Review warns that risks of long term HRT outweigh benefits

BMJ 2002; 325 doi: (Published 28 September 2002) Cite this as: BMJ 2002;325:673
  1. Susan Mayor
  1. London

    The overall increased risk of serious adverse effects—including breast cancer, stroke, and pulmonary embolism—with long term hormone replacement therapy (HRT) outweighs the potential benefits in disease prevention, warns a review of major trials published last week.

    Researchers at the Cancer Research UK's epidemiology unit in Oxford were asked by the Lancet to review all trials of long term HRT after the early termination of one part of the women's health initiative trial showed increased risk of cardiovascular events (JAMA 2002;288:321-33)

    They analysed four randomised trials, including more than 20000 women followed up for an average of 4.9 years. Results showed that HRT users had significantly increased incidence of breast cancer, stroke, and pulmonary embolism; a significantly reduced incidence of colorectal cancer and fractured neck of femur; but no significant change in endometrial cancer or coronary heart disease (Lancet 2002;360:942-4)

    Overall, the excess estimated incidence of breast cancer, stroke, and pulmonary embolism (compared with non-users) was 1 in 170 for healthy women aged 50-59 years taking HRT for five years; this was balanced by an estimated reduction in incidence of colorectal cancer and fractured neck of femur of 1 in 600 users. For healthy women in their 60s, the excess risk of breast cancer, stroke, and pulmonary embolism was 1 in 80, with a reduction in colorectal cancer and fractured femur of 1 in 180 users.

    Three of the trials in the review included women with previous cardiovascular disease, whereas the fourth recruited healthy women. Combined oestrogen and progestogen HRT was used in three trials and oestrogen alone in one. The authors noted: “There was no significant heterogeneity in any of the results across the trials, suggesting that the relative risks associated with the use of HRT did not vary substantially across women with different underlying risks of cardiovascular disease or using different hormonal preparations.”

    They pointed out that existing trials were too small to assess reliably the effect of HRT on cause specific mortality, and that they did not provide information about oestrogen or progestogen preparations other than those already tested. Ongoing trials—including ESPRIT-UK and the second part of the women's health initiative trial—will provide more information on oestrogen alone. WISDOM (the women's international study of long duration oestrogen after the menopause) is randomising about 22000 healthy women to similar oestrogen and progestogen combinations as the women's health initiative, but results are not expected for a decade.

    The Medical Research Council is reviewing all HRT trials and will make a recommendation soon on whether the WISDOM trials should continue.

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