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Horm Res Paediatr. 2019;91(3):153-163. doi: 10.1159/000500050. Epub 2019 Jun 5.

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

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Glasgow University School of Medicine, Glasgow, United Kingdom,
Institution of Clinical Science, Pediatrics, Umeå University, Umeå, Sweden.
Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Belgian Study Group of Paediatric Endocrinology and Diabetes, Brussels, Belgium.
Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pediatrics and Pediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pediatric Endocrinology, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Diabeter, National Diabetes Care and Research Center, Rotterdam, The Netherlands.



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 17β-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 17β-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.


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.


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.


17β-estradiol; Oral induction; Puberty; Transdermal induction; Turner syndrome

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