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Observational Study
. 2025 May;48(5):1237-1248.
doi: 10.1007/s40618-024-02522-z. Epub 2025 Jan 2.

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

Chiara Ceolin #  1   2   3 , Alberto Scala #  4   5 , Maria Santa Rocca  5 , Bianca Scagnet  5 , Massimiliano Marton  5 , Cristina Simonato  6 , Chiara Ziliotto  6 , Marina De Rui  6 , Valentina Camozzi  4   7 , Sandro Giannini  4   8 , Daniela Basso  4   9 , Giulia Musso  4   9 , Alberto Ferlin  4   5 , Giuseppe Sergi  6   4 , Andrea Garolla  4   5 ; Gender IncongruenceInterdisciplinary Group (GIIG)
Affiliations
Observational Study

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

Chiara Ceolin et al. J Endocrinol Invest. 2025 May.

Abstract

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.

Keywords: Androgen receptor; Bone geometry; Bone mineral density; Genetics; Transgender.

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Conflict of interest statement

Declarations. Authorship Confirmation/Contribution Statement Conceptualization: Chiara Ceolin, Alberto Scala, Maria Santa Rocca, Andrea Garolla. Data collection: Daniela Basso, Maria Santa Rocca, Giulia Musso, Cristina Simonato, Chiara Ziliotto. Data curation: Chiara Ceolin, Alberto Scala, Massimiliano Marton, Bianca Scagnet. Formal analysis: Chiara Ceolin. Supervision: Alberto Ferlin, Giuseppe Sergi, Andrea Garolla. Visualization: Maria Santa Rocca, Marina De Rui, Valentina Camozzi, Sandro Giannini, Alberto Ferlin, Giuseppe Sergi, Andrea Garolla. Writing– original draft: Chiara Ceolin, Alberto Scala. Writing– review & editing: Chiara Ceolin, Alberto Scala, Maria Santa Rocca, Bianca Scagnet, Massimiliano Marton, Cristina Simonato, Chiara Ziliotto, Marina De Rui, Valentina Camozzi, Sandro Giannini, Daniela Basso, Giulia Musso, Alberto Ferlin, Giuseppe Sergi, Andrea Garolla. Author Disclosure Statement: Conflicts of interest/Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval: statement: This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Padua (approval number 0025087). Patient consent statement: Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patients to publish this paper. Permission to reproduce material from other sources: not applicable. Clinical trial registration: not applicable.

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