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

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.

Growth hormone therapy and Quality of Life: possibilities, pitfalls and mechanisms

“…The cardiac hypertropy may be transient, since it subsides after 2 years of continuous treatment, but improvements in cardiac performance persist for up to 10 years (Ter Maaten et al 1999). Other studies using AOGHD patients (Nass et al 1995) did not observe any improvement in cardiac morphology or function following GH treatment.…”

“…GH replacement increases ventricular mass and/or performance in COGHD patients (Amato et al 1993, Sartorio et al 1997, Ter Maaten et al 1999. The cardiac hypertropy may be transient, since it subsides after 2 years of continuous treatment, but improvements in cardiac performance persist for up to 10 years (Ter Maaten et al 1999).…”

Safety aspects of GH replacement

“…During 38 months of GH replacement therapy, cardiac structure was normalized, whereas heart rate and cardiac index increased to supernormal levels (34). In 38 young men with childhood-onset GHD followed openly for 55 (range 39-69) months, GH replacement increased stroke volume and maximal exercise capacity without any long-term increase in left ventricular mass (35). In seven adults with adult-onset GHD, 42 months of GH replacement increased left ventricular mass and decreased the atrial emptying index, which reflects diastolic function, as compared with healthy matched controls (36).…”

Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults

“…Ample and robust evidence supports the remedial effects of GH replacement on body composition, including gradual normalization of lean body mass (LBM) and reduction in fat mass (10,11). A number of studies have also demonstrated improvements in psychological well-being, with specific improvements in energy, emotional reactions and social isolation (12,13).…”