Pharmacokinetics and pharmacodynamics of oral and transdermal 17β estradiol in girls with Turner syndrome

Martha Taboada, Richard Santen, John Lima, Jobayer Hossain, Ravinder Jit Singh, Karen Oerter Klein, Nelly Mauras

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3502-3510
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number11
DOIs
StatePublished - Nov 2011

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Pharmacodynamics
Turner Syndrome
Pharmacokinetics
Estradiol
Estrone
Corpus Luteum
Tandem Mass Spectrometry
Insulin-Like Growth Factor I
LDL Lipoproteins
Biological Assay
HDL Cholesterol
Estrogens
Bioassay
Mass spectrometry
Assays
Research

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Pharmacokinetics and pharmacodynamics of oral and transdermal 17β estradiol in girls with Turner syndrome. / Taboada, Martha; Santen, Richard; Lima, John; Hossain, Jobayer; Singh, Ravinder Jit; Klein, Karen Oerter; Mauras, Nelly.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 11, 11.2011, p. 3502-3510.

Research output: Contribution to journalArticle

Taboada, Martha ; Santen, Richard ; Lima, John ; Hossain, Jobayer ; Singh, Ravinder Jit ; Klein, Karen Oerter ; Mauras, Nelly. / Pharmacokinetics and pharmacodynamics of oral and transdermal 17β estradiol in girls with Turner syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 11. pp. 3502-3510.
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abstract = "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.",
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AU - Klein, Karen Oerter

AU - Mauras, Nelly

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