The Dr Louise Newson Podcast - 097 - Trying to right 20 years of misinformation and hysteria about HRT - Professor Rob Langer and Dr Louise Newson

Episode Date: May 4, 2021

Dr Newson speaks with Professor Robert Langer in this episode. Robert Langer is Professor Emeritus in Family and Preventive Medicine at the University of California in San Diego. He was also an investigator of the Women's Health Initiative (WHI) Study. Together, they discuss how the WHI Study from 2002 turned the world upside down for women and how they have both been trying to right it ever since.   Professor Langer describes in detail what was understood about the benefits of hormone replacement therapy before the WHI study, how the notorious study came about and why it was finished prematurely and so badly misreported in the media. His unique account of how the events unfolded helps listeners to understand the bigger picture of why healthcare professionals and women remain unaware of the benefits of HRT and are often overly cautious of the perceived risks to this day.   Professor Langer's 3 top tips are: 1. All of the evidence shows that for women who are within 10 years of their menopause, or under the age of 60, if she has reason to take HRT, there is absolutely no need to be concerned about HRT. For these women the benefits strongly outweigh the risks. 2. There's no reason to stop taking HRT at any age, if you've been taking it from the time of your perimenopause or within 10 years of your menopause. 3. With a knowledgeable practitioner, there's no reason that a woman who is past her menopause or over 60, can't start taking HRT, as long as the clinician is aware of how to start slowly and get hormone levels to the right point.

Welcome to the Newsome Health Menopause podcast. I'm Dr Louise Newsome, a GP and menopause specialist, and I'm also the founder of the Menopause charity. In addition, I run the Newsome Health Menopause and Well-Being clinic here in Stratford-upon-Avon. So today I'm really excited to have with me, Professor Robert Langer, who is a Professor Emeritus of Family Medicine and preventative medicine from the University of California in San Diego. And I first heard him talk at a conference in Prague. It was one of the International Menopause Society conferences a few years ago. And at the end of his speech, he just had this most amazing words that I've used in quite a few slides,

which were, let's get past the misinformation and hysteria of the WHOHI and stop denying the benefits of hormone replacement therapy. So I'm going to explain what that means in a bit, but firstly, welcome Robert. Thank you so much for coming and joining me on the podcast today. My pleasure. Very happy to be here and to do what I can to dispel misinformation about the Women's Health Initiative and about hormone replacement in general. Brilliant.

So before we get started on that, would you mind just telling me a bit about your background and your professional career up to now if that's all right? Sure. I started out as a family doctor in private practice. I was quite interested in what I might do in order to maintain people's health as they progressed through the years. And as I developed my practice originally, I became interested in longitudinal outcomes in the patients I was going to take care of. So I was starting practice in the early 1980s, in the age when microcomputers were first becoming available. And so I wrote one of the first electronic health information systems for use and outpatient

practice initially from my practice. And eventually some of my colleagues were interested in it. So early on, I was writing and using longitudinal medical records. as a means of trying to understand what I was doing right and what I might improve for the health of my patients. And fundamentally, my interest in medicine has always been from the health side rather than the disease side. And as I continued my practice for the first couple of years, it turned out that many of my patients were saying, gee, it's interesting, Dr. Langer, you're asking us some of these same questions

that this doctor at University of California, San Diego, was asking about our health. She's just a couple of miles away. Do you guys talk with one another? It turned out that I had set up my practice in a community called Rancho Bernardo, which became the site of one of the longest running studies of health and disease over time in older people. And so, yes, I did start to correspond with Dr. Elizabeth Barrett Connor, who was directing that study.

