Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial.

Abstract

OBJECTIVE:

To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner's syndrome receiving a standard dose of growth hormone.

DESIGN:

Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals.

PARTICIPANTS:

Girls with Turner's syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m(2)/week).

INTERVENTIONS:

Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 μg daily; year 3, 4 months each of 6, 8, and 10 μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14.

MAIN OUTCOME MEASURE:

Final height. Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P = 0.001, n = 82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P = 0.05, n = 48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P < 0.001). No cases of virilisation were reported.

CONCLUSION:

Oxandrolone had a positive effect on final height in girls with Turner's syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner's syndrome. Trial registration Current Controlled Trials ISRCTN50343149.

• Authors: Emma Jane Gault, Rebecca J Perry, Tim J Cole, Sarah Casey, Wendy F Paterson, Peter C Hindmarsh, Peter Betts, David B Dunger, Malcolm D C Donaldson, British Society for Paediatric Endocrinology and Diabetes
• Journal: BMJ (Clinical research ed.) (BMJ) Vol. 342 Pg. d1980 (Apr 14 2011) ISSN: 1756-1833 [Electronic] England
• PMID: 21493672 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anabolic Agents
• Oxandrolone

Topics

• Adolescent
• Anabolic Agents (therapeutic use)
• Body Height (physiology)
• Child
• Double-Blind Method
• Female
• Growth Disorders (drug therapy)
• Humans
• Oxandrolone (therapeutic use)
• Puberty
• Time Factors
• Turner Syndrome (drug therapy)