Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. This led us to set up a French network on POF for the purpose of better characterizing POF patients and understanding the mechanisms involved in this pathology. Over the last 10 years, we have evaluated 360 women who were referred to our center with a diagnosis of POF, and performed a study of clinical, biological, histological, morphological and genetic data relating to these patients. Seventy-seven percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 29%. The presence of follicles was suggested at ultrasonography in 45% of the patients, and observed in 28% at histology; the negative predictive value of the presence of follicles at ultrasonography was 80%. A genetic cause of POF was identified in 22 patients, 8 of whom had chromosomal abnormalities other than Turners syndrome, 5 evidenced FMR1 pre-mutation and 9 showed molecular alterations in candidate genes possibly or certainly associated with POF (FSHR, GDF-9, BMP-15 or meiosis gene and Congenital Disorders of Glycosylation). Two patients had autoimmune polyendocrine syndrome (APS) type 2 and 1 with multiple autoimmune diseases. POF remained idiopathic in all the other cases. Over 57% of POF patients experienced BMD alteration, highlighting the importance of estrogen therapy. Our data indicate that global phenotyping of POF patients is of importance to improve clinical management and to orient the search for the identification of genetic mutations, particularly the screen for FMR1 premutation and FSHR mutations. This is expected to be relevant to the detection, in the near future, of women who are at risk for POF and to the development of new therapeutic approaches.
25 - 29 Apr 2009
European Society of Endocrinology