Update on Growth Hormone Therapy for Turner's Syndrome

Abstract

With the development of recombinant DNA technology and the ability to mass produce synthetic human growth hormone (hGH), critical evaluation of the efficacy of hGH in patients with Turner's syndrome has become possible. Table 1 summarizes the literature published to date on hGH studies in Turner's patients. Earlier trials were limited by the small numbers of patients studied, the generally low-dose regimens employed, and the short-term follow-up of subjects. However, several large scale studies from the USA, Japan and Europe are beginning to yield important data concerning the short-term and longer-term efficacy of hGH, both alone and in combination with anabolic steroids or oestrogens.While these studies all vary in their entry criteria, age of subjects, hGH preparations and regimens used, and dosages of androgens or oestrogens given, all clearly demonstrate that hGH, both alone and in combination with sex steroids, can stimulate growth over a period of 1 year. Given alone, hGH has resulted in an increment in annual growth rate of 2.7 cm/year (19), 2.4 cm/year (20-22), 3.8 cm/year (23), 1.5 cm/year (24), 3.6 cm/year (25), and 3.2 cm/year (26). Further review of the cumulative data from these studies points to the following cautious conclusions.hGH alone. Given alone, hGH results in a modest, but significant, increase in growth rate over the first year of administration. This increase is all the more noteworthy given that the natural history of growth in Turner's syndrome is one of progressive growth deceleration (30,31). In the Genentech Collaborative Study (20-22), annual growth rate (expressed as SDS for Turner's syndrome patients) was -0.1 for the control group and +3.1 for the hGH group during the first year of therapy (Table 2).High-dose hGH therapy. While careful dose-response studies have not yet been performed, it is noteworthy that many of the clinical trials employed relatively high doses of hGH, and that the results suggest an enhanced growth response at rhGH doses as high as 1.22-1.35 IU/kg/week' . Combination therapy with low-dose oestrogens. Data accumulated to date indicate that the addition of low-dose oestrogen preparations to optimal hGH regimens does not significantly augment the clinical response to hGH.Vanderschueren-Lodeweyckx et al. (26) have shown that the addition of ethinyloestradiol, 25 ngikglday, to hGH increased incremental growth from +3.6 to +4.9 cm/year (Table l), but this increase did not achieve statistical significance. Similarly Ross et al. (32) have demonstrated that while ethinyloestradiol, 50 ng/kg/day , enhanced the lower leg growth response to hGH, 0.09 IU/kg three times a week, larger doses of ethinyloestradiol (100 ng/kg/day) did not alter the response to hGH, 0.15 IU/kg three times a week. Furthermore, oestrogen administration may be associated with undesirable feminization, as well as advancement of skeletal maturation.Combination therapy with oxandrolone. The original observation by Rudman et at. (10) of a synergism between oxandrolone and hGH appears to be substanti...

The Effects of Growth Hormone Therapy on Spontaneous Sexual Development

“…Of course, children with GH deficiency treated with GH only attain a final height appropriate to their final-height prognosis at the onset of treatment [25]. The only condi tion associated with short stature where there is evidence that GH treatment may improve final height prognosis is the Turner syndrome [26] but. of course, in this condition puberty is almost always induced exogenously.…”

Recombinant Human Growth Hormone and Oxandrolone in Treatment of Short Stature in Girls with Turner Syndrome

“…No other signs of virilisation were noted in the girls of this treatment group. Since the occur rence of those side effects seem to be dose related [66] and the anabolic steroid-induced increase in HV was found to be unaffected by doses over a wide range [67], the oxan drolone dose was reduced to 0.05 mg/kg/day in the 2nd year of treatment. Subsequent to this, no further enlarge ments of the clitorides were noticed.…”

Growth and Metabolic Data Following Growth Hormone Treatment of Children with Intrauterine Growth Retardation

“…Certainly short normal children produce less growth hormone (GH) than taller peers [1] and this has lent enthusiasm to the treat ment of such children with GH. However, the prelimi nary results of these studies have demonstrated an im provement in short-term growth rate without evidence of improved final height except in girls with the Turner svn-drome [2], Pharmacological dose regimens of GH have usually been in the range of 20-30 IU/m2/week given as a daily subcutaneous injection, although dose regimens of up to 40 IU/m2/weck have been used more recently [3].…”