Primary ovarian insufficiency (POI), also called premature ovarian insufficiency and premature ovarian failure, is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular (egg producing area) dysfunction or early loss of eggs. POI can be seen as part of a continuum of changes leading to menopause that differ from age-appropriate menopause in the age of onset, degree of symptoms, and sporadic return to normal ovarian function. POI affects approximately 1 in 10,000 women under age 20, 1 in 1,000 women under age 30, and 1 in 100 of those under age 40. A medical triad for the diagnosis is amenorrhea, hypergonadotropism, and hypoestrogenism.

Physical and emotional symptoms are similar to those seen during menopause and can include hot flashes, night sweats, dry skin, vaginal dryness, irregular or absent menstruation, anxiety, depression, mental fog, irritability, nervousness, decreased libido, and increased autoimmune disruption. The sense of shock and distress on being informed of the diagnosis can be overwhelming. Hormonal therapy with estrogen and progesterone is the first line treatment and is associated with improvement of symptoms and possibly improvement in other parameters such as bone density, mortality and cardiovascular risk. The general treatment is for symptoms, bone protection, and mental health. Although 5 to 10% of women with POI may ovulate sporadically and become pregnant without treatment, others may use assisted reproductive technology including in vitro fertilization and egg donation or decide to adopt or remain childless.

The causes of POI are heterogeneous and are unknown in 90% of cases. It can be associated with genetic causes, autoimmune disease, enzyme deficiency, infection, environmental factors, radiation, or surgery in 10%. Two to 5% of women with POI and a premutation in FMR1, a genetic abnormality, are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability.

The diagnosis is based on ages less than 40, amenorrhea, and elevated serum follicle-stimulating hormone (FSH) levels. Typical serum FSH levels in POI patients is in the post-menopausal range. Treatment will vary depending on the symptoms. It can include hormone replacement therapy, fertility management, and psychosocial support, as well as annual screenings of thyroid and adrenal function.

The signs and symptoms of POI can be seen as part of a continuum of changes leading to menopause. POI contrasts with age-appropriate menopause in the age of onset, degree of symptoms and sporadic return to normal ovarian function. As some women retain partial ovarian function, symptoms may not be as severe as regular menopause. In others, particularly with coexistent depression, symptoms such as decreased quality of life can be severe.

Hormonally, POI is defined by abnormally low levels of estrogen and high levels of FSH, which demonstrate that the ovaries are no longer responding to circulating FSH by producing estrogen and developing fertile eggs. The ovaries will likely appear smaller than normal.^{[medical citation needed]} The age of onset can be as early as 11 years. POI can be seen as part of a continuum of changes leading to menopause that differ from age-appropriate menopause in the age of onset, degree of symptoms, and sporadic return to normal ovarian function. A contrasting problem can be when a girl never begins menstruation due to a genetic condition causing primary amenorrhea.

The cause of POI is idiopathic in 39-67% of cases. Some cases of POI are attributed to autoimmune disorders such as autoimmune oophoritis, Hashimoto thyroiditis, Addison disease, type I diabetes mellitus, pernicious anemia, genetic disorders such as Turner syndrome and Fragile X syndrome, metabolic defects, and enzyme defects. One study showed a strong correlation between incidence of POI and certain variants in the inhibin alpha gene. Chemotherapy and radiation treatments (especially radiation to the pelvis) for cancer can sometimes cause POI. The effect of chemotherapy or radiation is variable and in a mouse model, with results consistent with observations in humans, cyclophosphamide can result in an 87% reduction in primordial follicles 72 hours after administration. Women who have had a hysterectomy tend to go through menopause early and have a nearly twofold increased risk of POI. Almost any pelvic surgery has the potential to damage the ovary by affecting its blood supply or causing inflammation in the area resulting in POI, especially surgery to the ovaries themselves (e.g. for treatment of ovarian cysts or endometriosis). Certain environmental toxins such as phthalates, bisphenols, and dioxins are also associated with POI. Certain infectious diseases, such as mumps or HIV may also damage the ovaries, leading to POI.

Women who have inherited classic galactosemia (galactose intolerance) may develop primary ovarian insufficiency.