What is the Origin of Healthy Endothelium Hypothesis?

This hypothesis emerged from the analysis of discrepancies between observational studies, which often showed cardiovascular benefits for hormone therapy, and randomized controlled trials, which sometimes showed neutral or even adverse effects in older populations. The term is a synthesis of the physiological role of the 'endothelium' as a regulator of vascular tone and the scientific necessity of a 'hypothesis' to explain the time-dependent effects of hormonal interventions. It has profoundly influenced clinical guidelines for hormone therapy initiation.

What is the Mechanism of Healthy Endothelium Hypothesis?

In a healthy endothelium, estrogen binds to its receptors, promoting the production and release of vasodilators like nitric oxide (NO), leading to improved blood flow and reduced arterial stiffness. In a compromised or already diseased endothelium, however, the inflammatory environment and plaque burden may alter the receptor response, potentially shifting the hormonal effect toward pro-thrombotic or pro-inflammatory pathways. This mechanism highlights the importance of a personalized approach to hormone therapy, considering a patient's vascular age and overall health status.

Healthy Endothelium Hypothesis

Meaning

The Healthy Endothelium Hypothesis posits that the beneficial effects of hormones, particularly estrogen, on the cardiovascular system are contingent upon the pre-existing health and integrity of the endothelial lining of the blood vessels. This concept suggests that hormone replacement therapy is most protective when initiated in younger, healthier individuals whose endothelium is not yet significantly compromised by atherosclerotic plaque or chronic inflammation. The hypothesis provides a critical explanation for the mixed results observed in large-scale clinical trials of hormone therapy.