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Back To Vidyya Heart Disease And Hormone Replacement Therapy


Before menopause, women get less in the way of symptoms from coronary artery disease than men of the same age. They also have a lower death rate from heart attacks. This observation has generally been explained by the ‘beneficial’ effect of the hormone oestrogen on coronary arteries. At menopause, levels of oestrogen fall and the incidence of coronary artery disease and death from heart attacks in women increases to levels seen in men. It was therefore thought that replenishing oestrogen levels after the menopause in the form of ‘hormone replacement therapy’ or ‘HRT’ would reduce the incidence of coronary artery disease and fatal heart attacks in postmenopausal women to the levels observed in premenopausal women.

There have been many reports that have suggested that HRT does reduce death from heart attack in healthy postmenopausal women. However, there has been criticism of these reports as they were purely observational. That is, women were not studied after being randomised to either receive HRT or ‘no HRT’. The women studied had made their own decision regarding treatment. The two groups were therefore not comparable. The women taking HRT were generally healthier and with less risk factors for coronary artery disease. These women were likely to have fewer heart attacks anyway, therefore biasing the results. This has led to much controversy over whether HRT does actually have a beneficial effect on the heart by preventing coronary artery disease.

Women with proven coronary artery disease have a higher incidence of acute heart attacks and fair less well afterwards than men. Fewer studies have been carried out to see whether HRT has any beneficial effect on the heart in this group. Again non-randomised reports suggest that women with proven coronary artery disease benefit from HRT but these reports can be viewed with the same scepticism as before.

The ‘HERS’ study, however, was a randomised study carried out in the USA which looked at combined oestrogen and progesterone HRT in the form of tablets in postmenopausal women with proven coronary artery disease.This study showed that 4 years treatment with oestrogen and progesterone HRT tablets did not reduce the rate of heart attacks or heart related deaths. It did not, however, look at the effect of oestrogen HRT alone and it is known that progesterone can have opposing effects to oestrogen.The PHASE study (Papworth HRT Atherosclerosis Study) is a randomised study of HRT, both oestrogen HRT and oestrogen-progesterone HRT in the form of patches, in postmenopausal women with proven coronary artery disease.


255 women with proven coronary artery disease were randomised to receive HRT patch, (134 women), or no patch (121 women).For those prescribed HRT, women who had a previous hysterectomy were prescribed oestrogen HRT patches (58 patients) otherwise women received oestrogen and progesterone HRT patches (76 patients).The groups of women were well matched.Women were monitored for up to 4 years.

During this period the most frequent occurrence was admission to hospital with angina.This occurred predominantly in the first 2 years and mostly in those women receiving HRT.Essentially there were no significant differences in the number of heart events comparing women who received HRT and women who did not, but those receiving HRT did have slightly more heart problems overall (angina requiring admission to hospital, heart attacks or death from heart disease).There was a fall in cholesterol level (a risk factor for heart disease) in those receiving HRT and also in those NOT receiving HRT, with no additional benefit from HRT.Furthermore, there was a trend towards increased thromboembolic complications such as stroke or transient stroke in the HRT group.In addition 40% of women receiving the HRT stopped the patches due to side effects (the most frequent being vaginal bleeding which occurs with the preparation of HRT used in the study).Only 7% women who were not receiving HRT withdrew from the study.

The PHASE study shows that HRT patches (both oestrogen alone and oestrogen and progesterone patches) do not reduce the risk of angina requiring admission to hospital, heart attacks or death from heart disease in postmenopausal women with proven coronary artery disease. There is also no additional reduction in cholesterol levels.There appears to be an increased risk of thromboembolic complications such as stroke that was also seen in the HERS study.It may be that certain women have a greater risk of thromboembolic complications and such women need to be identified and not prescribed HRT. Although the PHASE study is at variance with previous reports of HRT in women with coronary artery disease, it is consistent with many of the findings seen in the HERS study, with early harm and later benefit (seen in the HERS study but not PHASE with shorter followup).It may therefore be appropriate that women with proven coronary artery disease should not commence HRT but those already receiving it for more than 2 years may continue.

For more information please contact:

Dr Sarah Clarke

Cardiac Unit
Papworth Hospital
CB3 8RE Cambridge

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