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."
