Premature ovarian insufficiency (POI)

This page covers POI diagnosis, work-up and fertility, plus how its hormone therapy differs from standard menopause treatment. For MHT regimens, prescribing mechanics and troubleshooting common to both, see Menopause Treatment. For general menopause definitions, see Overview.

Definition and diagnosis

POI should be considered in any woman <40 years with menstrual disturbance (oligomenorrhoea or amenorrhoea) — regardless of whether oestrogen-deficiency symptoms are present. A woman who has not reached menarche by 15 years should also be investigated.

Diagnostic criteria (both required):

• FSH >25 IU/L — a single elevated result is diagnostic; repeat after 4–6 weeks only if the result is equivocal or diagnostic uncertainty remains.
• ≥4 months of amenorrhoea or menstrual irregularity, in a woman <40 years, after other secondary causes have been excluded.

AMH is not used for primary diagnosis, but a very low level (<0.25 ng/mL) supports it and can shorten the diagnostic pathway. A single random oestradiol is not diagnostic — levels fluctuate too much in early POI.

Causes

Spontaneous POI

Category	Detail
Idiopathic	Most common cause
Genetic (~10%)	Turner syndrome (45X0) most common; Fragile X premutation (FMR1); rarer genes (FOXL2, NR5A1, BMP15, FSHR, G-protein alpha)
Autoimmune (~20%)	Addison’s disease, autoimmune polyendocrine syndromes 1 & 2, Hashimoto’s thyroiditis; also seen with coeliac disease, T1DM, SLE, RA, Sjögren’s and other autoimmune conditions
Metabolic (rare)	Galactosaemia
Infectious	Mumps oophoritis; also HIV, TB, malaria, shigellosis, HSV/HZV, CMV
Environmental	Smoking — associated with earlier menopause

Iatrogenic POI

Chemotherapy (particularly alkylating agents, dose-dependent); radiotherapy (dose/field-dependent); bilateral oophorectomy; other pelvic surgery associated with earlier menopause (single oophorectomy, hysterectomy, uterine artery embolisation, bilateral ovarian cyst/endometriosis surgery).

Work-up once diagnosed

Per the 2024 international guideline, all women with non-iatrogenic POI should have:

• Karyotype and FMR1 premutation testing — for all women with spontaneous POI, not just those with a suggestive phenotype/family history.
• 21-hydroxylase adrenal antibodies (not anti-ovarian antibodies, which have no proven clinical utility) to screen for autoimmune POI/adrenal insufficiency.
• TSH at diagnosis and 5-yearly thereafter.
• DXA bone density at diagnosis.
• Baseline cardiometabolic risk assessment (BP, lipids, glucose).
• Screening for psychological impact — anxiety, depression, grief around fertility loss.

Management

How this differs from standard menopause treatment

Hormone therapy is physiological replacement in POI, not an optional symptom treatment — this differs from postmenopausal treatment, which is symptom-driven. Four key differences from the standard MHT approach:

• Give it to everyone: HT is recommended for all women with POI until at least the average age of natural menopause (~51yrs), regardless of vasomotor symptoms, to protect bone, cardiovascular and (per emerging evidence) cognitive/neurological health.
• Higher dose: generally ≥2mg oral estradiol/day or ≥100microg/24hr transdermal patch — titrated to symptom control and, where checked, oestradiol levels in the normal cycling range.
• COCP is not preferred: it delivers supraphysiological, non-fluctuating ethinylestradiol and may be less bone/cardiovascular-protective than physiological-dose estradiol — though it remains reasonable if a woman strongly prefers it (e.g. for contraceptive certainty; HT alone is not reliably contraceptive).
• Breast cancer risk framing is different: risk is not clearly increased relative to women who reach menopause naturally at the same age — discuss this explicitly, as patients may otherwise extrapolate postmenopausal-HT messaging inappropriately.

Everything else — progestogen requirement with a uterus, contraindications, troubleshooting, GSM management — follows the same approach as standard MHT; see Menopause Treatment.

Testosterone (transdermal, physiological dosing) may be considered for persistent low sexual desire (HSDD) despite adequate oestrogen replacement.

Puberty induction (adolescent POI, e.g. Turner syndrome): low-dose transdermal or oral estradiol from around 11yrs, gradually increased over 2–3 years; progestogen added after ~2 years or with breakthrough bleeding. Combined oral contraceptives are not recommended for induction (supraphysiological dosing, wrong oestrogen).

Fertility

• Spontaneous conception is uncommon but not impossible — roughly 5% overall (up to ~15% in some cohorts). HT does not need to be stopped to “allow” a chance of natural conception, and does not reduce that chance.
• No intervention has been shown to reliably restore fertility (ovarian stimulation, DHEA and other supplements lack good evidence).
• Oocyte donation is the established, effective option for women wanting biological pregnancy.
• Turner syndrome pregnancies (donor oocyte or spontaneous) are very high risk, particularly for aortic dissection — pre-pregnancy cardiac assessment (echo ± MRI) is essential, and a sister/relative as oocyte donor carries a higher cycle cancellation rate than an unrelated donor due to shared genetic background.
• Discuss fertility preservation proactively when POI is anticipated (e.g. before gonadotoxic chemotherapy/radiotherapy).

Genitourinary symptoms

Vaginal dryness/GSM is common even on systemic HT — topical vaginal oestrogen is recommended as an add-on and is safe in combination with systemic HT.

Ongoing surveillance

• DXA repeated per bone density trajectory and HT adherence.
• Continue periodic cardiometabolic risk review.
• Reassess psychological wellbeing at review, not only at diagnosis.
• Continue HT at least until the average age of menopause, then transition to standard postmenopausal decision-making.