The basics - Secondary amenorrhoea

It is essential to exclude pregnancy in patients with amenorrhoea, explains Dr Louise Newson.

Polycystic ovarian syndrome is the cause of almost a third of cases of secondary amenorrhoea (Photograph: SPL)
Polycystic ovarian syndrome is the cause of almost a third of cases of secondary amenorrhoea (Photograph: SPL)

Amenorrhoea is the absence or cessation of menstruation. It can be physiological (before the menarche, after the menopause or in pregnancy), pathological or iatrogenic (for example, following a hysterectomy).

It is essential to exclude pregnancy in any female who presents with amenorrhoea.

Amenorrhoea can be divided into:

  • Primary - this is when menses have never occurred.

Primary amenorrhoea is considered at 14 years in the absence of secondary sexual characteristics or at 16 years if features of sexual development are present.

  • Secondary - this is when menstruation has stopped for at least six months.

Secondary amenorrhoea is more common than primary amenorrhoea.

Secondary amenorrhoea affects about 3 per cent of women. Up to 50 per cent of competitive long-distance runners (running about 80 miles per week) and up to 44 per cent of ballet dancers have amenorrhoea.

1. Causes of secondary amenorrhoea
The causes of secondary amenorrhoea are classified depending on whether there is a presence or absence of androgen excess.

No signs of androgen excess
Premature ovarian failure can be spontaneous (likely to be autoimmune1) or occur following radiotherapy or chemotherapy.

This can lead to hot flushes and other menopausal symptoms occurring.

Progesterone contraceptives, commonly the depot and implant, lead to secondary amenorrhoea but this should be clear from the patient's history.

Asherman's syndrome leads to cervical stenosis and intrauterine adhesions.

This is a recognised complication of a uterine curettage.

Patients who are very underweight (usually with a BMI<19) can present with secondary amenorrhoea.

This is fairly common in patients with eating disorders, especially anorexia nervosa.

Hyperprolactinaemia can also present with secondary amenorrhoea. Causes include drugs (for example, phenothiazines), hypothyroidism and pituitary tumours.

Sheehan's syndrome is a rare condition in which pituitary infarction occurs after severe postpartum haemorrhage.

Post-pill amenorrhoea occurs in some women after stopping the combined oral contraceptive pill. This usually settles spontaneously three months after discontinuing the pill.

Signs of androgen excess
Polycystic ovarian syndrome is the cause of nearly a third of cases of secondary amenorrhoea. Other causes include Cushing's syndrome, late-onset congenital adrenal hyperplasia and adrenal or ovarian carcinoma.

2. Investigations
It is recommended that investigations should be undertaken in women who have a history of six months of amenorrhoea. They can be undertaken earlier if clinically indicated (for example, if hirsutism is present) or if the patient is anxious. Investigations can be delayed for nine months following cessation of depot contraception.2

A detailed history should be undertaken to assess for any obvious underlying cause. As already mentioned, it is important to ensure the patient is not pregnant.

The patient's BMI should be calculated and documented. An examination should be undertaken to determine any underlying cause. In particular, patients should be examined for signs of excessive androgens (hirsutism, acne, temporal balding), thyroid disease and Cushing's syndrome.

The following investigations should be done:

  • Pregnancy test (if appropriate).
  • FSH and LH.
  • Prolactin.
  • Total testosterone and sex hormone-binding globulin.
  • TSH.

A pelvic ultrasound may be useful in patients with suspected polycystic ovarian syndrome.

3. Management
The management of this condition depends on the underlying cause. If it is apparent (for example, hypothyroidism) then it may be possible to manage the patient in primary care.3

Patients with eating disorders may need to be referred to a psychiatrist.The management will also depend on whether infertility is an issue. If this is the case, prompt referral may be appropriate.

Patients with secondary amenorrhoea should still be offered contraception, as there is still a risk of pregnancy.

Patients with amenorrhoea associated with low estrogen levels (premature ovarian failure, hypopituitarism, hyperprolactinaemia) will need to be assessed for their risk of osteoporosis.

These patients should be advised to have an adequate calcium (1,500mg/day) and vitamin D (400IU/day) intake.

If the amenorrhoea persists for more than 12 months, then the patient should be offered estrogen replacement, either as cyclical combined HRT or a combined oral contraceptive. This can be stopped for six months after a year of treatment to determine whether or not menses returns.

  • Dr Newson is a GP in the West Midlands
Key Points
  • Pregnancy must be excluded.
  • Amenorrhoea is common in athletes.
  • Polycystic ovarian syndrome is a common cause of amenorrhoea.
  • Many patients with secondary amenorrhoea can be managed in primary care.

References
1. Kauffman RP, Castracane VD. Premature ovarian failure associated with autoimmune polyglandular syndrome: pathophysiological mechanisms and future fertility. J Womens Health 2003; 12: 513-20.

2. Dickerson EH, Raghunath AS, Atkin SL. Initial investigation of amenorrhoea. BMJ 2009; 339: b2184.

3. Amenorrhoea, Clinical Knowledge Summaries (2009)

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