Recombinant human growth hormone (rhGH) injections combined with Anastrozole are increasingly used to treat adolescent idiopathic short stature (ISS), warranting further research. This study evaluated their effects on height, growth rate and adverse reactions in 72 adolescents with ISS treated at our hospital from December 2021 to December 2022. Patients were divided into a control group (rhGH alone) and a study group (rhGH + Anastrozole). Post-treatment, the study group showed significant improvements in height, weight and levels of insulin-like growth factor-1 and binding protein-3 (P<0.05). Both groups experienced increased levels of calcium, magnesium, zinc, 25-hydroxyvitamin D, osteocalcin and procollagen type I N-terminal propeptide, with the study group showing greater increases (P<0.05). Adverse reactions were slightly higher in the control group but not statistically significant (P>0.05). The combined treatment significantly enhances linear growth, body mass and trace element levels, demonstrating high efficacy and safety. This innovative approach is highly recommended for broader clinical adoption, offering a transformative solution for managing adolescent idiopathic dwarfism.

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