Work

Effects of combined GnRHa and letrozole on serum steroid profiles in girls with advanced bone age

Year: 2026

Type: article

Abstract: Objective To evaluate the impact of combined GnRHa and letrozole on serum steroid profiles (classical, 11‐oxygenated, and backdoor androgen pathways) in girls with advanced bone age, and to monitor adverse events. Methods 28 girls with advanced bone age were enrolled. Of these, 15 received add‐on letrozole after GnRHa monotherapy (Group B); the remaining 13 started combination therapy from baseline (Group A). Blood was collected at baseline, 1, and 6 months. Steroids were measured by LC‐MS/MS. Results At baseline, Group A had higher classical androgens, progestogens, estrogens, INB, SHBG, and FAI than Group B (all P < 0.05), while 11‐oxygenated androgens were similar. In Group A, classical androgens, P, 17‐OHP, 5α‐DHP, 17OH‐DHP, 3α‐diol, E1, E2, and FAI decreased markedly (all overall P < 0.01) and remained lower at 6 months; 11‐KT showed a modest reduction at 1 month ( P = 0.02), but other 11‐oxygenated androgens were unchanged. In Group B, add‐on letrozole reduced E1, E2, AMH, and INB (all overall P < 0.05), while most androgens and progestogens were stable. No hyperandrogenism or adverse events were observed. Conclusions Over 6 months, combined GnRHa and letrozole was not associated with hyperandrogenism in girls with advanced bone age. In Group A, gonadal androgens and estrogens were markedly suppressed, while adrenal androgens remained stable. In Group B, add‐on letrozole had limited effects on most androgens. Estrogen suppression was observed in both groups. These findings appear to support short‐term safety, although longer‐term data are needed.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1984633