Frontiers in neuroendocrinologyApr 15, 2023

Estrogen therapy and heart-health effects on the brain in healthy and unhealthy aging models

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Estrogens may exert neuroprotective effects on cognitive aging, but clinical data on menopausal estrogen therapy remain unclear.

Preclinical models indicate that estrogens are associated with neuroprotection and improved cognitive aging.
Clinical evidence regarding the benefits of menopausal estrogen therapy for brain health is mixed.
Cardiometabolic disease may influence how estrogens affect cognitive decline, potentially reducing their protective effects.
Mechanisms suggested include alterations in estrogen actions on both brain memory systems and cardiometabolic systems.
Exploring how estrogen effects vary by health status aligns with the goals of precision medicine.
Understanding estrogen impacts in different aging models is essential for bridging preclinical findings with clinical applications.

Simplified

Research in preclinical models indicates that estrogens are neuroprotective and positively impact cognitive aging. However, clinical data are equivocal as to the benefits of menopausal estrogen therapy to the brain and cognition. Pre-existing cardiometabolic disease may modulate mechanisms by which estrogens act, potentially reducing or reversing protections they provide against cognitive decline. In the current review we propose mechanisms by which cardiometabolic disease may alter estrogen effects, including both alterations in actions directly on brain memory systems and actions on cardiometabolic systems, which in turn impact brain memory systems. Consideration of mechanisms by which estrogen administration can exert differential effects dependent upon health phenotype is consistent with the move towards precision or personalized medicine, which aims to determine which treatment interventions will work for which individuals. Understanding effects of estrogens in both healthy and unhealthy models of aging is critical to optimizing the translational link between preclinical and clinical research.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Estrogen therapy and heart-health effects on the brain in healthy and unhealthy aging models

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief