Management of precocious puberty in girls with McCune Albright syndrome using letrozole

Objective: To evaluate the safety and efficacy of letrozole in girls with progressive precocious puberty (PP) associated with McCune-Albright syndrome (MAS). Design: Monocentric retrospective cross-sectional and longitudinal study of consecutive patients. Patients: Ten MAS patients treated at Peking Union Medical College Hospital between September 1999 and December 2017 were retrospectively reviewed; those with complications due to PP were followed. Results: The mean age at letrozole initiation was 4.5 +/- 2.6 years, while the mean duration of treatment was 3.3 +/- 2.4 years. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a significant decrease in the bone age-to-chronological age (BA/CA) ratio from 1.9 +/- 1.1 pre-treatment to 1.5 +/- 1.2 on letrozole treatment (P=0.016). Moreover, growth velocity Z-scores declined from 0.41 +/- 0.5 to -0.2 +/- 0.31 with treatment (P< 0.001). Predicted adult height Z-scores increased significantly from -2.03 +/- 2.33 at baseline to 1.13 +/- 0.84 following treatment initiation (P=0.029). Moreover, vaginal bleeding declined significantly on letrozole. Conclusions: Our findings suggest that letrozole may be an effective therapy in some girls with MAS, as treatment results in improved BA/CA ratio, growth velocity and predicted adult height. Possible adverse effects include nettle rash.