And after several years, decided to move beyond just being a GP and to go back and get additional training in public health, preventive medicine, and epidemiology. And Dr. Barrett Connor became my mentor. Now, she was really an incredibly groundbreaking female physician. and as would be natural in her position, she was particularly interested in women's health, and very little had been studied in women's health at that point in time. So together, she and I got involved in some of the very earliest clinical trials of women's health. And that was the beginning of my career in research, and it grew from there.

can talk further about some of the other things that I did afterwards. Excellent. So have you always been interested in women's health as well as preventative medicine? Yes, women's health and in general health at advanced ages pioneered some studies in longevity. I was for about almost 10 years a member of a national institutes of aging consortium called the Longevity Consortium. called the Longevity Consortium, where we pulled together information from most of the large population studies on the oldest old, as well as quite interestingly, studies that were being done on not just animals, but the very most primitive species, fruit flies and worms and things like that, to try to leverage understanding of the aging process and how we might

best promote good health across species and across all ages. Very interesting, is it? So I, as you know, probably have come from a medicine background, but I've also got a degree in immunology and pathology. And I'm very interested in disease prevention as well, although we only get really taught about diseases in medical school, and it's focusing on a diagnosis, not preventing diseases. And I think it's only maybe with age experience,

then I've considered more about, wouldn't it be lovely to keep people away from doctors rather than coming and making these diagnoses? And a lot of disease, sadly now is as a result of lifestyle, which often can be improved. But that's still quite difficult. But certainly for me specialising in the menopause, it is a marker of disease, not having hormones and a real risk factor for future diseases. And certainly when I first saw you lecture in Prague, A few years ago, I had just started really to do more menopause work and found it really fascinating.

And I think it was around that time that the nice guidance had come out in the UK for the menopause. And it sort of made me realise that actually I could be a bit more confident because before this time, I was quite scared of actually saying to other doctors that I prescribed HRT because none of my colleagues did. And everyone was very frightened of it. And I've always read the evidence and thought, no, actually, it is very safe, but no one believe me. So actually to have the nice guidance and then the International Medical Society guidance and then coming to Prague and listening to very learned people like yourself, just reiterating the safety of HRT was very interesting but also very frustrating

because I was thinking actually women aren't listening to this, women aren't getting HRT, the minority of women are getting it. what can we do about it? And it was then that I thought I'm going to dedicate as much time as possible to helping women. But your presentation just resonated so much because you started to unpick the evidence more and actually explain what went wrong. Because when I qualified as a doctor in 1994, people gave HRT. It was like giving baroxin or giving insulin if someone was diabetic. It would be a knee-jerk reaction almost. And then it all went wrong, didn't it, in the early 2000s, 2002? So do you mind just talking through what it was and what your involvement was and a bit more about

everything if that's okay? Certainly. Well, let's set the background for this women's health initiative study, which is what sadly turned the world upside down still yet to be righted. But prior to the WHA starting in 1992, there had been a large number of not experimental studies, what we call observational studies, that looked at women who took hormones and women who did not. And almost universally found that women who took hormones had better health as they continued to age than women who did not take hormone. One of the problems with observational studies, though, is that there's something we call in epidemiology a healthy user bias. And what that jargon actually means is that sometimes

people are more likely to go to the doctor or take initiatives to do things that impact their health if they're already health-focused. And so those people may not be representative of all people in that same category because they have better health habits. And when that happens, something like taking hormones, which back then was considered a healthy habit, might also be associated with exercising more or eating better, or monitoring your blood pressure and your bone health.

and things like that, that could also be disease risk factors. And so in an observational study where we just look at people who did or didn't do things without randomly assigning them in an experiment to have something or not have something, we could end up making a wrong call because of this healthy user bias. And so based on probably more. than 10 long-running studies that showed better health. Back in the 1980s, the National Institutes of Health for the first time ever decided to do a clinical trial and experiment focused on health in women. This was just, when you think about it, it's absolutely absurd that this agency that had been doing

things now already for 30-some years had focused almost exclusively on men up until that time. And so this was groundbreaking, this first study in the mid-1980s, which was called Pepe, postmenopausal estrogen progestin's interventions trial. And it was an experimental study, a randomized study that was the first step to look at whether taking hormone replacement, therapy actually might be truly associated with better health. And I mentioned Dr. Elizabeth Barrett Connor, my mentor at UCSD, she and I were lucky to get one of the original Pepe clinical trial sites. She, because of her reputation, was actually chosen as the overall chairperson of that study. and I was the study director for it at the University of California, San Diego.

