[A-List] Unhealthy accumulation: HRT

["Michael Keaney" <michael011@xxxxxxxxxxx>]

The truth about HRT

Survey after survey has linked hormone replacement therapy to cancer,
strokes, blood clots and heart disease. Why, then, are so many women so
relaxed about using it? And why do some doctors insist that the dangers
are exaggerated? Sarah Boseley investigates 

Wednesday June 6, 2007
The Guardian 

It was the mid-60s and sex had emerged into the daylight. Young women
had the pill and those who felt so inclined shortened their skirts and
slept around. But why should they have all the fun? The hormone industry
was about to deliver for their mothers, too - or perhaps one should say
for their fathers.

In 1966, one of those epoch-changing books was launched on a generation
of women around the age of 50. It told them that they did not have to
lose out on the hormonal revolution. In fact, it implied it was their
duty not to lose out. Forever Feminine, by Dr Robert Wilson, a
gynaecologist in Manhattan, told them that the menopause was a disease
that could be treated. They could stay well, beautiful and sexually
active - they could, in fact, continue to please their husbands - if
they took hormone therapy. They must simply replace the oestrogen their
bodies had stopped producing.

It was the beginning of a myth that has resolutely refused to die - that
HRT will undo the ageing process. Over most of the past four decades,
women have been prescribed HRT for all sorts of reasons, not just to
stop menopausal hot flushes and night sweats and strengthen their bones,
but to improve their sex life, their hair, their skin and their morale.
For a long time it was almost a case of, well, why not?

Wilson's book was funded by Wyeth, one of the biggest manufacturers of
HRT. But that fact did not emerge until 2002, when his son admitted it
to the New York Times just the day after a major trial - astonishingly,
the first randomised controlled trial on the effect of HRT on women -
was stopped three years early. The trial, known as the Women's Health
Initiative (WHI), was set up after repeated calls from women's health
activists to find out whether, as drug companies and doctors believed,
HRT prevented heart disease. Shockingly, it found the opposite to be
true. By far the most common form of treatment, which combines oestrogen
and progestin, actually increases the risk of heart attacks, blood clots
and strokes. The investigators pulled the plug when they found that
women taking it also had a greater chance of invasive breast cancer. The
WHI is one of the two biggest and most important studies ever carried
out on the effects of HRT. The other is the Million Women Study in the
UK, which has published a series of papers on breast cancer and other
risks with HRT. The latest bad news from this hugely respectable study,
published in the Lancet in April, is that HRT must have caused 1,000
deaths from ovarian cancer between 1991 and 2005.

So that means HRT has now been linked to ovarian cancer, invasive breast
cancer, womb cancer (if you just take oestrogen), stroke, blood clots
and coronary heart disease. This is just not an elixir of youth. Oh yes,
there is a medical case for taking it if you are having a miserable
menopause, flushing beetroot red at embarrassing moments and waking up
with the sheets soaked - when you can sleep at all - at night. But the
relief you get for those things, which don't in themselves kill you, has
to be set against the alarming array of pretty nasty possible side
effects.

Given all this bad news, you might think women would be deserting HRT.
But that is not what is happening. It is true that the numbers in the UK
have dropped from two million to one million in the past four years but
that one million British women is considerably more than you would
expect if they were just taking it because they were suffering horribly
from menopausal symptoms. Only 300,000 women a year enter the menopause
and only 20% of those - 60,000 - suffer severely the debilitating hot
flushes and night sweats that HRT can genuinely help. There will also be
some older women taking it for brittle bones - which it is very
effective at strengthening - but because of the side effects HRT is no
longer recommended for that purpose.

The rest appear to be sold on the myth that replacing their disappearing
hormones will preserve their youth, beauty and sexual pleasure. What you
hear from women, when you ask why they are still on HRT, is not horror,
alarm or aversion to the hormonal pills but a belief that dodgy side
effects have not been proven.

