Sex Does Matter! The Influence of Sex on Outcomes of Transcranial Direct Current Stimulation (tDCS)

Background: Transcranial direct current stimulation (tDCS) produces heterogeneous outcomes across cognitive, behavioural, and clinical studies. Sex-related differences may contribute to this variability. Objective: This narrative review examined whether and how sex moderates tDCS outcomes across behavioural, physiological, clinical, and modelling studies and considered potential underlying mechanisms. Materials and Methods: A structured literature search identified studies examining sex, or variables reported by the original authors as gender but operationalised through female-male group comparisons, as moderators of tDCS outcomes. After screening, 41 studies met the inclusion criteria, and 6 additional studies were identified through citation searching, yielding 47 studies. Because of substantial heterogeneity in populations, protocols, and outcomes, findings were synthesised narratively. Results: Sex-related effects were common but highly context-dependent, varying by montage, cortical target, stimulation intensity, reference placement, and outcome domain. They often emerged as interaction effects rather than main effects and were most apparent during demanding tasks, later learning phases, or delayed after-effects. Computational models indicated that identical stimulation settings may produce different intracranial electric fields in women and men because of anatomical differences. Hormonal and endocrine states, particularly in females, may further modify or amplify these effects. Sensation, tolerability, and blinding may also contribute under higher-intensity protocols but do not fully explain sex-contingent outcomes. Conclusions: Sex influences tDCS outcomes through interacting anatomical, hormonal, and task-related mechanisms rather than in a uniform manner. Future studies should treat sex as a mechanistically relevant moderator, incorporate dose- and hormone-aware designs, and use adequately powered analyses to improve reproducibility and support individualised neuromodulation.