And Pepe, in a three-year study, looked at 875 women who were aged 45 to 64. And so right in the mid-range of menopause. And they had to be within 10 years of menopause, even within that age range. So they had to be within the first decade of menopause. And because it was a kind of a proof of concept study, it was just three years and we focused really, really hard on the details of things that we thought might change with hormones that could be beneficial in terms of preventing things like heart disease, things like fractures and even quality of life and other general ways that are in some ways more important than the risk. factors that we often focus on to a woman's everyday feeling. And so we conducted the Peppy study. And as we were about to finish it, things were looking good in all of the reviews. And it was then decided to go forward with this much more ambitious study, the women's health

initiative. And what happened then was a bit of a leap of faith in some ways, but it turned out to be an Achilles heel. And what happened was based on the results from Pepe that showed that hormone replacement seemed to improve things like blood cholesterol, didn't have an effect on blood pressure, so it was safe there, dramatically improved. proved bone density, so we produce fracture rates, had a positive effect on overall mood and how women felt every day. Based on that as a proof of concept for hormone replacement therapy, and then based on the other information that I mentioned earlier from the observational studies with Pepe is kind of an endorsement for that. The leap of faith was made that since this stuff seems to be

so good for women who are within 10 years of menopause. Women who are older than that, maybe would get even more benefit. And the reason for that leap of faith was because in the cardiovascular studies that had been done up until that time, mostly in men, in general, people with worse degrees of blood pressure, worse degrees of cholesterol, actually got greater benefit from interventions that would improve blood pressure and cholesterol. So the idea was if this stuff is so good for recently menopausal women, wow, maybe we really can do some still greater good for much older women. And so the decision was made to focus this new study, an ambitious, much longer study with many, many more women involved on older ages with that leap of

faith that having worse blood pressure, worse cholesterol, worse change in your bones, this treatment would do still better. And everybody expected that that was going to be what happened. But in fact, what we learned, what the WHA is really a landmark in, in terms of understanding science of human physiology is that once a woman is well-past menopause and hasn't had estrogen for a long time, and we say 10 years because we have to set some kind of a limit to do these analyses, once a woman is past that and hasn't had estrogen for that amount of time, estrogen is a important factor in just about every place in a woman's body, just about every tissue has estrogen receptors.

And when estrogen levels are real low for that amount of time, it turns out that giving back estrogen isn't a good thing. It actually can be harmful. And the degree of harm depends on a lot of other factors for each woman. And 10 years is not an absolute. Some women can take hormone well beyond that. And what the WHA found was that for women in that study who were on average 12 years postmenopausal, we enrolled women who were from age 50 all the way up to age 79.

And the average age was 63, where the typical age of menopause, is 51, so on average 12 years post-menopal. Overall, looking at all the women in the study, which is the first way to look at it, there was no benefit. In fact, at the oldest stages, there was harm. And so the hope that this might be a return to a fountain of youth was dashed. On the other hand, what we found when we looked at the data better in much more targeted analyses, what we found was that for women who were within 10 years of menopause, consistent with all of the other studies that had been done before, those women actually overall did get benefit. They overall did not have an increase in heart attacks.

In fact, in general, they had a reduction in heart attacks. There was not an increase in breast cancer, and we should come back to that a little bit more. There was a reduction in fractures. And so overall, if it were to be looked at in the same context as all of the studies that had been done before, the WHOI verified that for women who were within 10 years of menopause, HART was overall a beneficial, not a harmful treatment. But after that age, after 10 years past menopause, as a shorthand after age 60, you need to be a little bit more cautious. I mean, this is really important actually because when people talk about WHOHI, they think about harms

