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Key Points:
NSAIDs are offered first-line as they will inhibit prostaglandin synthesis,
one of the main causes of dysmenorrhea pains
Urinary incontinence - first-line treatment:
o Urge incontinence: bladder retraining; Oxybutinin
o Stress incontinence: pelvic floor muscle training
Bloating and abdominal cramps in females over the age of 50 should
raise suspicion of ovarian cancer. The most appropriate investigation is
to test the serum CA125 level. If raised, an abdominal and pelvic
ultrasound should be arranged. NICE CG122
Endometrial cancer is a common cancer in post-menopausal women
and it is important to rule this out in all women that present with postmenopausal bleeding.
Using hormone replacement therapy is a risk factor along with:
Late menopause
Early menses
Polycystic ovarian syndrome
Family history
The first step: TVUS scan to measure the endometrial thickness.
If the endometrial lining is thickened then a hysteroscopy+ endometrial
Treatment laparoscopic hysterectomy with BSO+/- RT
FIGO is the classification of cervical cancer stage.
Gleason is the grade of prostate cancer

source: Passmed

TNM is the stage of many cancers; breast, kidney, lung, testicular

Dukes is used in colon cancer
Ann-arbour lymphoma
The key signs and symptoms of endometriosis are cyclical abdominal
pain and deep dyspareunia. It can be associated with fertility problems.
Pelvic inflammatory disease can also cause sub-fertility, dyspareunia
and pelvic pain, but this pain is not typically associated with
A bicornuate uterus is an embryological abnormality giving the uterus
2 fundi, giving a 'heart-shaped' uterus. It is thought to be associated
with an increased risk of recurrent miscarriages.
Cervical carcinomas typically cause abnormal bleeding such as postcoital and inter-menstrual bleeding. It is unlikely to have such a long
history as 3 years.
Uterine fibroids are more common in women older than this patient,
usually presenting between the ages of 30 and 50. They can cause
menorrhagia when large and submucosal fibroids can cause infertility.
This is usually reversed on removal
NICE guidelines state that the diagnosis of pelvic inflammatory disease
should be made on clinical grounds and that clinicians should have a
low threshold for initiating treatment in the form of antibiotics.
Although investigations should be performed - including taking
endocervical and high vaginal swabs for microscopy and culture - these
should not delay treatment. Negative swab results do not rule out the
diagnosis. Blood cultures are unlikely to be indicated unless the patient
appears systemically unwell. Transvaginal ultrasound is not first-line
but may be indicated if an abscess is suspected.
Any ovarian mass in a post-menopausal woman needs to be
HRT: unopposed oestrogen increases risk of endometrial cancer
Cervical cancer screening
o 25-49 years: 3-yearly
o 50-64 years: 5-yearly

source: Passmed

Chlamydia - treat with azithromycin or doxycycline. The 2009 SIGN

guidelines suggest azithromycin should be used first-line due to
potentially poor compliance with a 7 day course of doxycycline.
The combination of menorrhagia, subfertility and an abdominal mass in
this patient points towards fibroids above everything else. It's
important to rule out ectopic pregnancy, but the patient would be more
unstable and complaining of pain. Endometriosis and endometrial
cancer are unlikely to present with an abdominal mass. You would also
want to rule out ovarian cancer in this patient, due to the unspecific
presentation of this, but it is not the most likely diagnosis.
Fibroids are benign tumours of the myometrium and are very common.
Symptoms of fibroids include:


Pain (with torsion)


As fibroids get larger they cause symptoms due to their size such as: dysuria,
hydronephrosis, constipation and sciatica.
First line treatment is often tranexamic acid, NSAIDS or
progesterones as they are used in menorrhagia, but surgery is
usually required for troublesome fibroids.
Use of a gonadotrophin-releasing hormone analogue could be
considered prior to surgery which helps to reduce the size of the

In a 'typical' 28 day menstrual cycle, a woman will ovulate on approximately

day 14 of her cycle. Following ovulation, the hormones Follicle Stimulating
Hormone (FSH) and Luteinising Hormone (LH) - produced in the anterior
pituitary gland - cause the dominant follicle to transform into the corpus
luteum. The corpus luteum produces a surge of progesterone which typically
peaks on day 21 of the cycle. Measuring this can give information as to
whether a woman has ovulated or not.
A low body mass index (BMI) can cause hypogonadotrophic hypogonadism,
where the anterior pituitary gland stops producing FSH and LH, thus meaning

source: Passmed

follicles do not develop sufficiently. Gaining weight should reverse the

Antiphospholipid antibodies (aPL) are present in 15% of women
with recurrent miscarriage, but in comparison, the prevalence of
aPL in women with a low risk obstetric history is less than 2%
Infertility in PCOS - clomifene is superior to metformin
An imperforate hymen would block passage of menses, causing
amenorrhoea without affecting development of secondary
characteristics such as pubic hair and breast development. This
can cause a build up of menstrual blood in the vagina
(haematocolpos), causing pelvic pain and bloating through a
pressure effect.
Chemotherapy at a young age has the potential to damage the
hypothalamic-pituitary-ovarian axis, while Turner's syndrome can cause
premature ovarian failure. PCOS is a common cause of secondary
amenorrhoea. In these conditions the development of secondary
characteristics by oestrogen is impaired. Excessive exercise and/or rapid loss
of body weight can also cause a reduction in oestrogen secretion.
Bacterial vaginosis - overgrowth of predominately Gardnerella
Trichomonas vaginalis + bacterial vaginosis are associated with a
pH > 4.5
Chlamydia is common, affecting around 1 in 10 young women
Naproxen is the best option out of the options given, as it works to
both treat the heavy bleeding and also the pain that is associated with
the bleeding. It belongs to the Non-Steroidal Anti-inflammatory class of
medication. Ibuprofen would be a suitable alternative.
o Tranexamic acid would be effective for the menorrhagia but not
help the dysmenorrhea.
o The intrauterine system is of course a very effective treatment
for menorrhagia and is often used as first line treatment for this

