Research Article: Effects of combined GnRHa and letrozole on serum steroid profiles in girls with advanced bone age
Abstract:
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.
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.
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, 5??DHP, 17OH?DHP, 3??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.
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.
Introduction:
Rapidly progressive puberty (RPP) is characterized by timely pubertal onset but accelerated progression, leading to rapid bone age advancement and compromised predicted adult height (PAH) ( 1 , 2 ). Although GnRHa is primarily indicated for central precocious puberty, the Chinese consensus on CPP (2022) recommends that girls with RPP may also be considered for GnRHa therapy when bone age advancement is rapid and height prognosis is severely compromised ( 2 ). However, clinical evidence suggests that GnRHa…
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