PASSMEDICINE TEXT BOOK (DOWNLOADED 28/01/2022)

GYNAECOLOGY

Amenorrhoea

Amenorrhoea may be divided into:

 primary: defined as the failure to establish menstruation by 15 years of age in girls with normal secondary
sexual characteristics (such as breast development), or by 13 years of age in girls with no secondary sexual
characteristics
 secondary: cessation of menstruation for 3-6 months in women with previously normal and regular menses,
or 6-12 months in women with previous oligomenorrhoea

Causes

Secondary amenorrhoea
Primary amenorrhoea (after excluding pregnancy)
 gonadal dysgenesis (e.g.  hypothalamic amenorrhoea
Turner's syndrome) - the (e.g. secondary
most common causes stress, excessive exercise)
 testicular feminisation  polycystic ovarian
 congenital malformations syndrome (PCOS)
 Secondary amenorrhoea
Primary amenorrhoea (after excluding pregnancy)
of the genital tract  hyperprolactinaemia
 functional hypothalamic  premature ovarian failure
amenorrhoea (e.g.  thyrotoxicosis*
secondary to anorexia)  Sheehan's syndrome
 congenital adrenal  Asherman's syndrome
hyperplasia (intrauterine adhesions)
 imperforate hymen

Investigation and management

Initial investigations

 exclude pregnancy with urinary or serum bHCG

 full blood count, urea & electrolytes, coeliac screen, thyroid function tests
 gonadotrophins
o low levels indicate a hypothalamic cause where as raised levels suggest an ovarian problem (e.g.
Premature ovarian failure)
o raised if gonadal dysgenesis (e.g. Turner's syndrome)
 prolactin
 androgen levels
o raised levels may be seen in PCOS
 oestradiol
Management

 primary amenorrhoea:
o investigate and treat any underlying cause
o with primary ovarian insufficiency due to gonadal dysgenesis (e.g. Turner's syndrome) are likely to
benefit from hormone replacement therapy (e.g. to prevent osteoporosis etC)
 secondary amenorrhoea
o exclude pregnancy, lactation, and menopause (in women 40 years of age or older)
o treat the underlying cause

*hypothyroidism may also cause amenorrhoea

Assisted reproductive technologies

Assisted reproductive technologies refer to techniques and procedures performed to achieve pregnancy and the term refers
to intrauterine insemination, in vitro fertilisation (IVF), intra-cytoplasmic sperm injection, donor insemination, egg donation,
pre-gestational testing and surrogacy.

Intrauterine insemination, also known as artificial insemination, refers to the process of introducing sperm directly into the
uterus. It may be used cases of cervical scarring, poor sperm count or poor mobility and where couples have difficulty with
penetrative sexual intercourse or those in whom unprotected sexual intercourse may not be recommended e.g. couples in
which one party is HIV positive and the other negative.
The sperm is collected following masturbation and is then 'washed' and filtered to form a concentrated specimen which can
then be introduced at ovulation into the uterus of the child-carrying party. It may be performed using donor sperm if
required. This procedure may be performed in the context of stimulated ovulation (using fertility agents) or a natural
ovulatory cycle. It is not recommended in patients suffering from unexplained infertility.

IVF refers to the process of stimulating egg production and then collecting the eggs, to be fertilised with harvested sperm in
vitro. In 'traditional' IVF, the egg and sperm are placed in a dish and the sperm must then penetrate the egg to ensure
successful fertilisation (as would occur during intra-uterine fertilisation). Another method that may be used is intra-
cytoplasmic sperm injection, in which the sperm is inserted directly into the egg cytoplasm using a micropipette. This
allows for fertilisation in cases were sperm mobility may be severely compromised or where the egg zona pellucida may be
difficult to penetrate e.g. when using eggs previously frozen.

The fertilised embryo is subsequently reintroduced into the uterus of the child-carrying party. It may be offered to women
under the age of 43 years in whom regular unprotected penetrative sexual intercourse for 2 years has not resulted in
pregnancy. The chance of success has been shown to decrease markedly with age, with success rates quoted as 2% in
women over 44 years. IVF may be performed with donor eggs or sperm as desired.

IVF allows for the screening of embryos for specific genetic disorders using pre-implantation genetic diagnosis. There are
over 600 conditions that can be tested for at present, examples including alpha thalassaemia, certain types of early-onset
dementia, certain types of motor neurone disease with an identified genetic cause and Huntingdon's disease. It may be
offered to patients that have terminated a pregnancy previously as a result of a serious genetic disease, those who already
have a child with a serious genetic disease and those with a family history of a serious genetic or chromosomal disease.

It is a technique which does carry the risk of damage to the embryos tested and it may also be the case that all embryos
carry the genetic/chromosomal disorder tested for. Once the testing is completed, the embryos identified as free from the
condition of concern may be re-implanted as per usual IVF procedure.

Surrogacy is the process of a third party carrying a foetus for another couple. It may be an appropriate option for couples
without a uterus (including same-sex couples), those with uterine abnormalities and in those who have suffered multiple
miscarriages/ failed IVF implantations. The Human Fertilisation and Embryology Authority makes a distinction between 'full'
surrogacy, in which the party carrying the foetus is not genetically related to the implanted foetus, and 'partial' surrogacy, in
which the surrogate's egg is fertilised via IVF and then re-implanted. It can be a highly controversial reproductive technology
as, by law, the party giving birth to the child is its legal mother. Patients pursuing this option are strongly advised to seek
legal counsel prior to commencing the procedure.

Bartholin's abscess
Bartholin's glands are a pair of glands located next to the entrance to the vagina. These are normally about the size of a pea,
but can become infected and enlarge - forming a Bartholin's abscess.

This can be treated by antibiotics, by the insertion of a word catheter or by a surgical procedure known as marsupialization.

Bartholin's cyst

Bartholin's cyst develops when the entrance to the Bartholin duct becomes blocked. The gland continues to produce mucus
which builds up behind the blockage, eventually leading to the formation of a mass. The initial blockage is most commonly
caused by vulvar oedema. These are usually sterile.

Bartholin's cysts are usually painless and commonly asymptomatic, often being detected at a routine pelvic examination or
by the woman herself. If the cyst is particularly large it may cause superficial dyspareunia and could be uncomfortable when
sitting. In contrast, Bartholin's abscess is extremely painful, with erythema and often gross deformity of the affected side of
the vulva. Bartholin's abscess is three times more common than the cyst in terms of presentations to gynaecology but this is
likely to reflect the asymptomatic nature of the cyst in a majority of cases to some extent.

