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 broad 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, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed 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 ± 1 s.d.) (range: 0.5–10.9) 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 treatment 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 were increased in comparison with 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.