Terapia ormonale di affermazione di genere in soggetti transgender AFAB: effetti epigenetici e ruolo dei polimorfismi dei recettori degli androgeni e degli estrogeni

Gender incongruence (GI) is defined as a marked and persistent incongruence between the gender experienced by an individual and the sex assigned at birth, possibly associated with strong discomfort and suffering, worsened by stigma and social discrimination, which can make psychological, medical and surgical intervention necessary. Standards of care for GI include the use of Gender Affirming Hormonal Therapy (GAHT) to induce and maintain desired sexual characteristics. However, it is common to find a fair amount of interindividual variability in response to treatment, both from a phenotypic point of view and in terms of adverse effects. At least in part, this variability may be caused by different modulations of androgenic and oestrogenic signalling which, in turn, is influenced by the type of molecule and the dosage used, but also by a non-negligible variability in individual response determined both on a genetic and epigenetic basis. In particular, the literature has focused on the possible modulatory role of genetic polymorphisms of androgen and oestrogen receptors on the sensitivity of hormone receptors and signal transduction. Furthermore, recent literature has investigated the possibility that changes in gene expression and epigenetic modifications could in some degree influence the response to treatment with sex steroids, but the extent of this effect in transgender subjects has not yet been studied in depth. Finally, although GATH conducted according to the most recent guidelines is considered a safe therapy, in analogy with the cisgender population it has been hypothesised that androgen receptor polymorphisms and induced epigenetic modifications could modulate the risk of adverse cardiovascular events in patients undergoing GAHT, especially in those subjects who have been on therapy for many years.