Abstract
Postmenopausal hormone replacement therapy (HRT) with oral oestrogen was predicted to reduce coronary heart disease (CHD) risk by 50%. Randomized controlled trials show no such benefit, however, pointing instead to an initial increase in CHD events. Although the cardiovascular effects of transdermal HRT are largely unknown, improvements in arterial function are maintained when oestrogen is administered transdermally. Transdermal HRT also avoids the increased plasma levels of C-reactive protein (CRP) that are seen with oral HRT. However, the clinical significance of this general reduction in hepatic over-synthesis of plasma proteins is difficult to assess. Nevertheless, the available evidence on transdermal HRT appears to justify a formal clinical trial.
Highlights
The claim that postmenopausal hormone replacement therapy (HRT) reduces coronary heart disease (CHD) risk by 50% has until recently been a mantra in female health care and, to a lesser extent, in preventive cardiology [1]
Whereas a few years ago the question of interest was whether transdermal HRT could match the cardiovascular benefits of oral HRT, we have entered a new phase in which the transdermal route might even be preferable
The severe mismatch between observed and expected results for oral HRT in randomized controlled trials of CHD end-points challenges the validity of observational epidemiology, animal studies, and traditional CHD surrogates
Summary
The severe mismatch between observed and expected results for oral HRT in randomized controlled trials of CHD end-points challenges the validity of observational epidemiology, animal studies, and traditional CHD surrogates. Transdermal HRT is considered inferior to oral HRT for CHD prevention, because of the lack of effect on HDL and PAI-1. If the apparent lack of activation of CRP by transdermal HRT can be confirmed, and if the increased CRP levels seen in oral HRT users can be linked to their adverse clinical outcomes, an adequately powered controlled trial of transdermal HRT in the prevention of CHD would be desirable. The lesson from recent HRT trials is that such a venture should not be started in the absence of a consensus regarding the study population (healthy women or CHD patients) and regarding the use of progestin
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