New evidence confirms that hormone replacement therapy (HRT) should not be prescribed to older women who are many years past menopause to help prevent chronic conditions such as heart disease.
But the authors support the view that HRT is a safe short term treatment for younger women in early menopause to relieve symptoms and improve quality of life.
In 2002, the Women's Health Initiative (WHI) trial found that postmenopausal women taking HRT had more heart attacks and strokes than non-HRT users. The trial was halted early and millions of women around the world stopped taking HRT. But scientists now believe that these risks may only apply to older women who do not normally use HRT.
In 1999, another trial (WISDOM) began to assess the long-term risks and benefits of HRT after the menopause. This trial was also stopped after the first WHI results appeared, but the WISDOM findings, published today, make an important contribution to the body of knowledge about HRT when it is initiated in older postmenopausal women.
The WISDOM team identified 5,692 healthy women registered at general practices in the UK, Australia and New Zealand with an average age of 63 years and 15 years after the menopause.
The women who had not had a hysterectomy were split at random into two groups. One was given a daily dose of combined hormone therapy (oestrogen and progestogen) and the other group was given a placebo pill. Women who had had a hysterectomy were split between combined hormone treatment, oestrogen only and a placebo.
All women were monitored for an average of 12 months and main outcomes such as cardiovascular disease, osteoporotic fractures, breast cancer and deaths, were recorded.
There was a significant increase in the number of major cardiovascular events (angina, heart attack or sudden coronary death) and blood clots (venous thromboembolisms) in the combined hormone therapy group compared to the placebo group. However, rates for cerebrovascular disease, breast or other cancers, fractures and overall deaths were not significantly different in these two groups.
This study confirms an early increase in thromboembolic and cardiovascular risk in older women starting hormone replacement therapy many years after the menopause, say the authors.
It shows that there is no overall disease prevention benefit, and some potential risk, for women who start hormone replacement therapy many years after menopause.
The results are also consistent with the early findings of the WHI and other trials, and support the conclusion that combined oestrogen and progestogen therapy should not be initiated to prevent cardiovascular disease in older postmenopausal women.
However, the authors stress that these results cannot necessarily be applied to younger menopausal women starting hormone replacement therapy to relieve symptoms such as hot flushes and night sweats. For these women, recent studies suggest there may be cardiovascular benefits of taking HRT around the time of menopause. The authors say that more research is needed to assess conclusively the long term benefits and risks among these women.
Those helping women make choices about treatment should consider both the results and limitations of the WHI and WISDOM trials, particularly those women who may be influenced by the timing of initiation of hormone replacement therapy, they conclude.
In an accompanying editorial, Dr Helen Roberts at the University of Auckland says that this study does not change current advice to postmenopausal women. Healthy women in early menopause are unlikely to face substantially increased risks when using hormones for a few years, she writes. However, long term use of hormone replacement therapy to prevent chronic disease is no longer recommended as the available randomised evidence shows that the negative outcomes outweigh the positive benefits.