ObjectiveTo investigate the relationship between estrogen levels and the efficacy and safety of anastrozole combined with growth hormone in pubertal male children with advanced bone age and short stature.MethodsA retrospective analysis was performed on the clinical data of 59 male patients with advanced bone age and short stature who were treated in the Department of Pediatrics, East Hospital Affiliated to Tongji University from January 2015 to December 2021. All patients received combined treatment with anastrozole (1 mg/d, oral) and recombinant human growth hormone [rhGH, 0.15-0.2 IU/(kg·d), subcutaneous injection before bedtime], with regular follow-up every 6 months. Clinical efficacy (predicted adult height and changes in bone age, sex hormone levels (including testosterone, estradiol, etc.), auxiliary clinical indicators (vitamin D levels, insulin-like growth factor-1, etc.), and adverse events were observed.ResultsAfter 24 months of treatment, the mean PAH increased significantly by (9.23±3.37) cm. There was no statistically significant difference in bone age changes before and after treatment (P>0.05). After 12 months of treatment, E2 levels decreased significantly by (15.33±0.66) pg/mL, while testosterone levels increased by (14.67±0.63) pg/mL. Transient alanine aminotransferase (ALT) elevation occurred in 2 cases (4.80%) within 6 months after treatment. Adverse events observed at 12 months included hyperuricemia (23 cases, 37.5%), hyperandrogenemia (12 cases, 20.30%), and vitamin D insufficiency (12 cases, 25.8%). The increase in PAH after 12 months was significantly negatively correlated with E2 levels (r=-0.541, P< 0.001), positively correlated with bone age increment (r=0.318, P=0.018), and negatively correlated with changes in uric acid levels (r=-0.401, P=0.002). The ROC curve for predicting hyperuricemia after 12 months showed an area under the curve (AUC) of 0.81 for E2 (P<0.001), with a sensitivity of 75%, specificity of 95.70%, and an optimal cutoff value of 0.70 corresponding to an E2 concentration of 11.67 pg/mL.ConclusionThe combination of anastrozole and growth hormone improves predicted height and significantly delays bone age progression in pubertal males with advanced bone age. Sex hormone concentrations exhibit dynamic changes and relative stability during treatment. Reversible adverse events such as hyperuricemia and hyperandrogenemia occur during follow-up, requiring close monitoring. E2 levels have high predictive value for hyperuricemia after 12 months of treatment, providing a reference for clinical practice.