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 14 or
menstruation has not started by the age of 16, even though puberty has otherwise progressed normally.
Causes
The most common cause is irreversible ovarian failure; often no onset of puberty.
Usually associated with chromosomal abnormalities, e.g. Turner's syndrome
Other ovarian defect (dysgenesis)
Malignancy treated in childhood
Pituitary causes; often no onset of puberty
Pituitary tumour (most often prolactinoma)
Medication increasing prolactin levels
Hypofunction of the pituitary gland
Hypothalamic causes; pubertal changes often lacking
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, increased hair growth, acne 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.
Bimanual pelvic examination should not be done if the patient is an adolescent who has not had sexual intercourses.
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.
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.
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.
Presence of intrauterine adhesions, e.g. after curettage (Asherman's syndrome)
Referral to a specialist
Systemic illness may cause amenorrhoea.
Hyperthyroidism, hypothyroidism, renal or hepatic insufficiency, severe untreated coeliac disease Coeliac Disease etc. Usually no withdrawal bleeding after progestogen challenge test.
If withdrawal bleeding occurs the patient is normoestrogenic and anovulatory.
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.
Obvious weight gain, truncal obesity, acne, hirsutism
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 Excessive Hair Growth (Hirsutism).
Note! If the testosterone level is very high, no withdrawal bleeding will occur after the progestogen challenge test.
References
Klein DA, Paradise SL, Reeder RM. Amenorrhea: A Systematic Approach to Diagnosis and Management. Am Fam Physician 2019;100(1):39-48. [PubMed]
Gordon CM, Ackerman KE, Berga SL et al. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2017;102(5):1413-1439. [PubMed]