Bartholin's cysts are usually unilateral and 1-3cm in diameter - the Bartholin's glands should not be palpable in health.

On examination, a cyst is characterised by the presence of a soft, painless lump in the labium. It is best felt between a finger
at the posterior vaginal introitus and a thumb lateral to the labium.

Limited data suggest that Bartholin's cysts are present in around 3000 in 100,000 asymptomatic women 1, while Bartholin's
gland abscesses and cysts account for 2% of all gynaecological appointments 2.

Risk factors for the development of Bartholin's cyst are poorly understood, but it is thought to increase in incidence with
increasing age up to the menopause before decreasing. In one published series, only 10% of cysts occurred in women over
age 40 3. Having one cyst is a risk factor for developing a second.

Asymptomatic cysts require no intervention in general, although in older women (over age 40) some gynaecologists advocate
incision and drainage with biopsy in order to exclude carcinoma. Cysts that are symptomatic and/or disfiguring should be
treated with either incision and drainage (with/without placement of a 'word' catheter to allow continuing drainage) or with a
procedure known as marsupialisation. The latter involves the creation of a new orifice through which the glandular secretions
may drain, by incising the gland open, everting it and suturing the epithelial lining against the skin. Marsupialisation is
thought to be more effective at preventing recurrence, but is a longer operation and is more invasive. There is no place for
antibiotic use in the setting of Bartholin's cyst with no evidence of abscess.

References
1. Berger MB, Betschart C, Khandwala N, et al. Incidental Bartholin gland cysts identified on pelvic magnetic resonance
imaging. Obstet Gynecol. 2012 Oct;120(4):798-802.
2. Kaufman RH, Faro S, Brown D. Benign diseases of the vulva and vagina. 5th ed. Philadelphia, PA: Elsevier Mosby;
2005:240-249.
3. Azzan BB. Bartholin's cyst and abscess: a review of treatment of 53 cases. Br J Clin Pract. 1978 Apr;32(4):101-2

Bleeding in the first trimester

Bleeding in the first trimester is a common reason women in early pregnancy seek medical attention.

The main differential diagnosis is as follows:

 miscarriage
 ectopic pregnancy
o the most 'important' cause as missed ectopics can be potentially life-threatening
 implantation bleeding
o a diagnosis of exclusion
 miscellaneous conditions
o cervical ectropion
o vaginitis
o trauma
o polyps
NICE released guidelines on the management of ectopic pregnancy and miscarriage in 2019. In these guidelines
they discussed how to manage early bleeding:

Worrying symptoms suggestive of an ectopic

If a woman has a positive pregnancy test and any of the following she should be referred immediately to an early
pregnancy assessment service:

 pain and abdominal tenderness

 pelvic tenderness
 cervical motion tenderness

>= 6 weeks gestation

If the pregnancy is > 6 weeks gestation (or of uncertain gestation) and the woman has bleeding she should be
referred to an early pregnancy assessment service

< 6 weeks gestation

If the pregnancy is < 6 weeks gestation and women have bleeding, but NO pain or risk factors for ectopic
pregnancy, then they can be managed expectantly. These women should be advised:
  to return if bleeding continues or pain develops
 to repeat a urine pregnancy test after 7–10 days and to return if it is positive
 a negative pregnancy test means that the pregnancy has miscarried

Cervical cancer

Around 50% of cases of cervical cancer occur in women under the age of 45 years, with incidence rates for cervical
cancer in the UK are highest in people aged 25-29 years, according to Cancer Research UK. It may be divided into:

 squamous cell cancer (80%)

 adenocarcinoma (20%)

Features

 may be detected during routine cervical cancer screening

 abnormal vaginal bleeding: postcoital, intermenstrual or postmenopausal bleeding
 vaginal discharge

Human papillomavirus (HPV), particularly serotypes 16,18 & 33 is by far the most important factor in the
development of cervical cancer. Other risk factors include:

 smoking
 human immunodeficiency virus
 early first intercourse, many sexual partners
 high parity
  lower socioeconomic status
 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. The main aim of cervical screening is to detect pre-malignant changes rather than to detect cancer. 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
  cervical screening cannot be offered to women over 64 (unlike breast screening, where patients can self
refer once past screening age)

Special situations

 cervical screening in pregnancy is usually delayed until 3 months post-partum unless missed screening or
previous abnormal smears.
 women who have never been sexually active have very low risk of developing cervical cancer therefore they
may wish to opt-out of 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

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.
Cervical cancer screening: interpretation of results

The cervical cancer screening programme has undergone a significant evolution in recent years. For many years
the smears were examined for signs of dyskaryosis which may indicate cervical intraepithelial neoplasia -
management was based solely on the degree of dyskaryosis. The introduction of HPV testing allowed patients with
mild dyskaryosis to be further risk-stratified, i.e. as HPV is such a strong risk factor patients who were HPV negative
could be treated as having normal results.

The NHS has now moved to an HPV first system, i.e. a sample is tested for high-risk strains of human
papillomavirus (hrHPV) first and cytological examination is only performed if this is positive.

Management of results

Negative hrHPV

 return to normal recall, unless

o the test of cure (TOC) pathway: individuals who have been treated for CIN1, CIN2, or CIN3 should be
invited 6 months after treatment for a test of cure repeat cervical sample in the community
o the untreated CIN1 pathway
o follow-up for incompletely excised cervical glandular intraepithelial neoplasia (CGIN) / stratified mucin
producing intraepithelial lesion (SMILE) or cervical cancer
o follow-up for borderline changes in endocervical cells

Positive hrHPV

 samples are examined cytologically

  if the cytology is abnormal → colposcopy
o this includes the following results:
o borderline changes in squamous or endocervical cells.
o low-grade dyskaryosis.
o high-grade dyskaryosis (moderate).
o high-grade dyskaryosis (severe).
o invasive squamous cell carcinoma.
o glandular neoplasia
 if the cytology is normal (i.e. hrHPV +ve but cytologically normal) the test is repeated at 12 months
o if the repeat test is now hrHPV -ve → return to normal recall
o if the repeat test is still hrHPV +ve and cytology still normal → further repeat test 12 months later:
o If hrHPV -ve at 24 months → return to normal recall
o if hrHPV +ve at 24 months → colposcopy

If the sample is 'inadequate'

 repeat the sample within 3 months

 if two consecutive inadequate samples then → colposcopy

The follow-up of patients who've previously had CIN is complicated but as a first step, individuals who've been
treated for CIN1, CIN2, or CIN3 should be invited 6 months after treatment for a test of cure repeat cervical sample
in the community.

