The Effect of Short Term Treatment With Growth Hormone and Ethinyl Estradiol on Lower Leg Growth Rate in Girls With Turner's Syndrome

Abstract

An important consequence of Turner's syndrome is short stature. We previously reported that the optimal doses of ethinyl estradiol (EE2) and GH for the stimulation of short term growth in such patients were 100 ng/kg.day and 0.15 U/kg (administered sc three times weekly), respectively. The aim of this study was to determine whether the combination of low dose estrogen and GH would stimulate short term growth more than either agent administered alone. Thirty-nine girls with Turner's syndrome (aged 5-15 yr) underwent one to three 6-month cycles, each consisting of a 2-month baseline period, a 2-month treatment period, and a subsequent 2-month washout period. During the first 2 yr of the study, the girls were assigned to receive the three treatments in random order. The treatments were EE2 (100 ng/kg.day, orally), GH (0.15 U/kg, sc, three times weekly), or the combination of EE2 and GH. Subsequently, some of the girls were treated with reduced doses of EE2 (50 ng/kg.day) and GH [0.09 U/kg, three times weekly (tid)] according to the same protocol. Lower leg length was measured every 2 months throughout the study. EE2 increased lower leg growth rate significantly at the dose of 100 ng/kg.day, but not at the dose of 50 ng/kg.day. Similarly, the higher dose of GH (0.15 U/kg, tiw) increased lower leg growth rate significantly, whereas the lower dose (0.09 U/kg, tiw) did not. However, combined treatment with the lower doses of EE2 (50 ng/kg.day) and GH (0.09 U/kg, tiw) stimulated lower leg growth rate significantly and to a similar degree as the higher dose of GH (0.15 U/kg, tiw). This higher dose of GH appeared to cause a maximal increase in lower leg growth rate, which was not further increased by combined administration with the higher dose (100 ng/kg.day) of estrogen. Thus, addition of low dose EE2 to an optimal dose of GH did not cause any apparent increase in short term lower leg growth rate in girls with Turner's syndrome. Whether the long term outcome of GH treatment would be altered by concurrent administration of low dose estrogen will require long term clinical trials.

Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome

“…Nevertheless, these findings show that during the course of an optimal treatment with rhGH the addition of EE2 in a dose of 100 ng/ kg day does not lead to an acceleration of height velocity in TS patients, at least in those with a pubertal bone age. This is in agreement with the short-term study of Ross et al (1988) who showed that the addition of 100 ng/kg day EE2 at the onset of GH therapy in an optimal dose did not lead to a further acceleration of lower leg growth rate. Moreover, height velocities during the first year of rhGH treatment in studies evaluating the effect of adding oestrogens from the beginning to rhGH treatment in doses comparable to ours and in TS patients with an age comparable to our patients with pubertal induction were lower than observed in our study (Ferrandez et al, 1991;Pavia et al, 1991).…”

Gradually increasing ethinyl estradiol for Turner syndrome may produce good final height but not ideal BMD

“…In adults, estradiol via transdermal administration was reported to be more beneficial for preventing thrombus; this type of administration, by bypassing the liver (avoiding the first-pass effect) and decreased clotting factors, minimizes the risk of thromboembolic events [24,25]. EE 2 was used for the estrogen treatment of group E in the present study in order to enable comparison with other historical studies where EE 2 was used [10,11,26].…”

Growth Hormone plus Childhood Low-Dose Estrogen in Turner's Syndrome

“…On the basis of the observations of childhood estrogen deficiency in Turner’s syndrome 16,17 and the biphasic nature of the estrogen-mediated growth response, 24–27 we postulated that lower, more physiologic estrogen replacement during childhood might increase adult height and have other potential benefits. 18,21,28 To test this hypothesis, we conducted a placebo-controlled trial to assess the effects on adult height of growth hormone treatment alone and in combination with childhood ultra-low-dose estrogen, followed by pubertal estrogen-replacement therapy.…”