BackgroundAlthough research on the relation between testosterone and aggression in humans is inconclusive, guidelines (including the World Professional Association for Transgender Health Standards of Care, edition 7) have warned for an increase in aggression in transgender men taking testosterone treatment. AimsTo investigate the association between levels of testosterone and aggression in treatment-seeking transgender people and explore the role of mental health psychopathology (anxiety and depressive symptoms) and social support in aggression in this population. MethodsEvery transgender person invited for assessment at a national transgender health clinic in the United Kingdom during a 3-year period (2012–2015) completed self-report measures for interpersonal problems, including levels of aggression (Inventory of Interpersonal Problems [IIP-32]), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), social support (Multidimensional Scale of Perceived Social Support), and experiences of transphobia before and 1 year after the initiation of gender-affirming hormonal therapy. Correlations between prospective scores for the IIP-32 factor “too aggressive” and prospective levels of sex steroids, prospective psychological (HADS), and baseline psychosocial measurements were tested. OutcomesProspective scores for the factor “too aggressive” were not correlated to prospective serum testosterone levels. ResultsResults of 140 people (56 transgender men, 84 transgender women) were analyzed. A prospective increase in scores for the factor “too aggressive” of the IIP-32 in transgender men 1 year after being treated with testosterone treatment or a decrease of the IIP-32 aggression scores in transgender women 1 year after gender-affirming hormonal therapy was not found. However, a positive correlation was found between increasing HADS anxiety scores and increasing scores for the IIP-32 “too aggressive” score in the entire study population and a positive correlation with lower support from friends in transgender women. Clinical ImplicationsHormone-prescribing physicians can be reassured that the long-term administration of testosterone in transgender men does not increase aggressive behavior. Strengths and LimitationsThis is the 1st prospective study to assess the effect of gender-affirming hormonal care on aggression. Limitations included the use of different laboratories, the use of a patient-reported outcome measure, and the lack of aggression subtypes. ConclusionsTestosterone therapy was not associated with an increase in levels of aggression in transgender men or a decrease in aggressive behavior in transgender women on antiandrogen and estrogen therapy, but other psychological and/or social factors, such as anxiety levels, appear to contribute to self-reported aggression in transgender people.Defreyne J, T'Sjoen G, Bouman WP, et al. Prospective Evaluation of Self-Reported Aggression in Transgender Persons. J Sex Med 2018;15:768–776.