Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome.
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.
Menke
Leonie A
LA
Department of Pediatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. l.a.menke@lumc.nl
Sas
Theo C J
TC
de Muinck Keizer-Schrama
Sabine M P F
SM
Zandwijken
Gladys R J
GR
de Ridder
Maria A J
MA
Odink
Roelof J
RJ
Jansen
Maarten
M
Delemarre-van de Waal
Henriëtte A
HA
Stokvis-Brantsma
Wilhelmina H
WH
Waelkens
Johan J
JJ
Westerlaken
Ciska
C
Reeser
H Maarten
HM
van Trotsenburg
A S Paul
AS
Gevers
Evelien F
EF
van Buuren
Stef
S
Dejonckere
Philippe H
PH
Hokken-Koelega
Anita C S
AC
Otten
Barto J
BJ
Wit
Jan M
JM
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
D000728:Androgens; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D010074:Oxandrolone