence
of vaginal/cervical infection,
should the smear be done
again (eg, in three months’
time) when the infection has
cleared?
If the pathologist has
reported a completely
normal Pap test in this situation, the test is repeated at
the normal two-year screening interval. A Pap test that
is reported as ‘negative with
inflammation’, should also
be repeated at the normal
two-year screening interval.
However, national guidelines indicate that when a
Pap test has been reported
as ‘unsatisfactory’, it should
be repeated in 6-12 weeks,
with correction (if possible)
of the problem that resulted
in the unsatisfactory smear.
Complete this quiz to earn 2 CPD points and/or 1 PDP point by marking the correct answer(s) with an X on this form.
Fill in your contact details and return to us by fax or free post.
FREE POST
How to Treat quiz
Reply Paid 60416
Chatswood DC NSW 2067
6. Vivienne, 69, presents with a history of two
days of vaginal spotting last week, which has
now resolved. She is generally well, with no
past gynaecological history and is not taking
HRT. She has not been sexually active for
15 years and had her last Pap smear at 65,
which was normal. Which TWO initial
investigations would you arrange for
Vivienne?
❏ a) Laparoscopy
❏ b) Pap smear
❏ c) Transvaginal ultrasound
❏ d) Chlamydia PCR test
7. Vivienne is worried that the bleeding may
indicate cancer. Which THREE factors in
Vivienne’s history or examination would
indicate an increased risk of endometrial
cancer?
❏ a) Her weight is 96kg
❏ b) She used the combined OCP for 20 years
❏ c) She previously used oestrogen-only HRT
❏ d) Her age
8. Brianna, 22, presents with postcoital
spotting over the last two months. Her
periods are regular and she has no additional
intermenstrual bleeding. Brianna uses
condoms inconsistently with her current
partner of four months. She had a normal
Pap smear six months ago. From the history
alone, which TWO causes would you
consider most likely to be causing Brianna’s
postcoital bleeding?
ONLINE
www.australiandoctor.com.au/cpd/
for immediate feedback
❏
❏
❏
❏
a) Cervical ectropion
b) Cervical carcinoma
c) Endometrial polyp
d) Cervicitis
9. Which THREE statements about
investigating irregular vaginal bleeding are
correct?
❏ a) Saline infusion sonohysterography is an
improved ultrasound technique for assessing
endometrial irregularities
❏ b) A Pap smear may be reported as normal in
up to 20% of women with cervical
abnormalities
❏ c) If a transvaginal ultrasound shows the
endometrial lining is <5mm in a postmenopausal woman, no further investigation
is generally needed unless bleeding persists
❏ d) Women of childbearing age who report
having had a period within the past four
weeks do not require a pregnancy test
10. Which TWO statements about chlamydia
cervicitis are correct?
❏ a) It is less common in Australia than
gonorrhoeal cervicitis
❏ b) All sexually active women ≤25 who are not
regularly using condoms should be offered
testing for chlamydial infection
❏ c) Partners of women with chlamydial
cervicitis should be tested and treated if
found also to be infected
❏ d) Azithromycin 1g orally provides adequate
treatment for chlamydial cervicitis
CONTACT DETAILS
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HOW TO TREAT Editor: Dr Marcela Cox
Co-ordinator: Julian McAllan
Quiz: Dr Marcela Cox
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. Your CPD activity will be updated on your RACGP records every January, April, July and October.
NEXT WEEK Adult sexual assault is a distressing and difficult problem. Counselling and a non-judgmental approach are mandatory, and high-quality forensic and medical sexual assault care critical to
successful patient outcomes. The next How to Treat focuses on these medical and forensic aspects of care for adult victims of sexual assault. The authors are Dr Vanita Parekh, staff specialist, Canberra
Sexual Health Centre and forensic and medical sexual assault care, the Canberra Hospital, and Secretary of FAMSAC Australia; and Dr Ronald McCoy, GP, St Kilda, Victoria.
34
| Australian Doctor | 18 May 2007
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