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Submitted: 20 Jul 2025
Revision: 27 Sep 2025
Accepted: 29 Sep 2025
ePublished: 06 Oct 2025
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Med J Tabriz Uni Med Sciences. Inpress.
doi: 10.34172/mj.025.35090
  Abstract View: 3

Psychiatry

Systematic Review

Epigenetic changes induced by gender-affirming hormone therapy in individuals with gender dysphoria: a systematic review

Parinaz Kalejahi 1 ORCID logo, Sara Pourrazavi 1 ORCID logo, alireza shafiee* ORCID logo

1 Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2 Research Center of Philosophy and History of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding Author: Email: shafieear@tbzmed.ac.ir

Abstract

Background. Epigenetic changes can be affected by gender-adaptive hormone therapy (GAHT) in individuals with gender dysphoria. These changes may help to regulate identity better and reduce sexual dissatisfaction. Therefore, this systematic review was conducted to investigate the epigenetic effects of GAHT on these individuals.

Methods. Using keywords related to the study topic, a comprehensive and structured search was conducted in Medline (PubMed), Scopus, and Web of Science databases without time limits until the publication date of December 2024. After reviewing the inclusion and exclusion criteria, relevant articles were selected and reviewed.

Results. Of the 421 articles identified after reviewing the title and abstract, 25 articles were included in the study, and 5 articles were selected for the final analysis. The research data demonstrated substantial epigenetic modifications through DNA methylation patterns in the ESR1, ESR2, AR, PRR4, and VMP1 genes following GAHT treatment, indicating that gender identity influences the development of secondary sex characteristics.

Conclusion. The present study demonstrated that GAHT may play a crucial role in regulating gene expression and cellular processes related to gender identity through epigenetic modifications. However, larger studies with larger samples and more advanced epigenetic methods are needed to develop optimal and effective hormonal protocols.

Practical Implications. Identifying epigenetic changes that can predict a favorable response or adverse effects of GAHT will pave the way for more precise and personalized medical care.


How to cite this article: Kalejahi P, Pourrazavi S, Shafiee-Kandjani A R. Epigenetic changes induced by gender-affirming hormone therapy in individuals with gender dysphoria: a systematic review. Med J Tabriz Uni Med Sciences. 2025;47(4):. doi: 10.34172/mj.025.35090. Persian.
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