London -- Thursday April 19 2007
Leading article: The balance has changed
Hormone Replacement Therapy was once hailed as the answer for women who had reached the age of menopause and those experiencing the menopause ahead of time. It negated or moderated most of the unpleasant symptoms; it gave women of a certain age a new lease of life. For a generation of women who had been liberated by the contraceptive pill, it held the promise of another liberation almost as great.
More recently, the reputation of HRT as the miracle treatment has taken a few knocks, which was probably only to be expected. The notion that there could be a magic pill that mitigated the worst effects of the menopause without causing any adverse side-effects was always likely to be too good to be true.
But although the negative evidence was mounting quite consistently, the grounds for successive scares were often called into question. In the most widely circulated case, a US trial that was halted in 2002 after detecting a link between heart disease and HRT, another group of scientists subsequently described the methodology as flawed.
Now, just as HRT was starting to return to popularity, come the latest conclusions of the Million Women Study in Britain. They do not make cheerful reading. In several respects they confirm the worst fears raised by previous studies - and add to them. According to these findings, HRT may have caused as many as many as 1,000 deaths from ovarian cancer between 1991 and 2005. The same study shows that rates of breast cancer and endometrial cancer are also markedly increased. Overall, women taking HRT are 63 per cent more likely to contract one of these three common cancers than women who do not. There is also an increased risk of stroke and thrombosis.
The Million Women Study - the name of the project means what exactly what it says - is an ongoing project that involves a vastly greater number than any trial group. A thoroughly admirable endeavour, it is funded largely by Cancer Research UK - not by pharmaceutical companies that might have a commercial interest in the results.
It is hard not to conclude that the latest figures completely alter the balance of advantage from HRT. The total of one million women who are still taking HRT in this country - half as many as before 2002 - is now likely to fall again sharply.
Hormones, it is perhaps worth observing, are problematical in pretty much any form and at pretty much any age. The latest findings of the Million Women Study show that where hormone treatment is not medically necessary to sustain normal health, it is probably best left well alone.
London -- Thursday April 19, 2007
HRT linked to 1,000 deaths from cancer
Hormone replacement therapy patches. Photograph: Ian Waldie/Getty Images
Hormone replacement therapy may have caused the deaths of more than 1,000 women in the UK from ovarian cancer since 1991, scientists reveal today.
HRT has been used by millions of women to alleviate the symptoms of menopause or - in some cases - because they hope it will help them remain youthful and active for longer.
But today's authoritative study by Professor Valerie Beral and colleagues from Oxford University reveals that those who take HRT for five years or more are risking death from a particularly lethal form of cancer. The research, published online by the Lancet medical journal today, will not be the last straw for HRT, but it may well reduce the numbers willing to take the risk of hormone treatment.
It is the first firm calculation of deaths related to HRT, but Prof Beral and her colleagues have already shown that women who take the therapy are at increased risk of breast cancer and womb cancer. The risks of breast cancer are the highest, accounting for a probable 20,000 cases over a decade.
The article says the ovarian cancer risks should not be taken in isolation. "In total ovarian, endometrial and breast cancer account for 39% of all cancers registered in women in the UK. The total incidence of these three cancers in the study population is 63% higher in current users of HRT than in never users," it says.
HRT leads to "a material increase" in these common cancers, the authors conclude. When women stop taking it, however, their risk returns to normal.
Asked whether the results of the study should lead to HRT being taken off the market, Prof Beral said that was up to the regulatory bodies, not her.
"The regulatory bodies have said for five years if you want to take HRT, take it for as short a time as possible and in as low a dose as possible," she said. "The trouble is that there are some people who say they couldn't survive without it.
"My personal view is that it would be quite hard to do that [ban HRT] but I think this is just more evidence that it is not a good idea to take HRT for very long because the risks do go up with duration, as with breast cancer."
Early findings about health risks attached to HRT were hugely controversial, but Prof Beral thinks the problems have now been generally accepted.
"People like to say there is a debate about HRT. I think that's not true," she said. "Some people like to make out that it is uncertain what is going on, but I don't think there has been a debate for a long time. GPs are increasingly aware and so are women. The important thing is that women know these figures are right and not exaggerated."
The Million Women Study recruited 1.3m women around the age of 50 between 1996 and 2001. They completed a questionnaire about their lifestyle, their social and demographic background and their use of HRT. Three years later they were sent a second one, which 64% filled in. Every participant is followed up for death, emigration or cancer registration.
The study is the largest of its kind in the world, with one in four women in the UK of the target age participating, and it shows that one woman in 2,500 will get ovarian cancer while a long-term user of HRT and one in every 3,300 will die from it.
For all its drawbacks, HRT is very effective in promoting stronger bones in elderly women with osteoporosis who are at risk of fractures if they fall. "My personal view is that the sensible thing is to take HRT when you are 80," said Prof Beral. "My mother is 90 and has had a lot of fractures. I was very happy to say to my mother take HRT at 90." What mattered at that point was her quality of life. "If she has breast cancer when she is 95 - so what?"
Prof John Toy, medical director of Cancer Research UK, which funded the work, said: "Women should think very carefully about whether to take HRT. And women who choose to take HRT should do so for clear medical need and for the shortest possible time."
In a commentary in the Lancet, Dr Steven Narod of the Women's College Research Institute at the University of Toronto said that use of HRT had declined dramatically in the UK and elsewhere since concerns were initially raised and it was thought this had led to a decline in breast cancer rates in the USA.
"With these new data on ovarian cancer, we expect the use of HRT to fall further. We hope that the number of women dying of ovarian cancer will decline as well," he said.
London -- Thursday April 19 2007
Women undergoing HRT face increased risk of getting cancer By Jeremy Laurance, Health Editor
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 1,000 deaths from ovarian cancer between 1991 and 2005.
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 by the treatment.
Overall, the incidence of these three common cancers are increased by 63 per cent among women currently taking HRT compared with those who have never taken it. That means 12 extra cases of cancer for every 1,000 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.
An estimated two million women were taking HRT at the height of its popularity in 2002 in the UK and millions more worldwide. 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 by later studies. 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."
Referring to a recent study published earlier this month in the Journal of the American Medical Association (Jama), which was claimed to show that HRT may 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 are lower for women who start HRT while still relatively young than for those who take 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 fiftysomething women, offering release from the mood swings, hot flushes and declining libido associated with the menopause.
In 2002, an American 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 the UK, 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 over the previous decade.
Use of HRT slumped on both sides of the Atlantic as regulatory agencies moved rapidly to revise their advice. Shares in pharmaceutical manufacturers of the products nosedived.
In Britain the numbers using HRT halved, but there are still an estimated one million women 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 Sean Kehoe, consultant gynaecologist at John Radcliffe Hospital, Oxford, and spokesperson for the charity Wellbeing of Women, said: "The use of HRT for five years means one extra woman would develop ovarian cancer out of 2,500 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."