Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis

Objective To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Design Cross-sectional study with retrospective analysis. Setting University pediatric hospital. Patient(s) Fifteen prepubertal subjects (median age 9.0 years, range 6.9–11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9–11.6 years). Intervention(s) None. Main Outcome Measure(s) We evaluated FSH, LH, and E 2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. Result(s) All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E 2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Conclusion(s) Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E 2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects.