Effect of oxandrolone and timing of pubertal induction on final height in Turner syndrome: final analysis of the UK randomised placebo-controlled trial.

The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and delaying ethinylestradiol induction of puberty by 2 years from 12 (E12) to 14 (E14) years in growth hormone-treated girls with TS. The study ran from 1999 to 2013. By 2011, eighty-two of 92 participants had reached final height and an interim analysis using the Super-Imposition by Translation And Rotation model showed significant increases in final height with both oxandrolone and E14. The analysis has been repeated now that all 92 patients have reached final height. Oxandrolone still significantly increased final height by 4.1 cm (95% CI 1.6 to 6.6, n=92) compared with 4.6 cm previously. However, the E14 effect was no longer significant at 2.7 cm (95% CI -0.8 to 6.1, n=56) compared with 3.8 cm previously.

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

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.

Fetal programming of body dimensions and percentage body fat measured in prepubertal children with a 4-component model of body composition, dual-energy X-ray absorptiometry, deuterium dilution, densitometry, and skinfold thicknesses.

BACKGROUND: Intrauterine programming of body composition [percentage body fat (%BF)] has been sparsely examined with multiple independent reference techniques in children. The effects on and consequences of body build (dimensions, mass, and length of body segments) are unclear. OBJECTIVE: The study examined whether percentage fat and relation of percentage fat to body mass index (BMI; in kg/m2) in prepubertal children are programmed during intrauterine development and are dependent on body build. It also aimed to examine the extent to which height can be predicted by parental height and birth weight. DESIGN: Eighty-five white children (44 boys, 41 girls; aged 6.5-9.1 y) had body composition measured with a 4-component model (n = 58), dual-energy X-ray absorptiometry (n = 84), deuterium dilution (n = 81), densitometry (n = 62), and skinfold thicknesses (n = 85). RESULTS: An increase in birth weight of 1 SD was associated with a decrease of 1.95% fat as measured by the 4-component model (P = 0.012) and 0.82-2.75% by the other techniques. These associations were independent of age, sex, socioeconomic status, physical activity, BMI, and body build. Body build did not decrease the strength of the associations. Birth weight was a significantly better predictor of height than was self-reported midparental height, accounting for 19.4% of the variability at 5 y of age and 10.3% at 7.8 y of age (17.8% and 8.8% of which were independent of parental height at these ages, respectively). CONCLUSIONS: Consistent trends across body-composition measurement techniques add strength to the suggestion that percentage fat in prepubertal children is programmed in utero (independently of body build and BMI). It also suggests birth weight is a better predictor of prepubertal height than is self-reported midparental height.