Availability, Usage, and Preferences of Estradiol and Progestogen Preparations for Puberty Induction from a Multicentral Perspective.

INTRODUCTION: Natural oestrogen administration as oral or transdermal 17ß-estradiol is recommended for pubertal induction in girls with hypogonadism. However, suitable low-dose formulations are not consistently available globally. This questionnaire study aimed to identify the current availability of oestrogen and progesterone preparations worldwide. METHODS: Endorsed by the ESPE Turner Syndrome Working Group, the questionnaire targeted paediatric endocrinologists. Questions focused on accessibility of oral/transdermal 17ß-estradiol and progestogen preparations. Responses were collected through a SurveyMonkey survey disseminated via ESPE channels, direct outreach, and conferences from June 2020 to December 2022. RESULTS: Participation included 229 healthcare professionals from 45 countries. Oral and transdermal 17ß-estradiol in adult dosage was highly accessible (86.5% and 84.3%), with transdermal administration the preferred form (62.8%). Most commonly available estradiol preparations included 50 µg patches (32 countries) and 1 or 2 mg tablets (65.8% and 71.1% countries). However, 0.5 mg 17ß-estradiol tablets were available in only 20% of respondents from 8 countries. Patches delivering 14 or 25 µg/day of 17ß-estradiol were available in 3 and 20 countries, respectively. Oral progestogen had widespread availability (96.0%) and preference (87.0%), while transdermal usage was limited to 15.2% of respondents. CONCLUSION: This study highlights global challenges in accessing suitable hormone preparations for female pubertal induction. In most countries, the lowest dose of the estradiol is 50 µg for patches and 2 mg for tablets. Appropriate low-dose 17ß-estradiol tablets are much less available than low-dose patches. Our survey underscores the importance of adapting guidelines to local availability, and the need for improved accessibility to address these global disparities.

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

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 17ß-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 17ß-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.

Between-centre variability versus variability over time in DXA whole body measurements evaluated using a whole body phantom.

This study aimed to compare the variability of whole body measurements, using dual energy X-ray absorptiometry (DXA), among geographically distinct centres versus that over time in a given centre. A Hologic-designed 28 kg modular whole body phantom was used, including high density polyethylene, gray polyvinylchloride and aluminium. It was scanned on seven Hologic QDR 4500 DXA devices, located in seven centres and was also repeatedly (n=18) scanned in the reference centre, over a time span of 5 months. The mean between-centre coefficient of variation (CV) ranged from 2.0 (lean mass) to 5.6% (fat mass) while the mean within-centre CV ranged from 0.3 (total mass) to 4.7% (total area). Between-centre variability compared well with within-centre variability for total area, bone mineral content and bone mineral density, but was significantly higher for fat (p<0.001), lean (p<0.005) and total mass (p<0.001). Our results suggest that, even when using the same device, the between-centre variability remains a matter of concern, particularly where body composition is concerned.