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

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.

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.

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.

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.

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.