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

This study of the hypothalamus-hypophysis-gonad axis in children and adolescents with nonmosaic triple X syndrome found that Triple X patients showed premature activation of the gonadotropin-releasing hormone pulse generator and reduced gonadal function.


Stefano Stagi, M.D., Mariarosaria di Tommaso, M.D., Ph.D., Perla Scalini, M.D., Elisabetta Lapi, M.D., Stefania Losi, M.D., Erica Bencini, M.D., Fabrizio Masoni, M.D., Laura Dosa, M.D., Sabrina Becciani, M.D., Maurizio de Martino, M.D.

Volume 105, Issue 6, Pages 1547-1553



To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome.


Cross-sectional study with retrospective analysis.


University pediatric hospital.


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).



Main Outcome Measure(s):

We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test.


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 E2 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.


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 E2 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.

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