Context: The type, dose,and route of 17β-estradiol (E 2) used to feminize girls with Turnersyndrome (TS) is not well established. Objective: The objective of the studywasto characterize pharmacokineticsandpharmacodynamics 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 2wk each to: low-dose daily oral (0.5mg)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(meanfollicular/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 longterm metabolic effects of estrogen differ using the same form of E 2, depending on route, awaits further study in TS.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical