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Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency
J C ter Maaten1, H de Boer, O Kamp
1Department of Endocrinology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Insights
Long term growth hormone (GH) replacement therapy in men with childhood-onset GH deficiency improves body composition, bone density, and cardiac function. This study confirms long term GH therapy is safe and beneficial for adults.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Cardiovascular Physiology
Background:
- Short-term growth hormone (GH) replacement therapy improves body composition and exercise capacity.
- Long-term benefits and safety of GH replacement are not well-established.
Purpose of the Study:
- To assess the long-term effects of GH replacement on body composition, bone mineral density, and cardiac function.
- To evaluate the safety and efficacy of sustained GH therapy in adults with childhood-onset GH deficiency.
Main Methods:
- A 3-5 year study of 38 men with childhood-onset GH deficiency.
- Measurements included anthropometry, CT scans, bone densitometry, echocardiography, and ergometry.
- GH dosage was adjusted to maintain physiological insulin-like growth factor I levels.
Main Results:
- Progressive increase in leg muscle mass (28.7%) and bone mineral density at lumbar spine (9.6%), femoral neck (11.1%), and trochanter (16.2%).
- Significant decrease in subcutaneous and intra-abdominal fat after 1 year, with partial regain later.
- Improved cardiac performance, including increased stroke volume (16.3%) and cardiac output (33.4%), without left ventricular hypertrophy.
- Maximal workload increased significantly (from 189 to 232 watts).
Conclusions:
- Long-term GH replacement therapy is safe and beneficial for adults with childhood-onset GH deficiency.
- Sustained therapy improves cardiac function, increases bone mineral density, and enhances exercise capacity.
- GH therapy effectively manages body composition changes associated with 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.