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

Dysmenorrhoea

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.

Features

 pain typically starts just before or within a few hours of the period starting
 suprapubic cramping pains which may radiate to the back or down the thigh
Management

 NSAIDs such as mefenamic acid and ibuprofen are effective in up to 80% of women. They work by inhibiting
prostaglandin production
 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:

 endometriosis
 adenomyosis
 pelvic inflammatory disease
 intrauterine devices*
 fibroids

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

Dyspareunia
Dyspareunia may be defined as pain during or after sexual intercourse. It is useful to classify dyspareunia according to where
the pain is felt, although there may be a degree of overlap.

Superficial dyspareunia Deep dyspareunia

Lack of sexual arousal Pelvic inflammatory disease

Vaginal atrophy (e.g. post-menopausal) Endometriosis
Vaginitis secondary to infection Cervicitis secondary to
e.g. Candida, Trichomonas infection e.g. Chlamydia
Painful episiotomy scar Prolapsed ovaries in the
Vaginismus pouch of Douglas
Adenomyosis
Fixed retroverted uterus

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*:

 obesity
 nulliparity
 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
  tamoxifen
 polycystic ovarian syndrome
 hereditary non-polyposis colorectal carcinoma

Features

 postmenopausal bleeding is the classic symptom

 premenopausal women may have a change intermenstrual bleeding
 pain and discharge are unusual features

Investigation

 women >= 55 years who present with postmenopausal bleeding should be referred using the suspected
cancer pathway
 first-line investigation is trans-vaginal ultrasound - a normal endometrial thickness (< 4 mm) has a high
negative predictive value
 hysteroscopy with endometrial biopsy

Management

 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 surgery

*the combined oral contraceptive pill and smoking are protective

Endometrial hyperplasia

Endometrial hyperplasia may be defined as an abnormal proliferation of the endometrium in excess of the normal
proliferation that occurs during the menstrual cycle. A minority of patients with endometrial hyperplasia may
develop endometrial cancer

Types

 simple
 complex
 simple atypical
 complex atypical

Features

 abnormal vaginal bleeding e.g. intermenstrual

Management

 simple endometrial hyperplasia without atypia: high dose progestogens with repeat sampling in 3-4 months.
The levonorgestrel intra-uterine system may be used
 atypia: hysterectomy is usually advised
Endometriosis

Endometriosis is a common condition characterised by the growth of ectopic endometrial tissue outside of the
uterine cavity. Around 10% of women of a reproductive age have a degree of endometriosis.

Clinical features

 chronic pelvic pain

 secondary dysmenorrhoea
o pain often starts days before bleeding
 deep dyspareunia
 subfertility
 non-gynaecological: urinary symptoms e.g. dysuria, urgency, haematuria. Dyschezia (painful bowel
movements)
 on pelvic examination reduced organ mobility, tender nodularity in the posterior vaginal fornix and visible
vaginal endometriotic lesions may be seen

Investigation

 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

Management depends on clinical features - there is poor correlation between laparoscopic findings and severity of
symptoms. NICE published guidelines in 2017:
  NSAIDs and/or paracetamol are the recommended first-line treatments for symptomatic relief
 if analgesia doesn't help then hormonal treatments such as the combined oral contraceptive pill or
progestogens e.g. medroxyprogesterone acetate should be tried

If analgesia/hormonal treatment does not improve symptoms or if fertility is a priority the patient should be
referred to secondary care. Secondary treatments include:

 GnRH analogues - said to induce a 'pseudomenopause' due to the low oestrogen levels
 drug therapy unfortunately does not seem to have a significant impact on fertility rates
 surgery: some treatments such as laparoscopic excision and laser treatment of endometriotic ovarian cysts
may improve fertility

Female genital mutilation

Female genital mutilation (FGM) refers to all procedures involving partial or total removal of the external female genitalia or
other injury to the female genital organs for non-medical reasons.

WHO FGM Classification:

Type Description

Type Partial or total removal of the clitoris and/or the prepuce

1 (clitoridectomy).

Type Partial or total removal of the clitoris and the labia minora, with
2 or without excision of the labia majora (excision).

Type Narrowing of the vaginal orifice with creation of a covering seal by

Type Description

3 cutting and appositioning the labia minora and/or the labia

majora, with or without excision of the clitoris (infibulation).

Type All other harmful procedures to the female genitalia for non-
4 medical purposes, for example: pricking, piercing, incising,
scraping and cauterization.

Source: RCOG

Fibroid degeneration

Uterine fibroids are sensitive to oestrogen and can therefore grow during pregnancy. If growth outstrips their blood supply,
they can undergo red or 'carneous' degeneration. This usually presents with low-grade fever, pain and vomiting. The
condition is usually managed conservatively with rest and analgesia and should resolve within 4-7 days.

Heavy menstrual bleeding: management

Heavy menstrual bleeding (also known as 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
woman needs contraception.

Investigations
  a full blood count should be performed in all women
 NICE recommend arranging a routine transvaginal ultrasound scan if symptoms (for example, intermenstrual
or postcoital bleeding, pelvic pain and/or pressure symptoms) suggest a structural or histological
abnormality. Other indications include abnormal pelvic exam 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 period
 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.
Flowchart showing the management of menorrhagia

Hormone replacement therapy: adverse effects

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.

Side-effects

 nausea
 breast tenderness
 fluid retention and weight gain
Potential complications

 increased risk of breast cancer

o increased by the addition of a progestogen
o in the Women's Health Initiative (WHI) study there was a relative risk of 1.26 at 5 years of developing
breast cancer
o the increased risk relates to the duration of use
o 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 HRT
 increased risk of endometrial cancer
o oestrogen by itself should not be given as HRT to women with a womb
o reduced by the addition of a progestogen but not eliminated completely
o the BNF states that the additional risk is eliminated if a progestogen is given continuously
 increased risk of venous thromboembolism
o increased by the addition of a progestogen
o transdermal HRT does not appear to increase the risk of VTE
o NICE state women requesting HRT who are at high risk for VTE should be referred to
haematology before starting any treatment (even transdermal)
 increased risk of stroke
 increased risk of ischaemic heart disease if taken more than 10 years after menopause

Hyperemesis gravidarum

Whilst the majority of women experience nausea (previously termed 'morning sickness') during the early stages of
pregnancy it can become problematic in a minority of cases. The Royal College of Obstetricians and Gynaecologists
(RCOG) now use the term 'nausea and vomiting of pregnancy' (NVP) to describe troublesome symptoms, with
hyperemesis gravidarum being the extreme form of this condition.
It occurs in around 1% of pregnancies and is thought to be related to raised beta hCG levels. Hyperemesis
gravidarum is most common between 8 and 12 weeks but may persist up to 20 weeks*.

Associations

 multiple pregnancies
 trophoblastic disease
 hyperthyroidism
 nulliparity
 obesity

Smoking is associated with a decreased incidence of hyperemesis.

Referral criteria for nausea and vomiting in pregnancy

NICE Clinical Knowledges Summaries recommend considering admission in the following situations:

 Continued nausea and vomiting and is unable to keep down liquids or oral antiemetics
 Continued nausea and vomiting with ketonuria and/or weight loss (greater than 5% of body weight), despite
treatment with oral antiemetics
 A confirmed or suspected comorbidity (for example she is unable to tolerate oral antibiotics for a urinary
tract infection)

They also recommend having a lower threshold for admitting to hospital if the woman has a co-existing condition
(for example diabetes) that may be adversely affected by nausea and vomiting.
Hyperemesis gravidarum

The Royal College of Obstetricians and Gynaecologists (RCOG) recommend that the following triad is present
before diagnosis hyperemesis gravidarum:

 5% pre-pregnancy weight loss

 dehydration
 electrolyte imbalance

Validated scoring systems such as the Pregnancy-Unique Quantification of Emesis (PUQE) score can be used to
classify the severity of NVP.

Management

 antihistamines should be used first-line

o oral cyclizine or oral promethazine is recommended by Clinical Knowledge Summaries (CKS)
o oral prochlorperazine is an alternative
 ondansetron and metoclopramide may be used second-line
o metoclopramide may cause extrapyramidal side effects. It should therefore not be used for more than
5 days
o ondansetron during the first trimester is associated with a small increased risk of the baby having
a cleft lip/palate. The Medicines and Healthcare products Regulatory Agency (MHRA) advise that if
ondanestron is used then these risks should be discussed with the pregnant woman
 ginger and P6 (wrist) acupressure: CKS suggest these can be tried but there is little evidence of benefit
 admission may be needed for IV hydration
Complications

 Wernicke's encephalopathy
 Mallory-Weiss tear
 central pontine myelinolysis
 acute tubular necrosis
 fetal: small for gestational age, pre-term birth

*and in very rare cases beyond 20 weeks

Infertility: initial investigations

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

Causes

 male factor 30%

 unexplained 20%
 ovulation failure 20%
 tubal damage 15%
 other causes 15%

Basic investigations
  semen analysis
 serum progesterone 7 days prior to expected next period. For a typical 28 day cycle, this is done on day 21.

Interpretation of serum progestogen

Level Interpretation
< 16 nmol/l Repeat, if consistently low refer to specialist
16 - 30 nmol/l Repeat
> 30 nmol/l Indicates ovulation

Key counselling points

 folic acid
 aim for BMI 20-25
 advise regular sexual intercourse every 2 to 3 days
 smoking/drinking advice

Menopause

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

It is recommended to use effective contraception until the following time:

  12 months after the last period in women > 50 years
 24 months after the last period in women < 50 years

Menopause: management

Menopause is defined as the permanent cessation of menstruation. It is caused by the loss of follicular activity.
Menopause is a clinical diagnosis usually made in primary care when a woman has not had a period for 12 months.

Menopausal symptoms are very common and affect roughly 75% of postmenopausal women. Symptoms typically
last for 7 years but may resolve quicker and in some cases take much longer. The duration and severity are also
variable and may develop before the start of the menopause and in some cases may start years after the onset of
menopause.

The CKS has very thorough and clear guidance on the management of menopause and is summarised below.

The management of menopause can be split into three categories:

 Lifestyle modifications
 Hormone replacement therapy (HRT)
 Non-hormone replacement therapy

Management with lifestyle modifications

Hot flushes
  regular exercise, weight loss and reduce stress

Sleep disturbance

 avoiding late evening exercise and maintaining good sleep hygiene

Mood

 sleep, regular exercise and relaxation

Cognitive symptoms

 regular exercise and good sleep hygiene

Management with HRT

Contraindications:

 Current or past breast cancer

 Any oestrogen-sensitive cancer
 Undiagnosed vaginal bleeding
  Untreated endometrial hyperplasia

Roughly 10% of women will have some form of HRT to treat their menopausal symptoms. There is a current drive
by NICE to increase this number as they have found that women were previously being undertreated due to
worries about increased cancer risk. If the woman has a uterus then it is important not to give unopposed
oestrogens as this will increase her risk of endometrial cancer. Therefore oral or transdermal combined HRT is
given.

If the woman does not have a uterus then oestrogen alone can be given either orally or in a transdermal patch.

Women should be advised that the symptoms of menopause typically last for 2-5 years and that treatment with
HRT brings certain risks:

 Venous thromboembolism: a slight increase in risk with all forms of oral HRT. No increased risk with
transdermal HRT.
 Stroke: slightly increased risk with oral oestrogen HRT.
 Coronary heart disease: combined HRT may be associated with a slight increase in risk.
 Breast cancer: there is an increased risk with all combined HRT although the risk of dying from breast cancer
is not raised.
 Ovarian cancer: increased risk with all HRT.

Management with non-HRT

Vasomotor symptoms

 fluoxetine, citalopram or venlafaxine

Vaginal dryness

 vaginal lubricant or moisturiser

Psychological symptoms

 self-help groups, cognitive behaviour therapy or antidepressants

Urogenital symptoms

 if suffering from urogenital atrophy vaginal oestrogen can be prescribed. This is appropriate if they are taking
HRT or not
 vaginal dryness can be treated with moisturisers and lubricants. These can be offered alongside vaginal
oestrogens if required.

Stopping treatment

For vasomotor symptoms, 2-5 years of HRT may be required with regular attempts made to discontinue treatment.
Vaginal oestrogen may be required long term. When stopping HRT it is important to tell women that gradually
reducing HRT is effective at limiting recurrence only in the short term. In the long term, there is no difference in
symptom control.
Although menopausal symptoms can be managed mainly in primary care, there are some instances when a woman
should be referred to secondary care. She should be referred to secondary care if treatment has been ineffective, if
there are ongoing side effects or if there is unexplained bleeding.

