Efficacy and Safety of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome

Leonie A. Menke, Theo C. J. Sas, Sabine M. P. F. de Muinck Keizer-Schrama, Gladys R. J. Zandwijken, Maria A. J. de Ridder, Roelof J. Odink, Maarten Jansen, Henriëtte A. Delemarre-van de Waal, Wilhelmina H. Stokvis-Brantsma, Johan J. Waelkens, Ciska Westerlaken, H. Maarten Reeser, A. S. Paul van Trotsenburg, Evelien F. Gevers, Stef van Buuren, Philippe H. Dejonckere, Anita C. S. Hokken-Koelega, Barto J. Otten, Jan M. Wit

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Abstract

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/m(2) . d) from baseline, combined with placebo(Pl) or Oxin 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. (J Clin Endocrinol Metab 95: 1151-1160, 2010)
Original languageEnglish
Pages (from-to)1151-1160
JournalJournal of clinical endocrinology and metabolism
Volume95
Issue number3
DOIs
Publication statusPublished - 2010

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