Clinical Study Of Anastrozole Combined With Recombinant Human Growth Hormone In The Treatment Of Adolescent Boys With Idiopathic Short Stature

Background Idiopathic short stature(ISS)refers to individuals whose height is below2 standard deviations(-2SD)or the 3rd percentile of the average height for their same race,gender,and age group in similar living conditions,while excluding other causes of short stature resulting from specific medical conditions,and with a peak growth hormone response in the standard stimulation test greater than 10 ng/m L.Short stature in ISS children can have negative effects on various aspects,including psychological and social well-being.If not treated and improved in a timely manner,these negative effects typically persist.Recombinant human growth hormone(rhGH)is the preferred treatment for ISS.Long-term administration of rhGH before epiphyseal closure can increase the growth rate and improve adult height in ISS children,demonstrating good treatment efficacy and safety.However,the use of rhGH alone in late puberty for improving final adult height has limited effectiveness.Higher doses of growth hormone may also increase the incidence of adverse reactions.Combining rhGH with anastrozole in treating ISS adolescents can slow down bone age progression,improve final adult height,and have good safety.However,there is limited available literature for reference both domestically and internationally,and these studies also suffer from small sample sizes and short follow-up periods,leading to controversies regarding treatment efficacy and adverse reactions.Objective The aim of this study is to evaluate the efficacy and adverse reactions of anastrozole combined with rhGH in the treatment of adolescent boys with ISS,and compared with the conventional classical treatment scheme of adolescent ISS boys:rhGH alone or rhGH combined with gonadotropin-releasing hormone analogues in terms of efficacy and safety,and to provide a reference for the clinical treatment of children with ISS.Methods Sixty adolescent males with advanced bone age who were diagnosed with idiopathic short stature and admitted to the Second Affiliated Hospital of Anhui Medical University between January 2019 and December 2021 were selected.Patients with severe allergies,congenital skeletal abnormalities,prior systemic growth hormone treatment,severe liver or kidney diseases,diabetes,impaired glucose tolerance,disproportionate short stature,definite chromosomal disorders,genetic metabolic diseases,poor compliance,irregular medication or follow-up were excluded.Based on the preferences of the families,the patients were divided into three groups and received different treatment regimens: rhGH monotherapy,Gn RHa combined with rhGH,and anastrozole combined with rhGH.The treatment duration was one year,during which relevant clinical indicators including height,bone age,height predicted by bone age,fasting blood glucose,liver and kidney function,FT3,FT4,TSH,IGF-1,IGFBP-3,etc.Statistical analysis was conducted using SPSS 26.0 software to explore the treatment efficacy and safety of anastrozole combined with recombinant human growth hormone in adolescent boys with idiopathic short stature.Results: After treatment,the levels of GV,PAH,IGF-1,and IGFBP-3 significantly increased compared to baseline in all three treatment groups.However,there were no significant changes in fasting blood glucose,Hb A1 c,FT3,FT4,and TSH levels compared to baseline.After 6 months of treatment,the GV in the rhGH monotherapy group was(10.29±2.32)cm/year,in the Gn RHa combined with rhGH group was(10.16±3.18)cm/year,and in the anastrozole combined with rhGH group was(9.91±1.87)cm/year.There were no significant differences in GV among the three groups.After 1 year of treatment,the GV in the Gn RHa combined with rhGH group was(8.27±2.14)cm/year,significantly lower than that in the rhGH monotherapy group(10.44±2.58)cm/year and the anastrozole combined with rhGH group(10.35±1.40)cm/year.After 1 year of treatment,the Δbone age/Δchronological age(ΔBA/ΔCA)in the anastrozole combined with rhGH group was(0.49±0.16),and in the Gn RHa combined with rhGH group was(0.52±0.15),both significantly lower than that in the rhGH monotherapy group(1.01±0.19).After 1 year of treatment,the increase in predicted adult height in the anastrozole combined with rhGH group was(7.33±1.08)cm,significantly higher than that in the Gn RHa combined with rhGH group(5.91±2.13)cm,and the Gn RHa combined with rhGH group was significantly higher than the rhGH monotherapy group(4.32±1.77)cm.In the anastrozole group,6 patients showed signs of significant hyperestrogenism,which improved after the addition of anastrozole.The overall incidence of adverse reactions among the three groups(rhGH monotherapy group: 20%,Gn RHa combined with rhGH group: 25%,anastrozole group: 30%)showed no significant difference(χ2=0.533,P=0.766>0.05).Conclusion The combination of anastrozole and rhGH in the treatment of adolescents with ISS can increase IGF-1 and IGFBP-3 levels,improve growth velocity,and effectively delay bone age progression,thereby improving predicted adult height.During the treatment process,the anastrozole group showed no significant increase in the incidence of adverse events compared to the control group,demonstrating good safety and tolerability,and providing clinical evidence for the treatment of adolescents with ISS.