Menopause: symptoms

The symptoms seen in the climacteric period are caused by reduced levels of female hormones, principally
oestrogen

Change in periods

 change in length of menstrual cycles

 dysfunctional uterine bleeding may occur

Vasomotor symptoms - affects around 80% of women. Usually occur daily and may continue for up to 5 years

 hot flushes
 night sweats

Urogenital changes - affects around 35% of women

 vaginal dryness and atrophy

 urinary frequency
Psychological

 anxiety and depression may be seen - around 10% of women

 short-term memory impairment

Longer term complications

 osteoporosis
 increased risk of ischaemic heart disease

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.

Causes

 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
 hypothyroidism
 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

Menstrual cycle

The menstrual cycle may be divided into the following phases:

Days

Menstruation 1-4

Follicular phase (proliferative phase) 5-13

Ovulation 14

Luteal phase (secretory phase) 15-28

 Image sourced from Wikipedia

Further details are given in the table below

Follicular phase (proliferative Luteal phase (secretory

phase) phase)

Ovarian A number of follicles develop. Corpus luteum

histology
One follicle will become
dominant around the mid-
follicular phase

Endometrial Proliferation of endometrium Endometrium changes to

histology secretory lining under
influence of
progesterone

Hormones A rise in FSH results in the Progesterone secreted

development of follicles which by corpus luteum rises
in turn secrete oestradiol through the luteal phase.

When the egg has matured, it If fertilisation does not

secretes enough oestradiol to occur the corpus luteum
trigger the acute release of LH. will degenerate and
This in turn leads to ovulation progesterone levels fall

Oestradiol levels also rise

again during the luteal
phase
 Follicular phase (proliferative Luteal phase (secretory
phase) phase)

Cervical Following menstruation the Under the influence of

mucus mucus is thick and forms a progesterone it becomes
plug across the external os thick, scant, and tacky

Just prior to ovulation the

mucus becomes clear,
acellular, low viscosity. It also
becomes 'stretchy' - a quality
termed spinnbarkeit

Basal body Falls prior to ovulation due to Rises following ovulation

temperature the influence of oestradiol in response to higher
progesterone levels

Miscarriage

Threatened miscarriage

 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

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.

Pathophysiology
  around 90% of ovarian cancers are epithelial in origin, with 70-80% of cases being due to serous carcinomas
 interestingly, it is now increasingly recognised that the distal end of the fallopian tube is often the site of
origin of many 'ovarian' cancers

Risk factors

 family history: mutations of the BRCA1 or the BRCA2 gene

 many ovulations*: early menarche, late menopause, nulliparity

Clinical features are notoriously vague

 abdominal distension and bloating

 abdominal and pelvic pain
 urinary symptoms e.g. Urgency
 early satiety
 diarrhoea

Investigations

 CA125
o NICE recommends a CA125 test is done initially. Endometriosis, menstruation, benign ovarian cysts
and other conditions may also raise the CA125 level
o if the CA125 is raised (35 IU/mL or greater) then an urgent ultrasound scan of the abdomen and pelvis
should be ordered
o a CA125 should not be used for screening for ovarian cancer in asymptomatic women
 ultrasound
Diagnosis is difficult and usually involves diagnostic laparotomy

Management

 usually a combination of surgery and platinum-based chemotherapy

Prognosis

 80% of women have advanced disease at presentation

 the all stage 5-year survival is 46%

*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 pregnancies.

Ovarian cysts: types

Benign ovarian cysts are extremely common. They may be divided into physiological cysts, benign germ cell
tumours, benign epithelial tumours and benign sex cord stromal tumours.

Complex (i.e. multi-loculated) ovarian cysts should be biopsied to exclude malignancy.

Physiological cysts (functional cysts)

Follicular cysts

 commonest type of ovarian cyst

 due to non-rupture of the dominant follicle or failure of atresia in a non-dominant follicle
 commonly regress after several menstrual cycles

Corpus luteum cyst

 during the menstrual cycle if pregnancy doesn't occur the corpus luteum usually breaks down and
disappears. If this doesn't occur the corpus luteum may fill with blood or fluid and form a corpus luteal cyst
 more likely to present with intraperitoneal bleeding than follicular cysts

Benign germ cell tumours

Dermoid cyst

 also called mature cystic teratomas. Usually lined with epithelial tissue and hence may contain skin
appendages, hair and teeth
 most common benign ovarian tumour in woman under the age of 30 years
 median age of diagnosis is 30 years old
 bilateral in 10-20%
 usually asymptomatic. Torsion is more likely than with other ovarian tumours
Benign epithelial tumours

Arise from the ovarian surface epithelium

Serous cystadenoma

 the most common benign epithelial tumour which bears a resemblance to the most common type of ovarian
cancer (serous carcinoma)
 bilateral in around 20%

Mucinous cystadenoma

 second most common benign epithelial tumour

 they are typically large and may become massive
 if ruptures may cause pseudomyxoma peritonei

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 torsion

Ovarian torsion may be defined as the partial or complete torsion of the ovary on it's supporting ligaments that
may in turn compromise the blood supply. If the fallopian tube is also involved then it is referred to as adnexal
torsion.

Risk factors

 ovarian mass: present in around 90% of cases of torsion

 being of a reproductive age
  pregnancy
 ovarian hyperstimulation syndrome

Features

 Usually the sudden onset of deep-seated colicky abdominal pain.

 Associated with vomiting and distress
 fever may be seen in a minority (possibly secondary to adnexal necrosis)
 Vaginal examination may reveal adnexial tenderness

Ultrasound may show free fluid or a whirlpool sign.

Laparoscopy is usually both diagnostic and therapeutic.

Ovulation induction

Ovulation disorders are the cause of infertility in approximately one-quarter of couples who have difficulty
conceiving naturally, and whilst ovulation may occur sometimes, natural spontaneous conception is usually
unlikely. Therefore, for these couples, ovulation induction is often required and will typically depend on the cause
of anovulation in the first place.

Normal ovulation requires the close functioning of a number of positive and negative feedback loops between the
hypothalamus, pituitary gland and ovaries.

 The early follicular phase requires an increase in gonadotropin-releasing hormone (GnRH) pulse frequency
which increases the release of follicle-stimulating hormone (FSH) and luteinising hormone (LH), to allow for
 stimulation and development of multiple ovarian follicles, and usually only one of which will become the
dominant ovulatory follicle in that menstrual cycle.
 In the mid-follicular phase, FSH gradually stimulates estradiol production, following which estradiol itself
produces a negative feedback loop on the hypothalamus and pituitary gland to suppress FSH and LH
concentrations.
 In the luteal phase, there is a unique switch from negative to positive feedback of estradiol, resulting in a
surge of LH secretion and this leads to subsequent follicular rupture and ovulation.

