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

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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 .cntdot. 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 .cntdot. day, orally), GH (0.15 U/kg, s.c., 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 .cntdot. 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 .cntdot. day, but not at the dose of 50 ng/kg .cntdot. 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 .cntdot. day) and GH (0.09 \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 .cntdot. 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 by concurrent administration of low dose estrogen will require long term clinical trials.

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