Long-Term Effects of Growth Hormone (GH) Replacement in Men with Childhood-Onset GH Deficiency 1

Abstract

Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function. Thirty-eight men with childhood-onset GH deficiency were studied for a period of 3-5 yr. Measurements included anthropometry, computed tomographic scanning of abdomen and upper leg, bone densitometry, echo cardiography, and bicycle ergometry. The initial GH dose of 1-3 IU/m2 x day (9-27 microg/kg) was gradually tapered to 1.30+/-0.38 IU/m2 x day (11 g/kg), aiming at physiological insulin-like growth factor I levels. During the study, leg muscle mass progressively increased by 28.7% (P<0.001). Subcutaneous and intraabdominal fat decreased by 30.9% and 46.0%, respectively, after 1 yr (both P<0.001), but demonstrated a partial regain thereafter. Bone mineral density at the lumbar spine, femoral neck, and trochanter gradually increased by 9.6%, 11.1%, and 16.2%, respectively (all P<0.001). Left ventricular mass exceeded baseline values by 14.1% after 1 yr (P<0.001), but returned to pretreatment values thereafter. Stroke volume and cardiac output increased by 16.3% (P = 0.002) and 33.4% (P<0.001), respectively. Maximal work load increased from 189+/-30 to 232+/-41 watts (P<0.001). Thus, long term GH replacement is safe and beneficial. It improves cardiac performance without inducing left ventricular hypertrophy and progressively increases bone mineral density.