Metabolic effects of oral versus transdermal 17β-estradiol (E₂): a randomized clinical trial in girls with Turner syndrome

TitleMetabolic effects of oral versus transdermal 17β-estradiol (E₂): a randomized clinical trial in girls with Turner syndrome
Publication TypeJournal Article
Year of Publication2013
AuthorsTorres-Santiago, L., Mericq V., Taboada M., Unanue N., Klein K. O., Singh R., Hossain J., Santen R. J., Ross J. L., & Mauras N.
JournalThe Journal of clinical endocrinology and metabolism
Volume98
Issue7
Pagination2716-24
Date Published2013 Jul
ISSN1945-7197
KeywordsAdministration, Oral; Adolescent; Adult; Basal Metabolism; Biotransformation; Body Composition; Bone Density; Drug Monitoring; Energy Metabolism; Estradiol; Estrogen Replacement Therapy; Estrone; Feasibility Studies; Female; Humans; Lipid Metabolism; Transdermal Patch; Turner Syndrome; Young Adult
Abstract

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 E₂ 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: E₂ 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 lower on oral 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. TD 17β-E₂ results in a more physiological estrogen milieu than oral 17β-E₂ administration in girls with TS.







DOI10.1210/jc.2012-4243
Alternate JournalJ. Clin. Endocrinol. Metab
Refereed DesignationRefereed