Synopsis
Confirm primary ovarian insufficiency before age 40, investigate genetic and autoimmune causes sensitively, replace sex steroids safely, and address bone, cardiovascular, fertility and psychological consequences.
- POI means loss or marked fluctuation of ovarian activity before age 40, presenting with irregular or absent cycles, oestrogen-deficiency symptoms or infertility; it is not synonymous with irreversible zero ovarian function.
- Exclude pregnancy and treatment effects. Current NICE NG23 diagnoses POI from symptoms and elevated FSH on two samples four to six weeks apart, and advises against diagnosis from one test or routine AMH.
- The newer 2025 international guideline uses at least four months of disordered cycles plus FSH above 25 IU/L, repeating FSH only if uncertainty remains; follow the current NHS or specialist pathway and document which criterion is applied.
- For non-iatrogenic POI, specialist assessment commonly includes chromosomal analysis, FMR1 premutation testing with genetic counselling, TSH and 21-hydroxylase antibodies when the cause is unknown.
- Offer sex-steroid replacement with HRT or an eligible combined hormonal contraceptive and continue until at least the usual age of natural menopause unless contraindicated; protect the endometrium whenever a uterus is present.
- HRT is not contraception. Intermittent ovulation and occasional spontaneous conception can occur, so discuss pregnancy testing, contraception and fertility goals explicitly.
- Assess bone health with DXA at diagnosis under current international guidance, support adequate calcium, vitamin D and weight-bearing activity, and avoid substituting supplements for adequate oestrogen replacement.
- No treatment reliably restores depleted ovarian activity; reproductive-medicine discussion includes unpredictable spontaneous ovulation, donor-oocyte conception and options shaped by age, previous treatment and personal values.
Key red flags
Collapse, hypotension, recurrent vomiting, abdominal pain, hypoglycaemia or electrolyte disturbance with autoimmune features requires urgent assessment for adrenal crisis.
A positive pregnancy test with pain or bleeding still requires ectopic-pregnancy assessment because intermittent ovulation can occur after a POI diagnosis.
Short stature, webbed neck, lymphoedema history, cardiac signs or a Turner-pattern karyotype requires specialist cardiovascular and aortic assessment before pregnancy treatment.
New neurological symptoms, galactorrhoea or low rather than raised gonadotrophins should trigger diagnostic reconsideration for central disease.
Severe distress, suicidal thoughts or acute crisis after an unexpected fertility diagnosis needs urgent psychological or mental-health support.
Investigation priorities
Exclude pregnancy and biochemically confirm the UK NICE diagnosis in a person under 40.
Management branches
A person younger than 40 has disordered cycles or oestrogen-deficiency symptoms.
- Exclude pregnancy, document at least the relevant duration of cycle change and review contraception, HRT, surgery and gonadotoxic treatment.
- Under NICE, demonstrate raised FSH twice four to six weeks apart with compatible symptoms; refer when results or treatment effects make classification uncertain.
- Explain the diagnosis sensitively and arrange early symptom, fertility, bone and cardiovascular care rather than waiting for every causal test.