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Amenorrhoea

Essentials

  • In primary amenorrhoea, the patient has never had a menstruation. In secondary amenorrhoea, menstruation remains absent for 6 consecutive months or, if the menstrual cycle is clearly longer than normal, three consecutive menstrual periods remain absent. In practice, the boundary between the different conditions is not always this clear-cut.

Primary amenorrhoea

  • Investigate further if
    • no signs of puberty have emerged by the age of 13–14 or
    • menstruation has not started by the age of 16, even though puberty has otherwise progressed normally.
Causes

  • The cause in 45% of cases is irreversible ovarian failure; often no onset of puberty.
    • Usually associated with chromosomal abnormalities, e.g. Turner's syndrome
    • Other ovarian defect (dysgenesis)
  • The cause in 15% of cases originates from the central nervous system; often no onset of puberty.
    • Pituitary tumour (often prolactinoma), other brain tumour, pituitary insufficiency, Kallman's syndrome
  • In 13% of cases the cause is physiological; pubertal changes often lacking.
    • Constitutional delay
    • Anorexia
    • Excessive physical exercise
  • In 17% of cases the cause is structural; development of puberty otherwise normal.
    • Rare: transverse vaginal septum, absent cervix or agenesis of the uterus
    • Rare: androgen insensitivity syndrome, i.e. an XY female, female external genitalia and body habitus, short vagina, absent internal genitalia
  • In 10% of cases primary amenorrhoea is caused by a systemic illness.
    • Hypothyroidism, untreated coeliac disease, Cushing's syndrome, adrenal hyperandrogenism etc.
    • Obesity
    • Malignancy treated in childhood

Diagnosis and treatment

  • Specialist referral (a referral both to a paediatrician and gynaecologist)
  • The referral should include the patient's growth charts, past medical history and the history of the parents’ puberty.

Secondary amenorrhoea

  • A normal functioning of both the hypothalamus-pituitary-ovary axis and endometrium are prerequisites for a regular menstrual cycle.
  • See also Abnormal menstrual bleeding (Abnormal menstrual bleeding)
History

  • Previous menstrual history, contraception (Contraception: initiation, choice of method and follow-up) (Hormonal contraception)
  • Pregnancies, deliveries and associated procedures
  • Weight loss or weight gain (assess the significance of the weight change in relation to baseline weight, i.e. if BMI is 18, a weight loss of a few kg may cause amenorrhoea)
  • History of increased physical exercise, recent stress, current diseases and their medication, earlier diseases and their treatments (e.g. history of cytotoxic chemotherapy or radiotherapy), family history as regards diseases (e.g. coeliac diseases) and menstrual abnormalities
  • Any other symptoms associated with amenorrhoea (sudden sweating, vaginal dryness etc.)

Status

  • Height, weight, blood pressure
  • Fat distribution (truncal obesity)
  • Striae, abnormal pigmentation of external genitalia and armpits
  • Hirsutism, greasy skin, acne
  • Thyroid gland
  • Breasts, possible galactorrhoea
  • Gynaecological examination: state of the vaginal epithelium, size of the uterus and ovaries.

Diagnosis and treatment

  • Exclude pregnancy.
  • Serum prolactin
    • Galactorrhoea? (4)
    • If increased prolactin and amenorrhoea, ask about antipsychotic medication (5)
    • Pituitary and hypothalamic tumours are possible (6).
    • Hyperprolactinaemia without a clear cause (lactation, antipsychotic medication) warrants a referral for further investigation.
  • Serum TSH
    • Hypothyroidism (7) is a more common cause of abnormal menstrual bleeding than hyperthyroidism (8).
  • Progestogen challenge test for 7–10 days (e.g. dydrogesterone 10–20 mg/day or medroxyprogesterone 10 mg/day)
    • If withdrawal bleeding occurs within 2 weeks of the last tablet, the level of oestrogen is sufficient to proliferate the endometrium. If no bleeding occurs, the level of oestrogen is low or the endometrium is nonresponsive.
  • If no withdrawal bleeding occurs, measure FSH and LH.
    1. Low FSH and LH
      • Hypothalamic/pituitary aetiology
      • Anorexia: refer to a psychiatric team
      • Excessive exercise: inform the patient about the risk of osteoporosis. The goal is to increase caloric intake.
      • If the amount of exercise and low body weight offer no explanation for the finding, refer the patient for further investigation, since the possibility of hypothalamic or pituitary tumour must be excluded.
    2. High FSH and LH, and additionally low AMH (anti-Müller-hormone, which may be determined as required)
      • Ovarian insufficiency
      • The aetiology and treatment (e.g. risk of osteoporosis) in a woman less than 40 years of age should be evaluated at an appropriate hospital.
      • Early menopause (familial tendency in 30–50% of cases; see (9))
      • Polyendocrinopathy
      • Iatrogenic aetiology (surgery, chemotherapy)
    3. Normal FSH and LH
      • The aetiology is related to endometrial response
      • Presence of intrauterine adhesions, e.g. after curettage, (Asherman's syndrome)
      • Referral to a specialist
    4. Systemic illness may cause amenorrhoea
      • Hyperthyroidism, hypothyroidism, renal or hepatic insufficiency, severe untreated coeliac disease (10) etc. Usually no withdrawal bleeding after progestogen challenge test.
  • If withdrawal bleeding occurs the patient is normoestrogenic and anovulatory.
    1. Ask about possible stress factors (problems with personal relationships, recent changes in employment status, death of a close family member etc.). The condition is transient.
      • Treat with cyclical progestogen (dydrogesterone 10 mg on days 15–24 of the cycle) for three months.
      • If normal menstrual cycle is not achieved without medication, refer the patient to a gynaecologist.
    2. Obvious weight gain, truncal obesity, acne, hirsutism
      • Polycystic ovary syndrome, see (11).
      • Ovulation disturbed by obesity alone, treated with cyclical progestogen until weight normalizes to avoid the risk of endometrial hyperplasia (12) (13)
      • Rare: Cushing's syndrome (14)
      • If there are clear signs of virilism (alopecia, marked hirsutism, enlargement of the clitoris, deepening of the voice) and serum testosterone level is increased, the patient must be referred to a gynaecologist. The patient may have an androgen-producing adrenal or ovarian tumor. See also (15).
      • Note! If the testosterone level is very high, no withdrawal bleeding will occur after the progestogen challenge test.


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Citation

"Amenorrhoea." Evidence-Based Medicine Guidelines, Duodecim Medical Publications Limited, 2019. Evidence Central, evidence.unboundmedicine.com/evidence/view/EBMG/456115/all/Amenorrhoea.
Amenorrhoea. Evidence-Based Medicine Guidelines. Duodecim Medical Publications Limited; 2019. https://evidence.unboundmedicine.com/evidence/view/EBMG/456115/all/Amenorrhoea. Accessed August 20, 2019.
Amenorrhoea. (2019). In Evidence-Based Medicine Guidelines. Available from https://evidence.unboundmedicine.com/evidence/view/EBMG/456115/all/Amenorrhoea
Amenorrhoea [Internet]. In: Evidence-Based Medicine Guidelines. Duodecim Medical Publications Limited; 2019. [cited 2019 August 20]. Available from: https://evidence.unboundmedicine.com/evidence/view/EBMG/456115/all/Amenorrhoea.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Amenorrhoea ID - 456115 BT - Evidence-Based Medicine Guidelines UR - https://evidence.unboundmedicine.com/evidence/view/EBMG/456115/all/Amenorrhoea PB - Duodecim Medical Publications Limited DB - Evidence Central DP - Unbound Medicine ER -