The case for a nonplasma lipoprotein etiology of reduced vascular risk in estrogen replacement therapy

High-density lipoprotein cholesterol plasma changes, as induced by liver first-pass effect of oral estrogens (parallel increase in high-density lipoprotein cholesterol and triglycerides and smaller, denser low-density lipoprotein particles) are not as beneficial as previously expected. According to experimental studies, the main vascular protective effects of estrogens are not located in the liver but in specific sites of the arterial wall and are largely independent of plasma lipid changes. Criteria for selecting optimal estrogens or antiestrogens might be revised accordingly.