Gender incongruence (GI) is defined as an individual’s discontent with their assigned gender at birth and their identification with a gender other than that associated with their sex based on physical sex characteristics. The origin of GI appears to be multifactorial. From the extensive research that has been conducted over the past few years, four main factors have been identified as key mechanisms: genes, hormones, epigenetics, and the environment. One of the current hypotheses suggests that GI could be related to a different sexual differentiation of the brain as a result of changes in the DNA sequence of the estrogen receptors ERs and androgen receptor AR genes. These changes in the DNA sequence would imply a variability in the sensitivity of the hormone receptors, causing a genetic vulnerability.