DEGREE OF ACTIVATION OF THE PITUITARY-TESTICULAR AXIS IN EARLY PUBERTAL BOYS WITH CONSTITUTIONAL DELAY OF GROWTH AND PUBERTY DETERMINES THEGROWTH-RESPONSE TO TREATMENT WITH TESTOSTERONE OR OXANDROLONE

Early pubertal boys (testicular volume, 4-6 mL) with constitutionally delayed growth and puberty were randomized to 3 months of treatment af ter a baseline 12-h overnight hormone profile: group 1 (n = 5), daily placebo; group 2 (n = 5), 2.5 mg oxandrolone daily; or group 3 (n = 6) , 50-mg testosterone monthly im injections. LH and GH profiles (15-min samples) were analyzed by peak detection (Pulsar), Fourier transforma tion, and autocorrelation. FSH and testosterone levels were measured h ourly, and insulin, sex hormone-binding globulin, insulin-like growth factor-I, and insulin-like growth factor-binding protein-3 levels were determined at 0800 h. Multiple regression was used to analyze the res ponse to treatment (growth) with respect to baseline features. Endocri ne variability was marked. Profiles ranged from unreactive to well est ablished LH pulsatility and adult testosterone levels. The areas under the curve (AUC) for LH, FSH, and testosterone ranged 10-fold (4.4-46. 3 IU/L . h), 8-fold (7.9-63.4 IU/L . h), and 45-fold (3.6-161.7 nmol/L . h), respectively. The growth response was individually varied, but significantly increased 0-6 months in the active treatment groups. Age , testicular volume, and LH AUC interacted significantly (r(2) = 0.95; P < 0.05). Allowance for these produced a highly significant treatmen t effect (P = 0.006). Age, testicular volume, LH AUG, and testosterone AUG, but not treatment, significantly increased growth by 0-12 months (r(2) = 0.88; P < 0.05). We demonstrate a spectrum of activation of t he reproductive axis despite tight clinical staging. This, and not GK status at treatment commencement, influenced the growth response.