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Sex hormones impact brain blood flow differently in men and women across different life stages. Understanding these sex- and age-specific hormone effects is key for developing dementia prevention strategies.

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Gerontology

Background:

  • Declining sex hormones with aging affect cerebrovascular health and dementia risk.
  • Early menopause is a significant dementia risk factor.
  • Estradiol benefits female vasculature and brain health, but its cerebrovascular effects are understudied; testosterone's role in males is unclear.

Purpose of the Study:

  • To investigate the sex- and life stage-specific associations between circulating sex hormones and cerebrovascular health indicators.
  • To understand how estradiol and testosterone influence cerebral blood flow (CBF), arterial transit time (ATT), and cerebrovascular reactivity (CVR) in relation to aging and menopausal status.

Main Methods:

  • 187 females (reproductive, perimenopausal, postmenopausal) and 157 males (younger, older) were recruited.
  • MRI quantified CBF, ATT, and CVR.
  • Blood samples measured circulating sex hormone levels; statistical analyses (ANCOVA, polynomial regressions) examined hormone-cerebrovascular relationships.

Main Results:

  • In females, estradiol showed inverse relationships with ATT (perimenopausal), while testosterone had varied associations with CVR, ATT, CBF, and CVR across reproductive, perimenopausal, and postmenopausal stages.
  • In males, testosterone positively correlated with CBF in younger individuals, whereas estradiol showed an inverse correlation with CBF in older males.

Conclusions:

  • Sex hormones exhibit distinct associations with cerebrovascular health markers (CBF, ATT, CVR) dependent on sex and life stage.
  • Estradiol generally correlated with better cerebrovascular health in females, while testosterone showed mixed effects.
  • Testosterone benefited younger males' CBF, but estradiol negatively impacted older males' CBF, highlighting potential for targeted hormone interventions in dementia risk reduction.