InnovAiT, 11(2), 80–88

Amenorrhoea
Holly Vickers
Speciality Trainee 3 in Obstetrics & Gynaecology, Sheffield Teaching Hospitals NHS Foundation Trust

Thomas Gray
Subspeciality Trainee in Urogynaecology, Sheffield Teaching Hospitals NHS Foundation Trust
Email: Thomas.Gray@sth.nhs.uk Twitter Handle: @Thomasgray007

Dr Swati Jha
Consultant Gynaecologist and subspecialist in urogynaecology, Sheffield Teaching Hospitals NHS Foundation Trust

A menorrhoea is the absence of menstruation in a female patient of reproductive age.

Patients with amenorrhoea may be concerned about puberty and fertility depending on
the age of presentation. It is important for clinicians to consider the underlying causes and
appropriately assess, investigate and counsel each patient. Approximately 0.3% of females
experience primary amenorrhoea, and 3–4% of females at reproductive age experience
secondary amenorrhoea. This article aims to outline the differential diagnoses for both
primary and secondary amenorrhoea and to consider investigation and management in
primary care, including indications for referral to secondary care.

The GP curriculum and amenorrhoea

Clinical module 3.06: Women’s health lists the learning objectives relevant to the assessment, investigation and management
of amenorrhoea in primary care. This requires GPs to:
. Recognise common signs and symptoms of, and know how to manage, gynaecological disease; be the first port of call for
pregnancy, eating disorders and other conditions confined to or more common in women, involving other members of the
healthcare team as appropriate
. Demonstrate knowledge of women’s health problems, conditions and diseases, and recognise that some non-gender
specific issues present differently in women, such as depression, alcoholism, eating disorders and domestic violence
. Provide information to patients on possible local support services, referral services, networks and groups for women (e.g.
family planning, breast cancer nurses, domestic violence resources)
. Be familiar with and implement the key national guidelines that influence healthcare provision for women’s problems
In addition, components of the following curriculum statements are pertinent to the assessment of amenorrhoea:
Clinical module 3.17: Care of people with metabolic problems require GPs to be familiar with:
. The clinical presentation of thyroid disease, pituitary disease (e.g. prolactinoma) and adrenal disease (e.g. Cushing’s syndrome)
Clinical module 3.04: Care of children and young people requires GPs to have:
. An understanding of normal growth and development of children and young people and be able to recognise delayed
development through childhood and adolescence
Clinical module 3.02: Genetics in primary care requires GPs to have:
. Knowledge of common chromosome anomalies

80 InnovAiT, 2018, Vol. 11(2), 80–88, ! The Author(s) 2018.

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InnovAiT

Definitions and normality Figure 1. The HPO axis.

Primary amenorrhoea is the absence of menstruation by age 16 years
in the presence of secondary sexual characteristics, or absent men-
struation and absent secondary sexual characteristics by 13 years of
age. Secondary amenorrhoea is the cessation of menstruation for 6
months in a patient with previously normal menstrual cycles.

Hypothalamic–pituitary–ovary axis and

normal menstruation
The hypothalamic–pituitary–ovary (HPO) axis controls normal men-
struation. Menarche (the commencement of menstrual periods) occurs
when gonadotrophin-releasing hormone (GnRH) is released by the
hypothalamus. This travels along the hypothalamo–hypophyseal
portal tract and stimulates release of gonadotrophins (follicle-stimulat-
ing hormone (FSH) and luteinizing hormone (LH)), from the anterior
lobe of the pituitary gland. Rising concentrations of gonadotrophins
act on the ovary causing ovarian follicles to mature. A surge in LH
causes further maturation and initiates the release of a dominant fol- Reproduced from BMJ, Hamilton Fairley, D., & Taylor, A. 327 doi:
licle from the outer surface of the ovarian cortex (ovulation). The 10.1136/bmj.327.7414.546, 2003 with permission from BMJ Publishing
empty follicle fills with blood and its wall luteinises to form the Group Ltd.
corpus luteum, which secretes oestradiol and progesterone.
Oestradiol has a paracrine effect on the new proliferative layer of
the endometrium within the uterus, causing rapid growth. Without Primary amenorrhoea
implantation and release of human chorionic gonadotrophin the
corpus luteum degenerates and progesterone levels fall. Hypogonadotrophic hypogonadism as a
Menstruation subsequently occurs with the superficial layer of the cause of primary amenorrhoea
endometrium being shed and passed out of the genital tract through
Increasing numbers of women in the UK are suffering from eating
the vagina.
disorders (Adult Psychiatric Morbidity Survey, 2007). Evidence sug-
A normal menstrual cycle requires interaction between the hypo-
gests that the onset of puberty is linked to body mass index (BMI)
thalamus, pituitary gland, ovaries and uterus (Fig. 1). An interruption
and body fat. Leptin and kisspeptin from adipocytes act as a primary
to this interaction may lead to disordered menses and can cause
signal to allow puberty to commence (Roa et al., 2010). A very-low
amenorrhoea.
value of the BMI can cause failure to initiate GnRH secretion from the
hypothalamus leading to hypogonadotrophic hypogonadism, result-
Secondary sexual characteristics ing in primary amenorrhoea. Primary amenorrhoea caused by weight
Pubertal development in girls usually commences between 8.5 and loss or low BMI is usually only associated with a 10–15% reduction in
13.5 years of age, with an average age of 12 years 9 months. Normal body weight or a BMI of less than 19 kg/m2.
adolescent development in females involves breast development (the- Constitutional delay is the most common cause of primary amen-
larche) followed by a period of rapid growth of long bones, develop- orrhoea. There is a delay in global pubertal development that is not
ment of pubic hair (pubarche) and finally the commencement of appropriate for age. Often there will be a family history of this prob-
menstruation (menarche). Breast and pubic hair development are lem, with mothers, aunts and sisters similarly affected. Each case must
known as secondary sexual characteristics. Tanner staging (Fig. 2) be investigated thoroughly, as constitutional delay is a diagnosis of
defines the stages of pubertal development. exclusion, even in the presence of a positive family history. Over time
It is important to understand the normal development of secondary females affected by constitutional delay will begin normal develop-
sexual characteristics and to be able to identify when these character- ment and spontaneously menstruate (Palmert & Dunkel, 2012). The
istics are absent. This can be a useful determining differential diag- prevalence of constitutional delay is unknown, as many patients
noses and their classifications (Table 1). affected by it do not present to a healthcare provider.

Ovarian causes of primary amenorrhoea

Physiological amenorrhoea Premature ovarian failure (POF), although rare, can occur in adoles-
Physiological amenorrhoea is a common cause of absent menstru- cence. This can be iatrogenic and secondary to cytotoxic drugs com-
ation. This occurs during pregnancy, breast-feeding (lactational amen- monly used in chemotherapy (5-flurouracil or cisplatin), radiotherapy
orrhoea) and after the menopause (greater than 40 years of age). or childhood malignancy.

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Figure 2. Tanner scale for females.

Illustration by Michał Komorniczak. Drawings based on photos published in Marshall WA, Tanner JM: Variations in patterns of pubertal changes in girls.
Archives of Disease in Childhood 44:291–303, 1969.

Table 1. Classification of conditions associated with amenorrhoea.

Absent secondary sexual characteristics

Normal secondary Normal height Short stature Heterosexual

sexual characteristics
. Imperforate hymen
. Transverse vaginal Septum
. XY female
. Constitutional delay
. Kallaman’s syndrome
. Weight loss/annorexia
. Excessive exercise
. Hyperprolactinaemia
. Gonadal dysgenesis
. Turner’s syndrome
. Congenital Infection
. Tumours
. Trauma to skull base
development (intersex)
. 5a-reductase deficiency
. Congenital adrenal Hyperplasia
. True hermaphradite

Uterine causes of primary amenorrhoea
Congenital anatomical causes of primary amenorrhoea include
imperforate hymen, vaginal septum or Mayer–Rokitansky–Kuster–
Hauser (MRKH) syndrome. The hymen is a membrane, typically
crescent shaped, which partially covers the vaginal opening. If
the hymen completely occludes the vaginal opening (imperforate
hymen) vaginal secretions and the menstrual flow will not be
able to pass through. This may present as a bulge at the intro-
itus, cyclical pain and absent menstruation due to haematocolpos.

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It is usually managed by a gynaecologist, who will remove the
hymen.
A transverse vaginal septum is another cause of haematocolpos,
due to a failure of the vagina to canalate (develop from a solid cylinder
into a tube) during foetal development. As a result the upper two
thirds and lower third of the vagina are separated by a septum of
tissue, causing a collection of menstrual blood. Vaginal examination
reveals a pink coloured membrane high up in the vagina and a mass
on abdominal palpation. Development of secondary sexual character-
istics is normal. Treatment requires excision of the septum.
MRKH syndrome or Müllerian agenesis is characterised by con-
genital absence of the uterus and upper two thirds of the vagina.
This results in a short blind-ending vagina. The ovaries are normally
developed and secondary sexual characteristics will be normal.
Diagnosis is confirmed on an ultrasound scan and supported by
normal karyotyping. Individuals with MRKH syndrome may also
have co-existing kidney problems. In the future, fertility may
become possible for affected individuals with the advent of uterine
transplantation.
Chromosomal abnormalities causing
primary amenorrhoea
Turner’s syndrome (45, XO) is a sex chromosome aneuploidy where
one X chromosome is missing. The phenotype of an individual with
Turner’s syndrome may include short stature, webbed neck, wide
spaced nipples, coarctation of the aorta, renal malformations, absent
secondary sexual characteristics, POF shortly after puberty and learn-
ing disabilities. Primary amenorrhoea is seen in these patients because
they have underdeveloped ovaries or streaks of non-functional ovar-
ian tissue, resulting in impairment of the HPO axis. Synthetic oestro-
gen hormone replacement therapy can be used to stimulate
menstruation and pregnancy is possible with a donor egg and assisted
reproductive techniques. Some individuals with Turner’s syndrome
have mosaicism with a combination of XO and XX cells, often result-
ing in a much milder phenotype. POF (before the age of 40 years) may
be the only presenting feature.
XY females encompass a group of conditions where there is a
failure in androgen production, due to anatomical or enzymatic
causes, resulting in an individual who is genotypically male and
phenotypically female.
During anatomical testicular failure, known as gonadal dysgenesis,
there is a failure of normal testicular differentiation and development.
In normal male development testicles produce antimüllerian hormone
(AMH), which antagonises the development of female müllerian struc-
tures. In the absence of AMH, the uterus, tubes and vagina develop.
There may be a degree of masculinisation depending on the volume
of rudimentary testicular tissue present. Alternatively, enzymatic fail-
ure can result in an XY female commonly caused by 5a-reductase
deficiency. This prevents the conversion of testosterone to 5-hydro-
xytestosterone. The external genitalia require 5-hydroxytestosterone
for development, and therefore, in the absence of this they automat-
ically revert to female development. This is usually discovered when a
young woman is found to be amenorrhoeic and genetic testing is
undertaken.
Secondary amenorrhoea
Hypothalamic and pituitary causes of
secondary amenorrhoea
There are some overlapping aetiological factors affecting the HPO axis
in both primary and secondary amenorrhoea, including weight loss,
and low BMI. In addition to this, excessive exercise can be a cause of
amenorrhoea and is more commonly a cause of secondary
amenorrhea.
Amenorrhoea affects 10–20% of athletes (Schwartz et al., 1981).
The female athlete triad is characterised by disordered eating, men-
strual disturbances and osteoporosis. Marathon runners, ballet dancers
and gymnasts are commonly affected. Patients with amenorrhoea
have low levels of oestrogen, due to a lack of follicular development.
Oestrogen is important for bone health, as it reduces bone reabsorp-
tion, and therefore reduces the risk of osteoporosis. Athletes with
prolonged episodes of amenorrhoea have consistently been shown
to have lower bone mineral density than athletes who menstruate
normally. It is therefore important to manage these individuals appro-
priately and reduce morbidity secondary to osteoporosis in later life.
Tumours of the hypothalamus and pituitary can disrupt the HPO
axis described above and cause amenorrhoea. The most common of
these tumours are microadenomas or macroadenomas, which cause
high circulating levels of prolactin (hyperprolactinaemia). This has a
negative feedback effect on GnRH release from the hypothalamus and
therefore reduces the level of FSH and LH released from the pituitary
gland, preventing follicular development and ovulation.
Sheehan’s syndrome is a rare complication of childbirth and causes
secondary amenorrhoea. Excessive blood loss at delivery causes a
hypotensive episode, resulting in permenant hypoxic ischemic injury
to the pituitary gland, and consequently, hormone deficiencies.
Ovarian causes
POF is a common cause of secondary amenorrhoea. There are 400 000
ovarian follicles at puberty, which throughout life are continuously
depleting and undergoing atresia. On average 400 follicles reach mat-
uration and are ovulated during a woman’s lifetime. Once these fol-
