氧甲氢龙和青春期诱导时间对特纳综合征患者最终身高的影响：随机、双盲、安慰剂对照试验

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 7-13years at recruitment, receiving recombinant growth hormone therapy (10mg/m2/week).

Interventions:

Participants were randomised to oxandrolone (0.05mg/kg/day, maximum 2.5mg/day) or placebo from 9years of age. Those with evidence of ovarian failure at 12years were further randomised to oral ethinylestradiol (year 1, 2μg daily; year 2, 4μg daily; year 3, 4months each of 6, 8, and 10μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25years 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 14years. 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 3).
Figure 3 Figure 3: SITAR fitted summary height curves by trial arm for randomisation 1 (left) and randomisation 2 (right). (Reprinted from Gault EJ, on behalf of the British Society for Paediatric Endocrinology and Diabetes. Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial. BMJ. 2011;342:d1980.)