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.

Fig 1 Flow chart of participation in UK Turner Study according to treatment groups, completions, and withdrawals. *Withdrawn before 12 years of age (that is, randomised only at randomisation 1 to oxandrolone or placebo). †Aged ≥12.25 years at recruitment; oestrogen treatment started at 14 years with no randomisation. ‡Withdrawn after 12 years of age (that is, randomised at randomisation 1 to oxandrolone or placebo and at randomisation 2 if oestrogen treatment needed)

Fig 2 Individual height growth curves according to randomisation 1: unadjusted (top) and SITAR adjusted (bottom)

Fig 3 SITAR fitted summary height curves by trial arm for randomisation 1 (top) and randomisation 2 (bottom)