SOURCE LOCALIZATION OF ANDROGEN EXCESS IN ADOLESCENT GIRLS

Functional ovarian hyperandrogenism (FOH) is characterized by an abnor mal ovarian response to challenge with the GnRH analogs nafarelin and leuprolide acetate, similar to that observed in women with well define d polycystic ovary syndrome, regardless of whether elevated LH levels or polycystic ovaries are present. We studied an unselected group of 4 2 hyperandrogenic adolescents (age range, 14-22 yr; mean, 18.1 +/- 2.5 yr) 1) to determine FOH incidence through the assessment of ovarian-s teroidogenic response to a single dose of leuprolide acetate, 2) to as sess the clinical characteristics of patients according to their respo nses to GnRH analog stimulation, and 3) to evaluate adrenal steroidoge nic function and its relation to ovarian hyperandrogenism in patients with either normal or abnormal responses to leuprolide acetate challen ge. All patients underwent leuprolide acetate and ACTH testing, dexame thasone and ovarian suppression tests, and pelvic ultrasonography. Twe nty-four (58%) patients had supranormal plasma 17-hydroxyprogesterone (17-OHP) responses to leuprolide acetate characteristic of FOH, and in 18, the 17-OHP response was similar to that of controls (n = 24; age, 17.1 +/- 2.3 yr). Seven patients (5 with FOH and 2 with normal respon ses to leuprolide acetate) had an abnormal response to ACTH, but only 1 had conclusive evidence of 21-hydroxylase deficiency. In 16 patients , the response to both stimulation tests was normal. Only 13 (54%) of the 24 FOH patients had polycystic ovaries on ultrasonography, and in 11 (46%), basal plasma LH levels were elevated. In FOH patients, reduc tion in testosterone and androstenedione plasma levels was significant ly greater after ovarian suppression than after dexamethasone challeng e (P < 0.0005 and P < 0.02, respectively). Peak plasma 17-OHP levels p ostleuprolide acetate stimulation correlated with dexamethasone-suppre ssed plasma testosterone concentrations, dexamethasone-suppressed plas ma androstenedione levels, and the free androgen index postdexamethaso ne treatment (r = 0.4, P = 0.01; r = 0.4, P < 0.05; and r = 0.41, P = 0.007, respectively). Plasma sex hormone-binding globulin levels after dexamethasone administration correlated negatively with the baseline free androgen index (r = -0.67; P < 0.0001). Considering our diagnosti c criteria, 26 (62%) of our collective of 42 patients had abnormal res ponses to one or both stimulation tests, whereas 16 (37%) had normal r esponses. FOH is the most common cause (in 58%) of androgen excess in adolescence. Short term leuprolide acetate stimulation is a reliable t ool for identification of the ovary as the source of their hyperandrog enism.