Amenorrhoea
Exam Tips
- In OSCEs and SBA questions, first-line investigation for any amenorrhoea in reproductive age is a pregnancy test, regardless of stated contraception.
- Know primary amenorrhoea triggers for investigation: no menses by 13 years with absent secondary sexual characteristics, or by 15 years with secondary sexual characteristics.
- Use hormone patterns: high FSH + low oestradiol suggests ovarian failure (POI); low/normal FSH/LH + low oestradiol suggests hypothalamic/pituitary suppression.
- Amenorrhoea with headache/visual field loss or marked hyperprolactinaemia is a pituitary red flag requiring urgent endocrine imaging/referral.
- Persistent oligomenorrhoea/amenorrhoea in PCOS needs endometrial protection (cyclical progestogen or combined hormonal contraception) to reduce hyperplasia risk.
- See Figure: menstrual axis feedback loop and amenorrhoea workup algorithm in your core endocrinology/gynaecology revision text for rapid pattern recognition.
Definition
Amenorrhoea is the absence of menstrual bleeding during the reproductive years and is classified as primary or secondary. In UK clinical practice, primary amenorrhoea is typically investigated when menses have not started by age 13 without secondary sexual characteristics or by age 15 with them; secondary amenorrhoea is cessation of established periods for at least 3 months (regular cycles) or 6 months (previously irregular cycles).
Pathophysiology
Normal menstruation requires an intact hypothalamic-pituitary-ovarian (HPO) axis, responsive endometrium, and a patent outflow tract. Amenorrhoea results from disruption at one or more levels: hypothalamic suppression (for example stress, weight loss, RED-S) lowers pulsatile GnRH and gonadotrophins; pituitary disease (especially hyperprolactinaemia) suppresses GnRH; ovarian failure (for example premature ovarian insufficiency) causes low oestradiol with compensatory high FSH/LH; uterine/outflow pathology (for example Asherman syndrome, cervical stenosis, imperforate hymen) prevents menstrual efflux despite hormonal cycling. In PCOS, chronic anovulation reflects disordered folliculogenesis with insulin resistance/hyperandrogenism. See Figure: HPO axis feedback diagram in an endocrinology textbook chapter on menstrual disorders.
Risk Factors
- Low energy availability, excessive exercise, and eating disorders (RED-S/functional hypothalamic amenorrhoea)
- Psychological stress and depression
- Very low BMI or rapid weight loss
- Obesity and insulin resistance (PCOS risk)
- Hyperprolactinaemia risk from dopamine-antagonist drugs (for example antipsychotics, metoclopramide) or pituitary adenoma
- Premature ovarian insufficiency risk factors: chemotherapy, pelvic radiotherapy, ovarian surgery, autoimmune disease, genetic/chromosomal conditions (for example Turner syndrome)
- Chronic systemic disease (coeliac disease, inflammatory bowel disease, renal/hepatic/cardiac disease, malignancy, tuberculosis, HIV)
- Postpartum major haemorrhage (Sheehan syndrome risk)
- Intrauterine procedures/instrumentation (risk of Asherman syndrome)
- Physiological states: pregnancy, lactation, menopause
Clinical Features
Symptoms
- Absent periods (primary: never menstruated; secondary: periods stopped)
- Infertility/subfertility
- Cyclical pelvic or lower abdominal pain (outflow obstruction such as imperforate hymen)
- Headache, visual disturbance, galactorrhoea (possible pituitary lesion/hyperprolactinaemia)
- Hot flushes, vaginal dryness, reduced libido (hypo-oestrogenism, especially POI)
- Weight loss, restrictive eating, high training load, or stress history
- Hirsutism/acne and cycle irregularity (hyperandrogenism, often PCOS)
Signs
- Absent or delayed secondary sexual characteristics in primary amenorrhoea
- BMI extremes (low BMI suggesting hypothalamic suppression; high BMI suggesting PCOS)
- Short stature, webbed neck, shield chest (Turner phenotype)
- Galactorrhoea
- Visual field defects or papilloedema (intracranial mass effect)
- Signs of thyroid disease
- Cushingoid features (central adiposity, striae, proximal weakness, bruising, hypertension)
- Virilisation/clitoromegaly (consider androgen-secreting tumour)
- Pelvic findings of outflow tract anomaly or absent uterus (assessment guided by age/sexual activity)
Investigations
Management
Lifestyle Modifications
- Correct low energy availability with dietetic input and reduced excessive training load in RED-S/FHA
- Treat eating disorders and comorbid psychological distress (multidisciplinary approach)
- Weight optimisation and exercise advice tailored to cause (including metabolic risk reduction in PCOS)
- Preconception counselling and fertility discussion early where relevant
- Bone health measures: weight-bearing exercise, smoking cessation, alcohol moderation, adequate calcium/vitamin D
Pharmacological Treatment
Hormone replacement for premature ovarian insufficiency (if uterus present, add progestogen)
- Estradiol oral 1-2 mg once daily or transdermal estradiol patch 50-100 micrograms/24 hours (changed per product schedule)
- Micronised progesterone 200 mg at night for 12 days of each 28-day cycle (sequential regimen) or continuous combined regimen when appropriate
Usually continue until around the natural age of menopause unless contraindicated. Unopposed oestrogen is contraindicated in patients with a uterus because of endometrial hyperplasia/cancer risk.