of HRT, they think about all the bad things. Whereas you've quite clearly and very eloquently said, actually, it was good because it showed how safe HRT is for women who started within 10 years of the menopause. And even if they continued it over the age of 60, if they'd started it within 10 years of the menopause, that's different to starting it when they're older. But so the sort of take-home message is that HRT actually, for most women, because we're most women we start when they're either perimenopausal or menopausal or within 10 years of the menopause, it's safe. And there are a couple of things really. One of the things is the type of HRT that was used in the study is actually quite different to the type that I prescribed for the

majority of my patients, for example, because it was oral estrogen, so tablet estrogen, wasn't it? And it was also synthetic progestogens as well, which actually have some risks as well as having tablets. So there was that difference. But the other problem with it was that breast cancer came out very top. And that was what reached the headlines quicker than any of the other analysis of the results,

isn't it? So can you explain what really went wrong with the reporting of the study? Because that I think is key, really, isn't it, to what us as lay people heard about the study? Yeah. I think that's a very, very important point. So the way that the first results came out was highly unusual. We were expecting to continue the study through 2005. And in fact, one part of the study, the study with combined estrogen and progestin, which I think is also a poor way of saying it,

It was actually a study of conjugated equine estrogens and madroxyprogesterone acetate given as a continuous dosage. And I'm making that point because I very much believe that all estrogens are not the same and all progestogens are not the same. And that's something that needs to be explored a little bit more. That said, the study was terminated prematurely, roughly three years early, and then published. And the way that came about is that we had, as we always do when we're doing experiments in people, exquisite attention to the safety of participants.

We're asking people to take an unknown and to really be in the blind, so to speak, for what's happening. So it's incumbent upon us as investigators to be exquisitely careful about safety. So we had something called a data safety and monitoring board, and they would meet every six months and look at the interim results for this study. And they had a set of rules that they had agreed on independent of the study investigators to use for me. monitoring and to recommend early stoppage if any of the potential harms cross a very conservative boundary. And by that I mean not a boundary that actually meant that there was statistically

meaningful harm, but something that was tending in that direction. So in an abundance of caution, we would stop and say, we don't want to continue this. because we're afraid of what could happen. And so when they met in early 2002, they saw that the breast cancer rates in the conjugated equine estrogen plus medroxyprogesterone acetate arm had crossed this very conservative boundary. What's interesting is that if you actually looked at their graphs,

it had been bouncing around, and at that point, it had had been. had just slightly bounced into the boundary. It had been bouncing in and out, but not to a point where it became serious. But they, based on that and the rules of engagement we had agreed on, made a recommendation to the director of the study that it be halted out of an abundance of caution.

That decision was all behind the scenes. when that decision was taken, a small group of people from our coordinating center and from the supervising office at the National Institutes of Health took it upon themselves to write a research report that described those findings. That was contrary to what's expected and really the standard of operations for a study like this where all of the investigators, including people like me who were conducting this study, are supposed to be engaged in writing that paper. They took that paper all the way to the point of submission and acceptance in a major journal, the Journal of the American Medical Association, JAMA, had the paper accepted. And then when the investigator group was about to get together for our every six-month meeting

in June of 2002, they sent that paper to just a handful of the investigators who were our leadership group on the executive committee and asked them to sign off on it. That was the first time that anybody outside of that handful of people had seen the paper. And eyebrows started to be raised, but those people were sworn to secrecy. About a week later, we got together in Chicago, which incidentally is where JAMA is published. And we had an agenda that was supposed to be same old, same old. We were all expecting to be bored and trying to figure out how we're going to not fall asleep. But 15 minutes into the meeting, they said,

we're tearing up the agenda and they circulated a copy of that paper. And when most of us looked at it, we were stunned. A handful of us were also epidemiologists, biostatisticians, as well as physicians. And we were very distressed by the way that the statistics were done and also by the way the report was framed. So, in essence, what was not a statistically significant finding in keeping with what the data safety monitoring board had seen, which was just a cautionary boundary, the study results were not significant for breast cancer.

They were also not significant for coronary heart disease, the main outcome of the study. But yet the paper was written as though those results were significant. That was a disaster. Absolute disaster. The small group of us who had the relevant expertise argued against publishing the paper, and we went back and forth for a little bit. Finally, we were told, okay, if you want to suggest edits, you may do that and circulate that to us before lunch. We'll take it down to the JAMA Publications Office and see if we can get it.

get that changed. So we did. About five of us got together and edited the paper to make it more appropriate and to qualify the statistics. And that went to the JAMA offices. And about an hour later, after lunch, the courier came back and said, well, I took the edits to JAMA, but they said it's way too late. The paper is actually already printed and in warehouses ready to be distributed to the U.S. Postal Service to be released in about 10 days. And so that whole effort was moot. Then the next chew that was about to fall was almost as bad, maybe in some ways worse. And that was after lunch, they then presented us with the press release that said in bold headline, major NIH study stopped for breast cancer harm. And I saw that. And I about fell off my chair.

And I told the lead program officer in front of the group, if you publish that, you have cut off all possible reasonable discourse. That will just set off a firestorm and we will never be able to have a rational discussion about this for years. But they insisted on that headline, and again, even though it was not statistically significant. Now, there have been many analyses done of that finding in the study over time. One of the things in the study protocol was that there was supposed to be adjustment for what we call covariates, other risk factors like body weight, obese people, obese women are at higher risk of breast cancer. Alcohol, women who drink alcohol are at higher risk of breast cancer. Those adjustments were supposed to be made in the formal statistics that were published.

They were not. Even without those adjustments, the breast cancer harm was not statistically significant to begin with. In some later analyses without those adjustments, it was just marginally significant. There's only one paper that's ever been published with those adjustments done and the result was not statistically significant. So the breast cancer was just a false flag that has had hugely damaging effects. And to make things worse, then the second part of the study, the study that was just with estrogen alone being conducted in women who had had a hysterectomy, so didn't have a uterus to protect with the progestin, that study continued for about another two years. And as that study was nearing

a close, it was also terminated prematurely, supposedly because of an increase in stroke. And it's true, overall in that study, there was a slight increase in stroke. That increase was not seen in women within 10 years of menopause. But what was also happening at that same time was that there was a nearly statistically significant decrease in breast cancer in women who took that estrogen alone. And so one needs to wonder whether or not that study was actually stopped prematurely because the powers that be could not tolerate the idea that they would have stopped one part of the study for breast cancer harm and then had to report that the other part of the study prevented breast cancer. It's also, it's so sad and it's so shocking and the more I hear

it and the more I read about it, it makes me beyond furious, beyond cross and it's so wrong actually and I just wonder what the reason is and I don't think we'll ever know that they misinterpreted in this way and the headlines were so incredibly wrong and detrimental and I do wonder is it because it's about women do you think do you think this would happen if it was a male study looking at testosterone for example or do you think I'm being too cruel to the investigators I I can't exclude some potential gender bias but I I will say that I've been aware of cardiovascular studies primarily in men also, where there has been misinterpretation for reasons of other hidden agendas,

particularly in statin studies, for example. And so I don't think that this is an exclusive bias against women. I think it happens in other studies. I think that there was just some form of hidden agenda that really worked to the huge detriment of women's health overall. If I were to speculate on it, I don't think it was particularly an anti-woman agenda at this point. And honestly, I think what may have been happening was that this was at a time when the economy was not doing very well. This was an extraordinarily expensive study just under $1 billion at that time. And the leadership at the Institute was asked to constantly justify the study to the study to the

Congress. And I think that they might have felt it was not practical to save face if they said we conducted this great study and we came up with nothing, which was actually the overall result. And we spent a billion dollars in the process. And so I think face saving may have been more the agenda than an anti-more. and bias. Yeah, and it's such a shame because there are still some very good results, actually, from that study. We've already said that it showed that there was a reduction in osteoporosis and heart disease and actually the estrogen-only arm, lower risk of breast cancer, even follow-up data from 18 years is very reassuring, actually. But whenever you talk about

