title: Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature.
abstract: Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion.
  
  
  
  To compare: 1) the efficacy and safety of aromatase inhibitors (AIs) vs GH vs AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and 2) differences in body composition among groups.
  
  
  
  Randomized three-arm open-label comparator.
  
  
  
  Outpatient clinical research.
  
  
  
  Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3 (0.0)].
  
  
  
  Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24-36 months.
  
  
  
  Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs.
  
  
  
  Height gain [mean (SE)] at 24 months was: AI, +14.0 (0.8) cm; GH, +17.1 (0.9) cm; AI/GH, +18.9 (0.8) cm (P < .0006, analysis of covariance). Height SDS was: AI, -1.73 (0.12); GH, -1.43 (0.14); AI/GH, -1.25 (0.12) (P < .0012). Those treated through 36 months grew more. Regardless of treatment duration, height SDS at near-final height [n = 71; age, 17.4 (0.2) years; bone age, 15.3 (0.1) years; height achieved, ∼97.6%] was: AI, -1.4 (0.1); GH, -1.4 (0.2); AI/GH, -1.0 (0.1) (P = .06). Absolute height change was: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; AI/GH, +22.5 (1.4) cm (P = .01) (expected height gain at -2.0 height SDS, +13.0 cm). AI/GH had higher fat free mass accrual. Measures of bone health, safety labs, and adverse events were similar in all groups. Letrozole caused higher T and lower estradiol than anastrozole.
  
  
  
  Combination therapy with AI/GH increases height potential in pubertal boys with ISS more than GH and AI alone treated for 24-36 months with a strong safety profile.
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Nelly
authors.initials: N
authors.lastname: Mauras
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Ross
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Priscila
authors.initials: P
authors.lastname: Gagliardi
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Y Miles
authors.initials: YM
authors.lastname: Yu
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Jobayer
authors.initials: J
authors.lastname: Hossain
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Joseph
authors.initials: J
authors.lastname: Permuy
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Ligeia
authors.initials: L
authors.lastname: Damaso
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Debbie
authors.initials: D
authors.lastname: Merinbaum
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Ximena
authors.initials: X
authors.lastname: Gaete
authors.affiliation: Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
authors.forename: Veronica
authors.initials: V
authors.lastname: Mericq
mesh_terms: D000293:Adolescent; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001823:Body Composition; D001827:Body Height / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004392:Dwarfism / Q000000981:diagnostic imaging / Q000188:drug therapy*; D013006:Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D017063:Outcome Assessment, Health Care; D011627:Puberty; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; D013006:Growth Hormone