It is the unique balance of hormones and their feedback loops which leads to normal ovulation with each menstrual
cycle, however with each class of ovulatory dysfunction, there is an alteration in this fine balance which may lead
to irregular or complete anovulation.

Categories of ovulatory disorders

 Before understanding the process of ovulation induction, it is paramount to understand the main causes of
ovulatory dysfunction first
 There are three main categories of anovulation:
o Class 1 (hypogonadotropic hypogonadal anovulation) - notably hypothalamic amenorrhoea (5-10% of
women)
o Class 2 (normogonadotropic normoestrogenic anovulation) - polycystic ovary syndrome (80% of cases)
o Class 3 (hypergonadotropic hypoestrogenic anovulation) - premature ovarian insufficiency (5-10% of
cases). In this class, any attempts at ovulation induction are typically unsuccessful and therefore
usually require in-vitro fertilisation (IVF) with donor oocytes to conceive

Goals of ovulation induction

 It is ideal to start with the least invasive and simplest management option first, and work the way up to more
complicated and intensive treatment
  For most women, it is the goal to induce mono-follicular development and subsequent ovulation as opposed
to multi-follicular development, and this is to ultimately lead to a singleton pregnancy, which tends to be far
lower risk and therefore preferable

Forms of ovulation induction

 Exercise and weight loss

o Typically this is the first-line treatment for patients with polycystic ovarian syndrome, as ovulation can
spontaneously return with even a modest 5% weight loss
o Therefore, particularly for overweight or obese women with polycystic ovarian syndrome, this should
be trialled solely first, and then artificial ovulation induction be considered

 Letrozole
o According to UptoDate, this is now considered the first-line medical therapy for patients with PCOS, due
to the reduced risk of adverse effects on endometrial and cervical mucous compared to clomiphene
citrate
o Mechanism of action: letrozole is an aromatase inhibitor, reducing the negative feedback caused by
estrogens to the pituitary gland, therefore increasing the amount of follicle-stimulating hormone (FSH)
production and promoting follicular development
o The rate of mono-follicular development is much higher with letrozole use compared to clomiphene,
which is a key goal in ovulation induction
o Side effects: fatigue (20%), dizziness (10%)

 Clomiphene citrate
 o While most women with PCOS will respond to clomiphene treatment and ovulate (80% of women), the
rates of live birth are higher with letrozole therapy, hence why it has become a first-line treatment
instead
o Mechanism of action: clomiphene is a selective estrogen receptor modulator (also known as SERMs),
which acts primarily at the hypothalamus, blocking the negative feedback effect of estrogens. This
subsequently leads to an increase in gonadotropin-releasing hormone (GnRH) pulse frequency and
therefore FSH and LH production, stimulating ovarian follicular development
o Side effects: hot flushes (30%), abdominal distention and pain (5%), nausea and vomiting (2%)

 Gonadotropin therapy
o This tends to be the treatment used mostly for women with class 1 ovulatory dysfunction, notably
women with hypogonadotropic hypogonadism
o For women with PCOS, this tends to be only considered after attempt with other treatments has been
unsuccessful, usually after weight loss, letrozole and clomiphene trial
o This is because the risk of multi-follicular development and subsequent multiple pregnancy is much
higher, as well as increased risk of ovarian hyperstimulation syndrome
o Mechanism of action: pulsatile GnRH therapy involves administration of GnRH via an intravenous (or
less frequently, subcutaneous) infusion pump, leading to endogenous production of FSH and LH and
subsequent follicular development

Ovarian hyperstimulation syndrome

 Ovarian hyperstimulation syndrome (OHSS) is one of the potential side effects of ovulation induction, and
unfortunately can be life-threatening if not identified and managed promptly
 In OHSS, ovarian enlargement with multiple cystic spaces form, and an increase in the permeability of
capillaries leads to a fluid shift from the intravascular to the extra-vascular space, which has the potential to
result in multiple life-threatening complications including:
 o Hypovolaemic shock
o Acute renal failure
o Venous or arterial thromboembolism
 This is a rare side effect which varies in severity, with the risk of severe OHSS occurring in less than 1% of all
women undergoing ovarian induction
 Depending on the severity, the management includes:
o Fluid and electrolyte replacement
o Anti-coagulation therapy
o Abdominal ascitic paracentesis
o Pregnancy termination to prevent further hormonal imbalances

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.

Causative organisms

 Chlamydia trachomatis

+ the most common cause

 Neisseria gonorrhoeae
 Mycoplasma genitalium
 Mycoplasma hominis
Features

 lower abdominal pain

 fever
 deep dyspareunia
 dysuria and menstrual irregularities may occur
 vaginal or cervical discharge
 cervical excitation

Investigation

 a pregnancy test should be done to exclude an ectopic pregnancy

 high vaginal swab
o these are often negative
 screen for Chlamydia and Gonorrhoea

Management

 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'
Complications

 perihepatitis (Fitz-Hugh Curtis Syndrome)

o occurs in around 10% of cases
o it is characterised by right upper quadrant pain and may be confused with cholecystitis
 infertility - the risk may be as high as 10-20% after a single episode
 chronic pelvic pain
 ectopic pregnancy

Pelvic pain

In women the most common cause of pelvic pain is primary dysmenorrhoea. Some women also experience transient pain in
the middle of their cycle secondary to ovulation (mittelschmerz). The table below gives characteristic features for other
conditions causing pelvic pain:

Usually acute

Condition Notes

Ectopic A typical history is a female with a history of 6-8

pregnancy weeks amenorrhoea who presents with lower
abdominal pain and later develops vaginal bleeding
Shoulder tip pain and cervical excitation may be seen

Urinary tract Dysuria and frequency are common but women may
 Condition Notes

infection experience suprapubic burning secondary to cystitis

Appendicitis Pain initial in the central abdomen before localising

to the right iliac fossa
Anorexia is common
Tachycardia, low-grade pyrexia, tenderness in RIF
Rovsing's sign: more pain in RIF than LIF when
palpating LIF

Pelvic Pelvic pain, fever, deep dyspareunia, vaginal

inflammatory discharge, dysuria and menstrual irregularities may
disease occur
Cervical excitation may be found on examination

Ovarian torsion Usually sudden onset unilateral lower abdominal

pain. Onset may coincide with exercise.
Nausea and vomiting are common
Unilateral, tender adnexal mass on examination

Miscarriage Vaginal bleeding and crampy lower abdominal pain

following a period of amenorrhoea

Usually chronic

Condition Notes

Endometriosis Chronic pelvic pain

 Condition Notes

Dysmenorrhoea - pain often starts days before

bleeding
Deep dyspareunia
Subfertility

Irritable bowel Extremely common. The most consistent features are

syndrome abdominal pain, bloating and change in bowel habit
Features such as lethargy, nausea, backache and
bladder symptoms may also be present

Ovarian cyst Unilateral dull ache which may be intermittent or

only occur during intercourse. Torsion or rupture
may lead to severe abdominal pain
Large cysts may cause abdominal swelling or
pressure effects on the bladder

Urogenital Seen in older women

prolapse Sensation of pressure, heaviness, 'bearing-down'
Urinary symptoms: incontinence, frequency, urgency

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.

