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Cited by 82Genetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and DisordersEstrogen and related hormone effects

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

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Taboada, Martha, Santen, Richard, Lima, John, Hossain, Jobayer, Singh, Ravinder, Klein, Karen Oerter, Mauras, Nelly·2011·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2011-1449PMC PMC3205885
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Abstract

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.

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  • The transdermal route resulted in E2, estrone, and bioestrogen concentrations closer to normal compared to oral hormone replacement therapy.

    “Additionally, the TD route resulted in E2, estrone, and bioestrogen concentrations closer to normal compared to oral HRT.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [286]

  • E2 values in typical menstruating women depend on phase of cycle with great variability between women and between cycles; follicular and luteal mean E2 values are around 183 and 521 pmol L−1 (50 and 142 pg mL−1), respectively.

    “E2 values in typical menstruating women depend on phase of cycle with great variability between women and between cycles; with follicular and luteal mean E2 values around 183 and 521 pmol L−1 (50 and 142 pg mL−1), respectively.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [286]

  • A study with transdermal E2 compared with oral E2 showed that a higher dose corresponded to higher concentration of E2, however without linear correlation.

    “A study with TD E2 compared with oral E2 showed that a higher dose corresponded to higher concentration of E2, however without linear correlation.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [286]

  • A suggested adult target is an E2 concentration of 350-500 pmol L−1 (100-150 pg mL−1).

    “A suggested adult target is an E2 concentration of 350-500 pmol L−1 (100-150 pg mL−1).”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [286]

  • Studies differ on whether oral E2 vs TD E2 leads to increased total cholesterol and decreased HDL.

    “Studies differ on whether oral E2 vs. TD E2 leads to increased total cholesterol and decreased HDL”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [286]

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1 of the 43 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [5]5. Drobac S, Rubin K, Rogol AD, Rosenfield RL 2006 A workshop on pubertalhormonereplacementoptionsintheUnitedStates.JPediatr Endocrinol Metab 19:55-64

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Authors
Taboada, M., Santen, R., Lima, J., Hossain, J., Singh, R., Klein, K. O., & Mauras, N.
Affiliations
  • Nemours Children's Clinic (US)
  • University of Virginia (US)
  • Wilmington, Delaware 19805 (J.H.)
  • Mayo Clinic (US)
  • University of California San Diego (US)
Corresponding author
Mauras, Nelly
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2011-11-01
Volume
96
Issue
11
Pages
3502-3510
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2011-1449
PMC
PMC3205885
OpenAlex
W1976544212
Cited by
82
References
43
Citations by year
2026: 4 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 3 · 2017: 6 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 5 · 2012: 5
FWCI
3.78
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Research Resources (UL1RR024150)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
Turner syndrome, estradiol, transdermal estrogen, oral estrogen, pharmacokinetics, pharmacodynamics, estrone, insulin-like growth factor I, cholesterol, feminization, girls, hormone replacement therapy, dose comparison, route of administration, estradiol metabolites, estradiol glucuronide, estradiol sulfate
MeSH terms
Administration, Cutaneous, Administration, Oral, Adolescent, Estradiol, Female, Humans, Turner Syndrome, Estrogen Replacement Therapy, Treatment Outcome, Young Adult

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