Anda di halaman 1dari 9

InnovAiT, 11(2), 80–88

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: 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.

Reprints and permissions:
DOI: 10.1177/1755738017737101

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
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.


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

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


It is usually managed by a gynaecologist, who will remove the young woman is found to be amenorrhoeic and genetic testing is
hymen. undertaken.
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
Secondary amenorrhoea
tissue, causing a collection of menstrual blood. Vaginal examination Hypothalamic and pituitary causes of
reveals a pink coloured membrane high up in the vagina and a mass secondary amenorrhoea
on abdominal palpation. Development of secondary sexual character-
istics is normal. Treatment requires excision of the septum. There are some overlapping aetiological factors affecting the HPO axis
MRKH syndrome or Müllerian agenesis is characterised by con- in both primary and secondary amenorrhoea, including weight loss,
genital absence of the uterus and upper two thirds of the vagina. and low BMI. In addition to this, excessive exercise can be a cause of
This results in a short blind-ending vagina. The ovaries are normally amenorrhoea and is more commonly a cause of secondary
developed and secondary sexual characteristics will be normal. amenorrhea.
Diagnosis is confirmed on an ultrasound scan and supported by Amenorrhoea affects 10–20% of athletes (Schwartz et al., 1981).
normal karyotyping. Individuals with MRKH syndrome may also The female athlete triad is characterised by disordered eating, men-
have co-existing kidney problems. In the future, fertility may strual disturbances and osteoporosis. Marathon runners, ballet dancers
become possible for affected individuals with the advent of uterine and gymnasts are commonly affected. Patients with amenorrhoea
transplantation. 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
Chromosomal abnormalities causing to have lower bone mineral density than athletes who menstruate
primary amenorrhoea normally. It is therefore important to manage these individuals appro-
priately and reduce morbidity secondary to osteoporosis in later life.
Turner’s syndrome (45, XO) is a sex chromosome aneuploidy where
Tumours of the hypothalamus and pituitary can disrupt the HPO
one X chromosome is missing. The phenotype of an individual with
axis described above and cause amenorrhoea. The most common of
Turner’s syndrome may include short stature, webbed neck, wide
these tumours are microadenomas or macroadenomas, which cause
spaced nipples, coarctation of the aorta, renal malformations, absent
high circulating levels of prolactin (hyperprolactinaemia). This has a
secondary sexual characteristics, POF shortly after puberty and learn-
negative feedback effect on GnRH release from the hypothalamus and
ing disabilities. Primary amenorrhoea is seen in these patients because
therefore reduces the level of FSH and LH released from the pituitary
they have underdeveloped ovaries or streaks of non-functional ovar-
gland, preventing follicular development and ovulation.
ian tissue, resulting in impairment of the HPO axis. Synthetic oestro-
Sheehan’s syndrome is a rare complication of childbirth and causes
gen hormone replacement therapy can be used to stimulate
secondary amenorrhoea. Excessive blood loss at delivery causes a
menstruation and pregnancy is possible with a donor egg and assisted
hypotensive episode, resulting in permenant hypoxic ischemic injury
reproductive techniques. Some individuals with Turner’s syndrome
to the pituitary gland, and consequently, hormone deficiencies.
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.
Ovarian causes
XY females encompass a group of conditions where there is a POF is a common cause of secondary amenorrhoea. There are 400 000
failure in androgen production, due to anatomical or enzymatic ovarian follicles at puberty, which throughout life are continuously
causes, resulting in an individual who is genotypically male and depleting and undergoing atresia. On average 400 follicles reach mat-
phenotypically female. uration and are ovulated during a woman’s lifetime. Once these fol-
During anatomical testicular failure, known as gonadal dysgenesis, licles have depleted the menopause will begin. Menopause prior to 40
there is a failure of normal testicular differentiation and development. years of age is also known as POF. Cytotoxic medications, chemother-
In normal male development testicles produce antimüllerian hormone apy and radiotherapy can cause POF due to direct toxic effects on the
(AMH), which antagonises the development of female müllerian struc- ovaries.
tures. In the absence of AMH, the uterus, tubes and vagina develop. Polycystic ovarian syndrome (PCOS) is the most common cause of
There may be a degree of masculinisation depending on the volume anovulation in young females and affects approximately 20–33% of
of rudimentary testicular tissue present. Alternatively, enzymatic fail- women (Michelmore, Balen, Dunger, & Vessey, 1999). In PCOS, sev-
ure can result in an XY female commonly caused by 5a-reductase eral small dysfunctional follicular cysts develop, taking variable dur-
deficiency. This prevents the conversion of testosterone to 5-hydro- ations to mature and undergo ovulation. In addition, ovarian stromal
xytestosterone. The external genitalia require 5-hydroxytestosterone hyperplasia leads to excessive production of testosterone. These
for development, and therefore, in the absence of this they automat- pathological processes may lead to oligomenorrhoea, amenorrhoea,
ically revert to female development. This is usually discovered when a dysmenorrhea, hirsutism, acne and infertility.


