Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome
article
Menke, L.A.
Sas, T.C.J.
Muinck Keizer de-Schrama, S.M.P.F.
Zandwijken, G.R.J.
Ridder, M.A.J. de
Odink, R.J.
Jansen, M.
Delemarre de-Waal, H.A. van
Stokvis-Brantsma, W.H.
Waelkens, J.J.
Westerlaken, C.
Reeser, H.M.
Trotsenburg, A.S.P. van
Gevers, E.F.
Buuren, S. van
Dejonckere, P.H.
Hokken-Koelega, A.C.S.
Otten, B.J.
Wit, J.M.
Context and 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. Design and Participants: 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/m2· d) from baseline, combined with placebo (Pl) or Ox in low(0.03mg/kg · d) or conventional (0.06 mg/kg · d) dose from the age of 8yr 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 Oxdosage (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. Copyright © 2010 by The Endocrine Society.
TNO Identifier
346416
ISSN
0021972X
Source
Journal of Clinical Endocrinology and Metabolism, 95(3), pp. 1151-1160.
Pages
1151-1160