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  • Uncovering the effects of gender affirming hormone therapy on skeletal muscle and epigenetics: protocol for a prospective matched cohort study in transgender individuals (the GAME study)

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Sports and exercise medicine
Protocol
Uncovering the effects of gender affirming hormone therapy on skeletal muscle and epigenetics: protocol for a prospective matched cohort study in transgender individuals (the GAME study)
  1. Patrice R Jones1,
  2. Sarah Voisin1,
  3. Brendan J Nolan2,3,
  4. Shanie Landen1,
  5. Macsue Jacques1,
  6. Beau Newell4,
  7. Sav Zwickl2,
  8. Teddy Cook4,
  9. Alex Wong2,
  10. Ariel Ginger2,
  11. Andrew Palmer1,
  12. Andrew Garnham1,
  13. Javier Alvarez-Romero1,
  14. Namitha Mohandas1,
  15. Kirsten Seale1,
  16. Ada Cheung2,3,
  17. Nir Eynon1
  1. 1 Institute for Health and Sport, Victoria University, Footscray, Victoria, Australia
  2. 2 Trans Health Research Group, Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia
  3. 3 Department of Endocrinology (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia
  4. 4 Pride in Sport, ACON Health, Surry Hills, New South Wales, Australia
  1. Correspondence to Professor Nir Eynon; Nir.Eynon{at}vu.edu.au

Abstract

Introduction Gender affirming hormone therapy (GAHT) is increasingly used by transgender individuals and leads to shifts in sex hormone levels. Skeletal muscle is highly responsive to hormone activity, with limited data on the effects of GAHT on different human tissues. Here, we present the protocol for the GAME study (the effects of Gender Affirming hormone therapy on skeletal Muscle training and Epigenetics), which aims to uncover the effects of GAHT on skeletal muscle ‘omic’ profiles (methylomics, transcriptomics, proteomics, metabolomics) and markers of skeletal muscle health and fitness.

Methods and analysis This study is a prospective age-matched cohort study in transgender adults commencing GAHT (n=80) and age-matched individuals not commencing GAHT (n=80), conducted at Austin Health and Victoria University in Victoria, Australia. Assessments will take place prior to beginning GAHT and 6 and 12 months into therapies in adults commencing GAHT. Age-matched individuals will be assessed at the same time points. Assessments will be divided over three examination days, involving (1) aerobic fitness tests, (2) muscle strength assessments and (3) collection of blood and muscle samples, as well as body composition measurements. Standardised diets, fitness watches and questionnaires will be used to control for key confounders in analyses. Primary outcomes are changes in aerobic fitness and muscle strength, as well as changes in skeletal muscle DNA methylation and gene expression profiles. Secondary outcomes include changes in skeletal muscle characteristics, proteomics, body composition and blood markers. Linear mixed models will be used to assess changes in outcomes, while accounting for repeated measures within participants and adjusting for known confounders.

Ethics and dissemination The Austin Health Human Research Ethics Committee (HREC) and Victoria University HREC granted approval for this study (HREC/77146/Austin-2021). Findings from this project will be published in open-access, peer-reviewed journals and presented to scientific and public audiences.

Trial registration number ACTRN12621001415897; Pre-results.

  • Sex steroids & HRT
  • SPORTS MEDICINE
  • MOLECULAR BIOLOGY
  • GENETICS
  • CLINICAL PHYSIOLOGY
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2022-060869

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    Footnotes

    • AC and NE are joint senior authors.

    • Twitter @smallscientist_, @BeauNewell6, @DrAdaCheungAU

    • AC and NE contributed equally.

    • Contributors All authors helped conceptualise and implement this study. PRJ, SV, SL, MJ, AP, JA-R and NE finalised the exercise and biochemical elements of the design. AC, BJN, AGa, SV, TC, BN, AW and AGi finalised the clinical and community aspects of the design. SV, NM and KS devised the analysis plan. PRJ drafted the manuscript. All authors reviewed and edited the manuscript and approved the final manuscript.

    • Funding NE is supported by a National Health & Medical Research Council (NHMRC) Career Development Fellowship (#1140644), SV is supported by a NHMRC Early Career Research Fellowship (#11577321), AC is supported by a NHMRC Early Career Fellowship (#1143333) and Investigator Grant (#2008956) and BJN is supported by a NHMRC Postgraduate Research Scholarship (#2003939).

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.