licles have depleted the menopause will begin. Menopause prior to 40
years of age is also known as POF. Cytotoxic medications, chemother-
apy and radiotherapy can cause POF due to direct toxic effects on the
ovaries.
Polycystic ovarian syndrome (PCOS) is the most common cause of
anovulation in young females and affects approximately 20–33% of
women (Michelmore, Balen, Dunger, & Vessey, 1999). In PCOS, sev-
eral small dysfunctional follicular cysts develop, taking variable dur-
ations to mature and undergo ovulation. In addition, ovarian stromal
hyperplasia leads to excessive production of testosterone. These
pathological processes may lead to oligomenorrhoea, amenorrhoea,
dysmenorrhea, hirsutism, acne and infertility.
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Uterine causes
There are relatively few anatomical causes of secondary amenorrhoea.
Asherman’s syndrome is characterised by adhesions and fibrosis of the
myometrium and endometrium. These are usually secondary to inva-
sive procedures or infection in a pregnant or postpartum uterus and
can cause amenorrhoea and infertility due to obliteration of the endo-
metrial cavity.
Medications
Contraceptive medications can induce menstrual irregularities in a
large proportion of patients. In women using levenorgestrel intrauter-
ine system (MirenaÕ ) and depot medroxy-progesterone acetate injec-
tions, 70% become amenorrhoeic 12 months post insertion, whereas
only 20% of patients on the progesterone-only pill experience similar
side effects. It is important to note that it may take up to a year for
fertility to resume after depot provera injections are discontinued.
Other prescription medications can cause amenorrhoea, including
serotonin selective reuptake inhibitors, antipsychotic medications,
ranitidine and opiates. Opiate-induced amenorrhoea is caused by a
reduction in gonadotrophin pulsatility and hyperprolactinaemia
(Grossman et al., 1982). Amenorrhoea is also a side-effect of multiple
antipsychotic medications such as risperidone, and this is often caused
by hyperprolactinaemia (Besnard, Auclair, Callery, Gabriel-
Bordenave, & Roberge, 2014).
Alcohol and drug misuse
Alcohol and drug addiction have been associated with amenorrhoea.
This is thought to be multifactorial. Long-term misuse can affect gona-
dal and pituitary function. Patients suffering from amenorrhoea sec-
ondary to drug and alcohol misuse often believe that they are infertile.
Thyroid dysfunction
Amenorrhoea and menstrual irregularities are common in both hypo-
thyroidism and hyperthyroidism and are seen often in general prac-
tice. Amenorrhoea is seen in around 6% of patients with
hypothyroidism and up to 2.5% of patients with severe hyperthyroid-
ism (Kakuno et al., 2010).
Assessment
History
A comprehensive history is essential to help establish the differential
diagnosis (Box 1). It is important to discuss a patient’s ideas, concerns
and expectations. Concerns about fertility are particularly important to
address and pertinent to formulation of a management plan.
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Box 1. History taking: Key features.
. Duration of amenorrhoea
. Normal menstrual cycle: Regularity, length, interval,
flow, age of menarche
. Any recent weight loss, stressors, excessive exercise
. Growth and secondary sexual characteristics
. Symptoms specific to diagnosis:
# Cyclical pain despite absent menses
# POF: Hot flushes, vaginal dryness,
# PCOS: Acne, hirsutism, weight gain
# Thyroid/endocrine symptoms
# Prolactinoma: Headache, visual disturbances,
galactorrhoea
# Features of syndrome
. Background:
# Contraceptive/sexual history: Pregnancy
# Obstetric history: Endometrial curettage
(Asherman’s)
# Past medical history: Systemic illness
# Medications: Chemo, radio, dopamine antagonists
# Family history: POF, age at menarche and meno-
pause, genetic anomalies
Physical examination
In primary amenorrhoea it is important to ascertain whether secondary
sexual characteristics are present, as this will narrow the differential
diagnosis, and together with gonadotrophin levels, will point towards
the likely aetiology.
Puberty begins with breast budding (thelarche) 2 to 3 years before
menarche, this is oestrogen-dependent and therefore demonstrates
that there has been normal ovarian function at some point. Pubic
hair (pubarche) develops a few months before menarche, and is
dependent upon adrenal androgen production.
Abdominal examination should be performed to exclude a pelvic
mass or gravid uterus. Breast examination should be delayed until
after serum prolactin has been checked, as this could falsely elevate
prolactin. Pelvic examination with a speculum should be omitted in
young females who are virgo intacta (have not had penetrative sexual
intercourse) although external examination of the genitalia for clitor-
omegaly, pubic hair or bulging hymen at the introitus is appropriate
with a chaperone. Other examinations may be performed if relevant
symptoms are elicited from the history, such as examination of the
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visual fields if a pituitary tumour is suspected and thyroid examination detect intrauterine adhesions of Asherman’s syndrome; however, it
for suspected hyper- or hypothyroidism. is not a reliable method for diagnosis.

