POSTPUBERTAL OUTCOME IN GIRLS DIAGNOSED OF PREMATURE PUBARCHE DURING CHILDHOOD - INCREASED FREQUENCY OF FUNCTIONAL OVARIAN HYPERANDROGENISM

The postpubertal outcome of a group of girls diagnosed of premature pu barche during childhood was assessed 1) to determine the incidence of functional ovarian hyperandrogenism (FOH) through the ovarian-steroido genic response to the GnRH agonist leuprolide acetate, 2) to validate leuprolide acetate stimulation in FOH diagnosis, and 3) to ascertain w hether FOH-predictive biochemical markers exist at the diagnosis of pr emature pubarche. Of 35 patients (age, 15.4 +/- 1.5 yr), 16 showed hir sutism, oligomenorrhea, and elevated baseline testosterone and/or andr ostenedione (DELTA4-A) levels. Subcutaneous administration of leuproli de acetate (500 mug) produced similar increases in gonadotropin levels in oligomenorrheic patients, regularly menstruating patients (n = 19) , and controls (n = 12; age, 15.3 +/- 1.3 yr) when tested at 6 h. Of a ll of the steroids measured, 17-hydroxyprogesterone (17-OHP) and DELTA 4-A levels 24 h postleuprolide acetate stimulation were significantly higher in oligomenorrheic patients than in the other two groups (P < 0 .0001). No overlapping in 17-OHP responses occurred between oligomenor rheic patients and the other groups. Baseline dehydroepiandrosterone s ulfate and DELTA4-A levels at the diagnosis of premature pubarche corr elated with 17-OHP values postleuprolide acetate challenge (r = 0.47; P < 0.005 and r = 0.67; P < 0.0001, respectively). These results show a distinct leuprolide acetate challenge response in 45% of the postpub ertal premature pubarche girls studied, suggestive of an increased inc idence of FOH, and support the need for continued routine postmenarche al evaluation of this group of patients. Responses of 17-OHP to leupro lide acetate challenge facilitate the identification of FOH patients, establish this test as a reliable diagnostic tool in FOH diagnosis, an d confirm the ovaries as the source of hyperandrogenemia in most patie nts with androgen excess. Although increased 17-OHP responses after le uprolide acetate stimulation seem to occur more frequently in girls wi th elevated dehydroepiandrosterone sulfate and/or DELTA4-A levels at t he diagnosis of premature pubarche, specific biochemical markers predi ctive of FOH in this group of patients are still lacking.