source: Passmed

condition, however it is a contraceptive, which the lady in this

question did not want.
o Leuprorelin should not be started in primary care and there are
alternatives until this should be considered.
o Norethisterone is useful for helping combat flooding for short
periods of time
Meig's syndrome: Benign ovarian tumour, ascites, and pleural effusion
The combination of purulent discharge and endocervical Gramnegative diplococci indicates a diagnosis of gonorrhoea. The BNF
recommends a single dose of oral azithromycin and intramuscular
ceftriaxone to treat uncomplicated infection.
Doxycycline is an appropriate choice for chlamydia, metronidazole is
recommended for bacterial vaginosis, benzylpenicillin is used in
treating syphilis, and Azithromycin can be used to treat chlamydia.
Ovarian cancers, which are stage 2-4: surgical excision of the tumor.
This may be accompanied by chemotherapy. NICE CG122
The majority of pathologists believe that uterine leiomyosarcomas
which may initially present as 'fibroids' are probably de novo lesions
rather than a transformation of existing fibroids
Need for contraception after the menopause

12 months after the last period in women > 50 years

24 months after the last period in women < 50 years

If a patient has had a complete miscarriage, the bleeding and pain

usually ceases within 7-14 days. Patients are advised to take a urine
pregnancy test after 3 weeks to confirm they are no longer pregnant.
If a Cervical smear is reported as borderline or mild dyskaryosis the
original sample is tested for HPV

source: Passmed

if HPV negative the patient goes back to routine recall

if HPV positive the patient is referred for colposcopy
Genital warts - 90% are caused by HPV 6 & 11
Genital wart treatment

multiple, non-keratinised warts: topical podophyllum, internal:

solitary, keratinised warts: cryotherapy

The National Institute for Health and Care Excellence (NICE) states that
if a woman has a small (<35mm) unruptured ectopic pregnancy with
no visible heartbeat, a serum B-hCG level of <1500 IU/L, no
intrauterine pregnancy and no pain, then first line treatment should be
with methotrexate as long as the patient is willing to attend for followup.
The other treatment option is laparoscopic salpingectomy (or
salpingotomy where there is risk of infertility). This should be offered
where the ectopic is larger than 35mm, is causing severe pain or if the
B-hCG level is >1500. There is a risk of infertility if a problem arises
with the remaining Fallopian tube in the future.
The NHS Breast Screening Programme is being expanded to include
women aged 47-73 years from the previous parameter of 50-70 years.
Women are offered a mammogram every 3 years. After the age of 70
years women may still have mammograms but are 'encouraged to
make their own appointments'.

Vaginal discharge
Vaginal discharge is a common presenting symptom and is not always
Common causes


source: Passmed


Trichomonas vaginalis

bacterial vaginosis

Less common causes


Chlamydia can cause a vaginal discharge although this is rarely the

presenting symptoms


foreign body

cervical cancer

Key features of the common causes are listed Below


Trichomonas vaginalis

Bacterial vaginosis

Key features
'Cottage cheese' discharge
Offensive, yellow/green, frothy discharge
Strawberry cervix
Offensive, thin, white/grey, 'fishy' discharge

source: Passmed

Bacterial vaginosis
Bacterial vaginosis (BV) describes an overgrowth of predominately anaerobic
organisms such as Gardnerella vaginalis. This leads to a consequent fall in
lactic acid producing aerobic lactobacilli resulting in a raised vaginal pH.
Whilst BV is not a sexually transmitted infection it is seen almost exclusively
in sexually active women.

vaginal discharge: 'fishy', offensive

asymptomatic in 50%

Amsel's criteria for diagnosis of BV - 3 of the following 4 points should be


thin, white homogenous discharge

clue cells on microscopy: stippled vaginal epithelial cells

vaginal pH > 4.5

positive whiff test (addition of potassium hydroxide results in fishy



oral metronidazole for 5-7 days

70-80% initial cure rate

relapse rate > 50% within 3 months

source: Passmed

the BNF suggests topical metronidazole or topical clindamycin as


Clue cells - epithelial cells

develop a stippled appearance
due to being covered with
Bacterial vaginosis in pregnancy

results in an increased risk

of preterm labour, low birth
weight and
chorioamnionitis, late

it was previously taught

that oral metronidazole should be avoided in the first trimester and
topical clindamycin used instead. Recent guidelines however
recommend that oral metronidazole is used throughout pregnancy. The
BNF still advises against the use of high dose metronidazole regimes

Trichomonas vaginalis
Trichomonas vaginalis is a highly motile, flagellated protozoan parasite

vaginal discharge: offensive, yellow/green, frothy


strawberry cervix

pH > 4.5

in men is usually asymptomatic but may cause urethritis


microscopy of a wet mount shows motile trophozoites

source: Passmed


oral metronidazole for 5-7 days, although the BNF also supports the
use of a one-off dose of 2g metronidazole

Trichomonas vaginalis - largely transparent core with finely granular eosinophilic

cytoplasm. Surrounded by neutrophils with segmented nuclei

Chlamydia is the most prevalent sexually transmitted infection in the UK and is
caused by Chlamydia trachomatis, an obligate intracellular pathogen.
Approximately 1 in 10 young women in the UK have Chlamydia. The incubation
period is around 7-21 days, although it should be remembered a large percentage of
cases are asymptomatic

asymptomatic in around 70% of women and 50% of men

women: cervicitis (discharge, bleeding), dysuria

men: urethral discharge, dysuria

Potential complications

source: Passmed


pelvic inflammatory disease


increased incidence of ectopic pregnancies


reactive arthritis

perihepatitis (Fitz-Hugh-Curtis syndrome)


traditional cell culture is no longer widely used

nuclear acid amplification tests (NAATs)

urine (first void urine sample), vulvovaginal swab or cervical swab may be
tested using the NAAT technique


in England the National Chlamydia Screening Programme is open to all men

and women aged 15-24 years

the 2009 SIGN guidelines support this approach, suggesting screening all
sexually active patients aged 15-24 years

relies heavily on opportunistic testing

source: Passmed

Pap smear demonstrating infected endocervical cells. Red inclusion bodies are


Doxycycline (7 day course) or azithromycin (single dose). The

2009 sign guidelines suggest azithromycin should be used first-line due
to potentially poor compliance with a 7 day course of doxycycline

If pregnant then erythromycin or amoxicillin may be used. The sign

guidelines suggest considering azithromycin 'following discussion of
the balance of benefits and risks with the patient'

Patients diagnosed with chlamydia should be offered a choice of

provider for initial partner notification - either trained practice nurses
with support from gum, or referral to gum

For men with symptomatic infection all partners from the four weeks
prior to the onset of symptoms should be contacted

For women and asymptomatic men all partners from the last six
months or the most recent sexual partner should be contacted

Contacts of confirmed chlamydia cases should be offered treatment

prior to the results of their investigations being known (treat then test)

Another Pap smear demonstrating infected endocervical cells. Stained with H&E


source: Passmed

Gonorrhoea is caused by the Gram negative diplococcus Neisseria

gonorrhoea. Acute infection can occur on any mucous membrane surface,
typically genitourinary but also rectum and pharynx. The incubation period of
gonorrhoea is 2-5 days

males: urethral discharge, dysuria

females: cervicitis e.g. leading to vaginal discharge

rectal and pharyngeal infection is usually asymptomatic


immunisation is not possible and reinfection is common due to antigen

variation of type IV pili (proteins which adhere to surfaces) and Opa
proteins (surface proteins which bind to receptors on immune cells)

Local complications that may develop include urethral strictures, epididymitis

and salpingitis (hence may lead to infertility). Disseminated infection may
occur - see below

2011 British Society for Sexual Health and HIV (BASHH) guidelines
recommend ceftriaxone 500 mg intramuscularly as a single dose with
azithromycin 1 g oral as a single dose. The azithromycin is thought to
act synergistically with ceftriaxone and is also useful for eradicating
any co-existent Chlamydia infections

if ceftriaxone is refused or contraindicated other options include

cefixime 400mg PO (single dose)

Disseminated gonococcal infection (DGI) and gonococcal arthritis may also

occur, with gonococcal infection being the most common cause of septic
arthritis in young adults. The pathophysiology of DGI is not fully understood
but is thought to be due to haematogenous spread from mucosal infection
(e.g. Asymptomatic genital infection). Initially there may be a classic triad of
symptoms: tenosynovitis, migratory polyarthritis and dermatitis. Later
complications include septic arthritis, endocarditis and perihepatitis (FitzHugh-Curtis syndrome)
Key features of disseminated gonococcal infection

source: Passmed


migratory polyarthritis

dermatitis (lesions can be maculopapular or vesicular)

Genital warts
Genital warts (also known as condylomata accuminata) are a common cause
of attendance at genitourinary clinics. They are caused by the many varieties
of the human papilloma virus HPV, especially types 6 & 11. It is now well
established that HPV (primarily types 16,18 & 33) predisposes to cervical

small (2 - 5 mm) fleshy protuberances which are slightly pigmented

may bleed or itch


Topical podophyllum or cryotherapy are commonly used as first-line

treatments depending on the location and type of lesion. Multiple, nonkeratinised warts are generally best treated with topical agents
whereas solitary, keratinised warts respond better to cryotherapy

Imiquimod is a topical cream which is generally used second line

Genital warts are often resistant to treatment and recurrence is

common although the majority of anogenital infections with hpv clear
without intervention within 1-2 years

Menstrual cycle
The menstrual cycle may be divided into the following phases:
Follicular phase (proliferative phase)


source: Passmed

Luteal phase (secretory phase)


Further details are given in the table below


l histology

Follicular phase
(proliferative phase)
A number of follicles develop.
One follicle will become
dominant around the midfollicular phase
Proliferation of endometrium

Endometrium changes to
secretory lining under
influence of progesterone
A rise in FSH results in the
Progesterone secreted by
development of follicles which in corpus luteum rises
turn secrete oestradiol
through the luteal phase.
When the egg has matured, it
secretes enough oestradiol to
trigger the acute release of LH.
This in turn leads to ovulation


Basal body

Luteal phase
(secretory phase)
Corpus luteum

Following menstruation the

mucus is thick and forms a plug
across the external os
Just prior to ovulation the mucus
becomes clear, acellular, low
viscosity. It also becomes
'stretchy' - a quality termed
Falls prior to ovulation due to
the influence of oestradiol

If fertilisation does not

occur the corpus luteum
will degenerate and
progesterone levels fall
Oestradiol levels also rise
again during the luteal
Under the influence of
progesterone it becomes
thick, scant, and tacky

Rises following ovulation

in response to higher
progesterone levels

source: Passmed

primary (failure to start menses by the age of 16 years) or
secondary (cessation of established, regular menstruation for 6 months or
Causes of primary amenorrhoea

Turner's syndrome

testicular feminisation / CAIS

congenital adrenal hyperplasia

congenital malformations of the genital tract

Secondary amenorrhoea is defined as when menstruation has previously

occurred but has now stopped for at least 6 months.
Causes of secondary amenorrhoea (after excluding pregnancy)

hypothalamic amenorrhoea (e.g. Stress, excessive exercise)

polycystic ovarian syndrome (PCOS)

hyperprolactinaemia PL >

premature ovarian failure


Sheehan's syndrome

Asherman's syndrome (intrauterine adhesions)

Initial investigations

exclude pregnancy with urinary or serum bHCG

source: Passmed

gonadotrophins: low levels indicate a hypothalamic cause where as

raised levels suggest an ovarian problem (e.g. Premature ovarian


androgen levels: raised levels may be seen in PCOS


thyroid function tests

*hypothyroidism may also cause amenorrhoea

Dysmenorrhoea is characterised by excessive pain during the menstrual
period. It is traditionally divided into primary and secondary dysmenorrhoea.
Primary dysmenorrhoea
In primary dysmenorrhoea there is no underlying pelvic pathology. It affects
up to 50% of menstruating women and usually appears within 1-2 years of
the menarche. Excessive endometrial prostaglandin production is thought to
be partially responsible.

pain typically starts just before or within a few hours of the period

suprapubic cramping pains which may radiate to the back or down the


NSAIDs such as mefenamic acid and ibuprofen are effective in up to

80% of women. They work by inhibiting prostaglandin production

source: Passmed

combined oral contraceptive pills are used second line

Secondary dysmenorrhoea
Secondary dysmenorrhoea typically develops many years after the menarche
and is the result of an underlying pathology. In contrast to primary
dysmenorrhoea the pain usually starts 3-4 days before the onset of the
period. Causes include:



pelvic inflammatory disease

intrauterine devices*


Clinical Knowledge Summaries recommend referring all patients with

secondary dysmenorrhoea to gynaecology for investigation.
*this refers to normal copper coils. Note that the intrauterine system (Mirena)
may help dysmenorrhoea

Menorrhagia: causes
Menorrhagia was previously defined as total blood loss > 80 ml per menses,
but it is obviously difficult to quantify. The assessment and management of
heavy periods has therefore shifted towards what the woman considers to be
excessive and aims to improve quality of life measures.
dysfunctional uterine bleeding: this describes menorrhagia in the
absence of underlying pathology. This accounts for approximately half
of patients
anovulatory cycles: these are more common at the extremes of a
women's reproductive life
uterine fibroids

source: Passmed

intrauterine devices*
pelvic inflammatory disease
bleeding disorders, e.g. von Willebrand disease

*this refers to normal copper coils. Note that the intrauterine system (Mirena)
is used to treat menorrhagia

Menorrhagia: management
Menorrhagia was previously defined as total blood loss > 80 ml per menses, but it is
obviously difficult to quantify. The management has therefore shifted towards what
the woman considers to be excessive. Prior to the 1990's many women underwent a
hysterectomy to treat heavy periods but since that time the approach has altered
radically. The management of menorrhagia now depends on whether a women
needs contraception.
a full blood count should be performed in all women
further investigations are based upon the history and examination findings
Does not require contraception
either mefenamic acid 500 mg tds (particularly if there is dysmenorrhoea as
well) or tranexamic acid 1 g tds. Both are started on the first day of the
if no improvement then try other drug whilst awaiting referral
Requires contraception, options include
intrauterine system (Mirena) should be considered first-line
combined oral contraceptive pill
long-acting progestogens
Norethisterone 5 mg tds can be used as a short-term option to rapidly stop heavy
menstrual bleeding.

The average women in the UK goes through the menopause when she is 51
years old. The climacteric is the period prior to the menopause where women
may experience symptoms, as ovarian function starts to fail

12 months after the last period in women > 50 years

source: Passmed

24 months after the last period in women < 50 years

It is recommend using effective contraception until the diagnosis has been

confirmed using the above criteria

Hormone replacement therapy

Hormone replacement therapy: indications
Hormone replacement therapy (HRT) involves the use of a small dose of
oestrogen, combined with a progestogen (in women with a uterus), to help
alleviate menopausal symptoms.
The indications for HRT have changed significantly over the past ten years as
the long-term risks became apparent, primarily as a result of the Women's
Health Initiative (WHI) study.

vasomotor symptoms such as flushing, insomnia and headaches

premature menopause: should be continued until the age of 50 years.

Most important reason is preventing the development of osteoporosis

The main indication is the control of vasomotor symptoms. The other

indications such as reversal of vaginal atrophy should be treated with other
agents as first-line therapies
Other benefits include a reduced incidence of colorectal cancer

Hormone replacement therapy: adverse effects



breast tenderness

source: Passmed

fluid retention and weight gain

Potential complications

increased risk of breast cancer: increased by the addition of a


increased risk of endometrial cancer: reduced by the addition of a

progestogen but not eliminated completely. The BNF states that the
additional risk is eliminated if a progestogen is given continuously

increased risk of venous thromboembolism: increased by the addition

of a progestogen

increased risk of stroke

increased risk of ischaemic heart disease if taken more than 10 years

after menopause

Breast cancer

in the Women's Health Initiative (WHI) study there was a relative risk of
1.26 at 5 years of developing breast cancer

the increased risk relates to duration of use

breast cancer incidence is higher in women using combined

preparations compared to oestrogen-only preparations

the risk of breast cancer begins to decline when HRT is stopped and by
5 years it reaches the same level as in women who have never taken

Pelvic inflammatory disease

Pelvic inflammatory disease (PID) is a term used to describe infection and
inflammation of the female pelvic organs including the uterus, fallopian
tubes, ovaries and the surrounding peritoneum. It is usually the result of
ascending infection from the endocervix

source: Passmed

Causative organisms

Chlamydia trachomatis - the most common cause

Neisseria gonorrhoeae

Mycoplasma genitalium

Mycoplasma hominis


lower abdominal pain


deep dyspareunia

dysuria and menstrual irregularities may occur

vaginal or cervical discharge

cervical excitation


screen for Chlamydia and Gonorrhoea


due to the difficulty in making an accurate diagnosis, and the potential

complications of untreated PID, consensus guidelines recommend
having a low threshold for treatment

oral ofloxacin + oral metronidazole or intramuscular ceftriaxone + oral

doxycycline + oral metronidazole

RCOG guidelines suggest that in mild cases of PID intrauterine

contraceptive devices may be left in. The more recent BASHH
guidelines suggest that the evidence is limited but that ' Removal of
the IUD should be considered and may be associated with better short
term clinical outcomes'

source: Passmed


infertility - the risk may be as high as 10-20% after a single episode

chronic pelvic pain

ectopic pregnancy

Endometriosis is a common condition characterised by the growth of ectopic
endometrial tissue outside of the uterine cavity. Up to 10-15% of women
have a degree of endometriosis
Clinical features

