title: Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome.
abstract: 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.
  
  
  
  Retrospective cohort analysis.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Section on Skeletal Disorders and Mineral HomestasisCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA Division of Endocrinology and Diabetes Bone Health ProgramDivision of Orthopaedics and Sports Medicine, Children's National Health System, Washington, District of Columbia, USA.
authors: Andrea
authors: A
authors: Estrada
authors: Section on Skeletal Disorders and Mineral HomestasisCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA Division of Endocrinology and Diabetes Bone Health ProgramDivision of Orthopaedics and Sports Medicine, Children's National Health System, Washington, District of Columbia, USA boyceam@mail.nih.gov.
authors: Alison M
authors: AM
authors: Boyce
authors: Section on Skeletal Disorders and Mineral HomestasisCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors: Beth A
authors: BA
authors: Brillante
authors: Section on Skeletal Disorders and Mineral HomestasisCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors: Lori C
authors: LC
authors: Guthrie
authors: Section on Skeletal Disorders and Mineral HomestasisCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors: Rachel I
authors: RI
authors: Gafni
authors: Section on Skeletal Disorders and Mineral HomestasisCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors: Michael T
authors: MT
authors: Collins
mesh_terms: D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001827:Body Height / Q000187:drug effects* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D000077289:Letrozole; D009570:Nitriles / Q000008:administration & dosage*; D010865:Pilot Projects; D011629:Puberty, Precocious / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole