Epigenetic Effects of Gender-Affirming Hormone Treatment: A Pilot Study of the ESR2 Promoter's Methylation in AFAB People

February 2022 in “ Biomedicines ”

Francesco Pallotti, Giulia Senofonte, Fanì Konstantinidou, Silvia Di Chiano, Fabiana Faja, Flavio Rizzo, Francesco Cargnelutti, Csilla Krausz, Donatella Paoli, Andrea Lenzi, Liborio Stuppia, Valentina Gatta, Francesco Lombardo

testosterone therapy ESR2 estrogen receptor 2 methylation androgenic treatment epigenetic regulation testosterone treatment

TLDR Testosterone treatment may change estrogen receptor methylation in AFAB individuals.

This pilot study investigated the relationship between the methylation of the estrogen receptor 2 gene (ESR2) and phenotypic changes in 13 AFAB individuals undergoing testosterone therapy. The study found that ESR2 promoter methylation significantly increased after 6 and 12 months of treatment, while no changes were observed for the H19 gene. Methylation levels were not linked to hormone receptor polymorphisms or hormone levels at baseline and 6 months, but were associated with total testosterone levels and age after 12 months. The study suggested that testosterone treatment could alter ESR2 methylation patterns, with significant changes occurring early in the treatment. The findings indicated that estrogen receptor methylation might serve as a marker of androgenic treatment, although further research with a larger sample size is needed to understand the role of epigenetic regulation in phenotypic changes.

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