The metabolic basis for the effects of HRT on coronary heart disease.

Hormone replacement therapy has profound effects on the cardiovascular system, through metabolic effects as well as direct effects on arterial function. Observational studies showing coronary heart disease benefit have appeared superficially to be at odds with the outcomes from randomized clinical trials, but the lack of benefit from the latter appears to arise from early harm caused by hormone replacement therapy that outweighs any later benefit. The early harm could arise from starting doses of such therapies that are inappropriately high for the women's age, and could therefore cause transient increases in thrombogenesis and adverse vascular remodeling. Later benefit could result from estrogen action on metabolic risk factors, such as lipids, glucose, and insulin metabolism, as well as direct arterial effects reducing atherogenesis. In contrast, this is avoided in observational studies because the women are 15 yr younger and those same starting doses of hormone replacement therapy are appropriate for their age. It is therefore possible that more appropriate hormone replacement therapy regimens, particular in terms of dose, could be devised to effect coronary benefit in older age groups. This concept needs to be tested as a priority before hormone replacement therapies are rejected as being of no cardiovascular benefit.