Red flag symptoms: Amenorrhoea

Know how to reveal an serious cause of amenorrhoea and when to refer. By Dr Harry Brown.

Ovarian cancer may be a serious cause of amenorrhoea (Photo: SPL)
Ovarian cancer may be a serious cause of amenorrhoea (Photo: SPL)

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

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 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.

In primary amenorrhoea, it may simply be a deferral in the onset of periods. However, there could also be rare, unusual and serious causes, such as genetic abnormalities. A loss of smell and amenorrhoea could suggest Kallman syndrome. Post-delivery amenorrhoea could suggest Sheehan's syndrome (and a risk of untreated hypopituitarism).

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

If hyperprolactinaemia is found (a raised level may have to be repeated and confirmed) and there are neurological symptoms or signs, brain imaging is required.


Always consider pregnancy. A pregnancy in a very young person could be a red flag for child protection.

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

Ask about medication (certain drugs can raise prolactin levels, leading to amenorrhoea), lifestyle (excessive exercise, stress, significant weight loss) and check if a recent pregnancy test or pelvic ultrasound has been requested or carried out.

Ask about sense of smell (Kallman syndrome) or galactorrhoea (hyperprolactinaemia). Prolactin can be raised without drugs. If found, referral to an endocrinologist may be necessary, as pituitary prolactinomas are commonly found in this group.

Possible causes
  • Pregnancy
  • Menopause
  • Medication
  • 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


Note the development or otherwise of secondary sexual characteristics. 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) 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 a vaginal examination. A chaperone should be present.

Visual fields may need to be assessed and an abnormality may suggest a pituitary cause, in which case, an endocrine screen may be needed.


Investigations may include an ultrasound and blood tests. Blood tests could include FSH, LH, testosterone, prolactin and TFTs, as well as a pregnancy test. Check if a cervical smear is due. Once an accurate diagnosis is established, this allows a management plan to be formulated.

When to refer

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

  • No clear diagnosis
  • Failure to conceive
  • Neurological symptoms or signs
  • Complex endocrine abnormality
  • Anatomical abnormality
  • Patient wants a second opinion
  • Full work-up may be outside the scope of primary care
  • Dr Brown is a GP in Leeds

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This is an updated version of an article that was originally published in January 2014.


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