Context. Optimizing pubertal estrogen replacement in girls with Turner syndrome.

Objective. To test the hypotheses that physiologic estradiol replacement administered early with growth hormone (GH) will preserve height potential as much as if administered late and will bring about a greater height gain than standard oral estrogen therapy combined with GH.

Design. Randomization to early or late estrogen treatment; follow-up 3.5 yr.

Setting. Multicenter outpatient study.

Patients. Turner syndrome girls 12.0-12.9 (n = 7) or 14.0-14.9 (n = 7) years of age who began GH before 12.0 yr of age. Matched to National Cooperative Growth Study (NCGS) registry patients who began GH and oral conjugated estrogen at similar ages and were similarly followed to adult or near-adult height.

Interventions. Depot estradiol 0.2 mg/mo IM initially and gradually increased; GH 0.05 mg/kg/daily.

Main outcome variable. Adult or near-adult height.

Results. Depot estradiol treatment resulted in height significantly taller than predicted at 12 yr of age (P < 0.02). All height potential was gained in the first two years of the study, during which the early group grew 3.5 cm more than the late group, which was receiving GH alone (P < 0.01). The early depot estradiol group also gained 5.9 cm more height after starting estrogen than did the early NCGS group (P < 0.05). Although feminization proceeded slowly on the lowest dose of estradiol, it advanced normally thereafter.

Conclusions. These results suggest that very low-dose parenteral estradiol permits relatively age-appropriate feminization without interfering with the effect of GH on the enhancement of height potential.