Hormone replacement therapy: the way forward

Recent prospective randomised data from the USA Women's Health Initiative (WHI) combined HRT study 1 have confirmed the previous observational data from the Imperial Cancer Research Fund 2 (now Cancer Research UK) regarding the risks of breast cancer with HRT. The WHI study was stopped prematurely by the study regulatory board after running a mean of 5.2 rather than 8.5 years. This was because it was deemed that the risk versus benefit statistic was exceeded due to an excess of breast cancer and coronary heart disease (CHD) cases in the treatment arm (continuous combined conjugated equine oestrogens 0.625 mg and medroxyprogesterone acetate 2.5 mg). The data from the WHI study suggested an excess risk of breast cancer with combined hormone therapy of 5, 8 and 13 cases per 10 000 women per year for the 50-59, 60-69 and 70-79 years age groups, respectively. A further analysis of the data this year detected a hazard ratio for breast cancer of 1.24 (p>0.001) for an average of 5.6 years exposure to HRT. This study reported, in a blaze of publicity, an increased risk of breast cancer diagnosis with all HRT regimens [relative risk (RR) 1.66; 95% CI 1.58-1.75]; there was a statistically significantly higher risk with oestrogen/progestogen HRT (RR 2.00; 95% CI 1.91-2.09) than that seen with oestrogen alone (RR 1.30; 95% CI 1.22-1.38]) or tibolone (RR 1.45; 95% CI 1.25-1.67). This was reported by the press as a doubling of risk of breast cancer with HRT, failing to mention the absolute risk in terms of actual numbers of cases. For oestrogen-only therapy it represented an additional 1.5 per 1000 cases after 5 years of use, and for oestrogen/progestogen therapy an additional 6 per 1000 cases after 5 years of HRT use. In women aged 50-64 years, whose baseline risk is 32 in 1000, this translated to 33.5 per 1000 and 38 per 1000 cases, respectively.