Pharmacokinetics and Pharmacodynamics of Oral and Transdermal 17β Estradiol in Girls with Turner Syndrome

CONTEXT: 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). SETTING: The study was conducted at a clinical research center. SUBJECTS: 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. INTERVENTIONS: 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.