Gender-affirming hormone therapy (GAHT) with masculinising testosterone or feminising estradiol treatment is used to align a person’s physical characteristics with their gender identity and to relieve dysphoria and depression. Sex steroids are critical for bone growth during puberty and bone maintenance in adulthood. Surprisingly however, the impact of GAHT on bone health in transgender people is poorly studied. As such, there is an unmet clinical need to definitively clarify the effects of sex steroids on bone in transgender people to prevent long term risks of bone disease. A critical step to understanding this is to examine how the circulating levels of testosterone and estradiol interact with the local synthesis of these steroids within bone to regulate bone cell function and strength. We will present data from preclinical mouse models which mirror GAHT in adolescent and adult male-to-female transitioning humans. Murine models are advantageous as they provide essential information relating to the testosterone and estradiol concentrations within bone, as well as bone microstructure, density, breaking strength, and cellular activity that are unable to be obtained from humans.
The most striking observation in this ongoing study is in the model of pubertal male-to-female transition whereby puberty is first arrested by orchidectomy followed by estradiol treatment. Estradiol treatment is sufficient to restore the loss of cortical and trabecular bone associated with puberty suppression, but does not restore bone size, consistent with the periosteal apposition of bone during puberty in males being mediated via testosterone action. The impact of these structural changes on bone strength and cell metabolism as well as the local concentrations of sex steroids within bone following GAHT are currently being assessed.
The findings from this study will provide significant insight into the actions of sex steroids within bone which will assist in informing treatment for maintaining bone health in transgender people undergoing GAHT.