Hormone replacement therapy: a 2008 perspective

Abstract

New clinical data and recent re-analyses of data from the Women’s Health Initiative (WHI) have greatly changed the perception of hormone replacement therapies (HRTs) since the media excitedly reported the first findings of the combined HRT arm of WHI in 2002. The initial adverse finding of an overall early increase in cardiovascular risk in both WHI and the Women’s International Study of long Duration Oestrogen after Menopause in women who start or recommence HRT on average 13–14 years after menopause has been overshadowed by recent evidence supporting a cardioprotective effect of HRT when it is commenced near menopause. Most HRT is commenced in this early ‘therapeutic window’ when coronary calcification and atherosclerosis appear to be inhibited by oestrogen. Some neuroprotective effects are also hypothesised when HRT is commenced at this time. The effect of HRT on stroke when prescribed near menopause is not clear as it is uncommon at this age. A doubling in the risk of thromboembolism is still the main risk of HRT. The absolute risk is small near menopause when thromboembolic risk factors are not present and may be much less with non-oral routes. Breast cancer is a fear for many users but WHI showed a reduction of eight breast cancers per annum per 10,000 women years in oestrogen-only users at 7 years and no significant increase in first-time users of combined HRT until after 7 years when it was 8/10,000 per annum or less than 0.1%. Weight gain in users of HRT and placebo is similar around menopause. The main indications for HRT remain the control of menopausal symptoms where quality of life is gained and for the prevention of osteoporotic fractures, particularly in younger menopausal women where the risks are low. Other benefits include a reduction in diabetes and death. HRT must be individualised and tailored to minimise the start-up symptoms of bleeding on combined continuous regimens and breast tenderness when oestrogen levels are too high. Menopausal therapies are moving towards safer regimens, which minimise or eliminate systemic progestogen, safer routes (non-oral), safer lower doses and safer women.