title: Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study.
abstract: BACKGROUND
  Girls with McCune-Albright syndrome (MAS) and related disorders have gonadotropin-independent precocious puberty due to estrogen secretion from ovarian cysts. Their puberty does not respond to GnRH agonist therapy, and short-acting aromatase inhibitors have had limited effectiveness.
  
  
  OBJECTIVE
  Our objective was to assess the effectiveness of the potent, third-generation aromatase inhibitor letrozole in decreasing pubertal progression in girls with MAS and to assess the response of indices of bone turnover associated with the patients' polyostotic fibrous dysplasia.
  
  
  METHODS
  Subjects were evaluated at baseline and every 6 months for 12-36 months while on treatment with letrozole 1.5-2.0 mg/m(2).d.
  
  
  METHODS
  This was an open-label therapeutic trial at a single clinical center.
  
  
  METHODS
  Patients included nine girls aged 3-8 yr with MAS and/or gonadotropin-independent puberty.
  
  
  METHODS
  Measures included rates of linear growth, bone age advance, mean ovarian volume, estradiol, episodes of vaginal bleeding, and levels of the indices of bone metabolism: serum osteocalcin, alkaline phosphatase, urinary hydroxyproline, pyridinoline, deoxypyridinoline, and N-telopeptides.
  
  
  RESULTS
  Girls had decreased rates of growth (P < or = 0.01) and bone age advance (P < or = 0.004) and cessation or slowing in their rates of bleeding over 12-36 months of therapy. Mean ovarian volume, estradiol, and indices of bone metabolism fell after 6 months (P < or = 0.05) but tended to rise by 24-36 months. Uterine volumes did not change. One girl had a ruptured ovarian cyst after 2 yr of treatment.
  
  
  CONCLUSIONS
  This preliminary study suggests that letrozole may be effective therapy in some girls with MAS and/or gonadotropin-independent precocious puberty. Possible adverse effects include ovarian enlargement and cyst formation.
authors.affiliation: National Institutes of Health, Bethesda, MD 20892, USA. feuillap@mail.nih.gov
authors.forename: Penelope
authors.initials: P
authors.lastname: Feuillan
authors.forename: Karim
authors.initials: K
authors.lastname: Calis
authors.forename: Suvimol
authors.initials: S
authors.lastname: Hill
authors.forename: Thomas
authors.initials: T
authors.lastname: Shawker
authors.forename: Pamela Gehron
authors.initials: PG
authors.lastname: Robey
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications* / Q000378:metabolism; D006128:Growth / Q000187:drug effects; D006801:Humans; D000077289:Letrozole; D008297:Male; D008598:Menstruation / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D010048:Ovarian Cysts / Q000188:drug therapy / Q000209:etiology; D010865:Pilot Projects; D011627:Puberty / Q000187:drug effects; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole