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Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome

Emily K Sims1*, Sally Garnett2, Franco Guzman3, Françoise Paris4, Charles Sultan4, Erica A Eugster1 and On behalf of the fulvestrant McCune-Albright study group

Author Affiliations

1 Section of Pediatric Endocrinology/Diabetology, Riley Hospital for Children, Indiana University School of Medicine, 705 Riley Hospital Drive, Room 5960, Indianapolis, IN 46202, USA

2 AstraZeneca, Macclesfield, United Kingdom

3 Former-AstraZeneca, Wilmington, Delaware, USA

4 Pediatric Gynecology and Endocrinology, University Hospital of Montpellier, Montpellier, France

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International Journal of Pediatric Endocrinology 2012, 2012:26  doi:10.1186/1687-9856-2012-26

Published: 22 September 2012

Abstract

Background

McCune-Albright Syndrome (MAS) is usually characterized by the triad of precocious puberty (PP), fibrous dysplasia, and café au lait spots. Previous treatments investigated for PP have included aromatase inhibitors and the estrogen receptor modulator, tamoxifen. Although some agents have been partially effective, the optimal pharmacologic treatment of PP in girls with MAS has not been identified. The objective of this study was to evaluate the safety and efficacy of fulvestrant (FaslodexTM), a pure estrogen receptor antagonist, in girls with progressive precocious puberty (PP) associated with McCune-Albright Syndrome (MAS).

Methods

In this prospective international multicenter trial, thirty girls ≤ 10 years old with MAS and progressive PP received fulvestrant 4 mg/kg via monthly intramuscular injections for 12 months. Changes in vaginal bleeding, rates of bone age advancement, growth velocity, Tanner staging, predicted adult heights, and uterine and ovarian volumes were measured.

Results

Median vaginal bleeding days decreased from 12.0 days per year to 1.0 day per year, with a median change in frequency of -3.6 days, (95% confidence interval (CI) -10.10, 0.00; p = 0.0146). Of patients with baseline bleeding, 74% experienced a ≥50% reduction in bleeding, and 35% experienced complete cessation during the study period (95% CI 51.6%, 89.8%; 16.4%, 57.3%, respectively). Average rates of bone age advancement (ΔBA/ΔCA) decreased from 1.99 pre-treatment to 1.06 on treatment (mean change -0.93, 95% CI -1.43, -0.43; p = 0.0007). No significant changes in uterine volumes or other endpoints or serious adverse events occurred.

Conclusions

Fulvestrant was well tolerated and moderately effective in decreasing vaginal bleeding and rates of skeletal maturation in girls with MAS. Longer-term studies aimed at further defining potential benefits and risks of this novel therapeutic approach in girls with MAS are needed.

Trial registration

NCT00278915

Keywords:
McCune Albright syndrome; Peripheral precocious puberty; Estrogen receptor antagonist