ESPE Abstracts

Introduction: Precocious Peripheral Puberty (PPP) due to autonomous ovarian activation is the most frequent endocrinopathy in girls with McCune-Albright Syndrome (MAS). Main goals of treatment for PPP are to reduce signs of estrogen exposure, also improving final height, and mitigate secondary psychological influence of sexual hormones exposure. This retrospective study analyzes the long-term safety and efficacy of letrozole treatment in a cohort of girls with MAS-associated PPP.

Patients and methods: Seven female girls affected by MAS showing signs of PPP were enrolled. A daily per os dose of 1.25-2,5 mg letrozole was administered. Subjects underwent serial anthropometric-clinical evaluation including history and physical examination, hormonal testing, bone age, and transabdominal pelvic ultrasound. Data were collected at five time points: at beginning (T0), ongoing (T1, 3 months; T2, 6 months; T3, 12 months) and (T4) at the time of discontinuation of the therapy.

Results: The mean age at PPP presentation was 2,4 ± 2,4 Years (0,2-8,0 years), the mean age of initiation therapy was 6,0 ± 2,3 years (2,7-9,3 years) with average duration of 2,6 ± 1,5 years (0,8-4,9 years). Thelarche regression was effective in 71% of patients at T1, reaching 86% at T2. Bleeding episodes were almost completely remitted, since decreased from 57% at T0 to 14% at T1. The size of ovarian cysts and uterus decreased in 100% of cases, with a complete regression of the cysts in 57%. Growth velocity decreased in 71% of patients; bone age in relation to chronological age decreased in 43% of patients after 1 year of therapy and in 4/5 patients (80%) upon therapy discontinuation, while predicted the predicted final height z-score improved 2 girls. Central Puberty (CPP) occurred in 4 patients, so GnRH analogue treatment was associated. In the total person-year observing period of 27 years no side effects occurred.

Discussion: Letrozole therapy seems to be effective in reducing clinical manifestation of PPP in MAS girls and in our experience no side effects occurred. The benefits on skeletal maturation and growth are still controversial since bone age and growth velocity tend to decrease without clear effectiveness on height improvement. Further studies with additional patients who have completed treatment and reached skeletal maturity are needed to confirm the effect of letrozole on final height.