HRT or one talks about HRT, it's always about breast cancer as well. And even if you go menopause in the UK, the NHS website will come up top. And the first thing it does is it tells you as a woman risk of breast cancer. It doesn't even tell me about benefits to my bones, my heart, my brain, my well-being. It just says risk of breast cancer. And this was so long ago now in 2002. So 18 years ago, we still, the minority of women take HRT because the majority of healthcare professionals are not prescribing it at all. And I've spoken today actually to a cardiologist talking about palpitations, benign palpitations in women and asking whether we could do a study showing how they improve with estrogen. And he said, what do you mean estrogen? That's so dangerous.

That increases risk of heart disease and clot and stroke. We would never prescribe it as cardiologists. And I said, but you must see hundreds of women who come to your clinic with palpitations who are in their early 50s. And he said, well, we don't see them because we're too busy. All we do is we see the results from their heart tracing and we send a letter back to say, this is benign, you don't need to worry about it. I said, right, so you're not even giving them any treatment. He said, no, but I'm too scared of HRT to prescribe it anyway. So if I may, you might refer your cardiology friends to a new position statement

from the American Heart Association that I'm a co-author on, just came out a few months ago on the menopausal transition. And we very carefully described the WHA results in there, along with many, many other sections. But one of the primary goals of writing that paper was to try to help cardiologists and internal medicine specialists understand the nuances of HRT, particularly for younger women. Yeah. I think there is so much evidence.

And I think it just keeps getting worse rather than better. There's sometimes I think actually know this is good. There's some other data that's come out. We know, for example, the transdermal, the easterns through the skin, actually don't have this risk that we're talking about. So actually even for women who start HRT in their 60s, 70s or even 80s, you can start no doses of a transdermal preparation that doesn't have this risk of clot and the natural progesterone, which is far better for clot risk and for heart disease risk.

But there's still, everyone goes back to the WHO study because it was a big study and they think it was the best. And just listening to how the results were interpreted or misinterpreted, how they were fed to the media, And also just looking even in America, the incidence of heart disease in women has increased, hasn't it, since the WHO, since H.R.T. rescribing has reduced. Well, actually, I did a lecture on that about two years ago, and it's a mixed bag. I had honestly feared that there would be a fairly dramatic increase, but in fact, it hasn't been such a dramatic increase in heart disease in. U.S. women, in part because women, especially at older ages now in the U.S., are privy to interventions that they were heretofore not given, things like stenting and much more aggressive lipid treatment and so on, which in the early 2000s were rarely given to women, have more recently been given to women

And so I think there's a mix of those effects, some worsening because of the lack of HRT, but also some better treatment and intervention. I would like to go back if you don't mind to a discussion of the types of HRT and transdermal and oral and conjugated estrogens and estradiol and also progestogens. Another story that has yet to be fully told of the WHOI is that since I was the only investigator on Pepe, who was also a WHOI investigator, I tried to bring as much information that we learned from Pepe as possible into the WHOI design. And Pepe was the first clinical trial to use micronized progesterone. And in Pepe, we demonstrated that micronized progesterone was considerably better than Medroxy progesterone acetate, which was the progestin used in the WHOI study. And I made a presentation to the study leadership early on before the design was finalized to try to get an additional arm with micronized progesterone in the WHOI.

And as part of that, I did some projections using statistical analysis of what we might see as differences with estrogen alone, estrogen plus micronized progesterone, and estrogen plus medroxy progesterone acetate. And it showed that the differences between estrogen alone and estrogen with progesterone would be negligible, and that that would almost certainly be our best. way to go. The study leadership did not want to use that combination because we had only tested it at that point in the clinical trial in a cyclical regimen where women took it for some days a month, but not continuously. And they were afraid that compliance, regular use of the medication, had not been proven with that option. And so it was not included in the design. I, for me, believe that the WHA would have been a very different study if we had that arm in there because we would have had a combined hormone arm with absolutely no hint of problems with breast cancer

or any sort of breast abnormalities whatsoever. Medroxy progesterone acetate is a very potent growth stimulus in the breast and so it can cause increased breast density and other abnormalities in mammograms, one of the reasons for the potentially slightly greater finding of breast cancer, even though not statistically significant, in the WHOI, is because repeat mammograms, second mammograms requested by the radiologists were much more frequent with that very potent progestin that stimulates growth of breast tissue. The flip side, with the estrogen, with the estrogen, is that conjugated equine estrogen in the WHAI is the only estrogen that has ever been shown in any study to potentially reduce breast cancer.

