Red flag symptoms: Amenorrhoea

Possible causes and red flag symptoms to look out for when menstrual periods either do not start, or stop unexpectedly.

(Picture: Alistair Berg/Getty Images)
(Picture: Alistair Berg/Getty Images)

Red flags

  • Older than 14 years and no signs of puberty
  • Visual field defects or lack of sense of smell
  • Virilisation
  • Excessive weight loss
  • Galactorrhoea
  • Presence of an abdominal mass
  • No obvious cause

Taking a history

Amenorrhoea, or failure to menstruate, can be divided into primary and secondary causes.
Primary amenorrhoea implies the woman has never had a menstrual bleed. Teenagers should usually have started their periods (menarche) before the age of 15 years. However, in some circumstances, investigations may be initiated before then.

Secondary amenorrhoea is when established menstruation ceases and can be defined as a lack of periods for at least six months.

A focused history and examination will help to reveal the important causes. In many cases of secondary amenorrhoea, no obvious hormonal cause may be found.

Causes of primary amenorrhoea

Primary amenorrhoea may simply be a deferral in the onset of periods. However, there could also be rare, unusual and serious causes, such as genetic abnormalities.

The most common cause of primary amenorrhoea is ovarian failure, usually secondary to chromosomal abnormalities such as Turner syndrome, also known as 45,X0.

Other causes include Kallman syndrome, which is associated with an absent sense of smell.

Endocrine abnormalities, including hyperprolactinaemia, must also be considered.

Psychiatric issues such as anorexia may also result in primary amenorrhoea.

A relatively uncommon cause for primary amenorrhoea is an imperforate hymen, with blood collecting in the vagina (haematocolpos). Vaginal absence is another possibility.

Causes of secondary amenorrhoea

Many cases of secondary amenorrhoea are a result of conditions that are commonly seen and managed in general practice.

Polycystic ovary syndrome, hypothyroidism, menopause and pregnancy are perhaps the most common causes.

Premature ovarian failure must be considered in women under the age of 40 with persistently elevated FSH and LH levels.

Post-delivery amenorrhoea could suggest Sheehan's syndrome, secondary to hypoperfusion of the pituitary gland.

Asherman’s syndrome can follow recent uterine or cervical surgery, secondary to adhesions within the uterus, cervix or both.

A short history of virilisation, which can cause amenorrhoea, may be associated with an ovarian or adrenal malignancy.

Endocrine causes to consider include hyperprolactinaemia (typically presenting with galactorrhoea), late-onset adrenal hyperplasia and Cushing’s syndrome.

Drugs including antipsychotics, metoclopramide, cimetidine, methyldopa, opiates, cocaine as well as radio- and chemotherapy can all result in secondary amenorrhoea.

Excessive exercise, stress or weight loss can cause hypothalamic-pituitary dysfunction, and as a consequence periods may cease.

Possible causes

  • Pregnancy
  • Menopause
  • Medication
  • Post-pill amenorrhoea
  • Lifestyle - exercise/stress
  • Genetic abnormalities, such as Turner syndrome
  • Kallman syndrome
  • Sheehan's syndrome
  • Ovarian or adrenal malignancy
  • Imperforate hymen
  • Cushing's syndrome
  • Polycystic ovary syndrome
  • Hypothyroidism

Remote examination during COVID-19

You may wish to undertake remote examination via video during the COVID-19 pandemic. This could include height and weight, and checking for features of PCOS such as a raised BMI, excessive hirsutism, and/or a cushingoid appearance. Signs of hypothyroidism may be evident. Any intimate examination would ideally require an in-person examination.

Points to note during examination

Note the development or otherwise of secondary sexual characteristics in teenage girls who have not yet started their periods. Check the BMI. A low BMI may suggest an eating disorder or malnourishment from a chronic disease; a higher BMI may suggest polycystic ovaries if there are other symptoms or signs to support this, such as hirsutism or obesity.

Consider an endocrine cause, such as an adrenal or pituitary problem, by looking for features such as virilisation, although they are uncommon.

Cushing's syndrome can cause amenorrhoea, so consider the typical clinical features if suspected. Primary amenorrhoea can be the presenting feature of a chromosomal or structural abnormality. However, this is uncommon.

A genital inspection (exclude ambiguous genitalia) may be necessary, as would be abdominal and vaginal examinations. A chaperone should be present.

Visual fields may need to be assessed and an abnormality - for example, a bitemporal hemianopia - may suggest a pituitary problem.

Investigations

Investigations may include a pelvic ultrasound and blood tests. Blood tests could include FSH, LH, testosterone, sex hormone binding globulin, prolactin and TFTs, as well as a pregnancy test. Check if a cervical smear is due.

If hyperprolactinaemia is found (a raised level may have to be repeated and confirmed) and if there are neurological symptoms or signs, brain imaging is required via a two-week wait referral for urgent head MRI.

Once an accurate diagnosis is established, a management plan can be formulated.

When to refer

In the following situations, it may be necessary to refer to secondary care:

  • Girls aged 16 who have failed to start their periods, or aged 14 if there is no menstruation plus an absence of secondary sexual characteristics
  • Infertility
  • Associated neurological symptoms or signs
  • Complex endocrine abnormalities
  • Anatomical abnormalities
  • Potential post surgical/delivery complication
  • Premature ovarian failure syndrome
  • Significant psychiatric pathology
  • For monitoring/management of osteoporosis prevention
  • No clear diagnosis

This article, originally by Dr Harry Brown, was reviewed and updated by Dr Pipin Singh in August 2020.

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