Etiologies of Primary Ovarian Insufficiency

Genetic or congenital abnormalities

Gonadal dysgenesis secondary to genetic defects (eg, Turner syndrome [45,X or mosaic 45,X/46,XX or 45,X/47,XXX] or mixed gonadal dysgenesis)

FMR1 premutation (Fragile X syndrome)

Trisomy X with or without chromosomal mosaicism

Rare autosomal genetic abnormalities

Myotonic dystrophy

Reduced germ cell number (due to defects in meiotic recombination, disorganization of the germ cell pool)

Autoimmune (causes or associated disorders)

Associated autoimmune disorders (most commonly, Hashimoto thyroiditis, Graves disease, Addison disease, systemic lupus erythematosus, and type 1 diabetes)

Metabolic disorders

Galactosemia

17-Alpha-hydroxylase deficiency

17,20-Lyase deficiency

Cholesterol desmolase deficiency

Toxic or infectious exposures

Infections (eg, mumps, tuberculosis)

Accelerated ovarian follicular atresia (idiopathic)

Cigarette smoking

Iatrogenic and other causes

Chemotherapeutic (especially alkylating) agents

Irradiation of the ovaries (total radiation dose > 6 Gy)

Bilateral oophorectomy