Secondary amenorrhea is defined as no menstruation for more than three months after previous regular menstrual periods. Consider assessment and investigation after three to six months. In women with previously infrequent irregular periods, consider investigating after six to twelve months.
Causes
- Pregnancy is the most common cause
- Menopause and premature ovarian failure
- Hormonal contraception (e.g. IUS or POP)
- Hypothalamic or pituitary pathology
- Ovarian causes such as polycystic ovarian syndrome
- Uterine pathology such as Asherman’s syndrome
- Thyroid pathology
- Hyperprolactinaemia
The hypothalamus reduces the production of GnRH in response to significant physiological or psychological stress. This leads to hypogonadotropic hypogonadism and amenorrhoea. The hypothalamus responds this way to prevent pregnancy in situations where the body may not be fit for it, for example:
- Excessive exercise (e.g. athletes)
- Low body weight and eating disorders
- Chronic disease
- Psychological stress
Pituitary causes of secondary amenorrhoea include:
- Pituitary tumours, such as a prolactin-secreting prolactinoma
- Pituitary failure due to trauma, radiotherapy, surgery or Sheehan syndrome
Hyperprolactinaemia
High prolactin levels act on the hypothalamus to prevent the release of GnRH. Without GnRH, there is no release of LH and FSH. This causes hypogonadotropic hypogonadism. Only 30% of women with a high prolactin level will have galactorrhea (breast milk production and secretion).
The most common cause of hyperprolactinaemia is a pituitary adenoma secreting prolactin. Where there are high prolactin levels, a CT or MRI scan of the brain is used to assess for a pituitary tumour. Often there is a microadenoma that will not appear on the initial scan, and follow up scans are required to identify tumours that may develop later.
Often no treatment is required for hyperprolactinaemia. Dopamine agonists such as bromocriptine or cabergoline can be used to reduce prolactin production. These medications treat hyperprolactinaemia, Parkinson’s disease and acromegaly.
Assessment
Assessment of secondary amenorrhoea involves:
- Detailed history and examination to assess for potential causes
- Hormonal blood tests
- Ultrasound of the pelvis to diagnose polycystic ovarian syndrome
Hormone Tests
Beta human chorionic gonadotropin (HCG) urine or blood tests are required to diagnose or rule out pregnancy.
Luteinising hormone and follicle-stimulating hormone:
- High FSH suggests primary ovarian failure
- High LH, or LH:FSH ratio, suggests polycystic ovarian syndrome
Prolactin can be measured to assess for hyperprolactinaemia, followed by an MRI to identify a pituitary tumour.
Thyroid stimulating hormone (TSH) can screen for thyroid pathology. This is followed by T3 and T4 when the TSH is abnormal.
- Raise TSH and low T3 and T4 indicate hypothyroidism
- Low TSH and raised T3 and T4 indicate hyperthyroidism
Raise testosterone indicates polycystic ovarian syndrome, androgen insensitivity syndrome or congenital adrenal hyperplasia.
Management
Management of secondary amenorrhoea involves establishing and treating the underlying cause. Where necessary, replacement hormones can induce menstruation and improve symptoms.
TOM TIP: It is worth remembering that women with polycystic ovarian syndrome require a withdrawal bleed every 3 – 4 months to reduce the risk of endometrial hyperplasia and endometrial cancer. Medroxyprogesterone for 14 days, or regular use of the combined oral contraceptive pill, can be used to stimulate a withdrawal bleed.
Osteoporosis
Patients with amenorrhoea associated with low oestrogen levels are at risk increased risk of osteoporosis. Where the amenorrhoea lasts more than 12 months, treatment is indicated to reduce the risk of osteoporosis:
- Ensure adequate vitamin D and calcium intake
- Hormone replacement therapy or the combined oral contraceptive pill
Last updated June 2020