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 examined the epigenetic effects of testosterone therapy on the methylation of the ESR2 gene promoter in 13 AFAB individuals undergoing gender-affirming hormone treatment. It found a significant increase in ESR2 promoter methylation after 6 months (p = 0.001) and 12 months (p = 0.05) of therapy, with no significant changes in the H19 promoter. The increase in ESR2 methylation was linked to total testosterone levels and patient age after 12 months, and changes from baseline to 6 months were associated with the number of CA repeats in the ERβ gene. These findings suggested that testosterone therapy could modify ESR2 methylation patterns, potentially serving as a marker of androgenic treatment, though further research with a larger sample size was needed.

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