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Menopause - Management
What advice should I give about the possible risks of HRT?

  • Advise the woman that there is a small increase in risk for:
    • Breast cancer.
    • Endometrial cancer.
    • Ovarian cancer.
    • Venous thromboembolism (deep vein thrombosis or pulmonary embolism).
    • Coronary heart disease for women who have started combined therapy more than 10 years after menopause.
    • Stroke.
Clarification / Additional information
  • The number of additional cases (compared with the background risk) of cancer and cardiovascular conditions in hormone replacement therapy users is discussed in Risks of HRT.
Basis for recommendation
  • The Medicines and Healthcare products Regulatory Agency (MHRA) and its independent adviser, the Commission on Human Medicines, have reviewed the safety data for hormone replacement therapy (HRT). The above recommendations are based on this safety review [MHRA and CHM, 2007b]. The MHRA found the following:
    • Breast cancer:
      • Combined HRT has been associated with the highest risk. The risk is lower with oestrogen-only HRT than with combined HRT.
      • Risk increases with duration of use and returns to baseline within 5 years of stopping treatment.
    • Endometrial cancer:
      • In women with a uterus, oestrogen-only HRT substantially increases the risk of endometrial hyperplasia and carcinoma in a dose- and duration-dependent manner.
      • Addition of progestogen cyclically for at least 10 days per 28-day cycle greatly reduces the risk, and addition of progestogen every day eliminates the risk.
    • Ovarian cancer:
      • Long-term use of oestrogen-only or combined HRT may be associated with a small increased risk of ovarian cancer. This risk returns to baseline a few years after stopping treatment.
    • Venous thromboembolism (deep vein thrombosis or pulmonary embolism):
      • The risk is higher with combined HRT than with oestrogen-only HRT, and events are more likely in the first year of use.
      • The level of risk associated with other routes of administration has not been clearly established, although it may be lower with transdermal HRT.
    • Stroke:
      • In randomized controlled trials, oestrogen-only and combined HRT increased the risk of stroke (mostly ischaemic) compared with placebo. Although the increase in relative risk seems to be similar irrespective of age, baseline risk of stroke increases with age and therefore older women have a greater absolute risk. Limited observational data suggest that this risk may depend on oestrogen dose.
    • Cognitive effects:
      • There is evidence that for women who start HRT after 65 years of age, conjugated equine oestrogen does not protect against mild cognitive impairment or probable dementia. Evidence suggests that combined HRT (conjugated equine oestrogen and medroxyprogesterone acetate) may increase the risk of dementia in women more than 75 years of age. The MHRA have advised that HRT not be prescribed for preventing a decline in cognitive function [CSM, 2004a].
  • Coronary heart disease (CHD):
    • No increased risk of CHD with the use of oestrogen-only HRT has been identified to date. Importantly, there are no data from randomized controlled trials to suggest a cardiovascular benefit with oestrogen-only or combined HRT [MHRA and CHM, 2007b].
    • Randomized controlled trials have found an increased risk of CHD in women who started combined (oestrogen-progestogen) therapy more than 10 years after menopause. Very few randomized controlled trials have assessed younger, newly menopausal women, and some have suggested a lower relative risk in these women compared with older women. The low baseline risk of CHD in most younger women, and the very low attributable risk due to HRT, means that their overall CHD risk is likely to be low.
    • For a more detailed discussion on the role of hormone replacement therapy and coronary heart disease in women see the website for the MHRA.

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