title: Pharmacokinetics and pharmacodynamics of oral and transdermal 17β estradiol in girls with Turner syndrome.
abstract: BACKGROUND
  The type, dose, and route of 17β-estradiol (E(2)) used to feminize girls with Turner syndrome (TS) is not well established.
  
  
  OBJECTIVE
  The objective of the study was to characterize pharmacokinetics and pharmacodynamics of oral vs. transdermal E(2).
  
  
  METHODS
  The study was conducted at a clinical research center.
  
  
  METHODS
  Ten girls with TS, mean age 17.7 ± 0.4 (se) yr and 20 normally menstruating controls (aged 16.8 ± 0.4 yr) participated in the study.
  
  
  METHODS
  TS subjects were randomized 2 wk each to: low-dose daily oral (0.5 mg) and biweekly transdermal E(2) (0.0375 mg) with 2 wk washout in between or high-dose oral (2.0 mg) and transdermal (0.075 mg), studied for 24 h each. Tandem mass spectrometry E(2) and estrone (E(1)) assays and a recombinant cell bioassay were used.
  
  
  RESULTS
  Controls consisted of the following: E(2), 96 ± 11 pg/ml (se), E(1), 70 ± 7 (mean follicular/luteal). TS consisted of the following: E(2), average concentration on low-dose oral, 18 ± 2.1 pg/ml, low-dose transdermal, 38 ± 13, high-dose oral, 46 ± 15, high-dose transdermal, 114 ± 31 pg/ml. E(1) concentrations were much higher on oral E(2) (low or high dose) than transdermal in TS and higher than controls. Bioestrogen was closest to normal in the high-dose transdermal group. LH and FSH decreased more in transdermal than oral low-dose routes and similarly in the high-dose oral and transdermal groups. IGF-I concentrations were variable (P = NS) among groups, and low-density lipoprotein/high-density lipoprotein cholesterol responses were variable.
  
  
  CONCLUSIONS
  Transdermal E(2) results in E(2), E(1), and bioestrogen concentrations closer to normal and achieves greater suppression of LH/FSH in lower doses compared with normal. Whether the long-term metabolic effects of estrogen differ using the same form of E(2), depending on route, awaits further study in TS.
authors: Nemours Children's Clinic, Jacksonville, Florida 32207, USA.
authors: Martha
authors: M
authors: Taboada
authors: Richard
authors: R
authors: Santen
authors: John
authors: J
authors: Lima
authors: Jobayer
authors: J
authors: Hossain
authors: Ravinder
authors: R
authors: Singh
authors: Karen Oerter
authors: KO
authors: Klein
authors: Nelly
authors: N
authors: Mauras
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000293:Adolescent; D004958:Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D006801:Humans; D016896:Treatment Outcome; D014424:Turner Syndrome / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D004958:Estradiol