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
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
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.
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.
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.
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.
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.
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.
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