Metabolic effects of oral versus transdermal 17β-estradiol (E 2): A randomized clinical trial in girls with turner syndrome

L. Torres-Santiago, V. Mericq, M. Taboada, N. Unanue, K. O. Klein, R. Singh, J. Hossain, R. J. Santen, J. L. Ross, Nelly Mauras

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Context: The long-term effects of pure 17β-estradiol (E2) depending on route of administration have not been well characterized. Objective: Our objective was to assess metabolic effects of oral vs transdermal (TD) 17β-E2 replacement using estrogen concentration-based dosing in girls with Turner syndrome (TS). Patients: Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited. Design: Subjects were randomized to 17β-E2 orally or TD. Doses were titrated using mean E 2 concentrations of normally menstruating girls as therapeutic target. E2, estrone (E1), and E1 sulfate (E1S) were measured by liquid chromatography tandem mass spectrometry and a recombinant cell bioassay; metabolites were measured, and dual-energy x-ray absorptiometry scan and indirect calorimetry were performed. Main Outcome: Changes in body composition and lipid oxidation were evaluated. Results: E 2 concentrations were titrated to normal range in both groups; mean oral dose was 2 mg, and TD dose was 0.1 mg. After 6 and 12 months, fat-free mass and percent fat mass, bone mineral density accrual, lipid oxidation, and resting energy expenditure rates were similar between groups. IGF-1 concentrations were loweronoral 17β-E2, but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin, or highly sensitive C-reactive protein between groups. However, E1, E1S, SHBG, and bioestrogen concentrations were significantly higher in the oral group. Conclusions: When E2 concentrations are titrated to the normal range, the route of delivery of 17β-E2 does not affect differentially body composition, lipid oxidation, and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E1, E1S, and total bioestrogen) is significantly higher after oral 17β-E2. TD17β-E2 results in amorephysiological estrogen milieu than oral 17β-E2 administration in girls with TS.

Original languageEnglish (US)
Pages (from-to)2716-2724
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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