Acceleration of growth in Turner syndrome patients treated with growth hormone: summary of three-year results. Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height. Psychological aspects of the Canadian randomized controlled trial of human growth hormone and low-dose ethinyl oestradiol in children with Turner syndrome. The Canadian Growth Hormone Advisory Group.
In 1983, a multicenter, collaborative, prospective study was begun to investigate the efficacy of human growth hormone (hGH), alone and in combination with oxandrolone, in girls with Turner syndrome. While subjects in the control group grew 3.8 cm/yr (-0.1 SD for untreated Turner patients), subjects receiving hGH alone grew 6.6, 5.4 and 4.6 cm/yr in years 1-3, respectively (+3.1, +2.0, +1.4 SD). Subjects in the combination therapy group grew 9.8, 7.4 and 6.1 cm/yr (+6.6, +4.3, +3.0 SD). Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights. A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS. Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height, sexual development and psychological status of girls with Turner syndrome. Girls entering the study were randomized either to be treated with recombinant human growth hormone or to act as controls. Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years. However, for the purposes of the psychological study at this time, children receiving oestrogen were excluded from analysis. Girls treated with GH for a period of 2 years showed a significant increase in growth rate, which declined with continued treatment, while the growth rate in the control group remained constant throughout. There was a correlation between the higher growth rate and the girls' perceptions of themselves as more intelligent, more attractive, having more friends, greater popularity and experiencing less teasing than the untreated group. Growth rate was not correlated with family or school functioning.
Recombinant human growth hormone (hGH) doses between 0.3 to 0.375 mg/kg/wk increase short-term growth in girls with Turner syndrome by approximately three (two) cm in the first (second) year of treatment. Treatment in one trial increased final height by approximately six cm over an untreated control group. Despite this increase, the final height of treated women was still outside the normal range. 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.