Exercise and Cognitive Function in Peri- and Postmenopausal Women: Evidence from Human RCTs and Mechanistic Preclinical Studies

PURPOSE: To synthesize randomized controlled trial (RCT) evidence on the effects of exercise on cognitive outcomes in peri- and postmenopausal women and to contextualize these findings using mechanistic insights from estrogen-deficit preclinical models.METHODS: PubMed and Web of Science were searched (December 14, 2025). Eligible human studies were RCTs in peri- and postmenopausal women reporting cognitive outcomes following chronic exercise interventions. Preclinical evidence was drawn from ovariectomized (OVX) or aged female animal studies reporting both behavioral and neurobiological outcomes. Findings were synthesized narratively by exercise modality and cognitive domain (global cognition, executive function, and memory) due to heterogeneity in population, prescriptions, and outcome measures.RESULTS: Eight RCTs met inclusion criteria. Global cognition was assessed mainly with screening tools (MMSE, RUDAS) and showed modest, heterogeneous signals, with relatively favorable trends reported in resistance-oriented, Pilates/mind-body, and selected lifestyle/multimodal interventions. Executive function outcomes appeared more consistently responsive when interventions combined feasible physiological loading with sustained cognitive engagement, whereas higher-load dance-based protocols and co-interventions limited exercise-specific attribution. Memory outcomes were reported in only two RCTs using non-uniform assessments, indicating preliminary evidence. Five OVX/aged female animal studies supported mechanistic plausibility, implicating neurotrophin signaling (BDNF-TrkBCREB), oxidative/mitochondrial regulation, and cell-survival/neurogenesis pathways as exercise-responsive mechanisms, while underscoring translational constraints.CONCLUSIONS: Exercise may support cognitive health across the menopausal transition, but effects appear domain-sensitive and contingent on outcome sensitivity and intervention “active ingredients.” Future trials should prioritize domain-sensitive cognitive batteries, mechanism-aligned biomarkers, and designs that strengthen causal attribution.