title: Metabolic effects of oral versus transdermal 17β-estradiol (E₂): a randomized clinical trial in girls with Turner syndrome.
abstract: BACKGROUND
  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).
  
  
  METHODS
  Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Nemours Children’s Clinic, Jacksonville, Florida 32207, USA.
authors.forename: L
authors.initials: L
authors.lastname: Torres-Santiago
authors.forename: V
authors.initials: V
authors.lastname: Mericq
authors.forename: M
authors.initials: M
authors.lastname: Taboada
authors.forename: N
authors.initials: N
authors.lastname: Unanue
authors.forename: K O
authors.initials: KO
authors.lastname: Klein
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: J
authors.initials: J
authors.lastname: Hossain
authors.forename: R J
authors.initials: RJ
authors.lastname: Santen
authors.forename: J L
authors.initials: JL
authors.lastname: Ross
authors.forename: N
authors.initials: N
authors.lastname: Mauras
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001481:Basal Metabolism / Q000187:drug effects; D001711:Biotransformation; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D016903:Drug Monitoring; D004734:Energy Metabolism / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D057968:Transdermal Patch; D014424:Turner Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate