In This Changes Everything: The honest guide to menopause and perimenopause, expert health writer Niki Bezzant shares the latest specialist research and advice along with personal stories from real women to answer the most important questions women have about the hottest of topics. In this excerpt, Bezzant reviews the history of Hormone Replacement Therapy—and the misconceptions that have left women suffering for decades.
Read an excerpt from This Changes Everything below.
I THE HISTORY OF HRT
For centuries the symptoms of menopause were documented, but women went through it with little intervention. It wasn’t until the advent of science as we know it that physicians (all male at the time obviously) started more commonly ‘treating’ its symptoms.
It’s clear now they had no idea what they were dealing with, since treatments ranged from the benign (cupping, cold water) to downright mutilation (clitoridectomy, anyone?).
You can read more about the shameful and frightening ways menopause has been treated in medicine and popular culture in chapter 14. Suffice it to say, the history of misogyny in medicine goes way, way back; all founded in the idea of women as inferior, and of menstrual blood as evil and poisonous.
Fast forward to the early twentieth century, when it was discovered that oestrogen, in the form of conjugated equine oestrogen — yes, from horses — could be used as a hormone treatment for the symptoms of menopause. In 1942 the first oestrogen product was marketed under the name Premarin.
Premarin was marketed as not only a ‘cure’ for menopause (which had by this time started to be framed as a disease to be treated) but as a fountain of youth. And it was promoted in ways that to our modern eyes are pretty blimmin’ sexist. Advertising of the era speaks of women’s misery and fear. One ad I found spells it out: ‘[a woman] is likely to feel that her charm is gone, and the golden days of her womanhood are irrevocably past’.
There were also ads targeted at men, who were obviously the real victims here. ‘Husbands, too, like Premarin’ said one ad from the 1950s. The hormone pills, men are assured, make a woman ‘pleasant to live with once again’.
A particularly low point was the publication in 1966 of Feminine Forever, by Robert A. Wilson,
an American gynaecologist. In the bestselling book, he called menopause ‘a serious, painful and often crippling disease’. Even more alarming: ‘All post-menopausal women are castrates’. Charming.
But no worries — all could be solved. HRT meant a woman’s ‘breasts and genital organs will not shrivel. She will be much more pleasant to live with and will not become dull and unattractive.’
These misogynistic assertions did the trick; the drug companies making HRT — one of which, it was later revealed, had paid Wilson for his trouble — got great value from their stealth salesperson. Sales of HRT quadrupled in the years after the release of Wilson’s book.
The ’70s to the ’90s — everyone’s on HRT
From the ’40s through until the mid-1970s, oestrogen for menopause was given to women on its own. But in 1975, evidence started to emerge that without another hormone — a progestogen — ‘unopposed’ oestrogen therapy led to an increased risk of endometrial cancer.
Sales of Premarin nosedived, until it was found that adding a progestogen to a lower dose of oestrogen mitigated this risk. The result was combined oestrogen– progestogen therapy, marketed as Prempro.
Sales of HRT took off again, along with aggressive marketing. This was helped by popular culture promoting the idea of menopause as a terrible disease of decline that needed treating. By the early ’90s,
Premarin was one of the most prescribed drugs in the US.
How HRT got its bad rep
Evidence over the first decades of its use backed HRT as an effective therapy, not only for menopause symptoms but also as a preventative treatment for some chronic diseases. Studies showed it as useful for bones and heart health. In 1988 it was approved by the FDA as a preventative treatment for osteoporosis. There was emerging evidence around HRT’s possible benefit in preventing heart disease, and so in 1991, a big study was started that changed the course of how HRT would be perceived for the next 30 years.
The Women’s Health Initiative (WHI) trial was the largest randomised study to date on HRT, and it would be a game changer. Unfortunately, not in a good way. It was, according to endocrinologist Megan Ogilvie, ‘one of the worst things to happen to women’s health in a long time. It did a whole generation of women, and probably two generations of women, a huge disservice.’
The reasons for that are many. The WHI was set up to find the effect of HRT (along with other, non-HRT-related interventions) on the most common causes of death and disability in post-menopausal women: things like cardiovascular disease, cancer and osteoporosis. It’s important to note that this study wasn’t about testing HRT’s effectiveness in treating actual menopause symptoms. What the researchers wanted to know was whether HRT could be used in other ways — to prevent other diseases that happened to women after menopause.
In 2002 a shocking announcement came from the researchers running the WHI study: the HRT arm of the study was being stopped early, after just five years.
In those first trial results, the researchers had observed that in women with a uterus who were taking combined HRT, there was an increased incidence of coronary heart disease and breast cancer. There was also, incidentally, some good news: a reduction of osteoporotic fractures and in incidence of colorectal cancer. Still, they concluded, it seemed the risks outweighed the benefits, and the trial was prematurely discontinued.
At the time, this was big news. The media published stories with sensational headlines and the message women — and doctors — took from them was that HRT was dangerous.
The effect was large-scale stopping of HRT. Women threw away their pills, and doctors — newly afraid of prescribing something that might do more harm than good — stopped prescribing HRT. The drug companies were spooked too — not least because, predictably, they started getting sued.
There’s nothing like a lawsuit to make a drug company wary of developing new drugs in the same area. Predictably, funding for and interest in research and development for HRT, and midlife women’s health in general, waned.
The effects of the HRT controversy
Fake news (before fake news was a thing)
First, the results of the WHI study were misreported — even by the people who wrote the initial results paper.
This emerged as a bit of a scandal, in a 2017 paper written by one of the WHI study’s authors, Professor Robert D. Langer. In it he revealed that ‘highly unusual circumstances prevailed’ when the WHI trial was stopped prematurely.
He went on to detail how he and other researchers were ‘aghast’ at what they read in the paper that had been submitted in their names to the Journal of the American Medical Association, which they only saw for the first time when the paper was about to be published. Though they tried
to submit edits to correct the misinterpretations and re-word the press release, it was too late. The paper was published, the press conference held, and the rest is history.
‘That headline,’ wrote Langer, ‘pandering to women’s greatest fear — the fear of breast cancer — ensured that word of the study would spread like wildfire. And it ensured that the conversation would be driven much more by emotion and politics than by science.’
Doctors stop prescribing (and learning)
The WHI reporting meant that many doctors were too scared to continue prescribing HRT to any woman. Now, they told women, basically, you’re on your own. Government health bodies didn’t help; they issued new advice to doctors to only prescribe HRT to the most severely affected women, and then in the lowest possible dose, for the shortest possible time.
Prescribing rates went down all over the world.
What this also meant was that doctors stopped learning much at all about menopause and its potential treatments.
‘One of the things the WHI reporting did is it allowed menopause education to be removed from medical schools,’ notes Ogilvie. ‘And it lost us funding on a lot of different HRT products.’
Even now, there’s limited education on menopause for trainee and practising doctors, unless they seek it out or are particularly interested. Dr Beverley Lawton does some teaching on it at Wellington’s University of Otago medical school. But not for every doctor.
A number of women I’ve talked to have reported the consequences of this outdated knowledge, or knowledge gap, in their visits to the GP. Our conversations always start the same way.
‘I love my GP,’ they say. But there’s a ‘but’. When the women have talked to the doctor about perimenopause or menopause or even asked directly if HRT is something they could try, they’ve been told, ‘No, we don’t like prescribing HRT; it’s not good for you.’
This is really sad, because it can lead to women suffering unnecessarily.
As Langer noted in his 2017 paper, ‘the “facts” that most women and clinicians consider in making the decision to use, or not use, HRT, are frequently wrong or incorrectly applied.’
Women fare worse
Sadly, as well as some women suffering in silence with menopause symptoms that might have been successfully addressed by HRT, there were also some even more serious impacts.
Subsequent research found an increase in deaths from heart attacks and strokes in women who discontinued HRT after the WHI study. An Italian analysis estimated 43,000 extra bone fractures per year in the US were associated with decreased HRT use.
Langer was scathing in a 2020 journal article. ‘Fear of HRT among women, and misunderstanding of the risk/benefit, along with lack of appropriate education among providers, has led to underutilization, unnecessary suffering, and excess chronic disease and mortality in post- menopausal women over the past two decades,’ he wrote.
Women turn to unproven treatments
In the vacuum left in the wake of the WHI controversy, with no real help from the medical sphere, where could women go to get relief from menopause symptoms that were still making them miserable?
Unfortunately the vacuum was filled in large part by the marketers of treatments with little or no science to back them up. This includes many herbal and other supplements — which are largely unregulated and unpoliced, including so-called ‘bioidentical’ hormones. Read on for more on this.
Commenting on alternative therapies, in a 2020 report on HRT published in the menopause journal Climacteric, the authors wrote: ‘None [of the alternative therapies] provide the range of benefits across multiple organ systems offered by oestrogen. Most have concerning adverse effects in their own right.’
What the WHI really showed
Remember, the WHI researchers were trying to see if the benefits of HRT that had been observed in menopausal women — lowered risk of osteoporosis, some cancers, heart disease, etc. — carried over into women past menopause. So this trial was actually on women well past menopause in most cases. The average age of the women studied was 63 — far older than the age most women might need or want to start on HRT.