Investigations Interpretation of biochemical investigations

Patients with primary amenorrhoea always require referral to second-
FSH and LH levels can be low in hypothalamic hypogonadism, due to
ary care for investigation. However, it may be possible to perform the
reduced release of GnRH from the hypothalamus. In POF, FSH and LH
baseline investigations (Table 2) to accelerate the diagnostic process,
levels are high, due to the lack of negative feedback from the ovaries
and reduce the interval time between referral and intervention.
on the hypothalamus. In PCOS, SHBG levels are low. Testosterone
In secondary amenorrhoea, investigations should be commenced
circulates bound to SHBG. Due to low levels of SHBG in PCOS, free
after 6 months of amenorrhoea or 9 months post injection if medrox-
testosterone levels are high. If the free androgen index has a value
yprogesterone acetate injections have been used. The most important
greater than 5 nanomol/L, then in the context of a moderately raised/
initial investigation is a pregnancy test, and this must be undertaken
normal testosterone level, this supports a diagnosis of PCOS. Prolactin
sensitively and with consent, even if the patient denies the possibility
is high in hyperprolactinaemia (Table 3). Normal levels of prolactin
of being pregnant.
are less than 500 mU/L. If prolactin levels are in the range 500–
Sex-hormone-binding globulin (SHBG) and testosterone profiles
1000 mlU/l, this must be repeated to ensure accuracy and, if levels
are recommended by the Royal College of Obstetricians and
remain elevated, this requires referral. Levels over 1000 mlU/l require
Gynaecologists in secondary amenorrhoea; however, oestradiol is
immediate referral to an endocrinologist. A summary of biochemical
prone to vast fluctuations at different times of the menstrual cycle,
investigations and their interpretation can be seen in Table 3.
and therefore, is not routinely tested. Thyroid-stimulating hormone
Benign causes of hyperprolactinaemia include stress, breast or
excludes hypothyroidism, prolactin is used to screen for hyperprolac-
vaginal examination and frequent venipuncture (Table 4). Micro- or
tinaemia and FSH and LH are used to assess for POF.
A pelvic ultrasound scan is used in primary amenorrhoea to assess
Table 4. Causes of hyperprolactinoma.
anatomy and exlude müllerian agenesis, haematocolpus and locate
ovaries. In secondary amenorrhoea, an ultrasound scan can aid the Prolactin levels Causes
diagnosis of PCOS by assessing for multiple ovarian cysts. It may (mlU/l)
Mild (less . Stress
Table 2. Investigations in amenorrhoea. than 1000)
. Hypothyroidism
Pregnancy test
. PCOS
Bloods . Prolactin . Breast/vaginal examination
. Thyroid-stimulating hormone . Venepuncture
. FSH and LH
Moderate . PCOS
. Total testosterone (secondary (1000–5000)
. Hypothalamic or pituitary
amenorrhoea and primary with
tumour (microprolactinoma)
signs of virilisation)
. Dopamine antagonists e.g.
. Sex-hormone-binding globulin
metoclopramide, risperidone
(secondary amenorrhoea only)
Severe (greater . Macroprolactinoma
Pelvic ultrasound scan
than 5000)

