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Conjugated Oral versus Transdermal Estrogen Replacement in Girls with Turner Syndrome: A Pilot Comparative Study

Section of Pediatric Endocrinology/Diabetology (Z.M.N., L.A.D., E.A.E.), James Whitcomb Riley Hospital for Children, and Division of Biostatistics (R.Q., S.M.P.), Indiana University School of Medicine, Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Zeina M. Nabhan, M.D., M.S., Pediatric Endocrinology/Diabetology, Riley Hospital for Children, 702 Barnhill Drive, Room 5960, Indianapolis, Indiana 46202. E-mail: znabhan{at}iupui.edu.

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

Objective: The objective of the study was to compare conjugated oral vs. transdermal estrogen (TD E2) on bone accrual, uterine growth, pubertal development, IGF-I, and lipids in girls with TS.

Methods: Prepubertal GH-treated girls aged 10 yr or older with TS were eligible. Subjects were randomized to conjugated oral estrogen or TD E2 for 1 yr. Assessments included dual-emission x-ray absorptiometry, pelvic ultrasound, Tanner staging, growth velocity, IGF-I, and lipid profile.

Results: Twelve girls (14.0 ± 1.7 yr) were enrolled. TD E2 resulted in a significantly greater change in spine bone density at 12 months compared with conjugated oral estrogen (bone mineral content 9.0 ± 0.9 vs. 5.8 ± 0.9 g, P = 0.04; bone mineral density 0.12 ± 0.01 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 vs. 1.98 ± 0.39 cm, P = 0.003) and volume (22.2 ± 4.4 vs. 4.0 ± 4.4 ml, P = 0.02) were also found in the TD vs. the oral group at 1 yr. 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.