Metabolic effects of oral versus transdermal 17β-estradiol (E 2): A randomized clinical trial in girls with turner syndrome

L. Torres-Santiago, V. Mericq, M. Taboada, N. Unanue, K. O. Klein, Ravinder Jit Singh, J. Hossain, R. J. Santen, J. L. Ross, Nelly Mauras

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Abstract

Context: The long-term effects of pure 17β-estradiol (E2) depending on route of administration have not been well characterized. Objective: Our objective was to assess metabolic effects of oral vs transdermal (TD) 17β-E2 replacement using estrogen concentration-based dosing in girls with Turner syndrome (TS). Patients: Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited. Design: Subjects were randomized to 17β-E2 orally or TD. Doses were titrated using mean E 2 concentrations of normally menstruating girls as therapeutic target. E2, estrone (E1), and E1 sulfate (E1S) were measured by liquid chromatography tandem mass spectrometry and a recombinant cell bioassay; metabolites were measured, and dual-energy x-ray absorptiometry scan and indirect calorimetry were performed. Main Outcome: Changes in body composition and lipid oxidation were evaluated. Results: E 2 concentrations were titrated to normal range in both groups; mean oral dose was 2 mg, and TD dose was 0.1 mg. After 6 and 12 months, fat-free mass and percent fat mass, bone mineral density accrual, lipid oxidation, and resting energy expenditure rates were similar between groups. IGF-1 concentrations were loweronoral 17β-E2, but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin, or highly sensitive C-reactive protein between groups. However, E1, E1S, SHBG, and bioestrogen concentrations were significantly higher in the oral group. Conclusions: When E2 concentrations are titrated to the normal range, the route of delivery of 17β-E2 does not affect differentially body composition, lipid oxidation, and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E1, E1S, and total bioestrogen) is significantly higher after oral 17β-E2. TD17β-E2 results in amorephysiological estrogen milieu than oral 17β-E2 administration in girls with TS.

Original languageEnglish (US)
Pages (from-to)2716-2724
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number7
DOIs
StatePublished - Jul 2013

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Turner Syndrome
Estradiol
Randomized Controlled Trials
Lipids
Sulfates
Estrogens
Body Composition
Oxidation
Reference Values
Fats
Indirect Calorimetry
Estrogen Replacement Therapy
Bioassay
Estrone
Osteocalcin
Liquid chromatography
Calorimetry
Metabolites
Tandem Mass Spectrometry
Chemical analysis

ASJC Scopus subject areas

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

Cite this

Metabolic effects of oral versus transdermal 17β-estradiol (E 2) : A randomized clinical trial in girls with turner syndrome. / Torres-Santiago, L.; Mericq, V.; Taboada, M.; Unanue, N.; Klein, K. O.; Singh, Ravinder Jit; Hossain, J.; Santen, R. J.; Ross, J. L.; Mauras, Nelly.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 7, 07.2013, p. 2716-2724.

Research output: Contribution to journalArticle

Torres-Santiago, L, Mericq, V, Taboada, M, Unanue, N, Klein, KO, Singh, RJ, Hossain, J, Santen, RJ, Ross, JL & Mauras, N 2013, 'Metabolic effects of oral versus transdermal 17β-estradiol (E 2): A randomized clinical trial in girls with turner syndrome', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 7, pp. 2716-2724. https://doi.org/10.1210/jc.2012-4243
Torres-Santiago, L. ; Mericq, V. ; Taboada, M. ; Unanue, N. ; Klein, K. O. ; Singh, Ravinder Jit ; Hossain, J. ; Santen, R. J. ; Ross, J. L. ; Mauras, Nelly. / Metabolic effects of oral versus transdermal 17β-estradiol (E 2) : A randomized clinical trial in girls with turner syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 7. pp. 2716-2724.
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abstract = "Context: The long-term effects of pure 17β-estradiol (E2) depending on route of administration have not been well characterized. Objective: Our objective was to assess metabolic effects of oral vs transdermal (TD) 17β-E2 replacement using estrogen concentration-based dosing in girls with Turner syndrome (TS). Patients: Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited. Design: Subjects were randomized to 17β-E2 orally or TD. Doses were titrated using mean E 2 concentrations of normally menstruating girls as therapeutic target. E2, estrone (E1), and E1 sulfate (E1S) were measured by liquid chromatography tandem mass spectrometry and a recombinant cell bioassay; metabolites were measured, and dual-energy x-ray absorptiometry scan and indirect calorimetry were performed. Main Outcome: Changes in body composition and lipid oxidation were evaluated. Results: E 2 concentrations were titrated to normal range in both groups; mean oral dose was 2 mg, and TD dose was 0.1 mg. After 6 and 12 months, fat-free mass and percent fat mass, bone mineral density accrual, lipid oxidation, and resting energy expenditure rates were similar between groups. IGF-1 concentrations were loweronoral 17β-E2, but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin, or highly sensitive C-reactive protein between groups. However, E1, E1S, SHBG, and bioestrogen concentrations were significantly higher in the oral group. Conclusions: When E2 concentrations are titrated to the normal range, the route of delivery of 17β-E2 does not affect differentially body composition, lipid oxidation, and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E1, E1S, and total bioestrogen) is significantly higher after oral 17β-E2. TD17β-E2 results in amorephysiological estrogen milieu than oral 17β-E2 administration in girls with TS.",
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AU - Unanue, N.

AU - Klein, K. O.

AU - Singh, Ravinder Jit

AU - Hossain, J.

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