title: Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome.
abstract: OBJECTIVE
  GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear.
  
  
  METHODS
  A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo (Pl) or Ox in low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed.
  
  
  RESULTS
  Compared with GH+Pl, GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- sd, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.02) and per-protocol analysis (9.8 +/- 4.9 vs. 6.8 +/- 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl (8.3 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.3). Breast development was slower on GH+Ox (GH+Ox 0.03, P = 0.02; GH+Ox 0.06, P = 0.05), and more girls reported virilization on GH+Ox 0.06 than on GH+Pl (P < 0.001).
  
  
  CONCLUSIONS
  In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. l.a.menke@lumc.nl
authors.forename: Leonie A
authors.initials: LA
authors.lastname: Menke
authors.forename: Theo C J
authors.initials: TC
authors.lastname: Sas
authors.forename: Sabine M P F
authors.initials: SM
authors.lastname: de Muinck Keizer-Schrama
authors.forename: Gladys R J
authors.initials: GR
authors.lastname: Zandwijken
authors.forename: Maria A J
authors.initials: MA
authors.lastname: de Ridder
authors.forename: Roelof J
authors.initials: RJ
authors.lastname: Odink
authors.forename: Maarten
authors.initials: M
authors.lastname: Jansen
authors.forename: Henriëtte A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.forename: Wilhelmina H
authors.initials: WH
authors.lastname: Stokvis-Brantsma
authors.forename: Johan J
authors.initials: JJ
authors.lastname: Waelkens
authors.forename: Ciska
authors.initials: C
authors.lastname: Westerlaken
authors.forename: H Maarten
authors.initials: HM
authors.lastname: Reeser
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
authors.forename: Evelien F
authors.initials: EF
authors.lastname: Gevers
authors.forename: Stef
authors.initials: S
authors.lastname: van Buuren
authors.forename: Philippe H
authors.initials: PH
authors.lastname: Dejonckere
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
authors.forename: Barto J
authors.initials: BJ
authors.lastname: Otten
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000728:Androgens / Q000008:administration & dosage / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D001827:Body Height / Q000187:drug effects*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D009426:Netherlands; D010074:Oxandrolone / Q000008:administration & dosage* / Q000009:adverse effects*; D011627:Puberty / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014424:Turner Syndrome / Q000188:drug therapy*; D014770:Virilism / Q000139:chemically induced
chemical_list: D000728:Androgens; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D010074:Oxandrolone