Metabolic effects of hormone replacement therapy.

Hormone replacement therapy (HRT) has profound metabolic effects which impact on the cardiovascular system. These effects include changes in lipids and lipoproteins, glucose and insulin metabolism, haemostatic factors, inflammatory markers and body composition, as well as changes in vascular function and remodelling. Observational studies have demonstrated coronary heart disease benefit with HRT use, in contrast to the outcomes from randomised clinical trials. Lack of benefit in the latter studies appears to arise from early harm caused by HRT which outweighs any later benefit. Such early harm could result from transient increases in thrombogenesis and adverse vascular remodelling, which in turn could arise from starting doses of such therapies that are inappropriately high for the women's age. This problem is avoided in observational studies because the women are much younger and those same starting doses are appropriate for their age. Later benefit could result from oestrogen action on metabolic risk factors and direct arterial effects resulting in reduced atherogenesis. It is therefore possible that more appropriate HRT regimens could be devised to provide coronary benefit without risk of stroke, even in older age groups. Such strategies need to be tested in large clinical trials. The metabolic effects of HRTs are key to providing cardiovascular benefit.