Table 3. Interpretation of hormone profiles.

Hypothalamic hypogonadism Ovarian failure PCOS Hyperprolactinaemia
FSH Low/normal High Normal Low/normal

LH Low/normal High Slight increase/normal Low/normal

Prolactin Normal Normal Slight increase/normal High

Testosterone Normal Normal High/normal Normal

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Box 2. When to refer to secondary care?
Refer to gynaecology if:
. Suspected POF and patient is less than 40 years in age
. Suspected PCOS and if diagnosis or management
uncertain in primary care
. History suggestive of Asherman’s syndrome
. Infertility
macroprolactinomas of the pituitary, polycystic ovaries and dopamine
antagonistic medications may also cause raised prolactin.
When to refer patients with amenorrhoea
to secondary care
A summary of the indications for referral to secondary care appears in
Box 2. Adolescents with primary amenorrhoea require referral to sec-
ondary care. If parents are concerned or an abnormality is suspected
prior to fulfilling the criteria for primary amenorrhoea, then referral
should be made, as often these concerns are well-founded. These
referrals would usually be to a gynaecologist with a special interest
in paediatric and adolescent gynaecology. If there is raised prolactin,
thyroid disease or androgen excess a referral should also be made to
paediatric endocrinology.
In secondary amenorrhoea, patients with PCOS and menopause
and who are greater than 40 years in age can be managed in primary
care. A gynaecological referral should be made for patients with sus-
pected POF under the age of 40 years to confirm their diagnosis.
These women should be screened for autoimmune diseases, moni-
tored and treated for reductions in bone density, and referred for fer-
tility treatment where appropriate. Women less than 30 years of age
may require karyotyping to exclude genetic causes (NICE, 2013).
Amenorrhoeic patients with a recent history of uterine surgery, such
as endometrial curettage, must be referred to secondary care to
exclude Asherman’s syndrome.
NICE guidance (NICE, 2013) suggests patients with PCOS require
referral to a gynaecologist if they have insulin intolerance (on a fasting
blood glucose or impaired glucose tolerance test), if they require
insulin-sensitising drugs such as metformin, if the patient has concerns
about infertility or is unwilling to take cyclical treatment to induce
withdrawal bleeds. If a patient is suffering from sleep apnoea asso-
ciated with PCOS, weight loss should be strongly advised and the
patient referred to a respiratory specialist.
An endocrinological referral is suggested in patients with hypothal-
amic hypogonadism, hyperprolactinaemia or raised testosterone that
cannot be explained by PCOS, Cushing’s syndrome or late onset con-
genital adrenal hyperplasia. When a diagnosis of hypothalamic hypo-
gonadism caused by weight loss, excessive exercise or stress is
confirmed, patients may be managed in primary care.
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Management of amenorrhoea
Management of amenorrhoea is dependent on the aetiology. General
principles for the management of primary and secondary amenor-
rhoea are outlined in this section, as well as management of
common causes of secondary amenorrhoea. Management of individ-
ual causes of primary amenorrhoea will not be considered in detail, as
this is usually the role of secondary care. The four most common
causes of secondary amenorrhoea (pregnancy, PCOS, hypothyroidism
and menopause over the age of 40 years) can usually be managed in
primary care if the clinician feels competent to do so.
Hypothalamic hypogonadism
Amenorrhoea caused by hypothalamic hypogonadism such as weight
loss, stress, excessive exercise and chronic illness may be managed in
