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PATIERNS OF OVARIAN-STEROIDOGENIC RESPONSE TO GnRH ANALOG CHALLENGE AT ONSET OF PUBERTY IN GIRLS DIAGNOSED OF PREMATURE PUBARCHE DURING CHILDHOOD

Post-pubertal girls diagnosed of premature pubarche (PP) during childhood shown an increased incidence of functional ovarian hyperandrogenism (FOH). We assessed ovarian-steroidogenic response to the GnRHa leuprolide acctate (500 μg sc) in to PP girls (chronological age (CA): 10.1 ± 1.0, bone age (BA): 10.8 ± 0.6) and in 10 controls (C) (CA: 11.9 ± 0.7, BA: 10.8 ± 0.5) at onset of true puberty (Tanner B2), to ascertain whether the supranormal 17-hydroxyprogesterone (17-OHP) response, characteristic of FOII, appears early in pubertal development; 21-hydroxylase and 3β-hydroxysteroid dehydrogenase deficiencies had been ruled out in all.Plasma LH and FSH levels were measured 0 and 6h post-GnRHa stimulation, and plasma estradiol (E2), and steroid intermediates were determined pre- and 24 h post-GnRHa challege, GnRHa administration elicited pubertal gonadotropin responses and a 10-fold increase in plasma E2 levels in all subjects. Six PP girls had basal and post-stimulated androstenedione (D4-A) responses similar to those of C (100.3 ± 11.8 vs 93.5 ± 15.2; 133.7 ± 29.4 vs 137.8 ± 11.1 ng/dl respectively), whereas in the remaining 10, basal and post-GnRHa stimulation and values of the same steroids at PP diagnosis. Our results show that the distinct 17-OHP response post-GnRHa stimulation typical of FOH is not present at onset of true puberty in PP girls; disregulation of cytochrome P450c 17a might occur later in puberty. Although 10 PP girls showed high basal and post-stimulated D4-A levels, the increase elicited by GnRHa was similar to that of C, ruling out ovarian hyperproduction of D4-steroids in early stages of pubertal development.Long-term follow-up of these patients through later stages of puberty is necessary to assess the significance of these elevated D4-A levels in the eventual development of FOH.