Why is this, when most scientists would say the evidence of potential
harm is clear cut? The answer is that a vocal minority of doctors -
mostly gynaecologists who specialise in treating the menopause and who
see thousands of middle-aged menopausal women in their clinics - refuse
to believe it. And the troops marching to their tune have been certain
patient groups - groups set up to help, advise and support women going
through the menopause. Just like Robert Wilson, they tend to receive
funding from drug companies that make HRT.

Astonishingly, the Royal College of Obstetricians and Gynaecologists -
one of the venerated medical royal colleges that is supposed to be
wedded to science and guide the rest of us on where the truth lies - is
in a mess over HRT. Asked for a spokesperson to give their views of the
ovarian cancer findings, it offered up gynaecologist Janice Rymer. "I
can't believe the Lancet has published yet another paper on the Million
Women Study," she says. "There has been so much criticism [of it]."

It was Rymer who wrote the college's original statement in response to
the ovarian cancer paper, a statement that rubbished the Million Women
Study, saying it had "received criticism" both for the methodology (the
way it was carried out) and for the conclusions it came to. It had
"already caused misplaced anxiety in a large number of women," the
statement said.

Yet the MWS has a hugely respectable pedigree - the lead author is
Professor Valerie Beral, of Oxford University's cancer epidemiology
unit, and it was funded by Cancer Research UK, the NHS and the Medical
Research Council. Beral rejects the methodology argument, and says the
idea that there is a problem with their extrapolation - the conclusions
they came to from the evidence - is "extraordinary". It was the same
time-tested way scientists established that smoking is a killer, she
says. You take a group of a significant size, work out what is happening
to them and extrapolate to the entire population.

The college, apparently in schism, has now quietly withdrawn its
original statement about the ovarian cancer paper, but has not yet
managed to clarify its official position on the HRT studies, or offer up
an alternative spokesperson.

Interestingly, Beral was made an honorary fellow of the college for her
work on women's health a couple of years ago. She has much of the rest
of the medical establishment on her side. She points out that regulators
in the UK and the US have changed their recommendations on the use of
HRT as a result of her findings. The Committee on the Safety of
Medicines has said since 2003 that HRT should now only be used to
alleviate menopausal symptoms, and only for a short time. In a letter to
all doctors, its chairman, Professor Gordon Duff, warned that the US and
UK studies "provide good evidence" that HRT increases the risk of
breast, womb and ovarian cancer. There was no evidence of a beneficial
effect on heart disease - in fact, it appeared to increase the risk of a
heart attack or blood clots, especially in the first year, and to raise
the risk of stroke. It should not be the first treatment of choice for
osteoporosis, even though it works well in strengthening bones.

So what is going on? Rymer talks of a consensus among "all of us who are
in the HRT world", but there is a relatively small band of like-minded
gynaecologists and endocrinologists (hormone specialists) whose names
crop up again and again linked to criticisms of the HRT trials. Unlike
Beral, they are the clinicians who prescribe the drugs. Many of them
also receive funding from the drug companies in the shape of lecture
fees and consultancies. Rymer herself has reported consultancy fees from
Organon, Wyeth, Janssen-Cilag and Pfizer.

Gynaecologists such as Rymer believe in HRT because it works for the
menopausal women they see suffering. And the misery of those who really
need HRT should not be underestimated. But some women still take it,
Rymer acknowledges, because they think it will help keep their hair and
skin looking good. Others want it because "it keeps your vagina in good
shape", making sex easier after the menopause. "I think HRT is great,"
she says.

And many women don't want to come off it. "We tend to find on the shop
floor that you start a woman on HRT because of her symptoms," says
Rymer. "She takes it for one to two years and then is the time to
consider what she wants to do. I say to women, if you take it up to five
years, it's fine. People who take it for five years want to carry on
because they feel so much better on it. If you are on oestrogen and
progestin for more than five years, you have to accept an increased risk
of breast cancer." But, she says, only two extra women out of 1,000 will
get breast cancer because they are on HRT.

