[Estrogen receptors and vascular aging].

Cardiovascular diseases represent the leading cause of mortality in women, despite being often perceived as predominantly male diseases.

• The paper notes a historical bias in CVD research toward men due to their higher incidence
• Female CVD and their pathophysiology are now receiving increased attention
• CVD mortality in women is highlighted as a major public health issue

Premenopausal women have a lower incidence of cardiovascular disease compared to men, but this disparity progressively diminishes after menopause.

• The reduction in cardiovascular protection after menopause highlights the key role of sex hormones
• The progressive loss of protection post-menopause implicates estrogen decline as a contributing factor
• This epidemiological pattern motivated investigation into estrogen's role in arterial protection

Many preclinical and fundamental studies have demonstrated protective effects of estrogens on arterial endothelium.

• Protective effects of estrogens are described as 'well established in young organisms'
• Studies suggest hormone therapy could improve cardiovascular health in menopausal women
• The review focuses specifically on estrogen's impact on endothelial function as a key mechanism

A major clinical trial conducted approximately two decades ago produced disappointing outcomes that questioned cardiovascular protection by estrogens with age.

• The clinical trial results challenged the translational application of preclinical estrogen cardioprotection findings
• The trial raised questions specifically about estrogen protection in the context of aging
• This discrepancy between preclinical and clinical findings motivated investigation into age-related changes in estrogen receptor expression and signaling

Aging is associated with abnormalities in the expression and signaling of estrogen receptors (ERs) in the arteries.

• Age-related changes in ER expression and signaling in arteries are identified as a key area of investigation
• These abnormalities are proposed to contribute to the diminished cardiovascular protection observed with aging
• The review examines the contribution of conventional estrogens to arterial protection during aging in this context

Recent advances in the mechanisms of action of ERα could help optimize hormone therapy for menopause.

• ERα mechanisms of action are identified as a focal point for improving menopausal hormone therapy
• Understanding ERα signaling pathways is presented as a strategy to potentially resolve the gap between preclinical benefits and clinical trial disappointments
• The review presents these mechanistic advances as a pathway toward safer or more effective hormone therapies for cardiovascular protection