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

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

“…However, mean voice frequencies of both Ox-treated groups are normal. Remarkably, no virilizing effects were found in the UK study of 106 TS girls treated with Ox in a dosage of 0.05 mg/kg per day with a maximum of 2.5 mg/day (14). A possible reason for this discrepancy with our study might be the use of a maximum Ox dose and also the lack of systematic assessments of virilization in that study.…”

“…Data of our original study and the US study point toward a dose-dependent effect of Ox on bone maturation (8,12). However, others could not confirm a faster bone maturation during Ox treatment when using a dosage of 0.05 mg/kg per day, with a maximum Ox dose of 2.5 mg daily (14).…”

“…Consequently, a further delay of breast development due to Ox (observed in the US study as well as in our pediatric study, while not specifically assessed in the UK study) is undesirable (8,12,14). Theoretically, Ox inhibits the estrogen effect on breast development (28).…”

“…The Ox-treated adult women still reported more subjective virilization, but actual virilization was only confirmed objectively in a few cases. Besides our study, two placebo-controlled trials have confirmed an increase in height gain with Ox (8,12,14). The mechanism by which Ox influences growth is unclear.…”

“…Ox has been shown to increase adult height and growth velocity in TS (8,9,10,11,12,13,14). Some of the initial studies used Ox dosages of 0.1 mg/kg per day or higher, which were subsequently lowered due to virilization and early bone maturation (9,10,11).…”