Endocrinology

Biography

Biography: Philippe Touraine

Abstract

Premature ovarian failure (POF) occurs in almost 1% of women under the age of 40. This encompasses a heterogeneous spectrum of conditions with phenotypic variability among patients. However, in most cases, the etiology remains unknown and POF is mostly irreversible. In such context, we had the opportunity to set up a network to better understand the current diagnosis management but also to discuss, on a case-by-case basis, the genetic studies and the opportunity for proposing hormonal regimens, to potentially increase their fertility prognosis. We performed a mixed retrospective and prospective study between 1997 and 2014. Five hundred and fifty-seven patients were included. Seventy-six percent of the patients presented normal puberty and secondary amenorrhea, and 28% were under the age of 20 at the time of diagnosis. Forty-five percent of women had detectable estradiol levels and 38% had detectable inhibin B levels. Fifty-six (15.7%) patients presented highly variable hormonal and clinical profiles, leading to the definition of a subgroup of patients with fluctuating POF. The presence of follicles was suggested at ultrasonography in 50% of patients, and in 29% at histology. The negative predictive value of ultrasonography for detection of follicles was 77%. According to us, AMH measure appeared to be a better marker for detecting a remaining ovarian reserve. Finally, a bone mineral density study revealed different patterns: 43% presented a normal BMD, whereas 44% had osteopenia and 13% osteoporosis. Karyotype and Xfra screening were systematically performed, at least in the most recent patients included for the last criteria, whereas genetic studies concerning genes involved in follicular maturation were performed, depending on the presence of follicles, and observed either on ultrasonography or ovarian biopsy. Various genetic mutations have been identified. Overall, the etiology of POF could be suspected or identified in 27 patients (7.5%). POF remained idiopathic in all other cases. Finally, a current prospective follow up of these patients is under evaluation in order to define the natural history of POF in these women, as well as of a subgroup of patients likely to be concerned by therapeutics in order to increase their fertility. Preliminary data suggest that patients who became spontaneously pregnant did so within the first year after POF diagnosis. Finally, different therapeutic strategies will be discussed.