Gender identity refers to an innate and deeply felt psychological identification as a female, male, or some other non-binary gender. Gender identity may be congruent or incongruent with the sex assigned at birth. Gender dysphoria refers to the discomfort or distress that gender incongruence may cause. If the distress is clinically significant, the individual may need gender-affirming treatment. The literature is sparse with respect to the etiology, prevalence, and long-term outcomes. The overall aim of this thesis is to further our understanding of gender dysphoria regarding neurobiological characteristics, epidemiology, and health following gender-affirming treatment. Study I explored the hypothesis that cerebral activation in hormone-naïve transgender women (assigned males at birth) on exposure to odorous steroids would be in line with their gender identity, and thus similar to cisgender women but different to cisgender men. Gender dysphoric transgender women demonstrated a cerebral activation pattern that corresponded predominately to that of cisgender females, but also some cisgender male characteristics. Study II described the prevalence and changes in incidence of applications for change of legal gender and applications to reverse the procedure during 1960-2010. The incidence of gender dysphoria increased three times for individuals assigned male at birth, and two and half time times for individuals assigned female at birth. The increase accelerated after 2001. The rate of reversal applications was 2.2% with a significant decline over the study period. Study III explored long-term mortality and psychiatric morbidity after sex reassignment in a nation-wide cohort study (1973-2003). The overall mortality rate was higher in individuals who had undergone legal and medical transition compared with the general population for the whole period, but not for the period 1989-2003. Probands had more psychiatric inpatient care and suicide attempts compared with controls for the whole period as well as the period ...