And it does have the downside of being associated with extra clots, and that is a concern. But in fact, it and micronized progesterone potentially could be even the best option, overall based on the data that we've got. That said, I prescribe about equal amounts of conjugated equine estrogen with micronized progesterone and transdermal estradial. And the older a patient is, the more likely I am to prescribe transdermal, I think, very much in keeping with your practice. Yeah. And I think what's really important to know is that there's a choice as well. I think for women to know that there's a choice but actually, regardless of the type of HRT, there's still a lot of benefits. It's not all bad and it should be looked at as a way of not just improving symptoms,

but looking at future health as well, which is really important. So I think we could talk forever and I'm really, really interested in everything, but I think because we've spent so long explaining it, I think it's been really, really interesting and I hope for a lot of people listening, it will reassure them about the benefits of HRT, but also the problems that went on with the WHOI study because I think it is really important because it's a pivotal time in medicine that has really changed or did change practice

and has still continued to. So there's a lot of change that needs to continue. But before I end, I'm putting you on the spot now because I always do three sort of take-home tips, but I'd really like, if you wouldn't mind, Robert, is to just say three key messages, actually, that might improve the way we think about HRT going forward. What are three things that people could learn from this in a positive way, almost?

Yes, I'm happy to. I think, number one, all of the evidence that we have, including the WHO, and many studies that were conducted before and many since shows that for a woman who is within 10 years of menopause or under the age of 60, if she has reason to take HRT because she has hot flashes, sleep disturbance, other things that are associated with the variation in estrogen levels associated with menopause, or if she has reason to take. to take hormones because she has high risk of fracture.

There is absolutely no need to be concerned about HRT. For women starting within 10 years of menopause, in general, the benefits strongly outweigh the risks. I think second, there is no reason to stop taking HRT at any age if you've been taking it right on through. The problems that we observed with women who were much older having some adverse effects were because their bodies hadn't had estrogen for such a long time that when estrogen was reintroduced in higher levels,

their bodies reacted as though this was a foreign substance, strangely enough. But in fact, that's what happened with some inflammation and some acute, some short-term changes due to that inflammation. Women who actually got past that are still potentially going to do fine, which I think is point number three. And that is with a knowledgeable practitioner, there is no reason that a woman who is even past the age of 60 or past 10 years after menopause,

who has reasons to want to take HRT, can't start on it. But it has to be done with a knowledgeable clinician who understands how to start slowly and how to get levels at the right point and then slowly adjust from there. But there is no absolute cut off either. It just has to be done quite carefully. And I'll add one further caveat that's just based on a chance finding in another study, but worth any clinicians who may be listening, may be taking to heart. And that is in some secondary analysis of another study of HRT in older women.

women who were taking statin drugs before they started on HRT at older ages did not have an increase in heart attacks when they were started on HRT. So it may be that taking statins as a preliminary to starting on HRT at older ages is a way to protect against that one potential worrisome factor. And it's really interesting and really reassuring, actually. And just as an aside, we recently started our oldest lady on HRT who was 91. She wanted it as her birthday present when she was 90, but no one would give it to her. So she came to the clinic and had a very low dose and she's absolutely delighted. So thank you so much for your time. I really, really appreciate it and lots to take on, but really interesting advice and information.

So thanks ever so much. My pleasure. Thanks very much for having me. For more information about the perimenopause and menopause, you can go to my website, menopausedoctor.com. Or you can download our free app called Balance, available through the App Store and Google Play.