Effectiveness and Safety of Hormonal Treatments in Children with Growth Disorders: A Systematic Review of Clinical Evidence

Background: Growth disorders, including central precocious puberty and delayed puberty, can significantly affect linear growth, skeletal maturation, metabolic regulation, and psychosocial development during childhood and adolescence. This systematic review synthesizes the current evidence regarding the effectiveness and safety of hormone-based therapies used in children with disorders of pubertal maturation. Methods: A PRISMA-guided systematic search was carried out between January 2016 and March 2026 in different databases, such as MEDLINE (PubMed), EMBASE, CENTRAL, Scopus, Web of Science, CINAHL, LILACS and OpenGrey; the protocol was previously registered in the PROSPERO database (CRD420251068048). Non-randomized, randomized controlled trials and observational research including participants aged 0–18 years receiving hormone therapies were eligible. Risk of bias was assessed using validated, design-specific tools. Results: Twenty studies involving 21,812 participants were included. GnRHa therapy improved final adult height (+3.5 to +4.5 cm) and reduced bone age advancement (−0.6 to −1.3 years) in children with central precocious puberty. rhGH therapy increased growth velocity (+3.0 to +5.0 cm/year) and height SDS (+0.3 to +0.9), particularly in idiopathic short stature and Prader–Willi syndrome. Combined GnRHa plus rhGH therapy showed greater short-term growth benefits than GnRHa alone. Both therapies showed favorable safety profiles, with predominantly mild adverse events and discontinuation rates below 2%. However, the evidence was limited by substantial heterogeneity and moderate-to-serious risk of bias. Conclusions: GnRHa and rhGH therapies are generally effective and safe for improving growth and pubertal outcomes in pediatric endocrine disorders. However, further long-term studies are needed to clarify their metabolic and psychosocial effects in adulthood. Nevertheless, these conclusions should be interpreted with caution due to the study’s moderate-to-serious risk of bias and heterogeneity.