Will the Route of Administration Influence the Potential Cardiovascular Benefits of Postmenopausal HRT?

Abstract

A widely held, though as yet unproven, belief is that HRT will reduce the incidence of myocardial infarction and stroke in postmenopausal women, in contrast to the slight increase in risk of venous thrombotic events. As oral HRT induces an unphysiological peak in the concentrations of oestrogen in the liver, hepatic protein synthesis is over-stimulated, leading to increased plasma levels of many of the proteins involved in vascular disease, such as apolipoproteins, coagulation factors and components of the renin-angiotensin system. Non-oral HRT minimises hepatic first-pass and so avoids these effects. This has led to a belief that the excess risk of venous thrombo-embolism seen in users of oral HRT will be negated. Non-oral HRT may also have less impact on aspects of the renin-angiotensin system; it may also reduce insulin responses to glucose and improve insulin sensitivity. However, plasma levels of PAI-1, are lowered by oral but not transdermal oestradiol. It is even more difficult to predict whether non-oral HRT will be better or worse in terms of the effect on lipoprotein risk markers for CHD. Non-oral oestrogens are less able to reduce plasma levels of LDL and Lp(a), but may protect these lipoproteins from oxidation. The increased HDL levels typical of oral therapy are not seen, but neither are the elevated triglycerides. Experimental studies, especially those using animal models of atherosclerosis, indicate that non-oral therapies will reduce the risk of arterial disease. It would seem unlikely that there will be any substantial differences between the effects of oral and non-oral HRT on CHD risk.