Long-term Outcomes of Letrozole Treatment for Precocious Puberty in Girls with McCune-Albright Syndrome

Abstract

Objective

McCune-Albright syndrome (MAS) is a rare disorder with a spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP.

Design

Retrospective cohort analysis.

Methods

Clinical data were reviewed, including history and physical, bone age, and pelvic ultrasounds on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height, and adult height.

Results

Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1SD) (0.5–10.9, range) and mean follow-up was 6.0 ± 3.3 years (range 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (ΔBA/ΔCA) from 1.7 (IQR 2.3) to 0.5 (IQR 0.4) (p<0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to −0.6 ± 1.6 (p = 0.0004). Predicted adult height Z-scores increased significantly from −2.9 ± 3.2 to −0.8 ± 1.5 for subjects on treatment (p = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from −1.5 to 1.7 (median −0.6), which was increased in comparison to untreated historical controls (p=0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period.

Conclusions

In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height.