Uterine causes Box 1. History taking: Key features.

. Duration of amenorrhoea
There are relatively few anatomical causes of secondary amenorrhoea.
Asherman’s syndrome is characterised by adhesions and fibrosis of the . Normal menstrual cycle: Regularity, length, interval,
myometrium and endometrium. These are usually secondary to inva- flow, age of menarche
sive procedures or infection in a pregnant or postpartum uterus and
. Any recent weight loss, stressors, excessive exercise
can cause amenorrhoea and infertility due to obliteration of the endo-
metrial cavity. . Growth and secondary sexual characteristics

. Symptoms specific to diagnosis:

Medications # Cyclical pain despite absent menses

Contraceptive medications can induce menstrual irregularities in a # POF: Hot flushes, vaginal dryness,
large proportion of patients. In women using levenorgestrel intrauter-
# PCOS: Acne, hirsutism, weight gain
ine system (MirenaÕ ) and depot medroxy-progesterone acetate injec-
tions, 70% become amenorrhoeic 12 months post insertion, whereas # Thyroid/endocrine symptoms
only 20% of patients on the progesterone-only pill experience similar
# Prolactinoma: Headache, visual disturbances,
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 # Features of syndrome
serotonin selective reuptake inhibitors, antipsychotic medications,
. Background:
ranitidine and opiates. Opiate-induced amenorrhoea is caused by a
reduction in gonadotrophin pulsatility and hyperprolactinaemia # Contraceptive/sexual history: Pregnancy
(Grossman et al., 1982). Amenorrhoea is also a side-effect of multiple
# Obstetric history: Endometrial curettage
antipsychotic medications such as risperidone, and this is often caused
by hyperprolactinaemia (Besnard, Auclair, Callery, Gabriel-
Bordenave, & Roberge, 2014). # Past medical history: Systemic illness

# Medications: Chemo, radio, dopamine antagonists

Alcohol and drug misuse # Family history: POF, age at menarche and meno-
pause, genetic anomalies
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. Physical examination

In primary amenorrhoea it is important to ascertain whether secondary

Thyroid dysfunction sexual characteristics are present, as this will narrow the differential
diagnosis, and together with gonadotrophin levels, will point towards
Amenorrhoea and menstrual irregularities are common in both hypo- the likely aetiology.
thyroidism and hyperthyroidism and are seen often in general prac- Puberty begins with breast budding (thelarche) 2 to 3 years before
tice. Amenorrhoea is seen in around 6% of patients with menarche, this is oestrogen-dependent and therefore demonstrates
hypothyroidism and up to 2.5% of patients with severe hyperthyroid- that there has been normal ovarian function at some point. Pubic
ism (Kakuno et al., 2010). 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
Assessment after serum prolactin has been checked, as this could falsely elevate
prolactin. Pelvic examination with a speculum should be omitted in
History young females who are virgo intacta (have not had penetrative sexual
A comprehensive history is essential to help establish the differential intercourse) although external examination of the genitalia for clitor-
diagnosis (Box 1). It is important to discuss a patient’s ideas, concerns omegaly, pubic hair or bulging hymen at the introitus is appropriate
and expectations. Concerns about fertility are particularly important to with a chaperone. Other examinations may be performed if relevant
address and pertinent to formulation of a management plan. symptoms are elicited from the history, such as examination of the


