Women were advised yesterday to think “very carefully” about taking hormone replacement therapy (HRT) after evidence was published showing that it has killed 1,000 women in Britain since 1991 by increasing their risk of ovarian cancer.

HRT increases the risk of the disease by 20 per cent, the biggest investigation of links between HRT and cancer has found. Although the absolute risk is low, millions of women took HRT in the 1990s and so the total impact is large: an extra 1,300 cases of the disease and 1,000 deaths between 1991 and 2005, according to the Million Women Study.

Previous results from the same study have linked HRT with an increased risk of breast and womb cancer. The latest findings suggest that HRT raises the combined risk of all three diseases by more than 60 per cent, the researchers say.

Despite a sharp decline in recent years in HRT use, there are believed to be about one million women in Britain still on it.

Valerie Beral, director of the Cancer Research UK epidemiology unit at the University of Oxford, said: “The results of this study show that not only does HRT increase the risk of getting ovarian cancer, it also increases a woman’s risk of dying of ovarian cancer.”

Ovarian cancer is the fourth most common cancer in women in Britain. Each year about 6,700 women develop the disease and 4,600 die from it.

The findings come from a study of 948,576 post-menopausal women, or a quarter of all women aged 50 to 64 in the country. It was largely funded by Cancer Research UK. About a third of those in the study were taking HRT, and another fifth had taken it in the past.

The women were followed for an average of more than five years for signs of ovarian cancer, and seven years for death. During the follow-up period a total of 2,273 women developed ovarian cancer and 1,591 died from it.

These results imply that the use of HRT — of whatever sort — increased the risk of developing and dying from ovarian cancer by 20 per cent, the team reports in the online version of The Lancet.

To put the findings in perspective, they mean that over a period of five years there is likely to be one extra case of ovarian cancer among every 2,500 women receiving HRT, and one additional death for every 3,300 women on the therapy.

HRT is used to combat unpleasant symptoms of the menopause, including hot flushes, vaginal dryness and night sweats. It was promoted strongly by doctors in the 1970s, and many women claimed that it had transformed their lives.

But in recent years numbers have plummeted after a series of health scares. According to the GP Research Database, the number of women in Britain on HRT fell from two million in 2002 to one million in 2005.

John Toy, the medical director of Cancer Research UK, said: “Considering this alongside the increases in risk for breast and endometrial cancer, women should think very carefully about taking HRT. Women who choose to take HRT should aim do so for clear medical need and for the shortest possible time.”

The findings were challenged by John Stevenson, of the Royal Brompton Hospital in London and the chairman of the charity Women’s Health Concern.

“The study grossly overestimates the breast cancer risk, and now we have findings from a five-year study that have to be extended to a 14-year time frame to make them more sensational,” he said. “This is not science, and the findings themselves fly in the face of cancer biology.”

Breast, ovarian and endo- metrial cancer, which affects the womb lining, account for almost 40 per cent of cancers in women in Britain, and a quarter of female cancer deaths.

HRT appears to raise the combined risk of all three diseases by 63 per cent, according to the Million Women Study.

“When ovarian, endometrial and breast cancer are taken together, use of HRT results in a material increase in these common cancers,” the study authors wrote.

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