Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of folliclular (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 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. 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%.
These result in a decrease of the ovaries general supply of eggs that normally lasts until an average age of 51 for age of age-appropriate menopause.Genetic causes such as Turner syndrome have initial ovarian development but then ovaries degenerate rapidly during prenatal life, often leading to gonadal dysgenesis with streak ovaries. In those cases where POI is associated with adrenal autoimmunity, histological examination almost always confirms the presence of an autoimmune oophoritis in which follicles are infiltrated by lymphocytes, plasma cells, and macrophages that attack mainly steroid-producing cells and eventually result in follicular depletion.In some women FSH may bind to the FSH receptor site, but be inactive. By lowering the endogenous FSH levels with ethinylestradiol (EE) or with a GnRH-a the receptor sites are free and treatment with exogenous recombinant FSH activates the receptors and normal follicle growth and ovulation can occur. (Since the serum Anti-Müllerian hormone (AMH) level is correlated with the number of remaining primordial follicles some researchers believe the above two phenotypes can be distinguished by measuring serum AMH levels.Genetic associations include genetic disorders, autoimmune diseases, enzyme defects, and resistant ovaries.Mutations in FOXL2 cause Blepharophimosis Ptosis Epicanthus inversus Syndrome (BPES). Premature ovarian failure is part of the BPES Type I variant of the syndrome but not of the BPES Type II variant. DNA repair deficiency
BRCA1 protein plays an essential role in the repair of DNA double-strand breaks by homologous recombination. Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final menorrhea appearing at a younger age.