A Systematic Review of the Impact of Growth Hormone Therapy on Final Adult Height of Children with Idiopathic Short Stature

Abstract

Abstract Introduction This review aims to systematically determine the effect of growth hormone (GH) therapy on adult height of children and adolescents with idiopathic short stature (ISS). Methods A systematic review was conducted to assess the effectiveness of GH therapy in children with ISS. Databases like ProQuest Central, journal @ Ovoid, EBSCOhost Medline Complete, Oxford University Press Journals, KB + JISC Collections Elsevier Science Direct Freedo, and BMJ, and cross-referencing of bibliographies were searched electronically. The randomized trials from 1989 to January 2023 were retrieved. Randomized trials with final adult height measurements and fit the inclusion criteria (height >2 standard deviation [SD] score below the mean with no comorbid conditions that would impair growth, peak growth hormone responses >10 μg/L, no previous history of GH therapy) were included in this review. The exclusion criteria are nonrandomized trials; trials include causes of short stature other than ISS, and studies include interventions other than GH and gonadotropin-releasing hormone analog (GnRH-a). A structured approach to the critical appraisal program by Oxford was used to analyze and extract the data. Results The study reviewed 14 eligible randomized trials, which recruited 2,206 assessable children for analysis. Seven trials compared different GH doses, four trials compared GH therapy with controls, and three trials compared a combination of GH and GnRH therapy with GH alone. Apart from one study, the overall dropout rate was not high. The high percentage of boys was a potential source of heterogeneity between trials. The change in height (HT)-SD score was 1.06 ± 0.30 and 0.18 ± 0.27 with treatment and control children, respectively, and the difference is statistically significant (p < 0.001). The overall mean height gain was 5 cm (0.84 SD score) more in treated children. The height velocity was found to be decreased significantly (p < 0.001) in the second and third years of treatment in the GH + GnRH-a treated group from 7 cm/year during the first year of treatment to 5.4 cm during the second year and 4.9 cm/year during the third year. They also found that using a higher dose of GH at 9 mg/m2/week leads to approximately 7 cm mean final height gain; however, lower dose regimens are less effective. Conclusion Although the magnitude of the effectiveness of GH therapy is, on average, less than that achieved in other conditions for which GH is licensed, GH therapy seems to be effective in children with idiopathic short stature, and it reduces the deficit in height as adults. Moreover, the effect seems to be dose-dependent, with better results at high GH doses, and the response variability is seen in different individuals. The use of combined GH with GnRH therapy needs to be balanced with their side effects.