KEY POINTS:
It was once described as the last frontier in the emancipation of women, a pill that would ease the transition through the menopause and allow those who took it to slip into a contented middle age.
Now the world's largest study of hormone replacement therapy (HRT) has shown that it may have caused 1000 deaths from ovarian cancer in Britain between 1991 and 2005.
A separate study due out today is expected to point to a similar trend - confirming the decline in breast cancer rates in American women since many stopped using HRT from 2003.
The new finding strengthens the evidence that HRT poses a serious danger to women. Previous results from the same study have shown that the risk of breast cancer and endometrial cancer (of the lining of the womb) is also increased.
Overall, the incidence of these three common cancers is increased by 63 per cent among women currently taking HRT compared with those who have never taken it.
That translates to 12 extra cases of cancer among 1000 women taking HRT over five years. The risk increases from 19 expected cases among women who had never taken the treatment to 31 among HRT users.
Two million women were estimated to be taking HRT at the height of its popularity in 2002 in Britain and millions more worldwide. New Zealand use has dropped to about a third of its 2001 level. The huge numbers exposed to the drug mean that tens of thousands will have developed cancer as a result.
On top of the cancer risk, HRT also increases the risk of stroke and thrombosis (blood clots). Earlier evidence suggesting it cut the risk of heart disease has not been borne out.
Professor Valerie Beral, chief author of the ovarian cancer study, published in the Lancet, said the argument about HRT was now settled. "In terms of the major health impact of HRT, the adverse effects outweigh the benefits. I don't think in the serious scientific literature there is any longer a debate about this.
"Some HRT specialists have over-stressed the benefits of HRT. They have pushed their case to the media and it has ended up confusing women." Referring to a study published this month in the Journal of the American Medical Association (Jama), which was claimed to show that HRT might protect some women against heart problems, Professor Beral said it had been misinterpreted. The study focused on the link between HRT and age and showed that the risks were lower for women who started HRT while still relatively young than for those who took it 20 or more years past the menopause.
But Professor Beral, of the Cancer Research UK Epidemiology Unit in Oxford, said it was wrong to suggest that this showed HRT was safe for younger women.
"There is a possible trend of increasing risk with age - though it is opposite for stroke where the risk is higher in younger women. But there is not a significant benefit for younger women. The Jama study concluded that still, on balance, the risks outweigh the benefits."
In the 1990s, HRT was presented as a panacea for 40 and 50-something women, offering release from the mood swings, hot flushes and declining libido associated with menopause.
High-achieving women proclaimed its benefits and by 2000 it was said two in every three middle-aged women were taking it. In 2002, a US trial of 16,000 women, half of whom were on HRT, was stopped three years early after researchers found a sharply increased risk of breast cancer, heart problems and stroke in women on the treatment.
The following year in Britain, the Million Women study, led by Professor Beral and largely funded by Cancer Research UK, which studied one million British women, a quarter of the female population aged 50-64, from 1996 to 2001, found the risk of breast cancer was doubled among those on HRT. It concluded the therapy had caused 20,000 extra cases of breast cancer in the previous decade.
Use of HRT slumped on both sides of the Atlantic as regulatory agencies moved rapidly to revise their advice.
In Britain the numbers using HRT halved, but there are still one million women thought to be taking it today. The risks associated with the treatment relate to current users and are thought to return to normal once the drug is stopped.
Professor Beral said yesterday: "At that time the regulatory agencies in the US, the UK and Europe said if women chose to take HRT they should do so for the shortest possible time and at the lowest possible dose. Everything that has happened since has not changed that advice."
Professor Sean Kehoe, consultant gynaecologist at John Radcliffe Hospital, Oxford and spokesman for the charity Wellbeing of Women said: "The use of HRT for five years means one extra woman would develop ovarian cancer out of 2500 using HRT compared with those not using HRT. Therefore this increase in a rare disease needs to be balanced against the potential effects on the woman's quality of life when ceasing HRT."
- INDEPENDENT
Q&A
Does hormone replacement therapy increase the risk of cancer?
Yes, say the authors of the world's largest study. They found 31 out of every 1000 women who used HRT over five years got cancer compared with a rate of 19 out of 1000 among non-users.
Is that much of a difference?
It translates into a 63 per cent higher rate of the disease - or tens of thousands more women around the world developing cancer after using the drug.
What kind of cancers are linked to HRT?
Mainly ovarian cancer but also breast cancer and endometrial cancer (of the lining of the womb).
Didn't another study this month say HRT was safe for younger women?
Yes but the authors of this study disagree. They say the risks outweigh the benefits for all women.
How do we know HRT causes the higher cancer rates?
Some of the strongest evidence comes from United States figures that show breast cancer rates fell dramatically in 2003, after many women stopped using the drug. Updated figures are expected to confirm that trend today.
