GIRLS DIAGNOSED WITH PREMATURE PUBARCHE SHOW AN EXAGGERATED OVARIAN ANDROGEN SYNTHESIS FROM THE EARLY STAGES OF PUBERTY - EVIDENCE FROM GONADOTROPIN-RELEASING-HORMONE AGONIST TESTING

Objective: To assess the gonadotropin and ovarian steroid responses to the GnRH agonist (GnRH-a) leuprolide acetate (LA) in premature pubarc he girls and in Tanner stage- and bone age-matched controls to ascerta in whether the ovarian 17-hydroxyprogesterone (17-OHP) hyperresponse t o GnRH-a challenge present in some subsets of adolescent premature pub arche girls is detectable during puberty and whether these patients ha ve a distinct pattern of pituitary-ovarian maturation. Design: Cross-s ectional study. Setting: A university teaching hospital. Patient(s): S eventy-six premature pubarche girls (early pubertal [B2; n = 31], midp ubertal [B3; n = 15], late pubertal [B4; n = 12], and postmenarcheal [ B5; n = 18]) and 45 controls. Intervention(s): Gonadotropins and plasm a steroid hormones (17-OHP, 17-OHP-pregnenolone [17-Preg], androstened ione [A], T, DHEA, DHEAS, E-2, and cortisol) were measured before and 3 and 24 hours, respectively, after LA challenge (500 mu g SC). Main O utcome Measure(s): Ovarian-steroidogenic responses to GnRH-a challenge . Result(s): Luteinizing hormone responsiveness increased significantl y during puberty in all subjects whereas FSH levels changed less consi stently. Peak E-2 levels differed among pubertal stages and were signi ficantly higher in premature pubarche girls than in controls at B4 and at B5. Both peak and incremental increases of 17-Preg and DHEA throug hout puberty and of 17-OHP and A. at B4 were significantly higher in p remature pubarche girls than in controls. This pattern of ovarian-ster oidogenic response was most evident during midpuberty and late puberty and resembled the adrenal hyper-response to ACTH of exaggerated adren arche, suggestive of increased ovarian activity of both the 17 alpha-h ydroxylase and the 17,20 lyase functions of cytochrome P450c17 alpha. Conclusion(s): Pubertal girls with a history of premature pubarche sho w a distinct pattern of ovarian maturation characterized by an exagger ated ovarian androgen synthesis throughout puberty. (C) 1997 by Americ an Society for Reproductive Medicine.