chronic pelvic pain

dysmenorrhoea - pain often starts days before bleeding

deep dyspareunia


Less common features

urinary symptoms e.g. dysuria, urgency

dyschezia (painful bowel movements)


laparoscopy is the gold-standard investigation

there is little role for investigation in primary care (e.g. ultrasound)- if

the symptoms are significant the patient should be referred for a
definitive diagnosis

source: Passmed

Management depends on clinical features - there is poor correlation between

laparoscopic findings and severity of symptoms

NSAIDs and other analgesia for symptomatic relief

combined oral contraceptive pill

progestogens e.g. medroxyprogesterone acetate

gonadotrophin-releasing hormone (GnRH) analogues - said to induce a

'pseudomenopause' due to the low oestrogen levels

intrauterine system (Mirena)

drug therapy unfortunately does not seem to have a significant impact

on fertility rates


some treatments such as laparoscopic excision and laser treatment of

endometriotic ovarian cysts may improve fertility

Pelvic congestion syndrome

Polycystic ovarian syndrome
Polycystic ovarian syndrome: management
Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian
dysfunction thought to affect between 5-20% of women of reproductive age.
Management is complicated and problem based partly because the aetiology
of PCOS is not fully understood. Both hyperinsulinaemia and high levels of
luteinizing hormone are seen in PCOS and there appears to be some overlap
with the metabolic syndrome.

weight reduction if appropriate

if a women requires contraception then a combined oral contraceptive

(COC) pill may help regulate her cycle and induce a monthly bleed (see
source: Passmed

Hirsutism and acne

a COC pill may be used help manage hirsutism. Possible options

include a third generation COC which has fewer androgenic effects or
co-cyprindiol which has an anti-androgen action. Both of these types of
COC may carry an increased risk of venous thromboembolism

if doesn't respond to COC then topical eflornithine may be tried

spironolactone, flutamide and finasteride may be used under specialist



weight reduction if appropriate

the management of infertility in patients with PCOS should be

supervised by a specialist. There is an ongoing debate as to whether
metformin, clomifene or a combination should be used to stimulate

a 2007 trial published in the New England Journal of Medicine

suggested clomifene was the most effective treatment. There is a
potential risk of multiple pregnancies with anti-oestrogen* therapies
such as clomifene. The RCOG published an opinion paper in 2008 and
concluded that on current evidence metformin is not a first line
treatment of choice in the management of PCOS

metformin is also used, either combined with clomifene or alone,

particularly in patients who are obese


*work by occupying hypothalamic oestrogen receptors without activating

them. This interferes with the binding of oestradiol and thus prevents
negative feedback inhibition of FSH secretion

Miscarriage: types
Threatened miscarriage

source: Passmed

painless vaginal bleeding occurring before 24 weeks, but typically

occurs at 6 - 9 weeks

the bleeding is often less than menstruation

cervical os is closed

complicates up to 25% of all pregnancies

Missed (delayed) miscarriage

a gestational sac which contains a dead fetus before 20 weeks without

the symptoms of expulsion

mother may have light vaginal bleeding / discharge and the symptoms
of pregnancy which disappear. Pain is not usually a feature

cervical os is closed

when the gestational sac is > 25 mm and no embryonic/fetal part can

be seen it is sometimes described as a 'blighted ovum' or
'anembryonic pregnancy'

Inevitable miscarriage

heavy bleeding with clots and pain

cervical os is open

Incomplete miscarriage

not all products of conception have been expelled

pain and vaginal bleeding

cervical os is open

An incomplete miscarriage occurs when some, but not all, of the products of
conception are expelled from the uterus. Retained products of conception
pose an infection risk to the mother and so should be treated promptly.
Bleeding in miscarriage can be serious and physiological signs of shock
should not be missed.
The National Institute of Health and Care Excellence (NICE) recommends that

source: Passmed

during an incomplete miscarriage, medical management of miscarriage

should be offered where 'expectant management' is unacceptable to the
patient. A single dose of misoprostol 600 micrograms as a vaginal pessary is
first line medical management of an incomplete miscarriage. If this is not
tolerated then oral administration is acceptable. Other management options
include manual vacuum aspiration under local anaesthetic and surgical
management under general anaesthetic.
Medical management as opposed to expectant management is often offered
to women who have previously had a traumatic experience of pregnancy,
such as a previous miscarriage or still birth.
References and resources: NICE pathways: Management of miscarriage

Recurrent miscarriage
Recurrent miscarriage is defined as 3 or more consecutive spontaneous abortions. It
occurs in around 1% of women
Antiphospholipid syndrome
Endocrine disorders: poorly controlled diabetes mellitus/thyroid disorders.
Polycystic ovarian syndrome
Uterine abnormality: e.g. Uterine septum
Parental chromosomal abnormalities

source: Passmed

Ectopic pregnancy
Implantation of a fertilized ovum outside the uterus results in an ectopic
A typical history is a female with a history of 6-8 weeks amenorrhoea who
presents with lower abdominal pain and later develops vaginal bleeding

lower abdominal pain: typically the first symptom. Pain is usually

constant and may be unilateral. Due to tubal spasm

vaginal bleeding: usually less than a normal period, may be dark brown
in colour

history of recent amenorrhoea: typically 6-8 weeks from start of last

period; if longer (e.g. 10 wks) this suggest another causes e.g.
inevitable abortion

peritoneal bleeding can cause shoulder tip pain and pain on defecation
/ urination

Examination findings

abdominal tenderness

cervical excitation (also known as cervical motion tenderness)

adnexal mass: NICE advise NOT to examine for an adnexal mass due to
an increased risk of rupturing the pregnancy. A pelvic examination to
check for cervical excitation is however recommended

source: Passmed

NICE recommend 'systemic methotrexate as a first-line treatment to women

who are able to return for follow-up and who have all of the following:

no significant pain

an unruptured ectopic pregnancy with an adnexal mass smaller

than 35mm with no visible heartbeat

a serum hCG level less than 1500 IU/litre

no intrauterine pregnancy (as confirmed on an ultrasound scan).'

