Serum α-Klotho and its association with testosterone in boys with central precocious puberty

Objectives α-Klotho is an anti-aging protein involved in insulin-like growth factor 1 (IGF-1) signaling and reproductive function. Studies in girls with central precocious puberty (CPP) reported elevated α-Klotho levels that declined with treatment, suggesting a potential biomarker role. Whether boys with CPP exhibit similar patterns remains unclear. Methods This study included 36 boys with CPP and 34 age-matched healthy controls. α-Klotho, gonadotropins, testosterone, IGF-1, and other biochemical parameters were measured at baseline. In 15 patients, measurements were repeated after 6 months of gonadotropin-releasing hormone (GnRH) agonist therapy. Results Boys with CPP showed advanced bone age, higher body mass index standard deviation score (SDS), and elevated luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and IGF-1 SDS compared with controls. Baseline α-Klotho levels did not differ. Serum α-Klotho correlated strongly with testosterone (r=0.755, p<0.001) and moderately with IGF-1 SDS (r=0.570, p<0.001), but not with gonadotropins. In multiple regression, testosterone (β=0.612, p=0.004) and IGF-1 SDS (β=0.317, p=0.033) were independent predictors of α-Klotho. After 6 months of GnRH agonist therapy, testosterone and gonadotropins decreased significantly, while α-Klotho showed a non-significant decline. Conclusions Unlike girls with CPP, boys did not show elevated or treatment-responsive α-Klotho levels. The correlation with testosterone suggests α-Klotho may reflect androgenic activity in boys rather than serve as a dynamic biomarker. These findings should be considered exploratory, and larger studies with longer follow-up are needed to clarify its role in puberty and potential sex-specific regulation.