Physiopathology of premature ovarian failure: facts and hypotheses

Premature ovarian failure (POF) is an heterogeneous syndrome. Women can pre sent with primary amenorrhea or secondary amenorrhea occurring before the a ge of 40. Nearly 2 % of the female population is affected this disorder, It s pathophysiology still remains obscure. Different hypotheses can be propos ed: a reduction in the number of primordial follicles, an accelerated or in creased atresia, a defect in the genes involved in follicular recruitement and finally a blockade in follicular growth. Up to now, few causes have bee n identified: toxic, autoimmune and genetic. Chemotherapy and radiotherapy lead either to a reversible or to a permanent gonadal dysfunction, accordin g to the type of drug, the doses and the patient's age at the time of treat ment. Polyendocrinopathies and animal models seem to involve autoimmune dis orders as a cause of premature ovarian failure. The mechanisms, through whi ch mutations in the AIRE gene responsable for the APECED syndrome can leed to ovarian insufficiency, are still unknown. It is likely that studies on t he function of the AIRE protein, a transcription factor, might improve our knowledge. Among genetic causes, X monosomy as in Turner syndrome or X dele tions and translocations are known to be responsible for POF. The genes or the X chromosome involved in ovarian function are still unknown. Furthermor e, autosomal abnormalities have been identified as mutations of LH and FSH genes, their receptor genes, chromosome 3q, Ataxia-telangiectasia genes, th e AIRE gene. Meanwhile, the cause of POF remains idiopathic in most cases. In the future, a better knowledge of the cellular and biochemical component s implied in folliculogenesis and apoptosis should elucidate the mechanisms of POF.