A UK study suggests that between 1991 and 2005, an extra 1,000 women in the UK have died of ovarian cancer because they were on Hormone Replacement Therapy (HRT).

The study is called the "Million Women Study" and its findings are published in The Lancet.

The research team, led by Professor Valerie Beral of the Cancer Research UK Epidemiology Unit, Oxford, UK, also suggest than an extra 1,300 new cases of ovarian cancer diagnosed in the same period were because of HRT.

Prof Beral and her team looked at data from nearly 1 million postmenopausal women who had not had their ovaries removed (bilateral oophorectomy) and had not had cancer for five years.

They were followed up for an average of 5.3 years for incident ovarian cancer and 6.9 years for death.

About 30 per cent of the participants were on HRT at the time of the study, and another 20 per cent had been on it previously.

During the period of the study, 2,273 women were diagnosed with ovarian cancer, and 1,591 died from it.

The researchers found that:

-- Current HRT users were on average 20 per cent more likely to get ovarian cancer and die from it than those who had never been on HRT.
-- For current HRT users, incidence of ovarian cancer increased with increasing duration of HRT use.
-- For every 1,000 women on HRT, an average of 2.6 developed ovarian cancer over 5 years.
-- This compared to 2.2 per 1,000 women who did not use HRT.
-- This equates to one extra ovarian cancer diagnosis per 2,500 HRT users, and
-- One extra death from ovarian cancer per 3,300 HRT users.

They also calculated that:

-- There was no significant difference in risk among different types of HRT or the way it was administered.
-- The effect of HRT on ovarian cancer risk was independent of: participants' socioeconomic status, previous use of oral contraceptives, reproductive history, body-mass index (BMI), and consumption of alcohol and tobacco.
-- The risk of developing ovarian cancer in participants who stopped taking HRT dropped to the same level as those who had never used it.

Ovarian cancer forms in the tissues of a woman's ovary, one of a pair of reproductive glands where eggs are made. Most ovarian cancers either begin on the surface of the ovary (ovarian epithelial carcinomas), or in the egg cells (malignant germ cell tumors).

About 6,700 women are diagnosed with ovarian cancer in the UK every year, and the disease also kills 4,600 women every year. It's the fourth most common cancer in women in the UK. In the US the annual figures for ovarian cancer are about 22,000 new cases and 15,000 deaths.

Together with endometrial and breast cancer, ovarian cancer accounts for about 40 per cent of new cases of cancer diagnosed in women in the UK.

The researchers said that the total incidence of these three cancers in the million women studied is 63 per cent higher in current HRT users than the never-users.

The study concludes that:

"Women who use HRT are at an increased risk of both incident and fatal ovarian cancer. Since 1991, use of HRT has resulted in some 1,300 additional ovarian cancers and 1,000 additional deaths from the malignancy in the UK."

Prof Beral and her team also commented on HRT and other cancers in women:

"The effect of HRT on ovarian cancer should not be viewed in isolation, especially since use of HRT also affects the risk of breast and endometrial cancer."

"When ovarian, endometrial and breast cancer are taken together, use of HRT results in a material increase in these common cancers," they added.

Commenting in an accompanying article, Dr Steven Narod, from the Women's College Research Institute, at the University of Toronto in Canada, said that HRT use had dropped dramatically in the UK and elsewhere after the Women's Health Initiative report.

He also referred to another study that has recently suggested a link between reduction in breast cancer incidence and reduced use of HRT in the US.

Dr Narod said that together with these findings on ovarian cancer, it is likely that HRT use will fall even further.

"We hope that the number of women dying of ovarian cancer will decline as well," he added.

No doubt for many women for whom HRT has made a significant impact on their quality of life, this news will come as a shock and a great disappointment.

Many experts reviewing this news are agreed on one message: women considering HRT should talk to their doctor. As with all medication there are benefits and there are risks.

If you are considering HRT, then make sure you have a thorough, fully informed discussion with your doctor who should be up to date with HRT information, and in a position to help you make the decision that gives you the best available assessment of benefits versus risks that applies to you personally.

"Ovarian cancer and hormone replacement therapy in the Million Women Study."
Valerie Beral and Million Women Study Collaborators.
The Lancet DOI:10.1016/S0140-6736(07)60534-0
Early Online Publication, 19 April 2007