1 School of Kinesiology and Health Science | Centre for Integrative and Applied Neuroscience, Faculty of Health, York University, Toronto Canada, M3J 1P3; Rotman Research Institute, Baycrest Academy for Research and Education, Toronto Canada, M6A 2E1. Electronic address: bnintzan@yorku.ca.
2 Department of Physics/School of Public Health, Concordia University, Montreal Canada, H4B 1R6; Research Center and Centre ÉPIC, Montreal Heart Institute, Montréal, Québec, Canada, H1T 1C8.

Circulating sex hormone levels decrease in aging, influencing cerebrovascular health. Estradiol has been shown to support female vascular and brain health, though its effects across the menopausal transition remain unknown. Similarly, the influence of testosterone and other hormones in females is not clear. In males, testosterone is associated with positive health outcomes, but the effects of estradiol and other hormones are undetermined. Here, 187 females were categorized as premenopausal, perimenopausal or postmenopausal and 154 males as younger [<50 years] or older [50-70 years]. Magnetic resonance imaging quantified cerebral blood flow (CBF), arterial transit time (ATT), relative cerebrovascular reactivity (CVR) and a blood draw for circulating sex hormones. In females, estradiol was associated with lower ATT during perimenopause. Testosterone exhibited a U-shaped relationship with CVR in premenopausal females, yet was linked to lower CBF and CVR, and longer ATT in postmenopausal females. In males, higher testosterone was correlated with greater CBF in younger participants, while higher estradiol and follicle-stimulating hormone were associated with lower CBF in older males. These findings highlight life stage- and sex-specific associations with between hormones and cerebrovascular markers, emphasizing the potential for hormone-targeted, age and stage-specific interventions to support cerebrovascular health.