Features
  subfertility and infertility
 menstrual disturbances: oligomenorrhea and amenorrhoea
 hirsutism, acne (due to hyperandrogenism)
 obesity
 acanthosis nigricans (due to insulin resistance)

Investigations

 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

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.

General

 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 below)
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 supervision

Infertility

 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 ovulation
 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
 gonadotrophins

*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

Premature ovarian insufficiency

Premature ovarian insufficiency 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.

Causes of premature menopause include:

 idiopathic
o the most common cause
o there may be a family history
 bilateral oophorectomy
o having a hysterectomy with preservation of the ovaries has also been shown to advance the age of
menopause
 radiotherapy
 chemotherapy
 infection: e.g. mumps
 autoimmune disorders
 resistant ovary syndrome: due to FSH receptor abnormalities

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

 climacteric symptoms: hot flushes, night sweats

 infertility
 secondary amenorrhoea
 raised FSH, LH levels
o e.g. FSH > 40 iu/l
o elevated FSH levels should be demonstrated on 2 blood samples taken 4–6 weeks apart
 low oestradiol
o e.g. < 100 pmol/l
Management

 hormone replacement therapy (HRT) or a combined oral contraceptive pill should be offered to women until
the age of the average menopause (51 years)
o it should be noted that HRT does not provide contraception, in case spontaneous ovarian activity
resumes

Premenstrual syndrome

Premenstrual syndrome (PMS) describes the emotional and physical symptoms that women may experience in the
luteal phase of the normal menstrual cycle.

PMS only occurs in the presence of ovulatory menstrual cycles - it doesn't occur prior to puberty, during pregnancy
or after the menopause.

Emotional symptoms include:

 anxiety
 stress
 fatigue
 mood swings

Physical symptoms
  bloating
 breast pain

Management

Options depend on the severity of symptoms

 mild symptoms can be managed with lifestyle advice

o apart from the usual advice on sleep, exercise, smoking and alcohol, specific advice includes regular,
frequent (2–3 hourly), small, balanced meals rich in complex carbohydrates
 moderate symptoms may benefit from a new-generation combined oral contraceptive pill (COCP)
o examples include Yasmin® (drospirenone 3 mg and ethinylestradiol 0.030 mg)
 severe symptoms may benefit from a selective serotonin reuptake inhibitor (SSRI)
o this may be taken continuously or just during the luteal phase (for example days 15–28 of the
menstrual cycle, depending on its length)

Pruritus vulvae

Vaginal itching is common. It is estimated that 1 in 10 women will seek help at some point.

In contrast to pruritus ani, pruritus vulvae usually has an underlying cause:

 irritant contact dermatitis (e.g. latex condoms, lubricants): most common cause
 atopic dermatitis
  seborrhoeic dermatitis
 lichen planus
 lichen sclerosus
 psoriasis: seen in around a third of patients with psoriasis

Management

 women who suffer from this should be advised to take showers rather than taking baths
 they should also be advised to clean the vulval area with an emollient such as Epaderm or Diprobase
 clean only once a day as repeated cleaning can aggravate the symptoms
 most of the underlying conditions will respond to topical steroids
 combined steroid-antifungal may be tried if seborrhoeic dermatitis is suspected

Recurrent miscarriage

Recurrent miscarriage is defined as 3 or more consecutive spontaneous abortions. It occurs in around 1% of

women

Causes

 antiphospholipid syndrome
 endocrine disorders: poorly controlled diabetes mellitus/thyroid disorders. Polycystic ovarian syndrome
 uterine abnormality: e.g. uterine septum
 parental chromosomal abnormalities
 smoking
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 values

Termination of pregnancy

The current law surround abortion is based on the 1967 Abortion Act. In 1990 the act was amended, reducing the
upper limit from 28 weeks gestation to 24 weeks*

Key points

 two registered medical practitioners must sign a legal document (in an emergency only one is needed)
  only a registered medical practitioner can perform an abortion, which must be in a NHS hospital or licensed
premise

The method used to terminate pregnancy depend upon gestation

 less than 9 weeks: mifepristone (an anti-progestogen, often referred to as RU486) followed 48 hours later by
prostaglandins to stimulate uterine contractions
 less than 13 weeks: surgical dilation and suction of uterine contents
 more than 15 weeks: surgical dilation and evacuation of uterine contents or late medical abortion (induces
'mini-labour')

1967 Abortion Act

Subject to the provisions of this section, a person shall not be guilty of an offence under the law relating to
abortion when a pregnancy is terminated by a registered medical practitioner if two registered medical
practitioners are of the opinion, formed in good faith

 that the pregnancy has not exceeded its 24th week and that the continuance of the pregnancy would involve
risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the
pregnant woman or any existing children of her family; or
 that the termination is necessary to prevent grave permanent injury to the physical or mental health of the
pregnant woman; or
 that the continuance of the pregnancy would involve risk to the life of the pregnant woman, greater than if
the pregnancy were terminated; or
  that there is a substantial risk that if the child were born it would suffer from such physical or mental
abnormalities as to be seriously handicapped.

*these limits do not apply in cases where it is necessary to save the life of the woman, there is evidence of
extreme fetal abnormality, or there is risk of serious physical or mental injury to the woman.

Urinary incontinence

Urinary incontinence (UI) is a common problem, affecting around 4-5% of the population. It is more common in
elderly females.

