Effectiveness and Safety of Combination Therapy with Herbal Medicine and Growth Hormone Compared to Growth Hormone Monotherapy for Short Stature Children: A Systematic Review and Meta-Analysis

INTRODUCTION: Herbal medicines (HM) and growth hormones (GH) are widely used to treat short stature (SS) in children. This systematic review aimed to evaluate the effectiveness and safety of combination therapy with HM and GH (CHG) compared to those of GH monotherapy (GHM) in children with SS. METHODS: We searched 17 electronic databases from inception to 1 April 2021. Only randomized controlled trials (RCTs) were included. Two authors independently performed the selection and quality assessment of the included studies using Cochrane Handbook criteria. Relative risk (RR) was used to measure dichotomous outcomes with a 95% confidence interval (CI). Mean difference (MD) or standard MD (SMD) was used to measure continuous outcomes with a 95% CI. RESULTS: Seven RCTs involving 455 participants with SS were included. Standard deviations in height (MD = 0.31, 95% CI: 0.24–0.38, p < 0.00001), and insulin-like growth factor binding protein-3 (MD = 1.39, 95% CI: 0.93–1.85, p < 0.00001) were significantly higher in the CHG group than in the GHM group. Growth velocity (MD = 1.82, 95% CI: 1.34–2.31, p < 0.00001) and insulin-like growth factor-1 (MD = 61.85, 95% CI: 55.80–67.90, p < 0.00001) were significantly higher in the CHG group. Adverse events were significantly lower in the CHG group (risk ratio: 0.10, 95% CI: 0.02–0.54, p = 0.007). However, the level of evidence was low. CONCLUSIONS: CHG demonstrated significantly better efficacy than GHM for treating SS, with a low incidence of adverse events. However, since the level of evidence is low, methodologically standardized RCTs are required to verify these results.