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)

Patrice R Jones; Sarah Voisin; Brendan J Nolan; Shanie Landen; Macsue Jacques; Beau Newell; Sav Zwickl; Teddy Cook; Alex Wong; Ariel Ginger; Andrew Palmer; Andrew Garnham; Javier Alvarez-Romero; Namitha Mohandas; Kirsten Seale; Ada Cheung; Nir Eynon

doi:10.1136/bmjopen-2022-060869

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)

BMJ Open. 2022 May 11;12(5):e060869. doi: 10.1136/bmjopen-2022-060869.

Authors

Patrice R Jones¹, Sarah Voisin¹, Brendan J Nolan^{2

3}, Shanie Landen¹, Macsue Jacques¹, Beau Newell⁴, Sav Zwickl², Teddy Cook⁴, Alex Wong², Ariel Ginger², Andrew Palmer¹, Andrew Garnham¹, Javier Alvarez-Romero¹, Namitha Mohandas¹, Kirsten Seale¹, Ada Cheung^#^{2

3}, Nir Eynon^#⁵

Affiliations

¹ Institute for Health and Sport, Victoria University, Footscray, Victoria, Australia.
² Trans Health Research Group, Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia.
³ Department of Endocrinology (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia.
⁴ Pride in Sport, ACON Health, Surry Hills, New South Wales, Australia.
⁵ Institute for Health and Sport, Victoria University, Footscray, Victoria, Australia Nir.Eynon@vu.edu.au.

^# Contributed equally.

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.

Keywords: CLINICAL PHYSIOLOGY; GENETICS; MOLECULAR BIOLOGY; SPORTS MEDICINE; Sex steroids & HRT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cohort Studies
Hormones
Humans
Muscle, Skeletal
Prospective Studies
Transgender Persons*
Victoria

Substances

Hormones