2 ESTROGEN TREATMENT OF PATIENTS WITH CONADAL DYSCENESIS

Commonly, estrogen therapy in patients with XO gonadal dysgenesis has been deferred until 15 yrs or later; it has been inferred that treatment with estrogen at an earlier age leads to rapid skeletal maturation and a lower adult height. In order to examine this hypothesis, we studied the effect of “low dose” early conjugated estrogen therapy on peak height velocity, bone age, and height. Seventeen patients (Group I), 11 with a 45,X karyotype and 6 with X chromosome mosaicism were given 0.3mg of conjugated estrogens daily starting at a mean age of 13.4 yrs. In comparison, 5 patients (Group II) were treated with 1.25mg of conjugated estrogens at a mean age of 15.5 yrs. In addition, growth was studied in 3 patients (Group III) with karyotypic evidence of a 45,X cell line, short stature and normal gonadal function at puberty. The mean height velocity in Group I prior to therapy was 2.7cm/yr and post-initial estrogen therapy was 5.2 cm/yr (p=.0002); the corresponding velocities for Group II were 2.4 and 4.4 cm/yr, respectively (p>0.5). The mean last measured height in Group I was 141.6 cm (135.4-145.8). The final height in Group II was 143.3 cm (136.9-150), and in Group III 135.8 cm (133.5-139). There was no significant difference between these 3 groups (p>0.1). These data suggest that low dose early estrogen therapy promotes secondary sexual development and stimulates a growth spurt without inordinate skeletal maturation or a reduction in final height. Thus, we recommend “low dose” estrogen treatment of patients with gonadal dysgenesis early in adolescence as it mitigates the undesirable psychologic effects of a prolonged delay in sexual maturation.