Ogilvie notes, ‘We are now using HRT in a safer way. It would be very rare to start someone at 63 on HRT for the first time if her last menstrual period was 10 years ago, without a very good reason and a good cardiac assessment.’
When the WHI data was reanalysed later and the ages of the women were looked at, in almost every area there were no
harmful effects of HRT in younger women who were actually going through menopause. And in many areas, there were benefits.
The type of HRT matters
Back in the 90s when the WHI started, they used different forms of HRT to those used today. And as you might expect, knowledge and technology have moved on. This has likely changed the risks, too.
The WHI trial tested only CEE (conjugated equine oestrogen), which is delivered as an oral pill, either alone or in combination with a single progestin (a synthetic form of progesterone), medroxyprogesterone acetate. In the combined form it was the previously mentioned Prempro. This is regarded today as an old-fashioned treatment; it’s not often prescribed by any up-to- date doctor.
Doctors looking to prescribe HRT now have more options, and treatments are much more customised to an individual woman depending on her personal risk factors and responses to treatment. It’s definitely not a one- size-fits-all scenario.
So we can’t really use the WHI as a direct comparison to treatments used today. And
it’s widely acknowledged by the experts that modern forms of HRT are generally less likely to cause either increased risk or unwanted side effects.
Breast cancer risk
This is the big scary one. The perception still persists today that we are taking a big risk by taking HRT; that by doing so we’re more likely to get breast cancer. But is that really true?
When we read in the WHI data that what was found (for the women in the study taking combined HRT — remember: average age 63) was a 26 per cent increase in the risk of developing breast cancer, it sounds pretty alarming, right? Even more so if we don’t notice the increased risk bit — you wouldn’t be alone if you assumed this means your risk of developing breast cancer is 26 per cent.
But as Langer noted in his report, ‘buried deep in the paper were much more user-friendly, far less inflammatory, numbers’. These were the event rates per 10,000 women per year, which were: eight more breast cancers per 10,000 women per year; roughly 1 in 1200.
When you look at it like that, Langer says, it’s ‘not particularly worrying, but [it was] lost in the sea of fear sparked by headlines about breast cancer’.
So while the relative risk was 26 per cent higher in the women on HRT in the WHI study, the absolute risk — the actual risk of an individual woman in the trial developing breast cancer — was about 1 in 1200 after at least five years of use. And for the women on oestrogen alone (i.e. women without a uterus) — the risk of developing breast cancer was actually lowered.
It’s worth noting that a 1 in 1200 risk is very similar to the risk of breast cancer a woman has if she has obesity; or if she is physically inactive. It’s also similar to the risk posed by drinking alcohol more than very moderately (i.e. more than one drink a day). Drink more than that and your risk is higher than the risk posed by taking HRT.
Also worth noting: breast cancer is not the thing that’s going to kill most of us. Women are far more likely to die from heart disease than we are of breast cancer. And HRT may even offer some benefits there in terms of lowering our risk. We need to remember our risk of any disease is a bigger picture, affected by much more than just one thing we’re doing or not doing.
The WHI data has been reanalysed in different ways many times since 2002. The most recent analysis confirmed that when adjusted for other risk factors (that means when you take out women with other reasons for an increased risk of breast cancer) the risk of breast cancer for women on HRT is not statistically significant.
That doesn’t mean the risk is zero. But it does mean it’s not as bad as we might have thought if we’d just read the headlines for the past 20 years.
Of course, it is important to know about your own personal breast cancer risk factors. If there’s a family history of breast cancer, for example, or you have the BRCA gene mutation, or you’ve had a suspicious breast lump removed before, all these things need to
be taken into account when you have a conversation about HRT. So does your lifestyle and behaviour. But all that doesn’t mean HRT is automatically off the table. Don’t let breast cancer risk be the reason you don’t ask about or try HRT if
you or your doctor think it might help you.
Heart attacks and stroke
The other bad news — much overshadowed by the (apparent) breast cancer bombshell — in the WHI trial was the reported increased risk in heart attacks and strokes. The increased risks here were said to be 29 per cent and 41 per cent respectively; pretty alarming.
Again, though, these findings were ultimately found to be misleading. When the data was reanalysed later, and they actually adjusted for age and other risk factors (remember, the women in the study were much older than typical HRT users) the results were reversed: the risk of heart disease was actually less, not more.
Similar reassurance was found for strokes when the WHI data was followed up after 13 years: we now know women who start HRT before they’re 60, or within 10 years of menopause, have no higher risk of stroke.
Also, again, the delivery method makes a difference — it’s thought transdermal methods (patches, for example) are a safer approach than oral HRT.
Extracted from This Changes Everything by Niki Bezzant, published by Penguin Random House NZ. Text © Niki Bezzant, 2022.
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