Premature Ovarian Insufficiency
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Direct answer
Premature ovarian insufficiency is loss of ovarian function before age 40, defined by amenorrhoea or oligomenorrhoea for at least four months with raised FSH on repeated testing. It arises from idiopathic, autoimmune, genetic, iatrogenic or infective damage to the ovary. Hormone replacement therapy is given until the natural age of menopause to protect bone and cardiovascular health, and it forms the core of management.
What you must remember
- Definition: loss of ovarian function before 40, with amenorrhoea or oligomenorrhoea and raised FSH.
- Confirmation: FSH above 25 IU/L with at least four months of disordered cycles; the older criterion needs two readings at least four weeks apart, while the 2024 ESHRE guideline accepts one raised FSH and repeats it after 4 to 6 weeks if uncertain.
- Idiopathic: the commonest cause, with no identifiable trigger.
- Autoimmune: associated with Addison disease, hypothyroidism, type 1 diabetes and polyglandular autoimmune syndromes.
- Genetic: FMR1 premutation (fragile X), Turner syndrome with a 45,X or mosaic karyotype, and galactosaemia.
- Iatrogenic: chemotherapy, pelvic radiotherapy, bilateral oophorectomy or ovarian surgery.
- Replacement: oestrogen until the natural age of menopause, with progestogen added if the uterus is present.
- Fertility: spontaneous pregnancy is possible in a minority; donor oocyte IVF is the most reliable route.
A diagnostic approach for a 31-year-old with missed periods
A 31-year-old woman has had no periods for five months and feels hot at night. The following steps separate premature ovarian insufficiency from other causes of amenorrhoea.
- Exclude other causes: pregnancy, thyroid dysfunction and hyperprolactinaemia are checked first, since they are more common than POI.
- Measure FSH and oestradiol: raised FSH above 25 IU/L with low oestradiol supports the diagnosis, and the test is repeated after 4 to 6 weeks if the picture is uncertain (older criteria required two readings).
- Check the karyotype: Turner syndrome, including mosaic forms, is excluded, and FMR1 premutation testing is considered.
- Screen for autoimmunity: TSH, glucose and adrenal function are checked, since Addison disease must be excluded when ovarian failure is autoimmune.
- Start replacement: oestrogen replacement with progestogen if the uterus is present is continued to the natural menopausal age, with calcium and vitamin D.
- Plan fertility and bone care: donor oocytes are discussed if pregnancy is wanted, and bone density is reviewed in the context of long-term oestrogen deficiency.
Where students lose marks
These traps recur in gynaecology and endocrinology questions.
- Trap: diagnosing POI from an FSH result without the menstrual history. Correct: FSH above 25 IU/L must accompany at least four months of oligomenorrhoea or amenorrhoea, and FSH fluctuates, so older criteria asked for two raised levels at least four weeks apart.
- Trap: believing the diagnosis rules out pregnancy for ever. Correct: a minority of women conceive spontaneously, so contraception is advised if pregnancy is not wanted.
- Trap: stopping HRT early for symptoms alone. Correct: oestrogen is continued to the natural menopausal age because oestrogen deficiency harms bone and cardiovascular health.
- Trap: missing Turner syndrome in a short girl with amenorrhoea. Correct: short stature with POI should prompt karyotype analysis.
Frequently asked questions
What is the FSH cut-off for premature ovarian insufficiency?
An FSH level above 25 IU/L together with at least four months of oligomenorrhoea or amenorrhoea supports premature ovarian insufficiency. Older criteria needed two readings at least four weeks apart, whereas the 2024 ESHRE guideline accepts a single raised value and repeats it after 4 to 6 weeks if the diagnosis is uncertain. Low oestradiol adds confirmation.
Why is hormone replacement continued until the natural menopausal age in POI?
Hormone replacement is continued until the natural age of menopause in premature ovarian insufficiency because oestrogen protects bone density and cardiovascular health. Stopping it early exposes the patient to osteoporosis and cardiovascular risk. Progestogen is added if the uterus is present.
Which genetic causes are linked with premature ovarian insufficiency?
Fragile X premutation (FMR1), Turner syndrome with a 45,X or mosaic karyotype, and galactosaemia are recognised genetic causes of premature ovarian insufficiency. Karyotype analysis forms part of the initial evaluation. Autoimmune polyglandular syndromes also cause it through ovarian autoimmunity.
Can women with premature ovarian insufficiency become pregnant?
Women with premature ovarian insufficiency can occasionally conceive spontaneously, but this is uncommon. Donor oocyte IVF is the most reliable route to pregnancy. Contraception is advised if pregnancy is not wanted, since ovulation can occur intermittently.