Dopamine agonists for prolactinoma/hyperprolactinaemia
- Cabergoline initially 250 micrograms twice weekly, titrated to prolactin response
- Bromocriptine initially 1.25 mg at night, then titrate (commonly 2.5 mg daily or more in divided doses)
Check for drug causes first. Warn about nausea, dizziness, postural hypotension, and impulse-control effects; monitor prolactin and tumour size where indicated.
Management of thyroid-related amenorrhoea
- Levothyroxine typically 50-100 micrograms once daily initially (individualised), titrated to TSH
- Antithyroid therapy for hyperthyroidism (for example carbimazole, specialist-guided dosing)
Correcting thyroid dysfunction often restores cycles. In pregnancy or suspected pregnancy, thyroid management needs urgent specialist-safe prescribing.
PCOS-related cycle control/endometrial protection
- Combined oral contraceptive pill, for example ethinylestradiol 30 micrograms/levonorgestrel 150 micrograms once daily in a 21/7 regimen
- Cyclic progestogen for endometrial protection, for example medroxyprogesterone acetate 10 mg once daily for 10-14 days every 1-3 months
- Metformin starting 500 mg once daily with food, titrating to 1.5-2 g/day as tolerated
Exclude pregnancy first. Combined hormonal contraception is contraindicated in important groups (for example migraine with aura, current VTE/high thrombosis risk, severe uncontrolled hypertension, smoker aged 35 or older). Metformin commonly causes gastrointestinal side effects; monitor renal function.
Fertility-induction (specialist reproductive care)
- Letrozole 2.5-7.5 mg once daily for 5 days (typically early cycle, for anovulatory infertility such as PCOS)
- Clomifene citrate 50 mg once daily for 5 days (alternative where used)
Not for unsupervised use; requires ovulation monitoring and counselling about multiple pregnancy risk.
Surgical / Interventional
- Imperforate hymen incision (hymenotomy) for outflow obstruction
- Resection of transverse vaginal septum where present
- Hysteroscopic adhesiolysis for Asherman syndrome/cervical stenosis in selected cases
- Pituitary surgery (for example transsphenoidal) for selected macroadenomas or medically refractory lesions
- Gonadectomy in selected disorders of sex development with malignancy risk (specialist MDT decision)
Complications
- Reduced bone mineral density, osteoporosis, and fragility fracture risk in prolonged hypo-oestrogenism
- Increased cardiovascular risk, particularly in premature ovarian insufficiency
- Subfertility/infertility due to chronic anovulation
- Adverse pregnancy outcomes in prior functional hypothalamic amenorrhoea (for example miscarriage, small-for-gestational-age infant)
- Psychological morbidity (anxiety, low self-esteem, body image distress)
- Cause-specific morbidity (for example metabolic disease and sleep apnoea risk in PCOS; neoplasia risk in some DSD conditions)
Prognosis
Prognosis depends on aetiology and treatment timeliness: constitutional delay and many functional hypothalamic cases can recover with targeted lifestyle and psychological intervention, while structural/genetic causes often need specialist long-term care. Early diagnosis improves fertility planning, protects bone and cardiovascular health, and reduces avoidable psychological harm; POI usually requires ongoing hormone replacement and fertility counselling.
Sources & References
✅NICE Guidelines(1)
- Amenorrhoea[overview]