Background: The optimal route of estrogen replacement in Turner syndrome (TS) is unknown.

Objective: To compare conjugated oral versus transdermal estrogen (TD E2) on bone accrual, uterine growth, pubertal development, IGF-1, and lipids in girls with TS.

Methods: Prepubertal growth hormone (GH) treated girls 10 yrs with TS were eligible. Subjects were randomized to conjugated oral estrogen or TD E2 for one year. Assessments included DXA, pelvic ultrasound, Tanner staging, growth velocity, IGF-1, and lipid profile.

Results: Twelve girls (14.0 ± 1.7 yrs) were enrolled. TD E2 resulted in a significantly greater change in spine bone density at 12 months compared with conjugated oral estrogen; (BMC 9.0 ± 0.9 g vs. 5.8 ± 0.9 g, p = 0.04; BMD 0.12 ± 0.01 g/cm2 vs. 0.06 ± 0.01 g/cm2, p = 0.004; Z-score 0.7 ± 0.1 vs. 0.3 ± 0.1, p = 0.03). Greater increases in uterine length (4.13 ± 0.39 cm vs. 1.98 ± 0.39 cm, p = 0.003) and volume (22.2 ± 4.4 cc vs. 4.0 ± 4.4 cc, p = 0.02) were also found in the TD vs. the oral group at one year. At study end, 66% of subjects in the TD group had a mature uterus vs. 0% in the oral group. No significant differences in other parameters examined were seen.

Conclusion: In girls with TS, TD E2 resulted in faster bone accrual at the spine and increased uterine growth compared with conjugated oral estrogen. This pilot study provides preliminary information for optimizing estrogen replacement in this population.