Recombinant growth hormone in children and adolescents with Turner syndrome.
BACKGROUND
Turner syndrome (TS) affects about one in 1,500 to 2,500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Untreated women are approximately 20-21 cm shorter than normal women within their respective populations. Recombinant human growth hormone (hGH) has been used to increase growth and final height in women who have Turner syndrome.


OBJECTIVE
To assess the effects of recombinant growth hormone on short-term growth and final height in children and adolescents with Turner syndrome.


METHODS
Published and unpublished randomised-controlled trials (RCTs) were sought by searching the Cochrane Central Register of Controlled Trials (Central) (2002, Issue 3), Medline (1981 to July 2002), Embase (1980 to June 2002), PubMed (search 30 July, 2002 for entries in last 180 days), Science Citation Index (search 30 July, 2002), BIOSIS (search 30 July, 2002) and Current Controlled Trials (search 30 July, 2002). Article reference lists were assessed for trials and experts and pharmaceutical companies were contacted.


METHODS
Randomised controlled trials were included if they were carried out in children with Turner Syndrome before achieving final height. Growth hormone had to be administered for a minimum of six months and compared with a placebo or no treatment control condition. A growth or height outcome measure must have been assessed. In addition, in the context of a growth assessment other outcomes reflecting psychological adjustment were also included.


METHODS
Two reviewers assessed studies for inclusion criteria and for methodological quality. Data were extracted by one reviewer and checked by a second. The main outcomes were final height (in cm or standard deviation score), growth (in velocity or velocity standard deviation score). Additional outcomes included bone age, quality of life, cognitive performance, and adverse effects. To estimate summary treatment effects, data were pooled using a random effects model (when data were sufficient and appropriate to combine) with calculation of weighted mean differences (WMD) for continuous outcomes.


RESULTS
Four RCTs that included 211 participants after one year of treatment were included. These were described in six publications. Three studies were included in the analyses of growth outcomes (one study did not report any data). Only one trial reported results on final height. This trial reported that average final height in 40 treated women was 146.2 cm and 141.4 cm in 29 untreated women (mean difference (MD) 4.8 cm, 95% CI 2.2 to 7.4). Short-term growth velocity was greater in treated than untreated girls after one year (two trials, weighted mean difference (WMD) 3.3 cm/yr, 95% CI 2.4 to 4.3) after 18 months (one trial, MD 2.6 cm/yr, 95% CI 2.1 to 3.1) and after two years (one trial, MD 1.8 cm/yr, 95% CI 1.3 to 2.3). Results were similar when reported as growth velocity standard deviation scores. Skeletal maturity was not accelerated by treatment with recombinant growth hormone (hGH). Bone age divided by chronological age was approximately one in both treated and untreated groups in one trial after both one and two years of treatment. One trial selectively reported psychological outcomes that suggested that psychological adjustment was better in girls treated with hGH, but selective reporting leaves these results in some doubt. Adverse effects were minimally reported. There is little evidence of serious short-term adverse effects in these trials, but they are underpowered to detect rare adverse effects.


CONCLUSIONS
Recombinant human growth hormone (hGH) doses between 0.3 - 0.375 mg/kg/wk increase short-term growth in girls with Turner Syndrome (TS) by approximately 3 cm in the first year of treatment and by approximately 2 cm per year after 2 years of treatment. There is little evidence on the effects of hGH on final height. Treatment in one trial increased final height by approximately 5 cm over an untreated control group. Despite this increase, the fated control group. Despite this increase, the final height of treated women was still outside the normal range (more than two standard deviations below the normal population mean). Additional trials of the effects of hGH carried out with control groups until final height is achieved would allow better informed decisions about whether the benefits of hGH treatment outweigh the requirement of treatment over several years at considerable cost.
Cave
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CB
Wessex Institute for Health Research and Development, University of Southampton, Bassett Crescent East, Mailpoint 728, Biomedical Sciences Building, Southampton, UK, SO16 7PX.
Bryant
J
J
Milne
R
R
D000293:Adolescent; D001827:Body Height; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D014424:Turner Syndrome / Q000150:complications*
D011994:Recombinant Proteins; D013006:Growth Hormone