The criticism she and others repeat over and again about the Million
Women Study is that it was limited to women going for breast screening,
of whom about half were taking or had taken HRT. It was not a randomised
controlled trial - often referred to as the "gold standard" - where two
groups of very similar women were recruited and half given HRT while the
rest got a placebo. The women were self-selecting and, critics would
argue, there may be something about women going for a mammogram, for
instance, that makes them higher risk for cancer or heart disease. They
may already suspect a lump in the breast, for instance.

Beral says this is nonsense. Yes, it is an observational study, she
says, but it recruited one in four of all women in the UK of the target
age. It is so big that it has to be representative, she says. "It has
been criticised for its methodology by the Menopause Society," she says
- a professional organisation for doctors who work in the menopause
field - and a few papers have been published in scientific journals
taking issue with the way the study was carried out and its findings.
"They were all funded by drug companies, and they acknowledge that," she
says.

Probably the most influential of the critical papers was by an
epidemiologist called Samuel Shapiro from Boston University. He says the
WHI recently found that women who took oestrogen on its own, instead of
combined with progestin, had a reduced, not increased, risk of breast
cancer. This, he claims, is "the most valid evidence published to date".

But oestrogen is not the answer for most women. Few dispute another
crucial finding of the MWS, that oestrogen on its own causes cancer of
the womb. So unless a woman has had a hysterectomy, it is not
recommended. Shapiro, by the way, declared funding in the Lancet in 2005
for attendance at conferences, expert testimony and consultancies from
"various pharmaceutical companies that manufacture oral contraceptives
and supplemental female hormones".

Another prominent voice raised against the negative HRT findings is that
of endocrinologist Dr John Stevenson, chairman of the menopause patient
group Women's Health Concern, which has as its slogan "Unbiased advice
for women!" and a member of the council of the British Menopause
Society.

When I called Women's Health Concern to ask for the group's position
after the ovarian cancer paper was published, Stevenson was away. It was
clear how tightly knit and influential the group of pro-HRT doctors is
when I was again offered Janice Rymer instead.

The official comment from Women's Health Concern on the Lancet ovarian
cancer study is on its website. It takes the form of what it bills as
"an extract" from a Daily Mail story on the subject, in which Stevenson
is quoted. Except two things have been edited out of the article - the
first paragraph, which states that the MWS study found 1,000 ovarian
cancer deaths, and Valerie Beral's quote.

Another headline on the website is equally tabloid-worthy:
"Investigators make dramatic U-turn on HRT safety claims". This is their
take on the latest heart disease findings from the WHI study in the US.
Investigators re-analysed their data showing an overall rise in heart
disease on HRT, and found that the youngest women taking hormones at the
start of the menopause - around the age of 50 - showed no increased
heart disease. The increase came later - in women aged around 60.

Stevenson is triumphant. "They didn't look at what age group they were
talking about," he tells me when we finally make contact. Furthermore,
older women might also be OK in his opinion if they had a lower dose of
drugs. "It is something we have been doing in the clinic for donkey's
years," he says. As for the Million Women's Study, he says, "its
findings are not accepted by the scientific community".

What are women supposed to think about HRT, when doctors - whose advice
we respect and rely on - cannot agree?

In a letter in 2002 to the Lancet, which requires all published writers
to declare their interests - Stevenson said he was on the scientific
advisory boards of Wyeth, Schering, Novartis and Lilly, all of which
manufacture HRT. What did he think of Beral's accusation that critics of
her study were funded by the drug companies? "That's a great way of
trying to get a kick in when you run out of ideas to defend yourself,"
he says. "It means she can't argue against the arguments we put forward,
so she says you must all be completely biased because you have got
funding from pharmaceutical companies."

But on the other side of the Atlantic, Jacques Roussow, the project
director at the National Institute of Health who oversees the Women's
Health Initiative, says there has been no U-turn on heart disease at
all. The original finding stands: HRT has not been shown to prevent
heart disease. But looking specifically at the younger age group, it now
appears that four or five years of hormone treatment does not increase
heart problems, although patients should not remain on it as they get
older. There might be a slight reduction in the numbers getting heart
disease in the younger age group but, he says, the numbers were too
small to be sure. And, he adds, "the increased risk for stroke applies
irrespective of age or years since menopause, as does the risk of breast
cancer on combined hormones."

