There are two oestrogen receptors (ERs), ERalpha and ERbeta. ERbeta protein is expressed in human skeletal muscle in the nuclei of both myofibres and endothelial cells, whether ERalpha protein is present in this tissue is unknown. We studied the expression of ERalpha protein in human skeletal muscle biopsies taken from vastus lateralis from four men, four women, two children and two postmenopausal women. Immunohistochemistry was used to determine the proportions of nuclei that were positively stained for ERalpha, the proportion of ERalpha-positive nuclei located in the muscle fibres and in capillaries and to test for possible co-expression of ERalpha and ERbeta. Both ERs were expressed in all subjects. Of all nuclei, 63% stained for ERalpha with no sex difference. ERalpha was localised both in myofibres and in endothelial cells of the capillaries, 25% of the ERalpha-positive nuclei were located in the capillaries. ERalpha and ERbeta were generally expressed in the same nuclei. The present study shows for the first time the expression of ERalpha protein in human skeletal muscle independently of age and sex. These results might improve understanding of the physiological role of oestrogen in human skeletal muscle and raise new questions about activation of ERs in skeletal muscle.

The present study shows for the first time ERbeta mRNA and protein expression in human skeletal muscle tissue in both males and females.

Context As many sports are divided in male/female categories, governing bodies have formed regulations on the eligibility for transgender individuals to compete in these categories. Yet, the magnitude of change in muscle mass and strength with gender-affirming treatment remains insufficiently explored. Objective This study explored the effects of gender-affirming treatment on muscle function, size, and composition during 12 months of therapy. Design, settings, participants In this single-center observational cohort study, untrained transgender women (TW, n = 11) and transgender men (TM, n = 12), approved to start gender-affirming medical interventions, underwent assessments at baseline, 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement, and 4 and 12 months after treatment initiation. Main outcome measures Knee extensor and flexor strength were assessed at all examination time points, and muscle size and radiological density (using magnetic resonance imaging and computed tomography) at baseline and 12 months after treatment initiation. Results Thigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density (6%). In TW, the corresponding parameters decreased by –5% (muscle volume) and –4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained their strength levels. Conclusions One year of gender-affirming treatment resulted in robust increases in muscle mass and strength in TM, but modest changes in TW. These findings add new knowledge on the magnitude of changes in muscle function, size, and composition with cross-hormone therapy, which could be relevant when evaluating the transgender eligibility rules for athletic competitions.