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Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy

Journal article
Authors M. Donaldson
B. Kristrom
Carina Ankarberg-Lindgren
S. Verlinde
J. van Alfen-van der Velden
A. Gawlik
Mmhj van Gelder
T. Sas
M. Agota
N. Akulevich
K. Albertsson-Wikland
C. Ankarberg-Lindgren
E. Bober
A. Buyukgebiz
J. C. Carel
C. Dacou-Voutetakis
S. D. Keizer-Schrama
M. Donaldson
E. J. Gault
L. Ghizzoni
C. Kanaka-Gantenbein
A. Gawlik
B. Kristrom
A. Kurtev
E. Malecka-Tendera
L. Mazzanti
E. Norjavaara
J. Popovic
M. Ranke
T. Sas
A. Sallai
S. Stagi
J. van Alfen-van der Velden
S. Verlinde
M. Wasniewska
D. Zenaty
N. Zuckerman-Levin
Endocrinology European Soc Paediat
Published in Hormone Research in Paediatrics
Volume 91
Issue 3
Pages 153-163
ISSN 1663-2818
Publication year 2019
Published at Institute of Clinical Sciences, Department of Pediatrics
Pages 153-163
Language en
Keywords Turner syndrome, Puberty, 17 beta-estradiol, Oral induction, Transdermal induction, sex steroid replacement, growth-hormone, women, management, secretion, Endocrinology & Metabolism, Pediatrics
Subject categories Pediatrics


Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17 beta-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17 beta-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. (C) 2019 S. Karger AG, Basel

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