A meta-analysis of combination therapy with gonadotrophin-releasing hormone agonist and growth hormone for children with idiopathic short stature and normal timed puberty

Abstract

Purpose The aim of this meta-analysis is to evaluate whether the combination therapy with gonadotrophin-releasing hormone agonist (GnRHa) and recombinant human growth hormone (rhGH) are effective in the treatment of children with idiopathic short stature (ISS) and normal timed puberty by interrogating data from clinical controlled trials. Methods Literature retrieval, trail selection, data abstraction and quality assessment were completed independently by two authors. STATA software (version 14.1) was used for data analyses. Results This meta-analysis was conducted based on 8 (4 randomized and 4 non-randomized) controlled trials. A total of 245 ISS children with normal timed puberty were financially analyzed. Overall, combination therapy with GnRHa and rhGH can slightly increase final height by 3.70 and 3.43 cm compared with GH treatment alone and no treatment, final height standard deviation score (FHSDS) by 0.10 and 0.22, final height minus predicted adult height (FH-PAH) by 1.5 and 5.32 cm, final height minus predicted adult height (FH-TH) by 7.70 and 4.32 cm, respectively. Subgroup and meta-regression analyses revealed that study type, sample size, GnRHa duration, and percentage of boys were potential sources of between-trial heterogeneity. There was a low probability of publication bias for above comparisons, as indicated by Egger’s tests. Conclusions Our meta-analytical findings indicate that the combination therapy with GnRHa and rhGH can slightly increase the final height of ISS children with normal timed puberty, and the effect was not more obvious than GH alone. We do not recommend the combination therapy as a routine treatment for ISS. Trial registration number CRD42019133438