Adult females receiving GH may be less sensitive to the metabolic effects of GH than males, however these differences are less well studied in adolescence. We aimed to investigate if metabolic effects of GH vary by gender during puberty.Sixteen adolescents (8M/8F, mean age (SE): 13.1±0.2yr) with significant short stature due to either GH insufficiency or idiopathic short stature were studied before and after 8w of daily GH therapy. Differences in rates of protein and glycerol turnover ( 13 C leucine and d5-glycerol infusions), substrate oxidation rates (indirect calorimetry), hormones, growth factors, lipid concentrations, body composition (DEXA) and 1yr growth velocity were measured.Protein synthesis rates per kg FFM were similar in boys and girls before and after GH and increased similarly on treatment in both genders. Rates of whole body lipolysis were similar at baseline and increased after GH in both genders comparably. Plasma lipids were similar between boys and girls before and after GH, and triglycerides increased post-GH in both. Insulin increased after GH comparably in both genders, yet no significant difference in glucose or adiponectin concentrations during treatment or between genders was observed. IGF-I concentrations were similar between boys and girls at baseline, but with a more robust increase in males after 8w of GH (boys: +629±65ng/ml, girls: +331±67, p=0.007). Body composition changes and bone mineral density were similar between genders after GH. HT SDS increased comparably after 1yr (boys −2.2±0.09 to −1.77±0.11, p=0.0002; girls −2.49±0.24 to −2.02±0.25, p=0.04). There were no gender differences on the linear growth responses after 12mo.As compared to girls, boys had: (1) similar sensitivity to GH for protein synthesis, lipolysis, lipid concentrations and body composition changes as well as comparable glucose and adiponectin concentrations; (2) higher IGF-I responses to 8w of GH. Differences in IGF-I during GH treatment may account in part for the gender differences in physique and strength that develop during human puberty; however, using conventional doses of GH, these differences do not translate into differences in linear growth after 12mo. Contrary to adults, these data do not support the need for different GH dosing depending on gender during puberty.