Aetiology of premature ovarian failure

Abstract

Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhoea in women under the age of 40 years. POF is idiopathic in 74-90% of cases but can be familial (4-33%) or sporadic. The known causes are: genetic aberrations; autoimmune ovarian damage; iatrogenic following surgery, radiotherapy or chemotherapy; environmental factors (viruses, toxins, etc.); and metabolic (galactosaemia, 17 OH deficiency, etc.) Genetic aberrations could involve the X chromosome (monosomy, trisomy or translocations) or be autosomal. Genetic mechanisms include reduced gene dosage and non-specific chromosome effect impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. The genes for POF-1 are localized to Xq 21.3-Xq27 and for POF-2 to Xq13.3-21.1. The FMR1 gene is responsible for the fragile X syndrome. It occurs due to CGG expansion of more than 55 repeats at the 5'UTR (Xq 27.3), which is associated with gene silence resulting in mental retardation in males, and POF in female carriers. Autoimmune ovarian damage is caused by the alteration of T-cell subsets and T-cell-mediated injury, increase of autoantibody producing B-cells and a low number of effector suppressor/cytotoxic lymphocyte and a decrease of number and activity of natural killer cells. POF can be associated with other non-endocrine and endocrine diseases. The mutations of AIRE gene are responsible for polyendocrinopathies (APS I-III). As the cause of POF is unknown in the majority of cases and the number of women with POF is increasing, the primary goal of scientific groups worldwide should be focused on the study of the aetiology of POF.