Hormone therapies and ischemic heart disease

Observational studies have consistently shown a benefit of HRT on CHD prevention, although it has been noted that the biggest beneficial impact has been seen in those women who initiated HRT close to the menopause. However, randomised clinical trials of HRT have not shown any significant benefit on CHD, and there has even been a report of harm from the initial publication of the Women's Health Initiative (WHI). This has led to the abandonment of HRT for prevention of CHD by cardiologists and other physicians, but they have failed to realise the shortcomings in the interpretation of the data. Firstly, the WHI finding of a significant increase in CHD events was published in the preliminary analysis of their data. Subsequent publications of the complete data showed that there was no significant increase in CHD events. Secondly, it is the older women in the randomised trials that failed to show benefit, whereas there was evidence of benefit in the younger ones. Thus, the age at initiation of HRT seems to be important for cardiovascular benefit and risk, with the biggest benefit being seen in women starting treatment below 60 years of age and within 10 years of onset of menopause as shown by a large meta-analysis of randomised clinical trials of HRT. This gives rise to the concept of a “window of opportunity” for HRT to help prevent CHD around the menopause. Further support comes from the findings of the Danish Osteoporosis Prevention Study. This was a prospective clinical trial of 1000 women in the early postmenopause who were randomised to either HRT or no treatment, studied for 10 years and followed up for a further 6 years. HRT produced a significant reduction in a composite end-point of myocardial infarction, death or heart failure. HRT may therefore prove useful for the primary prevention of CHD in women. This could be an important option, as agents that are effective for the primary prevention of CHD in men do not appear as effective in women.