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
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


Box 2. When to refer to secondary care? Management of amenorrhoea

Refer to gynaecology if: Management of amenorrhoea is dependent on the aetiology. General
principles for the management of primary and secondary amenor-
. Suspected POF and patient is less than 40 years in age
rhoea are outlined in this section, as well as management of
. Suspected PCOS and if diagnosis or management common causes of secondary amenorrhoea. Management of individ-
uncertain in primary care ual causes of primary amenorrhoea will not be considered in detail, as
this is usually the role of secondary care. The four most common
. History suggestive of Asherman’s syndrome
causes of secondary amenorrhoea (pregnancy, PCOS, hypothyroidism
. Infertility 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
macroprolactinomas of the pituitary, polycystic ovaries and dopamine Amenorrhoea caused by hypothalamic hypogonadism such as weight
antagonistic medications may also cause raised prolactin. 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
When to refer patients with amenorrhoea cause. Patients with weight-related amenorrhoea may benefit from
referral to a dietician or psychotherapist/psychiatrist if there is
to secondary care
believed to be an underlying eating disorder. Patients should be reas-
A summary of the indications for referral to secondary care appears in sured that weight gain normally results in resumption of menstruation.
Box 2. Adolescents with primary amenorrhoea require referral to sec- Exercise-related amenorrhoea, commonly associated with athletes,
ondary care. If parents are concerned or an abnormality is suspected can be managed with a reduction in training intensity. Stress-related
prior to fulfilling the criteria for primary amenorrhoea, then referral amenorrhoea may be managed by cognitive behavioural therapy or
should be made, as often these concerns are well-founded. These psychiatric referral.
referrals would usually be to a gynaecologist with a special interest
in paediatric and adolescent gynaecology. If there is raised prolactin, Polycystic ovary syndrome
thyroid disease or androgen excess a referral should also be made to
PCOS may be managed largely by appropriate changes in lifestyle.
paediatric endocrinology.
Weight gain and obesity worsen the severity of symptoms, and
In secondary amenorrhoea, patients with PCOS and menopause
increase the risk of infertility, and the long-term risk of cardiovascular
and who are greater than 40 years in age can be managed in primary
disease and type 2 diabetes mellitus. Metformin reduces androgen and
care. A gynaecological referral should be made for patients with sus-
insulin concentration and improves menstrual irregularity, but is usu-
pected POF under the age of 40 years to confirm their diagnosis.
ally started in secondary care. Regular screening for type 2 diabetes
These women should be screened for autoimmune diseases, moni-
mellitus and cardiovascular disease is recommended.
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 A small proportion of patients with amenorrhoea become pregnant
exclude Asherman’s syndrome. spontaneously; even POF has a 5–10% possibility of natural concep-
NICE guidance (NICE, 2013) suggests patients with PCOS require tion (NICE, 2013). It is therefore important that clinicians consider
referral to a gynaecologist if they have insulin intolerance (on a fasting contraception in patients not wanting to conceive.
blood glucose or impaired glucose tolerance test), if they require The combined oral contraceptive pill (COCP) used in PCOS
insulin-sensitising drugs such as metformin, if the patient has concerns improves cycle control and reduces acne. Low androgen and
about infertility or is unwilling to take cyclical treatment to induce weaker progestogenic preparations such as ethinylestradiol and dris-
withdrawal bleeds. If a patient is suffering from sleep apnoea asso- pirenone (YasminÕ ) and ethinylestradiol and desogestrel (MarvelonÕ )
ciated with PCOS, weight loss should be strongly advised and the are the most effective in this treatment group.
patient referred to a respiratory specialist. There is an increased risk of endometrial hyperplasia in oligome-
An endocrinological referral is suggested in patients with hypothal- norrhoeic or amenorrhoeic patients, due to a lack of endometrial
amic hypogonadism, hyperprolactinaemia or raised testosterone that shedding, and due to this problem, a withdrawal bleed should be
cannot be explained by PCOS, Cushing’s syndrome or late onset con- induced every 3 months. The COCP can be used or cyclical proges-
genital adrenal hyperplasia. When a diagnosis of hypothalamic hypo- togens taken for 12 days every 3 months. A suitable alternative to this
gonadism caused by weight loss, excessive exercise or stress is is insertion of a levenorgestrel intrauterine system which causes endo-
confirmed, patients may be managed in primary care. metrial atrophy through local actions of progesterone.


