Cognitive functioning in older transgender individuals receiving long-term gender-affirming hormone therapy

Background: Cognitive functioning can be negatively influenced by age, cardiovascular risk (CVR) and mental health challenges, and sex-hormones can have neuroprotective effects. Little is known about cognitive functioning in older transgender individuals receiving long-term gender-affirming hormone therapy (GHT). In a previous, smaller study, cognitive differences between transgender women and cisgender groups were minimal yet statistically significant. Aims: This study assessed cognitive differences between larger samples of older transgender and cisgender individuals, and the contribution of CVR and mental/social health to these differences. Methods: This cross-sectional study compared 73 transgender women and 39 transgender men (56–84 y) receiving long-term GHT (10–47 y) with matched (age; education level) cisgender women and men from the Longitudinal Aging Study Amsterdam on cognitive functioning assessed with neuropsychological tests. Mean z-scores per cognitive domain were calculated and analyzed using linear regression. Models were subsequently adjusted for CVR ((history of) cardiovascular disease; smoking) and mental/social health (anxiety; loneliness) factors. Results: Transgender women had lower scores than cisgender women and men, respectively, on information-processing speed (b = −0.62, 95% CI −0.90 to −0.35; b = −0.33, 95%CI −0.60 to −0.05), episodic memory (b = −1.28, 95%CI −1.53 to −1.04; b = −0.77, 95%CI −1.01 to −0.52), and crystallized intelligence (b = −0.42, 95%CI −0.75 to −0.10; b = −0.41, 95%CI −0.75 to −0.08). Transgender men scored lower on episodic memory than cisgender women but scored equal to cisgender men (b = −0.43, 95%CI −0.79 to −0.08; b = −0.01, 95%CI −0.36 to 0.35). Mental/social health factors (particularly depressive symptoms) largely, and CVR factors slightly, explained cognitive differences between the trans- and cisgender groups. Discussion: Small cognitive differences between transgender men and cisgender groups do not suggest adverse or beneficial long-term testosterone effects on cognitive functioning. However, transgender women had lower cognitive functioning than cisgender groups, which was largely explained by mental/social health. This warrants further research and clinical awareness of mental and cognitive health in older transgender individuals.