Effect of low dose oxandrolone and testosterone treatment on the pituitary-testicular and GH axes in boys with constitutional delay of growth and puberty.
OBJECTIVE
To investigate the effect of low dose oxandrolone and testosterone on the pituitary-testicular and GH-IGF-I axes.


METHODS
Prospective double-blind placebo-controlled trial.


METHODS
Sixteen boys with constitutional delay of growth and puberty (CDGP) with testicular volumes 4-6 ml were randomized to 3 months treatment: Group 1 (n = 5), daily placebo: Group 2 (n = 5), 2.5 mg oxandrolone daily or Group 3 (n = 6), 50 mg testosterone monthly intramuscular injections with assessment (growth, pubertal development and overnight hormone profiles) at 0, 3, 6 and 12 months.


METHODS
LH and GH profiles (15-minute samples) were analysed by peak detection (Pulsar), Fourier transformation and autocorrelation. Testosterone levels were measured hourly and insulin, SHBG, IGF-I, and IGFBP-3 levels at 0800 h. Statistical analysis was by multivariate analysis of variance for repeated measures.


RESULTS
LH and testosterone parameters increased significantly with time in all 16 (LH AUC, P < 0.001; peak amplitude, P = 0.02; number of peaks, P = 0.02; testosterone AUC, P = 0.02; morning testosterone, P = 0.002). In Group 2, however, LH and testosterone parameters decreased at 3 months followed by a rebound increase at 6 and 12 months. SHBG levels were markedly reduced at 3 months (P = 0.006) and a wider range of dominant GH frequencies was present although GH AUC was not increased until 6 months, with an increase in GH pulse frequency but not amplitude. IGF-I levels were increased at both 3 and 12 months. In Group 3, pituitary-testicular suppression was not apparent, but GH levels increased with an increase in GH amplitude at 3 and 12 months.


CONCLUSIONS
Oxandrolone transiently suppressed the pituitary-testicular axis and altered GH pulsatility. Testosterone increased GH via amplitude modulation.
Crowne
E C
EC
Department of Endocrinology, Christie Hospital Trust, Manchester, UK.
Wallace
W H
WH
Moore
C
C
Mitchell
R
R
Robertson
W H
WH
Holly
J M
JM
Shalet
S M
SM
D000293:Adolescent; D045930:Anabolic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006130:Growth Disorders / Q000188:drug therapy*; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010074:Oxandrolone / Q000008:administration & dosage* / Q000627:therapeutic use; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D011628:Puberty, Delayed / Q000188:drug therapy*; D012636:Secretory Rate / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000627:therapeutic use*
D045930:Anabolic Agents; D013739:Testosterone; D010074:Oxandrolone; D007986:Luteinizing Hormone; D013006:Growth Hormone