Yet another potential negative side effect to hormone replacement therapy has emerged with a new study that claims HRT appears to increase the chances of developing ovarian cancer.

The British study of the effects of the menopause treatment was released online Thursday by the journal The Lancet.

Further supporting those results, another study published Thursday in the New England Journal of Medicine fleshed out earlier reports from researchers at the University of Texas who found breast cancer rates dropped off in relation to a decline in HRT use.

The Canadian Cancer Society has been urging caution in relation to HRT since mid-2002, when researchers found hormone therapy put patients at risk of heart attack, stroke and breast cancer in women who have already gone through menopause.

"It's just adding more concern about the role of hormone replacement therapy in the development of certain cancers," Heather Logan, the cancer society's director of cancer control policy, told The Canadian Press in relation to the new studies.

"And in the absence of particular health benefits, when women have other options (for the relief of menopausal symptoms) I think they very strongly should consider them.''

And those who do choose to use hormone replacement therapy should use caution, said Dr. Valerie Beral, the lead author of the Lancet study.

"I think the general 'If you have to take it, take it for a short time' is still the right message," she told CP.

Lancet study

Though the increased risk of ovarian cancer is small, it is considered statistically significant by the Lancet study.

Over five years, just one additional woman out of 2,500 that took HRT, would be diagnosed with the disease, and one in 3,300 would die.

"It's not a big effect, but it's a fatal effect,'' said Beral, a professor of epidemiology at Oxford.

"And so it's sort of that balance between saying `No it's not huge, but people are more likely to die and die in a rather awful way."

The article is based on information compiled for the massive Million Women Study.

That project included women 50 and older who were screened for breast cancer between 1996 and 2001.

Participants were asked for information such as how much alcohol they drank, how much they exercised and whether they took HRT -- all with the goal of answering questions about the possible impact of HRT use on breast and ovarian cancer rates.

In the recent Lancet analysis, researchers compared ovarian cancer rates and deaths between women who were currently on HRT, those who had taken it but stopped, and those who had never taken the treatment.

On average, researchers found, those women currently on HRT were 20 per cent more likely to develop ovarian cancer and die from it, than women who never used it.

That means that 2.6 women out of every 1,000 women on HRT would develop ovarian cancer over five years.

Among 1,000 women who never used HRT, 2.2 would develop the often deadly disease.

Since 1991, the U.K. study found, 1,300 additional cases of ovarian cancer resulting from HRT had occurred in Britain. Of those, 1,000 had died.

Use of HRT has been on the decline in many countries since 2002, when the Women's Health Initiative reported about the increased risks of heart attack, stroke and breast cancer.

In Canada, data shows annual HRT prescriptions dropped from 12.6 million in 2001 to 5.5 million in 2006 -- with an annual decline each year between 2002 and 2006.

That drop should begin to result in lower rates of ovarian cancer.

Last December, researchers at the University of Texas M.D. Anderson Cancer Center reported that breast cancer rates had gone down sharply in connection with the drop in HRT use.

The results were dramatic, with the rate of new cases in 2003 dropping by a whopping 6.7 per cent.

New England Journal article

The findings were fleshed out in this week's New England Journal article, with the researchers -- biostatistics professor Dr. Peter Ravdin, and Donald Berry, head of the division of quantitative sciences -- reporting that the trend levelled off but remained low in 2004.

The new results suggest the 2003 decline wasn't just a blip or an anomaly, but may be a lasting trend, Ravdin said.

"This kind of study can't prove causality, but the data present a very compelling link between hormone replacement therapy and breast cancer," Berry said.

Others agreed, the results prove there is a connection, said Dr. Julie Gralow, a spokeswoman for the American Society of Clinical Oncology and cancer expert at the University of Washington in Seattle.

"Because it didn't bump back up again," it supports the idea that the rate has stabilized at a new lower level, Gralow, who had no role in the study, told The Associated Press.

Brenda Edwards, one of the journal authors who is a National Cancer Institute researcher, agreed.

"Now we have a statistically significant decline" over three years and clear proof of a trend, she said.

And adding greater weight to the argument, the decline was predominantly seen in estrogen-receptor positive cancer -- a form of the disease that is fuelled by estrogen, which is the major ingredient in HRT. Among ER-positive cancer patients, cancer rates dropped by 14.7 per cent, compared to a 1.7 per cent decline in ER-negative cancers.

With files from The Associated Press and The Canadian Press