Treatment Outcomes in 84 Male Children with Accelerated Pubertal Progression: A Comparative Analysis ofGnRHa, Combined GH Therapy and Aromatase Inhibitor

<title>Abstract</title> <p>Background Accelerated pubertal progression (APP) in boys, encompassing central precocious puberty (onset &lt; 9 years) and rapidly progressive puberty (onset 9–14 years with accelerated advancement), leads to premature epiphyseal fusion and compromised adult height. The optimal treatment strategy remains debated. This study compared the efficacy and safety of gonadotropin-releasing hormone analog (GnRHa) monotherapy, aromatase inhibitor (AI) monotherapy, and GnRHa combined with recombinant human growth hormone (rhGH) in improving predicted adult height (PAH) in male children with APP. Methods This retrospective cohort study included 84 male children diagnosed with APP at our center between January 2018 and December 2022. Patients were divided into three groups: GnRHa monotherapy (n = 44, triptorelin or leuprorelin 3.75 mg/4 weeks), AI monotherapy (n = 24, letrozole 2.5 mg/day or anastrozole 1 mg/day), and GnRHa+rhGH combination therapy (n = 16, GnRHa plus rhGH 0.15–0.18 IU/kg/day). Primary outcomes were change in PAH (ΔPAH) and annualized height velocity (ΔH/y). Secondary outcomes included hormonal changes, bone age advancement, and metabolic parameters. Statistical analyses used paired t-tests, ANOVA, and Kruskal-Wallis tests. Results All three treatments effectively delayed bone age advancement (P &lt; 0.05 for all). GnRHa and combination therapy suppressed LH and testosterone and reduced testicular volume (P &lt; 0.05), whereas AI paradoxically increased LH and testosterone (P &lt; 0.05) without affecting testicular volume. Combination therapy yielded superior ΔH/y (8.49 ± 3.22 vs 6.73 ± 1.95 [GnRHa] vs 7.75 ± 1.92 [AI] cm/y, P &lt; 0.01) and ΔPAH (7.41 ± 4.67 vs 3.43 ± 3.27 vs 4.69 ± 3.26 cm, P &lt; 0.01). In patients treated ≥ 2 years, AI and combination achieved comparable ΔPAH (6.58 ± 2.52 vs 7.90 ± 3.01 cm), both superior to GnRHa alone (3.50 ± 2.43 cm, P = 0.01). GnRHa and AI increased BMI (P &lt; 0.01); combination did not. No serious adverse events occurred. Conclusion GnRHa+rhGH combination therapy provides the greatest PAH improvement in male APP patients. AI monotherapy offers an effective, less burdensome alternative for late-presenting patients with advanced bone age. Treatment decisions should be individualized based on baseline characteristics and family preferences.</p>