ESPE Abstracts (2015) 84 FC4.3

An Updated and Final Analysis of a Randomised Placebo-controlled Trial of the Effect of Oxandrolone and Timing of Pubertal Induction on Final Height in Turner Syndrome

Emma-Jane Gaulta, Tim J Coleb, Rebecca J Perryc, Sarah Caseyc, Wendy F Patersonc, Peter C Hindmarshb, Peter Bettsd, David B Dungere & Malcolm D C Donaldsona

aUniversity of Glasgow, Glasgow, UK; bUniversity College London, London, UK; cRoyal Hospital for Sick Children, Glasgow, UK; dSouthamptom University Hospitals NHS Trust, Southampton, UK; eUniversity of Cambridge, Cambridge, UK

Background: While GH therapy forms the mainstay of growth promoting treatment for Turner syndrome (TS), adjunctive use of oxandrolone and optimal timing of pubertal induction remain controversial. The previously published interim analysis of this randomised double-blind placebo-controlled trial demonstrated that oxandrolone and pubertal induction at 14y vs 12y significantly increased final height. However, these effects were not additive.

Objective: To update the analysis now the remaining participants have reached adult height.

Method: Girls with TS aged 7–13y receiving GH (10 mg/m2 per week) were randomised to oxandrolone (0.05 mg/kg per day, max. daily dose 2.5 mg) or placebo from 9y. At 12y, those with ovarian failure were further randomised to oral ethinylestradiol (year 1, 2 μg daily; year 2, 4 μg daily; year 3, 4 months each of 6/8/10 μg daily) or placebo (until the age of 14y, when puberty was induced using the same protocol). The primary outcome measure was final height.

Results: 106 participants were recruited from 36 hospitals (1999–2003); 14 participants withdrew leaving 92 who completed therapy and reached final height by 2013. Mean (S.D.) final height was 151.8 (6.3) cm. As in the interim analysis, oxandrolone significantly increased final height – by 4.1 cm (95% CI 1.6 to 6.6 cm (P=0.002, n=92). Delaying pubertal induction to 14y increased final height by 2.7 cm (95% CI −0.8 to 6.1 cm) but this was no longer statistically significant (P=0.13, n=56). No excess virilisation was reported.

Conclusion: This study confirms the positive effect of oxandrolone, consistent with other reports. Failure to demonstrate a similar effect of delaying pubertal induction may be due to the study being underpowered. However, since the effects in the interim analysis were not additive, there can be little support for delaying pubertal induction much beyond 12y (already relatively late compared to normal) when oxandrolone is available.

Funding: Funding was provided by the Scottish Executive Chief Scientist Office (1999–2004) (K/MRS/50/C2713) and the British Society for Paediatric Endocrinology and Diabetes (2004–2013), with a contribution to funding of pharmacy staff from the Child Growth Foundation.