(source: NICE,

Gestational trophoblastic disorders

Describes a spectrum of disorders originating from the placental trophoblast:

complete hydatidiform mole

partial hydatidiform mole


Complete hydatidiform mole

Benign tumour of trophoblastic material. Occurs when an empty egg is
fertilized by a single sperm that then duplicates its own DNA, hence the all
46 chromosomes are of paternal origin

bleeding in first or early second trimester

source: Passmed

exaggerated symptoms of pregnancy e.g. hyperemesis

uterus large for dates

very high serum levels of human chorionic gonadotropin (hCG)

hypertension and hyperthyroidism* may be seen


urgent referral to specialist centre - evacuation of the uterus is


effective contraception is recommended to avoid pregnancy in the next

12 months

Around 2-3% go on to develop choriocarcinoma

In a partial mole a normal haploid egg may be fertilized by two sperms, or
by one sperm with duplication of the paternal chromosomes. Therefore the
DNA is both maternal and paternal in origin. Usually triploid - e.g. 69 XXX or
69 XXY. Fetal parts may be seen
*hCG can mimic thyroid-stimulating hormone (TSH)

Infertility affects around 1 in 7 couples. Around 84% of couples who have
regular sex will conceive within 1 year, and 92% within 2 years

male factor 30%

source: Passmed

unexplained 20%

ovulation failure 20%

tubal damage 15%

other causes 15%

Interpretation of serum progestogen

< 16 nmol/l
16 - 30 nmol/l
> 30 nmol/l

Repeat, if consistently low refer to specialist
Indicates ovulation

Basic investigations

semen analysis

serum progesterone 7 days prior to expected next period

Key counselling points

folic acid

aim for BMI 20-25

advise regular sexual intercourse every 2 to 3 days

smoking/drinking advice

Key Points:
Women age is greater than 35 she should be investigated for infertility
earlier after having regular intercourse for 6 months. Regular sexual
intercourse is defined a intercourse every 2-3 days.
In a women below 35 investigation should wait until after 12 months of
regular intercourse.

source: Passmed

Early referral should be considered when:

Age above 35

Previous pelvic surgery

Previous STI
Abnormal genital

Previous surgery on
Significant systemic illness
Abnormal genital


Semen analysis
Semen analysis should be performed after a minimum of 3 days and a
maximum of 5 days abstinence. The sample needs to be delivered to the lab
within 1 hour
Normal semen results*

volume > 1.5 ml

pH > 7.2

sperm concentration > 15 million / ml

morphology > 4% normal forms

motility > 32% progressive motility

vitality > 58% live spermatozoa

*many different reference ranges exist. These are based on the NICE 2013

source: Passmed

With an abnormal semen analysis a fresh sample should be collected 3

months after the initial abnormal result to allow for the cycle of spermatozoa
to be completed.
If the result was severely abnormal (azoospermia or severe oligospermia) or
the man is particularly anxious regarding the result then it can be tested 2-4
weeks after the original.
If one is normal then no further investigation n is required
Once 2 abnormal samples have been collected the man should be referred for
further investigated.

Uterine fibroids
Fibroids are benign smooth muscle tumours of the uterus. They are through
to occur in around 20% of white and around 50% of black women in the later
reproductive years

more common in Afro-Caribbean women

rare before puberty, develop in response to oestrogen, don't tend to

progress following menopause


may be asymptomatic


lower abdominal pain: cramping pains, often during menstruation


urinary symptoms, e.g. frequency, may occur with larger fibroids


source: Passmed


transvaginal ultrasound


medical: symptomatic management e.g. with combined oral

contraceptive pill. GnRH agonists may reduce the size of the fibroid but
are typically useful for short-term treatment

surgery is sometimes needed: myomectomy, hysterscopic endometrial

ablation, hysterectomy

uterine artery embolization


red degeneration - haemorrhage into tumour - commonly occurs during


Polycystic ovarian syndrome

Polycystic ovarian syndrome: features and investigation
Polycystic ovary syndrome (PCOS) is a complex condition of ovarian
dysfunction thought to affect between 5-20% of women of reproductive age.
The aetiology of PCOS is not fully understood. Both hyperinsulinaemia and
high levels of luteinizing hormone are seen in PCOS and there appears to be
some overlap with the metabolic syndrome.

subfertility and infertility

menstrual disturbances: oligomenorrhea and amenorrhoea

hirsutism, acne (due to hyperandrogenism)

source: Passmed


acanthosis nigricans (due to insulin resistance)


pelvic ultrasound: multiple cysts on the ovaries

FSH, LH, prolactin, TSH, and testosterone are useful investigations:

raised LH:FSH ratio is a 'classical' feature but is no longer thought to be
useful in diagnosis. Prolactin may be normal or mildly elevated.
Testosterone may be normal or mildly elevated - however, if markedly
raised consider other causes

check for impaired glucose tolerance

PCOS is a common disorder, which is often complicated by chronic

anovulation and hyperandrogenism.
Long-term complications include:


Diabetes mellitus

Stroke & transient ischaemic attack

Coronary artery disease

Obstructive sleep apnoea

Endometrial cancer

These complications are further increased in patients who are obese.

The increased risk of endometrial hyperplasia and carcinoma is due to
oligo/amenorrhoea in the presence of pre-menopausal levels of oestrogen.
This risk is greatest in women who have menstrual cycle lengths of
>3months. This risk can be reduced by inducing a withdrawal bleed every 13 months (using a combined contraceptive pill or cyclical
medroxyprogesterone) or with insertion of a mirena coil. Optimising BMI in
overweight patients will help to regulate menstrual cycles, thereby reducing

source: Passmed

the risk of endometrial hyperplasia.

There is no increased risk of osteoporosis because there is no oestrogen
RCOG Greentop guidelines. Long-term consequences of polycystic ovary

Premature ovarian failure

Premature ovarian failure is defined as the onset of menopausal symptoms
and elevated gonadotrophin levels before the age of 40 years. It occurs in
around 1 in 100 women.

idiopathic - the most common cause




Features are similar to those of the normal climacteric but the actual
presenting problem may differ

climacteric symptoms: hot flushes, night sweats


secondary amenorrhoea

raised FSH, LH levels

Ovarian enlargement

source: Passmed

Ovarian enlargement: management

The initial imaging modality for suspected ovarian cysts/tumours is
ultrasound. The report will usually report that the cyst is either:

simple: unilocular, more likely to be physiological or benign

complex: multilocular, more likely to be malignant

Management depends on the age of the patient and whether the patient is
symptomatic. It should be remembered that the diagnosis of ovarian cancer
is often delayed due to a vague presentation.
Premenopausal women

a conservative approach may be taken for younger women (especially

if < 35 years) as malignancy is less common. If the cyst is small (e.g. <
5 cm) and reported as 'simple' then it is highly likely to be benign. A
repeat ultrasound should be arranged for 8-12 weeks and referral
considered if it persists.

Postmenopausal women

by definition physiological cysts are unlikely

any postmenopausal woman with an ovarian cyst regardless of nature

or size should be referred to gynaecology for assessment

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a complication seen in some
forms of infertility treatment. It is postulated that the presence of multiple
luteinized cysts within the ovaries results in high levels of not only
oestrogens and progesterone but also vasoactive substances such as
vascular endothelial growth factor (VEGF). This results in increased
membrane permeability and loss of fluid from the intravascular compartment
Whilst it is rarely seen with clomifene therapy is more likely to be seen
following gonadotropin or hCG treatment. Up to one third of women who are

source: Passmed

having IVF may experience a mild form of OHSS

The RCOG uses the following classification of OHSS



As for mild
Nausea and
evidence of

As for moderate
Clinical evidence
of ascites
Haematocrit >


As for severe
Acute respiratory
distress syndrome
Tense ascites

Cervical ectropion
On the ectocervix there is a transformation zone where the stratified
squamous epithelium meets the columnar epithelium of the cervical canal.
Elevated oestrogen levels (ovulatory phase, pregnancy, combined oral
contraceptive pill use) result in larger area of columnar epithelium being
present on the ectocervix
The term cervical erosion is used less commonly now
This may result in the following features

vaginal discharge

post-coital bleeding

Ablative treatment (for example 'cold coagulation') is only used for

troublesome symptoms

Human papilloma virus vaccination

It has been known for a longtime that the human papilloma virus (HPV)
which infects the keratinocytes of the skin and mucous membranes is

source: Passmed

There are dozens of strains of HPV. The most important to remember are:

6 & 11: causes genital warts

16 & 18: linked to a variety of cancers, most notably cervical cancer

HPV infection is linked to:

over 99.7% of cervical cancers

around 85% of anal cancers

around 50% of vulval and vaginal cancers

around 20-30% of mouth and throat cancers

It should of course be remembered that there are other risk factors important
in developing cervical cancer such as smoking, combined oral contraceptive
pill use and high parity.
Testing for HPV has now been integrated into the cervical cancer screening
programme. If a smear is reported as borderline or mild dyskaryosis the
original sample is tested for HPV

if HPV negative the patient goes back to routine recall

if HPV positive the patient is referred for colposcopy

A vaccination for HPV was introduced in the UK back in 2008. As you may
remember the Department of Health initially chose Cervarix. This vaccine
protected against HPV 16 & 18 but not 6 & 11. There was widespread
criticism of this decision given the significant disease burden caused by
genital warts. Eventually in 2012 Gardasil replaced Cervarix as the vaccine
used. Gardasil protects against HPV 6, 11, 16 & 18.
Girls aged 12-13 years are offered the vaccine in the UK

the vaccine is normally given in school

source: Passmed

information given to parents and available on the NHS website make it

clear that the daughter may receive the vaccine against parental

given as 2 doses - girls have the second dose between 6-24 months
after the first, depending on local policy

Injection site reactions are particularly common with HPV vaccin

Cervical cancer
The incidence of cervical cancer peaks around the 6th decade. It may be
divided into

squamous cell cancer (80%)

adenocarcinoma (20%)


may be detected during routine cervical cancer screening

abnormal vaginal bleeding: postcoital, intermenstrual or

postmenopausal bleeding

vaginal discharge

Risk factors

human papilloma virus (HPV) 16,18 & 33


human immunodeficiency virus

early first intercourse, many sexual partners

high parity

lower socioeconomic status

source: Passmed

combined oral contraceptive pill*

Mechanism of HPV causing cervical cancer

HPV 16 & 18 produces the oncogenes E6 and E7 genes respectively

E6 inhibits the p53 tumour suppressor gene

E7 inhibits RB suppressor gene

*the strength of this association is sometimes debated but a large study

published in the Lancet (2007 Nov 10;370(9599):1609-21) confirmed the link

Cervical cancer screening

The UK has a well established cervical cancer screening program which is
estimated to prevent 1,000-4,000 deaths per year. It should be noted that
cervical adenocarcinomas, which account for around 15% of cases, are
frequently undetected by screening
Who is screened and how often?
A smear test is offered to all women between the ages of 25-64 years

25-49 years: 3-yearly screening

50-64 years: 5-yearly screening

How is performed?
There is currently a move away from traditional Papanicolaou (Pap) smears
to liquid-based cytology (LBC). Rather than smearing the sample onto a slide
the sample is either rinsed into the preservative fluid or the brush head is
simply removed into the sample bottle containing the preservative fluid.
Advantages of LBC includes

reduced rate of inadequate smears

increased sensitivity and specificity

source: Passmed

It is said that the best time to take a cervical smear is around mid-cycle.
Whilst there is limited evidence to support this it is still the current advice
given out by the NHS.
In Scotland women from the ages of 20-60 years are screened every 3 years.

*Cervical cancer screening detects squamous cell cancer and may miss

Cervical cancer screening: interpretation of results

The table below outlines the management of abnormal cervical smears
(around 5% of all smears). Cervical intraepithelial neoplasia is abbreviated to
Borderline or mild

Severe dyskaryosis
Suspected invasive

The original sample is tested for HPV*

if negative the patient goes back to

routine recall

if positive the patient is referred for


Consistent with CIN II. Refer for colposcopy

Consistent with CIN III. Refer for colposcopy
Refer for urgent colposcopy (within 2 weeks)
Repeat smear - if persistent (3 inadequate
samples), assessment by colposcopy

*high-risk subtypes of HPV such as 16,18 & 33

Cervical cancer and Pregnancy

Less than 16 weeks of pregnancy it is recommended that treatment
for the cervical cancer is started immediately. Treatment is usually with largeloop excision of the transformation zone (LLETZ)
Over 16 weeks pregnant and have early stage disease then it may be
recommended to delay treatment until the foetus has matured and expedite
If the women has late stage cervical cancer, and before 20 weeks
immediate delivery of baby and treatment. If after 20 weeks delivery within 4
weeks and treatment of cervical cancer

source: Passmed

Endometrial cancer
Endometrial cancer is classically seen in post-menopausal women but around
25% of cases occur before the menopause. It usually carries a good
prognosis due to early detection
The risk factors for endometrial cancer are as follows*:



early menarche

late menopause

unopposed oestrogen. The addition of a progestogen to oestrogen

reduces this risk (e.g. In HRT). The BNF states that the additional risk is
eliminated if a progestogen is given continuously

diabetes mellitus


polycystic ovarian syndrome


post-menopausal bleeding is the classic symptom

pre-menopausal women may have a change intermenstrual bleeding

pain and discharge are unusual features


first-line investigation is trans-vaginal ultrasound - a normal

endometrial thickness (< 4 mm) has a high negative predictive value

source: Passmed

hysteroscopy with endometrial biopsy


localised disease is treated with total abdominal hysterectomy with

bilateral salpingo-oophorectomy. Patients with high-risk disease may
have post-operative radiotherapy

progestogen therapy is sometimes used in frail elderly women not

consider suitable for surgeryo

*the oral contraceptive pill is protective

Postcoital bleeding
Postcoital bleeding describes vaginal bleeding after sexual intercourse.

no identifiable pathology is found in around 50% of cases

cervical ectropion is the most common identifiable causes, causing

around 33% of cases. This is more common in women on the combined
oral contraceptive pill

cervicitis e.g. secondary to Chlamydia

cervical cancer



Ovarian tumours
There are 4 main types of ovarian tumours

surface derived tumours

source: Passmed

germ cell tumours

sex cord-stromal tumours


Surface derived tumors

These account for around 65% of ovarian tumors, including the greatest
number of malignant tumors.





Brenner tumour



Most common benign ovarian
tumor, often bilateral
Cyst lined by ciliated cells (similar
to Fallopian tube)
Often bilateral
Psammoma bodies seen
(collection of calcium)
Cyst lined by mucous-secreting
epithelium (similar to endocervix)
May be associated with
pseudomyxoma peritonei
(although mucinous tumor of
appendix is the more common
Contain Walthard cell rests (benign
cluster of epithelial cells), similar
to transitional cell epithelium.
Typically have 'coffee bean' nuclei.

Germ cell tumours

These are more common in adolescent girls and are account for 15-20% of
tumours. Similar cancer types to those seen in the testicle.

Mature teratoma
(dermoid cyst) - most
common: benign

Account for 90% of germ cell
Contain a combination of

source: Passmed

Immature teratoma:


Yolk sac




ectodermal (e.g. hair),

mesodermal (e.g. bone) and
endodermal tissue
Most common malignant
Histological appearance similar
to that of testicular seminoma
Associated with XO
hCG and LDH
Schiller-Duval bodies are
Rare tumour
increased hCG levels
early haematogenous spread
to the lungs

Sex cord-stromal tumours

Represent around 3-5% of ovarian tumours. Often produce hormones.
cell tumour


Sertoli-Leydig Benign
cell tumour


Estrogen leading to precocious puberty
if in children or endometrial hyperplasia
in adults.
Call-Exner bodies (small eosinophilic
fluid-filled spaces between granulosa
Produces androgens masculinizing
Associated with Peutz-Jegher syndrome
Associated with Meigs' syndrome
(ascites, pleural effusion)
Solid tumour consisting of bundles of
spindle-shaped fibroblasts
Typically occur around the menopause,
classically causing a pulling sensation
in the pelvis

source: Passmed

Metastatic tumours
Account for around 5% of tumours.


Metastases from a gastrointestinal tumour
resulting in a mucin-secreting signet-ring
cell adenocarcinoma

It is possible to perform immunohistochemical studies to help in the

classification of ovarian tumours. There are many cell markers and many
overlap between tumour types, but the presence of stem cell proteins is
typically associated with germ cell tumours. The most well-known markers of
pluripotency are SOX2, Oct4 and NANOG.

Ovarian cancer
Ovarian cancer is the fifth most common malignancy in females. The peak
age of incidence is 60 years and it generally carries a poor prognosis due to
late diagnosis. Around 90% of ovarian cancers are epithelial in origin.
Risk factors

family history: mutations of the BRCA1 or the BRCA2 gene

many ovulations: early menarche, late menopause, nulliparity

It is traditionally taught that infertility treatment increases the risk of

ovarian cancer, as it increases the number of ovulations. Recent evidence
however suggests that there is not a significant link. The combined oral
contraceptive pill reduces the risk (fewer ovulations) as does having many
Clinical features are notoriously vague

abdominal distension and bloating

abdominal and pelvic pain

urinary symptoms e.g. Urgency

source: Passmed

early satiety


Diagnosis is difficult and usually involves diagnostic laparotomy

source: Passmed