Influence of androgen receptor on bone health in transgender adults: insights from the COMET study

Purpose: Previous studies show that transgender and gender-diverse (TGD) individuals, especially those assigned male at birth (AMAB), often have low bone mineral density (BMD) before beginning gender-affirming hormone therapy (GAHT). The reasons for this are not fully understood, and the potential role of androgen receptor (AR) polymorphisms - known to affect bone density in the general population - has not been explored. This study aims to assess the impact of AR polymorphisms on bone health in the TGD population.

Methods: This is an observational study involving 135 TGD and 107 cisgender participants. Collected data included hormonal profiles and phospho-calcium metabolism, bone geometry and density (Dual Energy X-ray Absorptiometry and peripheral Quantitative Computed Tomography). For the genetic study related to the AR, genomic DNA was extracted from peripheral blood leukocytes.

Results: TGD individuals had lower BMD values compared to their cisgender peers. In a subgroup of 129 individuals (86 TGD and 43 cisgender), we assessed the length of the polymorphic tracts of the AR gene and observed no differences between the groups. AR polymorphisms showed significant correlations only with cortical BMD in both TGD and cisgender assigned females at birth (AFAB) individuals, and negative correlations with trabecular BMD in both cisgender men and women.

Conclusions: Our study suggests that AR polymorphisms do not play a significant role in the low BMD values observed in TGD individuals at baseline. Further research is necessary to better understand the impact of factors such as lifestyle on the bone health of TGD individuals.