Hormone replacement therapy continues to increase the risk of cancer even after a woman stops taking it, a study has shown.

Three years after treatment ceased, the risk of breast cancer remained 27 per cent higher while risks of any type of cancer were 24 per cent higher.

The findings, published in the Journal of the American Medical Association, imply that cancer risks persist, while other health risks such as blood clots and strokes – which are elevated while the women were taking the pills – returned to normal.

The results come from a follow-up to the Women’s Health Initiative study, which gave warning in 2002 of cancer risks while taking HRT. After those findings were published and backed by results from the Million Women Study in 2003, about half the two million British women who had been taking HRT stopped.

More recently, the health initiative study has been criticised for failing to break down the results by age. Among women in their fifties, defenders of HRT said, the risks were much smaller.

The new study, led by Gerardo Heiss, of the University of North Carolina, follows 15,730 women originally included in the trial, with an average age of 63. All had been randomised to take either the combined HRT pill (oestrogen plus progestagen, called progestin in the US) or a placebo.

In 2002, when researchers discovered an increased risk of breast cancer and heart and artery disease in women assigned to HRT, the trial was terminated. All the women were advised to stop taking the pills. The study looks at what happened in the following three years, up to 2005.

At the end of that time the numbers of heart attacks, strokes and blood clots in women from both the active and placebo treatment groups were similar, showing that the risk of cardio-vascular disease had fallen substantially for former HRT users.

While taking the treatment, the women had experienced a 29 per cent increased risk of heart attacks, a 41 per cent increased risk of strokes and nearly twice the normal risk of serious blood clots. These returned to normal after stopping.

But the increased risk of breast cancer remained at about the same level. During the follow-up study there were 63 more diagnoses of cancer among former HRT users than among women who did not have the treatment, or three per 1,000 participants per year.

Marcia Stefanick, one of the study authors, from Stanford University, California, said: “The continued increased risk of breast cancer clearly plays a role in the increased overall risk of cancer, years after stopping long-term oestrogen plus progestin therapy, and it is important that we continue to follow these women.”

Leslie Ford, from the US National Institutes of Health, which funded the Women’s Health Initiative, said: “The hormones’ effects on breast cancer appear to linger. These findings reinforce the importance of women getting regular breast exams and mammograms even after they stop hormone therapy.”

A summary of risks and benefits, called the “global index”, was included in the results and covered outcomes for heart disease, invasive breast cancer, stroke, lung blood clots, cancer of the womb lining, bowel cancer, hip fracture and death. This overall measure showed an increased risk of 12 per cent for women taking HRT, which did not change after treatment stopped.

Michael Lauer, director of the National Heart Lung and Blood Institute at the US National Institutes of Health, said: “This study provides further evidence that five years of combination hormone therapy is harmful. All the accumulated risks do not simply disappear.”

The advice from drug regulators in Britain is that HRT should be used for the control of symptoms of the menopause at the minimum effective dose and for the shortest possible time.

That maximises the benefit and reduces the risks, since the evidence is that most of the damaging effects of HRT occur after the age of 60. In particular, HRT in younger women appears to cut heart attacks rather than increase them.

The new study does not attempt to break down the results by age so it is impossible to tell whether the persistent cancer risk is age-related. In the US, some researchers have linked a rapid fall in breast-cancer rates of 6.3 per cent in 2003 to the abandonment of HRT by so many women.

The new trial fails to corroborate this claim because it contained too few women to detect a change of this order. Further follow-up was needed, the authors said.

Pros and cons

Q What are the benefits of HRT?
A Many women – but not all – suffer a range of symptoms when they reach the menopause. These can include hot flushes, night sweats, vaginal dryness, mood swings, falling libido and a lack of energy. HRT can relieve these symptoms, but it does not reverse ageing.

Q What about long-term benefits?
A The evidence is that five years’ use of HRT reduces the risk of bone fractures through osteoporosis, and of colorectal cancer.

Q And what are the risks?
A Studies have shown an increased risk of heart disease, stroke and breast and ovarian cancer. This latest study shows that the cancer risks persist for several years even after stopping HRT.

Q Why are these results controversial?
A Some doctors argue that the studies have been misread, and show no increased heart risks for younger women, those whose menopause has just begun.

Q So what do medical authorities recommend?
A HRT is an effective treatment for the short-term relief of menopausal symptoms, used at a minimum effective dose for the shortest possible time. But it should not be used in women who do not suffer symptoms. Nor should it be used purely to prevent osteoporosis, except in women for whom other treatments do not work.

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