Hormone replacement therapy and ischaemic heart disease among postmenopausal women

The beneficial effect of hormone replacement treatment (HRT) on osteoporosis and menopausal symptoms has been well documented in randomised trials, but the impact of oestrogen-mediated metabolic changes on the risk of ischaemic heart disease (IHD) is still debated. Randomised studies have shown that HRT increases levels of high-density lipoprotein cholesterol while causing a reduction in the levels of low-density lipoprotein cholesterol, serum fibrinogen, plasminogen activator inhibitor and homocysteine. In addition, HRT increases insulin sensitivity in both normoglycaemic and diabetic women. Unlike oral contraceptives, HRT has not been associated with an increase in arterial blood pressure, whereas a small increase in the risk of breast cancer and of venous thromboembolism appears to occur with both treatments. Interestingly, some data suggest that oestrogen preparations may have different effects on lipids. For instance, the beneficial effect on cholesterol metabolism observed with oral conjugated oestrogen does not occur with transdermal oestradiol, suggesting that the first-pass effect through the portal circulation may be necessary to achieve the full metabolic effect of oestrogen treatment. Nevertheless, although a wealth of observational studies show that HRT is associated with a significant reduction in morbidity and mortality from IHD, the only randomised data available to date do not support these findings in postmenopausal women with established coronary artery disease.