Risk factors

 advancing age
 previous pregnancy and childbirth
 high body mass index
 hysterectomy
 family history

Classification

 overactive bladder (OAB)/urge incontinence

o due to detrusor overactivity
o the urge to urinate is quickly followed by uncontrollable leakage ranging from a few drops to complete
bladder emptying
  stress incontinence: leaking small amounts when coughing or laughing
 mixed incontinence: both urge and stress
 overflow incontinence: due to bladder outlet obstruction, e.g. due to prostate enlargement
 functional incontinence
o comorbid physical conditions impair the patient’s ability to get to a bathroom in time
o causes include dementia, sedating medication and injury/illness resulting in decreased ambulation

Initial investigation

 bladder diaries should be completed for a minimum of 3 days

 vaginal examination to exclude pelvic organ prolapse and ability to initiate voluntary contraction of pelvic
floor muscles ('Kegel' exercises)
 urine dipstick and culture
 urodynamic studies

Management depends on whether urge or stress UI is the predominant picture. If urge incontinence is
predominant:

 bladder retraining (lasts for a minimum of 6 weeks, the idea is to gradually increase the intervals between
voiding)
 bladder stabilising drugs: antimuscarinics are first-line
o NICE recommend oxybutynin (immediate release), tolterodine (immediate release) or darifenacin (once
daily preparation)
o Immediate release oxybutynin should, however, be avoided in 'frail older women'
 mirabegron (a beta-3 agonist) may be useful if there is concern about anticholinergic side-effects in frail
elderly patients
If stress incontinence is predominant:

 pelvic floor muscle training

o NICE recommend at least 8 contractions performed 3 times per day for a minimum of 3 months
 surgical procedures: e.g. retropubic mid-urethral tape procedures
 duloxetine may be offered to women if they decline surgical procedures
o a combined noradrenaline and serotonin reuptake inhibitor
o mechanism of action: increased synaptic concentration of noradrenaline and serotonin within the
pudendal nerve → increased stimulation of urethral striated muscles within the sphincter → enhanced

contraction

Uterine fibroids

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

Associations

 more common in Afro-Caribbean women

 rare before puberty, develop in response to oestrogen

Features

 may be asymptomatic
  menorrhagia
o may result in iron-deficiency anaemia
 lower abdominal pain: cramping pains, often during menstruation
 bloating
 urinary symptoms, e.g. frequency, may occur with larger fibroids
 subfertility
 rare features:
o polycythaemia secondary to autonomous production of erythropoietin

Diagnosis

 transvaginal ultrasound

Management

Asymptomatic fibroids

 no treatment is needed other than periodic review to monitor size and growth

Management of menorrhagia secondary to fibroids

 levonorgestrel intrauterine system (LNG-IUS)

o useful if the woman also requires contraception
o cannot be used if there is distortion of the uterine cavity
  NSAIDs e.g. mefenamic acid
 tranexamic acid
 combined oral contraceptive pill
 oral progestogen
 injectable progestogen

Treatment to shrink/remove fibroids

 medical
o GnRH agonists may reduce the size of the fibroid but are typically useful for short-term treatment
o ulipristal acetate has been in the past but not currently due to concerns about rare but serious liver
toxicity
 surgical
o myomectomy: this may be performed abdominally, laparoscopically or hysteroscopically
o hysteroscopic endometrial ablation
o hysterectomy
 uterine artery embolization

Prognosis and complications

Fibroids generally regress after the menopause.

Some of the complications such as subfertility and iron-deficiency anaemia have been mentioned previously.

Other complications
  red degeneration - haemorrhage into tumour - commonly occurs during pregnancy

Vaginal candidiasis

Vaginal candidiasis ('thrush') is an extremely common condition which many women diagnose and treat
themselves. Around 80% of cases of Candida albicans, with the remaining 20% being caused by other candida
species.

The majority of women will have no predisposing factors. However, certain factors may make vaginal candidiasis
more likely to develop:

 diabetes mellitus
 drugs: antibiotics, steroids
 pregnancy
 immunosuppression: HIV

Features

 'cottage cheese', non-offensive discharge

 vulvitis: superficial dyspareunia, dysuria
 itch
 vulval erythema, fissuring, satellite lesions may be seen

Investigations
  a high vaginal swab is not routinely indicated if the clinical features are consistent with candidiasis

Management

 options include local or oral treatment

 local treatments include clotrimazole pessary (e.g. clotrimazole 500mg PV stat)
 oral treatments include itraconazole 200mg PO bd for 1 day or fluconazole 150mg PO stat
 if pregnant then only local treatments (e.g. cream or pessaries) may be used - oral treatments are
contraindicated

Recurrent vaginal candidiasis

 BASHH define recurrent vaginal candidiasis as 4 or more episodes per year

 compliance with previous treatment should be checked
 confirm the diagnosis of candidiasis
o high vaginal swab for microscopy and culture
o consider a blood glucose test to exclude diabetes
 exclude differential diagnoses such as lichen sclerosus
 consider the use of an induction-maintenance regime
o induction: oral fluconazole every 3 days for 3 doses
o maintenance: oral fluconazole weekly for 6 months
Vaginal discharge

Vaginal discharge is a common presenting symptom and is not always pathological

Common causes

 physiological
  Candida
 Trichomonas vaginalis
 bacterial vaginosis

Less common causes

 Gonorrhoea
 Chlamydia can cause a vaginal discharge although this is rarely the presenting symptoms
 ectropion
 foreign body
 cervical cancer

Key features of the common causes are listed below

Condition Key features

Candida 'Cottage cheese' discharge
Vulvitis
Itch
Trichomonas Offensive, yellow/green, frothy discharge
vaginalis Vulvovaginitis
Strawberry cervix
Bacterial vaginosis Offensive, thin, white/grey, 'fishy'
discharge

Vulval carcinoma
Around 80% of vulval cancers are squamous cell carcinomas. Most cases occur in women over the age of 65 years.
Vulval cancer is relatively rare with only around 1,200 cases diagnosed in the UK each year.

Other than age, risk factors include:

 Human papilloma virus (HPV) infection

 Vulval intraepithelial neoplasia (VIN)
 Immunosuppression
 Lichen sclerosus

Features

 lump or ulcer on the labia majora

 inguinal lymphadenopathy
 may be associated with itching, irritation

Vulval intraepithelial neoplasia

Vulval intraepithelial neoplasia (VIN) is a pre-cancerous skin lesion of the vulva, and may result in squamous skin
cancer if untreated. The average of an affected women is around 50 years

Risk factors

 human papilloma virus 16 & 18

 smoking
  herpes simplex virus 2
 lichen planus

Features

 itching, burning
 raised, well defined skin lesions