Primary Ovarian Insufficiency (POI)

What happens in POI

The ovaries contain a supply of follicles, each holding an egg. In POI, follicles are either too few, run out early, or do not respond properly to hormones from the pituitary gland (FSH and LH). Estrogen and progesterone fall, so periods become irregular or stop, and the pituitary releases more FSH trying to stimulate the ovaries.

POI is now preferred over "premature ovarian failure" because the ovaries often do not fail completely. For more on the term and symptom picture, see premature ovarian failure.

POI vs early menopause

Causes

• Unknown (idiopathic): the majority of cases
• Genetic: - Turner syndrome and other X chromosome changes - FMR1 premutation (fragile X carrier), found in a significant minority of women with POI, especially those with a family history - other single-gene changes
• Autoimmune: associated with Hashimoto's thyroiditis, Addison's disease, type 1 diabetes and others
• Medical treatments: chemotherapy (especially alkylating agents), pelvic radiation, ovarian surgery
• Infections: rarely, mumps affecting the ovaries
• Metabolic disorders: such as galactosemia

Symptoms

• irregular, infrequent or absent periods
• hot flashes and night sweats
• vaginal dryness and pain with sex
• reduced libido
• trouble sleeping
• mood changes, low mood, anxiety and poor concentration
• difficulty conceiving

Some women have few symptoms apart from changes in their periods.

Diagnosis

Current international guidance (ESHRE 2024) diagnoses POI with:

1. Disordered periods: irregular or absent periods for at least 4 months, and
2. Raised FSH: an FSH level above 25 IU/L. A repeat test after 4 to 6 weeks is advised if the result is borderline or unclear. AMH can help when the diagnosis is uncertain.

Further tests after diagnosis:

• pregnancy test, prolactin and thyroid function to exclude other causes
• chromosome analysis (karyotype)
• FMR1 premutation testing
• adrenal antibodies and thyroid antibodies
• bone density scan (DXA) at diagnosis
• blood sugar and cholesterol

Treatment

Hormone replacement

Estrogen replacement, with a progestogen if the uterus is present, is recommended until at least the average age of natural menopause (about 50 to 51) unless there is a reason not to use it. It:

• relieves hot flashes and vaginal dryness
• protects bone density
• likely lowers the long-term risk of heart disease and cognitive decline

Hormone replacement in POI replaces hormones the body would normally make at this age. The increased breast cancer risk seen with HRT in older women does not appear to apply in the same way to young women with POI. Options include HRT patches, gels or tablets, or a combined hormonal contraceptive pill when contraception is also wanted.

Bone and heart health

• weight-bearing exercise
• calcium and vitamin D
• no smoking
• regular blood pressure, cholesterol and blood sugar checks

Fertility

• natural conception is possible but unpredictable; use contraception if pregnancy is not wanted
• IVF with donor eggs has high success rates
• egg or embryo freezing before cancer treatment can preserve fertility
• adoption and other options
• fertility counseling early after diagnosis

Emotional support

A POI diagnosis can be very distressing, affecting identity, relationships and family plans. Counseling and peer support groups help many women.

Complications

• osteoporosis and fractures
• cardiovascular disease
• infertility
• anxiety and depression
• vaginal and urinary symptoms
• associated autoimmune conditions, including thyroid disease and Addison's disease

Outlook

POI is usually permanent, though function can return intermittently. With hormone replacement and attention to bone and heart health, women with POI can expect good long-term health.

Frequently asked questions

What is primary ovarian insufficiency?

Primary ovarian insufficiency is when the ovaries stop working normally before age 40. It leads to irregular or absent periods, low estrogen and reduced fertility. Unlike menopause, ovarian function can sometimes return, and a small proportion of women still conceive naturally.

Is primary ovarian insufficiency the same as early menopause?

Not exactly. POI occurs before 40 and ovarian function may fluctuate, with occasional ovulation. Menopause is the permanent end of periods. The terms overlap, and both are treated with hormone replacement until the usual age of menopause.

Can you get pregnant with POI?

About 5 to 10% of women with POI conceive naturally, though it is unpredictable. IVF with donor eggs offers the highest chance of pregnancy. Women not wanting pregnancy should use contraception.

What causes primary ovarian insufficiency?

Most cases have no known cause. Known causes include genetic conditions such as Turner syndrome and fragile X premutation, autoimmune diseases, chemotherapy and radiation, and ovarian surgery. Genetic testing is recommended after diagnosis.

Do I need hormone therapy if I have POI?

In most cases, yes. Hormone replacement until around age 50 relieves symptoms and protects bones, heart and brain health. Discuss the best type for you, including whether a contraceptive pill might suit your needs.