Human sex-specific hormone effects on cerebrovascular health in males and females

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.