Women on HRT should be aware that there is a small chance of an increased risk of blood clots and possibly stroke.

Hormone replacement therapy (HRT) pills have mixed risks and benefits in relation to heart disease and stroke, depending on when women take them, a large-scale evidence review has found.

Overall the analysis showed that oral HRT does not protect against heart disease and may increase the risk of stroke.

But data from a sub-group of younger women more representative of the majority of patients found a reduced risk of death from any cause and heart disease linked to the treatment, even though the likelihood of blood clots was slightly raised.

The review looked at almost 4,000 studies from around the world involving some 40,000 participants, and included two large American investigations which recruited women as old as 79. Around 9,000 women formed the sub-group who were prescribed the treatment at, or not long after, the menopause.

Lead researcher Henry Boardman, from Oxford University, said: “The evidence we have provides some support for the so-called ‘timing hypothesis’, but we should bear in mind the size of this effect.

“When we looked at the results according to the age of women, or by how long since their menopause they had started treatment, we found that if 1,000 women under 60 years old started hormone therapy we would expect six fewer deaths, eight fewer cases of heart disease and five extra blood clots over about seven years, compared to a thousand similar women who did not start hormone therapy.”

The treatment was associated with a small 24 per cent increased risk of stroke

The findings are published in the Cochrane Library, which produces information intended to inform health policy.

It only included evidence from studies of women prescribed HRT pills containing oestrogen, rather than skin patches or creams and gels. Death rates from any cause, and specifically from cardiovascular disease, were not affected by whether or not women were on HRT, the general findings showed. Similarly, HRT appeared to have no protective effect on non-fatal heart attacks or angina. But the treatment was associated with a small 24 per cent increased risk of stroke.

In women under 60 or who started HRT treatment within 10 years of the menopause there was a 30 per cent reduction in deaths from any cause and a 48 per cent reduced risk of coronary heart disease. As well as a small increased risk of blood clots in this group, there was a suggestion of a higher likelihood of stroke. However, this was inconclusive. Boardman said: “The evidence adds to a large bank of evidence that helps GPs advise their patients, but you need to weigh up the severity of the symptoms and all the benefits and harms.

“The findings of this Cochrane review need to be carefully considered. This is a complicated health issue, where the same treatment offers benefits in some women, but harms in others.”

David Tovey, editor-in-chief of the Cochrane Library, said: “This review adds a few more pieces to a complicated jigsaw of evidence relating to the use of HRT to treat symptoms of the menopause.

“The main analysis that the authors did found no benefit, and so we need to apply caution to the results from the sub-group analysis. However, if true, this apparent benefit in preventing heart disease in younger women should be considered alongside other possible benefits and emerging evidence of harms, including the risk of breast cancer, ovarian cancer and DVT.”

Boardman said more research was needed focusing more closely on younger women on HRT and following their progress for a long period of time. But such an investigation, which might have to recruit 30,000 women and monitor their health for 15 years, would be prohibitively expensive.