I've studied HRT for years – and I'm still convinced it raises women's risk of cancer
Professor Klim Mcpherson
01:25 GMT, 29 May 2012
01:25 GMT, 29 May 2012
The link between breast cancer and HRT has gained credibility over the past decade
Fears about HRT’s link to breast cancer and heart disease are misplaced, an international panel of experts reported last week.
Their conclusions were based on a major reassessment of the evidence.
Yet controversially this expert believes the findings are flawed…
How safe is HRT
This is one of the most fiercely debated medical questions of the 21st century — and, as such, is a major source of confusion for women themselves.
In such circumstances, we as researchers have a duty to provide clear, evidence-based advice to help women make up their minds on this effective but controversial medication.
How very sad and worrying then, that a newly published review — which made the headlines last week by giving HRT a clean bill of health for menopausal women — is seriously flawed, thereby putting women’s health at risk.
The report was the work of an American team of clinicians, who carried out a review of the ten-year Women’s Health Initiative (WHI) study.
This major U.S. study, which recruited 26,000 women and cost $625 million (almost 400 million), was halted dramatically early in 2002 because of evidence that HRT increased women’s risk for heart problems and breast cancer.
Now, in a special issue of the international journal, Climacteric, the researchers have concluded that the WHI team had made a fundamental error — they had generalised from findings on post-menopausal women to make recommendations for women who were going through the menopause.
What these latest researchers are suggesting is that the way women’s bodies respond to a drug at the age of 50 is mysteriously different from the way they respond three, five or ten years later.
But the evidence they put forward is simply wrong.
Furthermore, I believe these scientists are risking women’s health by downplaying the raised risk of breast cancer found in the WHI study — and also shown in the UK’s Million Women Study, published in 2003.
The link between breast cancer and HRT has gained credibility over the past decade, as breast cancer rates have fallen in areas where women have stopped using HRT.
How can Climacteric’s researchers have got it so wrong
Back in the late Nineties, HRT was being heralded as a panacea not just for the unpleasant symptoms of the menopause, but possibly as a means for protecting women’s hearts.
New evidence How the Mail reported the story last week
Oestrogen has been considered to protect pre-menopausal women against cardiovascular disease — indeed, for many years, doctors believed, probably wrongly, that the menopause caused a sudden worsening of women’s heart health as oestrogen levels dropped.
Indeed, evidence from several large but not terribly rigorous studies led the manufacturers to claim HRT halves a woman’s risk of having a heart attack after the menopause.
They demanded that HRT be licensed as preventative cardiac medication, in a similar way to statins are today.
HRT was on the brink of becoming a blockbuster drug, a must-have for 50-plus women.
Yet the American Food and Drug Agency (FDA) was rightly cautious.
After all, research on the drug’s cardiac benefits was relatively weak.
As an epidemiologist, then at the London School of Hygiene and Tropical Medicine, I had collaborated with Finnish scientist Professor Elina Hemminki in assessing the impact on the heart of taking HRT from the time of the menopause for an average of seven years — based on the findings of 200 randomised (and therefore rigorous) studies.
In a paper published in 1997 in the British Medical Journal, we reported there was no evidence whatsoever of a beneficial effect.
But we wanted to go further — and so looked at the 17 studies that had been funded by the pharmaceutical industry, but not published.
In 2000, after Professor Hemminki went to the High Court in Helsinki to force the companies to release these data, we were finally able to review this previously unpublished evidence in a paper in the Lancet.
We reported that rather than protecting women’s hearts, taking HRT almost doubles a woman’s risk of a heart attack.
In view of this, the FDA insisted the drug would be granted a licence for heart disease only once a properly organised double-blind placebo controlled study had been carried out.
First, the researchers had to find a way to eliminate a well-known bias that occurs when patients in a trial are aware of whether they are taking the active ingredient or the placebo.
As HRT is so effective in controlling menopausal symptoms, women still going through the menopause would know immediately if they’d been given it or not and it would no longer be a proper trial.
That’s why the WHI researchers selected women who’d passed the menopause — so no one would know whether they were on HRT or a placebo. It was a difficult call, but I am certain it was the right one.
When the WHI study was published in 2002, it confirmed earlier findings of a raised risk of heart disease as well as identifying new concerns about breast cancer.
Not long after, the UK’s Million Women Study demonstrated there was a raised risk of breast and ovarian cancer in women taking HRT. (The study involved a million women of all ages who’d undergone mammograms — they were then tracked between 1996 and 2001).
This new finding was hardly surprising: a woman’s naturally produced oestrogen is known to be linked to the development of these cancers.
So it makes sense that oestrogen as a hormone supplement has the same impact (and further that progesterone, also found in most HRT, increases this effect).
It’s against this background that the UK Medicines and Healthcare Products Regulatory Agency issued advice to GPs in 2003 to prescribe HRT only at the lowest possible doses for the shortest possible time — leaving women able to make an informed choice as to whether they wish to take these risks.
Now, however, the ‘new evidence’ has effectively overturned the WHI study, thereby ending the ‘mass fear’ that has led to ‘a wasted decade’ for menopausal women.
In fact, there is no new evidence in the Climacteric papers.
Further, I am horrified at the significant flaws that appear in what should be an accurate review of existing evidence.
First, there’s the researchers’ glaring selective amnesia — they claim to have reviewed all the available evidence on the health consequences of taking HRT at the time of the menopause.
Unfortunately, these four leading scientists omitted the papers I published with Professor Hemminki, a curious omission as they were published in leading journals.
By focusing exclusively on the WHI study, the researchers have ignored the Million Women Study — a hugely relevant and internationally recognised piece of research.
I know U.S. researchers have a reputation for ignoring UK research. But this case of whitewashing HRT by ignoring UK data is extraordinary.
Had the UK papers been included in the review, there is no possibility it could have concluded HRT is safe for women going through menopause.
More outrageous, however, is their suggestion the strong association between breast cancer and HRT is simply a coincidence, even in post-menopausal women in the study.
Ten years ago, the combination of the WHI study and the Million Women Study led to a dramatic drop in the use of HRT worldwide.
The positive impact of that reduction is plain to see: at the turn of this century, breast cancer incidence in the UK and other countries was rising.
Over the past five years, the incidence of oestrogen receptive breast cancer — the type directly related to levels of oestrogen in the body — is falling. It is quite clearly a beneficial consequence of the reduced use of HRT.
If women are taken in by the so-called new evidence on HRT and large numbers feel sufficiently reassured to take the supplement again, I have no doubt many women will develop breast cancer who wouldn’t if they’d listened to evidence-based advice.
The truth may not suit the pharmaceutical industry — but women deserve the full facts.
Klim McPherson is Professor of Public Health Epidemiology at Oxford University