OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN:Placebo-controlled, randomized, double blind trial. SETTING:Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 +/- 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P =.0004) as well as the exercise alone (+47.8%, P =.0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P =.027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study.
RCT Entities:
OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant humangrowth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING:Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 +/- 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P =.0004) as well as the exercise alone (+47.8%, P =.0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P =.027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study.
Authors: Fred R Sattler; Carmen Castaneda-Sceppa; Ellen F Binder; E Todd Schroeder; Ying Wang; Shalender Bhasin; Miwa Kawakubo; Yolanda Stewart; Kevin E Yarasheski; Jagadish Ulloor; Patrick Colletti; Ronenn Roubenoff; Stanley P Azen Journal: J Clin Endocrinol Metab Date: 2009-03-17 Impact factor: 5.958