Medication-induced 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.
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.
Infertility is associated with amenorrhoea and can be one of the main
concerns for patients with amenorrhoea. After treating the underlying
Alcohol and drug misuse cause, patients should, if appropriate, be referred to a gynaecologist.
In patients with hypothalamic amenorrhoea, hyperprolactinaemia and
Amenorrhoea secondary to alcohol or drug addiction requires com- PCOS, ovulation induction may be trialled with clomiphene citrate or
plex multi-disciplinary team management of the underlying problem.
laparoscopic ovarian drilling. POF requires in vitro fertilisation with a
Bone health is an important consideration, and it has been shown that
donor egg.
there is a lifelong increased risk of bone fractures in this population
(Clark, Sowers, Dekordi, & Nichols, 2003).

Thyroid dysfunction The mainstay of management of hyperprolactinaemia secondary to
pituitary adenoma is with dopamine receptor agonists such as caber-
When amenorrhoea is secondary to thyroid disease, appropriate man-
goline and bromicriptine. Cabergoline is the treatment of choice, due
agement of thyroid dysfunction will usually result in restoration of the
to superior efficacy and a reduced side-effect profile. The main aim of
menstrual cycle. However, this may take several months following this is to reduce tumour size and restore gonadal function.
initiation of treatment (Kakuno et al., 2010). 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
Bone mineral density and hormone repla- the tumour size has reduced by 50%, withdrawal can be considered.
cement therapy in amenorrhoea Management of pituitary adenomas is usually undertaken by an endo-
crinologist in secondary care.
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. ORCID iD
First line management is to modify the cause. Lifestyle factors such Thomas Gray
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 . Primary amenorrhoea is rare and causes of primary and
to their potential for teratogenicity in women of child-bearing age. secondary amenorrhoea have overlapping aetiologies
Oestrogen replacement should be considered after 12 months of
. Presence or absence of secondary sexual characteristics
amenorrhoea, to improve bone mineral density and prevent further
and FSH levels are essential in initial assessment of pri-
loss. There is a role for oestrogen replacement in in hypothalamic
mary amenorrhoea
amenorrhoea, hypoprolactinaemia and POF. Hormone replacement
therapy (HRT) or a COCP can be used depending on patient prefer- . History and examination provide important information
ence. In 2007, the British Menopause Society stated that there is ‘no for diagnosis
evidence that oestrogen increases the risk of breast cancer to a level . Key initial investigations include pregnancy testing, hor-
greater than that found in normally menstruating women’. Cyclical monal profile and pelvic ultrasound scan
combined HRT should be used when the patient has not got a
. All patients with primary amenorrhoea must be referred
uterus, due to the risk of endometrial hyperplasia with unopposed
to secondary care
oestrogen. If POF presents as primary amenorrhoea, the oestrogen
dose should be gradually increased over 2 years to mimic puberty. . Management of secondary amenorrhoea is dependent
HRT should be reviewed at least annually, and if the cause of amen- upon cause and most patients can be managed in pri-
orrhoea is reversible, HRT and the COCP should be stopped every 12 mary care
months to determine if menses have resumed (NICE, 2014). In POF,