Far from causing harm by scaring women off HRT, as Women's Health
Concern alleges, "the WHI findings have probably prevented tens of
thousands of strokes, heart attacks, blood clots, and breast cancers in
the US population alone," Roussow says.

Last month, a study in the New England Journal of Medicine found breast
cancer rates fell by 8.6% in the US in the two years after the WHI study
was published, which the authors attribute to a drop in the numbers of
women taking HRT. "Women die from these conditions," Roussow points out,
"but they do not die from hot flashes and night sweats. Bothersome
though they may be, they typically last for two to three years only."

He does not know why gynaecologists are so unwilling to accept the
findings, given that nobody is arguing that women should not use HRT in
the short term for menopausal symptom relief. "There is nothing normal
about a postmenopausal woman maintaining reproductive hormone levels,"
he says. "There is a penalty to pay."

He, too, thinks the industry is influencing the debate. "It is a sad
fact that many professional organisations are heavily subsidised by the
pharmaceutical companies, that many physicians do get their information
from pharmaceutical representatives, that their meetings are sponsored
and so forth. Even people with the best of intentions are human.
Personally, I don't take any sponsorship from any drug company for that
reason. Even though I think I'm objective, I do not want to be
influenced even subconsciously."

Most women get their information on HRT from menopause clinics run by
gynaecologists. The message that seems to have filtered through is one
of doubt - not doubt about HRT, but doubt about the studies warning of
the risks of HRT. Irene Addis, from Norwood Green in London, took HRT
for 15 years following a hysterectomy at the age of 46. She had breast
cancer two years after starting it - not the oestrogen-fuelled variety
so not caused by HRT - but after treatment, went back on the drugs. She
was not troubled by talk of possible side effects. At the time and even
now, she says, her feeling is that scientists don't really know.

"There may be a slight increase in risk but it is minimal," she says.
"But the quality of life HRT gave me personally far outweighed any risk.
If they had told me there was a definite risk, I would have stayed on
it. I was on [the breast cancer drug] tamoxifen for five years, which
had dreadful side effects. HRT cut those down greatly. It improved my
skin and my hair and my bones and my husband could live with me, and I
didn't take his head off. I just generally felt better. I didn't feel
old."

Jennifer Gapp, who lives in Norfolk, was diagnosed with breast cancer in
September 1996. She had been on HRT only since the previous March. As
deputy headteacher of a senior school, she found menopausal hot flushes
and sleeplessness hard to deal with. "I needed to get a good night's
sleep," she says. Besides, taking HRT at that time was the normal thing
to do.

She wonders whether her cancer could have been triggered by HRT. "I
said, 'Could it be anything to do with that?' but the oncologist and the
surgeon didn't think there would be any link at all," she says. She had
been on HRT for too short a time.

Both women have been supported by and now work for Breast Cancer Care.
Kath McLachlan is the clinical nurse specialist at the charity and
speaks to women with cancer who phone the helpline. She also thinks the
jury is still out on HRT. "We know it is a risk factor, but there is
conflicting evidence," she says. "There are differing opinions. There is
much to learn about HRT and breast cancer risk."

Professor Adriane Fugh-Berman, of Georgetown University in Washington
DC, would not agree. She is co-author of a paper published last year in
Perspectives in Biology and Medicines, entitled Gynecologists and
Estrogen: An Affair of the Heart. The evidence, throughout HRT's
history, has pointed only one way, she says. But some doctors just won't
accept it.

"It is mysterious why gynaecologists seem to be so much more susceptible
to drug company influence. They really do seem to believe they are doing
something for public health, but they are against science. About 10 to
20 years ago, HRT was really promoted as a panacea: like snake oil, it
cured and prevents everything - dementia, incontinence, wrinkles. It
made you look better and feel better. But whenever you see something
promoted as a panacea, it is a fake," says Fugh-Berman.

"It is true in alternative medicine," she says, "and it is true in
conventional medicine."


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