Can HRT reduce the chance of my developing heart disease?

Women have relatively few problems attributable to coronary heart disease before the menopause because oestrogen during reproductive years confers protection (23). The majority of heart attacks before the age of sixty occur in men. After the menopause nature’s protection (oestrogen) is withdrawn. One study found that by the age of seventy, women are as likely to suffer a heart attack as men.

When the ovaries are surgically removed (oophorectomy) before the menopause the oestrogen protection of the coronary arteries is suddenly lost and without hormone replacement therapy the likelihood of heart problems is increased.

To assess the potential benefits of HRT, we have to look at evidence from large on-going studies. In 1976, The American Nurses Health Study recruited 121,700 female registered nurses aged 30-55 years. These women are now aged 54 - 79 years. The latest reports from this study shows reduced incidence of heart problems and deaths from coronary heart disease in association with HRT.

One review of the literature found twenty studies all consistently demonstrating cardioprotection (cardio heart) associated with HRT following oophorectomy. When considering evidence from large studies, we are always concerned that there may have been some hidden bias. It has been suggested, for example, that those nurses thought to be at particular risk of heart disease might have been advised not to take HRT – twenty years ago heart disease was thought to be a contraindication (should not be prescribed). A study specifically designed to exclude such possible bias investigated a case-control analysis of 858 women presenting aged 45-69 between 1986 and 1990 with their first heart attack. The results again showed that oestrogen replacement reduced the risk of heart attack.

Two recently published controlled studies, however, have failed to confirm a beneficial effect of HRT on cardiovascular disease. The Heart and Estrogen/progestin Replacement Study (HERS - 1998) was designed to test the hypothesis that treatment with conjugated e quine estrogen 0.625 mg/d with MPA 2.5 mg/d would reduce the combined incidence of nonfatal myocardial infarction (MI) and coronary heart disease (CHD) death compared with placebo in women with prior history of MI, coronary revascularization, or angiographic evidence of CHD. This was the first large-scale randomized clinical-outcome trial of HRT for prevention of CHD in postmenopausal women. After an average of 4.1 years of follow-up, there was no difference in the primary outcome of nonfatal MI and coronary death between the hormone and placebo arms. Numerous explanations have been proposed for the overall null effect of HRT in HERS. These include inadequate duration of follow-up, adverse effects of MPA, bidirectional effects of estrogen (early risk and late benefit), a population of women too old to benefit from therapy (average age was 66.7 years), a preparation of HRT that was not ideal, chance, or that HRT is ineffective in preventing recurrent cardiovascular events in women with established disease. Similarly, The Women's Health Initiative(WHI - 2003) have reported no benefit with HRT on progression of cardiovascular disease.

Interestingly, for those who have been taking HRT for a while, the HERS recommended that "Given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue." However, according toHERS II. Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD."

As a result of The WHI and HERS studies, the majority of clinicians accepted that, on current evidence, HRT should not be initiated to reduce the risks of coronary heart disease. The debate, however, continues. Perhaps the major criticism of the HERS study is that the mean age at enrollment was 63 and that the results may not be relevant for those starting in their early 50s.

Five years ago, the investigators of the US Women's Health Initiative (WHI) published their first paper on the effects of hormone replacement therapy (HRT), stating that combined oestrogen/progestogen HRT resulted in increases in coronary heart disease, stroke, blood clots and breast cancer.

This led to widespread adverse publicity about HRT, and to regulatory authorities issuing safety restrictions on its use throughout Europe and the USA. The effect of this was to dissuade both women and their doctors from using HRT, with the results that thousands of women have subsequently suffered from menopausal complaints and may have done untold harm to their future health.

Many international groups of experts, including the British Menopause Society and Women's Health Concern, had expressed disquiet about the initial conclusions of the WHI, and further publications from the same study showed in fact that the risks for coronary disease with combined HRT were not significantly increased, and were actually lower with oestrogen-alone HRT, particularly in the younger age group of 50-59 years.

April 2007:

The WHI investigators have now published the combined results of their trials of HRT on cardiovascular disease, using oestrogen both with and without additional progestogen.

They have confirmed that those women aged below 60 years and less than 10 years past menopause have a lower risk of coronary disease, a lower risk of death from any cause, and no increased risk for stroke.

It is only in the older age groups where increased risks are seen, ages at which it is unusual to commence HRT. Furthermore, the WHI gave the same dose of HRT to all women irrespective of their age, yet there are good reasons to think that the dose was too high for the older women, hence causing vascular harm. The WHI investigators signally failed to comment on this important issue. It also emerged last year that the increase in risk of breast cancer was confined to women using combined HRT who had previously taken HRT before entering into the study.

Women taking oestrogen-alone HRT actually had a lower risk of breast cancer.

It is quite astonishing that the study which initially warned us of all the dangers of HRT is now showing us virtually the opposite.

But where is the publicity about this? And will the regulatory authorities act with the same speed as they did to warn against HRT to now correct their advice? There were calls from an International Consensus Group last year for them to revisit their recommendations. The British Menopause Society and Women's Health Concern re quest that the regulatory authorities, including the European Agency for the Evaluation of Medicinal Products (EMEA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) now do so as a matter of urgency.

A study in Scandinavia has shown that the majority of postmenopausal gynaecologists or female partners of male gynaecologists are taking HRT

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