References and further information

Bachmann, G., & Kemmann, E. (1982). Prevalence Medical Journal, 339, 455–457. doi: 10.1136/ NICE. (2013). Clinical knowledge summaries: training-exams/gp-curriculum-overview/online-
of oligomenorrhea and amenorrhoea in a college bmj.b2184 Polycystic ovarian syndrome guideline. Retrieved curriculum.ashx
population. Americal Journal of Obstetrics and from
Edmonds, K. (2012). Dewhurst textbook of obstet- RCGP. Clinical module 3.06: Women’s health.
Gynecology, 144(1), 98–102 syndrome
rics & gynaecology, eighth edition. West Sussex, Retrieved from
Besnard, I., Auclair, V., Callery, G., Gabriel- UK: Wiley-Blackwell NICE. (2014). Clinical knowledge summaries: gp-curriculum-overview/online-curriculum.ashx
Bordenave, C., & Roberge, C. (2014). Amenorrhoea guideline. Retrieved from https://
Grossman, A., Moult, P. J., McIntyre, H., Evans, J., RCGP. Clinical module 3.17: Care of people with
Antipsychotic-drug-induced hyperprolactinemia:
Silverstone, T., Rees, L. H., . . . Besser, G. M. (1982). metabolic problems. Retrieved from www.rcgp.or-
Physiopathology, clinical features and guidance. NICE. (2015). Clinical knowledge summaries:
Opiate mediation of amenorrhoea in hyperprolac-
L’encephale, 40(1), 86–94 Menopause guideline. Retrieved from https://
tinaemia and in weight-loss related amenorrhoea. online-curriculum.ashx
Birch, K. (2005). Female athletic triad. BMJ, Clinical Endocriology, 17(4), 379–388
Roa, J., Garcia-Galiano, D., Castellano, J. M.,
330(7485), 244–246. doi: 10.1136/bmj NICE. (2016). Clinical knowledge summaries:
Kakuno, Y., Amino, N., Kanoh, M., Kawai, M., Gaytan, F., Pinilla, L., & Tena-Sempere, M.
330.7485.224 Osteoporosis - prevention of fragility fractures
Fujiwara, M., Kimura, M., . . . Miyauchi, A. (2010). (2010). Metabolic control of puberty onset: New
British Menopause Society. (2015). NICE guide- Menstrual disturbances in various thyroid diseases. guideline. Retrieved from players, new mechanisms. Molecular and
line: Diagnosis and management of the meno- Endocrinology Journal, 57(12), 1017–1022 osteoporosis-prevention-of-fragility-fractures Cellular Endocrinology, 324(1-2), 87–94
pause. Retrieved from Palmer, M., & Dunkel, L. (2012). Delayed puberty.
Michelmore, K. F., Balen, A. H., Dunger, D. B., & Schwartz, B., Cumming, D., Riordan, E., Selye, M.,
nice-guideline/overview/ New England Journal of Medicine, 336, 443–453.
Vessey, M. P. (1999). Polycystic ovaries and asso- Yen, S., & Rebar, R. (1981). Exercise-associated
Clark, M., Sowers, M., Dekordi, F., & Nichols, S. ciated clinical and biochemical features in young doi: 10.1056/NEJMcp1109290 amenorrhea: A distinct entity? American Journal
(2003). Bone mineral density and fractures among women. Clinical Endocrinology, 51(6), 779–786 RCGP. Clinical module 3.02: Genetics in primary of Obstetrics and Gynecology, 141(5), 662–670
alcohol-dependent women in treatment and in care. Retrieved from
NHS Digital. (2007). Adult Psychiatric Morbidity in Urmi, S., Begum, S., Fariduddin, M., Mahmud, T.,
recovery. International Journal of Osteoporosis, exams/gp-curriculum-overview/online-
England – 2007. Results of a household survey. Banu, J., & Khanam, A. (2015). Hypothyroidism
4(5), 396–403 curriculum.ashx
Retrieved from and its effect on menstrual pattern and fertility.
Dickerson, E., Raguhunath, A., & Atkin, S. (2009). PUB02931 RCGP. Clinical module 3.04: Care of children and Mymensingh Medical Journal, 24(4), 765–769
Initial investigation of amenorrhoea. British young people. Retrieved from

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