Comparative effects of growth hormone, testosterone, and aromatase inhibitors on height gain in children and adolescents with idiopathic short statures: a network meta-analysis.

Background: Idiopathic short stature (ISS) is defined as height more than two standard deviations below the mean for age and sex, without an identifiable pathological cause. Pharmacologic options such as growth hormone (GH), testosterone, and aromatase inhibitors (AIs) have been studied for their potential to promote height gain in affected children and adolescents.

Aim: To compare the efficacy of GH, testosterone, and AIs in promoting height gain in children and adolescents with ISS, considering both individual and combination treatments using a network meta-analysis.

Subjects and methods: This meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. A systematic search was performed across PubMed, Embase, Web of Science, Google Scholar, Semantic Scholar, and ResearchRabbit. Eligible studies were selected on the basis of predefined inclusion criteria. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed via the chi-square test and I² index. Publication bias was evaluated via funnel plots and Egger's test.

Results: All the treatment groups (GH, anastrozole, letrozole, AI+GH) demonstrated significantly greater height gains than did the placebo group. Letrozole was associated with the greatest increase in height (SMD = 0.83, 95% CI = 0.38-1.28). No statistically significant differences were observed among the active treatments. Oxandrolone did not significantly differ from the placebo (SMD = 0.52, 95% CI = -0.03-1.07).

Conclusion: GH, AIs, and combination therapies improve height in children and adolescents with ISS, with letrozole showing a modest advantage but no clear superiority, highlighting the need for individualised treatment.