primary care after an endocrinologist has excluded a hypothalamic or
pituitary tumour. Management is dependent on treating the underlying
cause. Patients with weight-related amenorrhoea may benefit from
referral to a dietician or psychotherapist/psychiatrist if there is
believed to be an underlying eating disorder. Patients should be reas-
sured that weight gain normally results in resumption of menstruation.
Exercise-related amenorrhoea, commonly associated with athletes,
can be managed with a reduction in training intensity. Stress-related
amenorrhoea may be managed by cognitive behavioural therapy or
psychiatric referral.
Polycystic ovary syndrome
PCOS may be managed largely by appropriate changes in lifestyle.
Weight gain and obesity worsen the severity of symptoms, and
increase the risk of infertility, and the long-term risk of cardiovascular
disease and type 2 diabetes mellitus. Metformin reduces androgen and
insulin concentration and improves menstrual irregularity, but is usu-
ally started in secondary care. Regular screening for type 2 diabetes
mellitus and cardiovascular disease is recommended.
Contraception
A small proportion of patients with amenorrhoea become pregnant
spontaneously; even POF has a 5–10% possibility of natural concep-
tion (NICE, 2013). It is therefore important that clinicians consider
contraception in patients not wanting to conceive.
The combined oral contraceptive pill (COCP) used in PCOS
improves cycle control and reduces acne. Low androgen and
weaker progestogenic preparations such as ethinylestradiol and dris-
pirenone (YasminÕ ) and ethinylestradiol and desogestrel (MarvelonÕ )
are the most effective in this treatment group.
There is an increased risk of endometrial hyperplasia in oligome-
norrhoeic or amenorrhoeic patients, due to a lack of endometrial
shedding, and due to this problem, a withdrawal bleed should be
induced every 3 months. The COCP can be used or cyclical proges-
togens taken for 12 days every 3 months. A suitable alternative to this
is insertion of a levenorgestrel intrauterine system which causes endo-
metrial atrophy through local actions of progesterone.
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Medication-induced
Where possible, amenorrhoea secondary to medication is usually
managed by dose or medication change after an appropriate risk–
benefit analysis. It is important to remember the risk to bone mineral
density in these patients with long-term amenorrhoea.
Alcohol and drug misuse
Amenorrhoea secondary to alcohol or drug addiction requires com-
plex multi-disciplinary team management of the underlying problem.
Bone health is an important consideration, and it has been shown that
there is a lifelong increased risk of bone fractures in this population
(Clark, Sowers, Dekordi, & Nichols, 2003).
Thyroid dysfunction
When amenorrhoea is secondary to thyroid disease, appropriate man-
agement of thyroid dysfunction will usually result in restoration of the
menstrual cycle. However, this may take several months following
initiation of treatment (Kakuno et al., 2010).
Bone mineral density and hormone repla-
cement therapy in amenorrhoea
The chronically low levels of oestrogen that are caused by amenor-
rhoea result in reduced bone mineral density and irrecoverable tra-
becular bone loss. Young athletes are particularly at high risk, as they
have yet to obtain peak bone mineral density.
First line management is to modify the cause. Lifestyle factors such
as weight-bearing exercise, smoking cessation and reduction of alco-
hol intake are important. Dietary intake of calcium and vitamin D are
vital and supplementation with 1500 mg calcium and 400 IU of vitamin
D per day is recommended. Bisphosphonates are contraindicated, due
to their potential for teratogenicity in women of child-bearing age.
