Growth Hormone and Muscle Strength in Children

Abstract

When I was asked to write an editorial to comment on the article by Simon et al (1) in this issue of the Journal, I felt it would be a real challenge. The use of GH therapy in children has provoked more discussion in the last few years from a legal, journalistic, economical, and even political point of view than from medical and scientific perspectives. I decided to take the challenge and to comment on the facts as I perceive them. An impact of recombinant human GH (rhGH) on muscle strength is controversial. As physicians, we are essentially warned about rhGH doping in professional and Olympic athletics, with the presumption that it has a beneficial effect on muscle strength. This is despite the fact that there appears to be no evidence that rhGH enhances muscle strength, power, or aerobic capacity in trained adult athletes. However, rhGH does increase modestly anaerobic exercise capacity when administered alone and to a greater extent when combined with testosterone (2). Thus, despite the abuse of rhGH by athletes, there is little support of performance benefit except for an effect on anaerobic exercise capacity (2). In GH-deficient patients, replacement of rhGH improves aerobic exercise capacity, although it remains to be elucidated whether this is due to the direct effect on muscle function or on other factors influencing cardiovascular function, well-being, and motivation. Long-term rhGH replacement in excess of 12 months seems to be required for improved muscle strength to take place in GH-deficient adult subjects (2). It has been reported that 10 years of rhGH replacement therapy in GH-deficient adults increased muscle strength during the first half of the study and then protected partly against the normal decline withage inmusclestrength,resulting inapproximatelynormalized muscle strength after 10 years (3). Even fewerdataareavailable inchildren,with theexception of data gathered from children affected with Prader-Willi syndrome(PWS),araregenetic formofobesitywithhypothalamic involvement that leads to GH deficiency. One group assessed the impact of rhGH therapy begun early in life on the natural history of PWS and compared height, body composition, and strength in similar-age children with PWS naive to rhGH with those treated with hGH for 6 years (4). Motor strength testing included broad jump, agility run, sit-ups, and upper arm strength assessments. The evaluator of motor strength testing was blinded to the treatment status of each child. PWS children treated with rhGH demonstrated greater motor strength (increased standing broad jump 22.9 2.1 vs 14.6 1.9 inches (P .001) and sit-ups 12.4 0.9 vs 7.1 0.7 repetitions in 30 seconds; P .001). Clear trends were seen in the 2 other areas of the testing, including improved agility run and weight-lift repetitions, although these did not reach statistical significance. Thus, thisnonrandomizedstudysuggestedabeneficialeffecton muscle strength in children affected by PWS. However, these few reports on young active adults, on GH-deficient adults, and on children affected by PWS may not be relevant to the chronically ill and less active children included in the study of Simon et al (1). In this study, the authors evaluated the effects of rhGH on muscle strength in children receiving long-term glucocorticoid therapy. Expected effects of growth hormone on height and body composition were assessed and confirmed, but those will not be commented upon here. This was a pilot study, randomized and controlled, with a delayed-start of rhGH for 12 months. rhGH was started after randomization (month 0) or 6 months later (month 6). A total of 30 children with various diagnoses, on glucocorticoid therapy for a chronic disease, startedat least1year earlierwithheight1SDorat2SDscore (SDS) below and bone age 15 years in boys and 13 years in girls. rhGH was administered at a dose of 0.065 mg/kg/d for 6monthsandtheninthedosagemaintainingserumIGF-1levels