estrone-sulfate and Turner-Syndrome

The long-term effects of pure 17β-estradiol (E₂) depending on route of administration have not been well characterized.. 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).. Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited.. 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.. Changes in body composition and lipid oxidation were evaluated.. 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.. 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.

Topics: Administration, 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