Oestrogen replacement should be considered after 12 months of
amenorrhoea, to improve bone mineral density and prevent further
loss. There is a role for oestrogen replacement in in hypothalamic
amenorrhoea, hypoprolactinaemia and POF. Hormone replacement
therapy (HRT) or a COCP can be used depending on patient prefer-
ence. In 2007, the British Menopause Society stated that there is ‘no
evidence that oestrogen increases the risk of breast cancer to a level
greater than that found in normally menstruating women’. Cyclical
combined HRT should be used when the patient has not got a
uterus, due to the risk of endometrial hyperplasia with unopposed
oestrogen. If POF presents as primary amenorrhoea, the oestrogen
dose should be gradually increased over 2 years to mimic puberty.
HRT should be reviewed at least annually, and if the cause of amen-
orrhoea is reversible, HRT and the COCP should be stopped every 12
months to determine if menses have resumed (NICE, 2014). In POF,
HRT should be continued until age 52 years (the average age of meno-
pause in the UK), at which point risk–benefit analysis should be made.
Infertility
Infertility is associated with amenorrhoea and can be one of the main
concerns for patients with amenorrhoea. After treating the underlying
cause, patients should, if appropriate, be referred to a gynaecologist.
In patients with hypothalamic amenorrhoea, hyperprolactinaemia and
PCOS, ovulation induction may be trialled with clomiphene citrate or
laparoscopic ovarian drilling. POF requires in vitro fertilisation with a
donor egg.
Hyperprolactinaemia
The mainstay of management of hyperprolactinaemia secondary to
pituitary adenoma is with dopamine receptor agonists such as caber-
goline and bromicriptine. Cabergoline is the treatment of choice, due
to superior efficacy and a reduced side-effect profile. The main aim of
this is to reduce tumour size and restore gonadal function.
Menstruation usually resumes if levels of prolactin reduce to less
than 1000 mlU/l. Prolactin levels fall within a few days, whereas
tumour size reduces over a few weeks. After 2 years of treatment, if
the tumour size has reduced by 50%, withdrawal can be considered.
Management of pituitary adenomas is usually undertaken by an endo-
crinologist in secondary care.
ORCID iD
Thomas Gray http://orcid.org/0000-0001-7719-4366
KEY POINTS
. Primary amenorrhoea is rare and causes of primary and
secondary amenorrhoea have overlapping aetiologies
. Presence or absence of secondary sexual characteristics
and FSH levels are essential in initial assessment of pri-
mary amenorrhoea
. History and examination provide important information
for diagnosis
. Key initial investigations include pregnancy testing, hor-
monal profile and pelvic ultrasound scan
. All patients with primary amenorrhoea must be referred
to secondary care
. Management of secondary amenorrhoea is dependent
upon cause and most patients can be managed in pri-
mary care
87
 InnovAiT

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DOI: 10.1177/1755738017746068
...............................................................................................................................................................................

AKT question relating to testicular pain

Single Best Answer A. Acute epididymitis

You see a 23-year-old patient with gradual onset of left-sided tes- B. Hydrocele
ticular pain over the past 3 days. He is feverish with a tender, swol- C. Strangulated inguinal hernia
len epididymis and a normally positioned non-tender testicle.
What is the SINGLE MOST likely diagnosis? Select ONE option D. Testicular torsion
only. E. Varicocele

Dr Yasser Abdel Kerim

GP Partner, Banks and Bearwood Medical Centre, Bournemouth Answer DOI: 10.1177/1755738017746069

88