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Menopause and brain health: what’s the link?

In this episode Dr Louise is joined by world-renowned neuroscientist Dr Lisa Mosconi, PhD. Dr Lisa is Director of the Alzheimer’s Prevention Clinic and Women’s Brain Initiative at Weill Cornell Medicine in New York and author of bestsellers The XX Brain and Brain Food.

Dr Lisa was studying nuclear medicine and neuroscience when her grandmother and her grandmother’s three sisters all developed Alzheimer’s. Dr Lisa became interested in the cause of Alzheimer’s and why women are more susceptible. Her research has shown that, rather than a disease of old age, it starts in midlife and menopause potentially plays a part.

Dr Lisa discusses her most recent paper, which found that women who took hormones in midlife to treat their menopause symptoms were less likely to develop dementia than those who hadn’t taken oestrogen.

Finally, Dr Lisa shares three things to consider about female hormones:

  1. Oestrogen, and oestradiol in particular, is the master regulator of women’s brains. It really is like saying that oestrogen is to your brain what fuel is for an engine. It keeps your brain running.
  2. Endogenous oestrogen (produced within your body) is different from exogenous oestrogen (synthetic). The bioidentical oestradiol is probably the best one to use because it really maps on the same circuits for your own endogenous oestrogen.
  3. I would love for all women to be able to make an informed decision about whether or not hormone therapy is a viable option for them. Many women who are eligible for HRT do not go on HRT out of fear and the fear comes from outdated information, mislabelling on some of the packages.

Follow Dr Lisa on Instagram @dr_mosconi

Click here to find out more about Newson Health


Dr Louise Newson: [00:00:11] Hello. I’m Dr Louise Newson. I’m a GP and menopause specialist, and I’m also the founder of the Newson Health Menopause and Wellbeing Centre here in Stratford-upon-Avon. I’m also the founder of the free balance app. Each week on my podcast, join me and my special guests where we discuss all things perimenopause and menopause. We talk about the latest research, bust myths on menopause symptoms and treatments and often share moving and always inspirational personal stories. This podcast is brought to you by the Newson Health Group, which has clinics across the UK dedicated to providing individualised perimenopause and menopause care for all women. So I’m very excited about this podcast. In fact, I’ve had sleepless nights because I’ve been very excited. I feel like Christmas has come early. We’re recording this in December, so I’ve got someone who I fangirl, but I fangirl her intelligence and integrity and her work actually, and obviously her as a person, of course. So I’ve got with me the neuroscientist Lisa Mosconi from New York. And we’re just going to talk a bit about her work. But before we start, Lisa, I’m very excited. I can’t contain myself, but thank you so much for agreeing to come on to my podcast. [00:01:31][80.8]

Dr Lisa Mosconi: [00:01:32] Thank you so much for having me. I also hardly slept, so that’s perfect. I have my cup of coffee. Cheers. [00:01:40][8.3]

Dr Louise Newson: [00:01:41] Oh, so it’s very interesting, actually. I’ve just been lecturing today, I know it’s the morning for you, for us, it’s mid-afternoon. So I lectured this morning to an NHS trust in the south of England. Some mental health work. So I’ve lectured psychiatrists, some nurses, some clinical nurse specialists and some crisis workers, all about mental health and hormones with a massive response. It was great. Then I’ve just gone over to a GP practice near where I live and I’ve lectured to some GPs and some nurses and some receptionists as well actually about hormones and actually I’ve screengrabbed a quote of yours to say about the menopause – is about the brain. And when I first learned about the menopause and even lots of people do, it’s about periods, it’s about fertility, it’s about waiting a year since you’ve had your periods stopping, and then you can make this amazing diagnosis of a one-word thing. But actually, because I’ve got a pathology background, I’m very interested in basic science, I have the last seven years have stopped reading many novels and I’m reading papers and I’m reading about the power of our hormones in our brains. And I’m also listening to women. And what are the most common symptoms? Oh, no, they’re not the flushes and sweats. They are the brain fog. They are the anxiety. They’re the low mood, they’re the poor sleep. It’s those symptoms that are stopping people working, stopping women function, really making them a shell of themselves. And of course, these symptoms are related to hormones in our brain. So for me, I’ve really changed the way I think about the menopause. I think it is more of a brain disorder, actually. It’s not just a ovarian disorder. And it wasn’t until fairly recently I realised that our sex hormones, oestrogen, progesterone and testosterone, are produced in our brain. I’ve been hoodwinked for the last 53 years, ever since I was born, thinking oestrogen is produced from my ovaries. It helps regulate our periods because that’s what we learn at school. Actually, it’s produced in our brains as well. Yes. So I’ve got loads I want to talk to you but we’re just going to really focus on you and your work. So, obviously you’re not American, but you work and live in America now. So tell me why you are interested or why you are still interested in the brain and just a bit of a history really about your work, if you don’t mind. [00:03:58][136.8]

Dr Lisa Mosconi: [00:03:59] Of course, I have been interested in the brain for the vast majority of my life, to be honest. So I was born and raised in Florence, in Italy, and my parents are both nuclear physicists, both of them, which was an interesting childhood in many ways. I had no idea who Cinderella was, but I knew everything about relativity and you know positron emission tomography and radioactive decay, which was fun in some ways. But my mother, my mum was teaching nuclear physics to students who then transitioned to work in nuclear medicine. And often enough, because this is Italy and nuclear physics is a very small university, there aren’t that many people so it was very family oriented. And the students would come over on weekends to talk with my parents and really ask more questions and learn things better, but they would babysit me at the same time. And so there was starting to remember, there’s a colleague of mine who is now a professor at the University of Florence who had just walked me around on his shoulders talking to me about atoms and, you know, different variety of isotopes and things you can do. And then I started looking at brains and I found it so incredibly fascinating. And when I was maybe ten, I think I told my grandmother that I wanted to be a psychologist and she did not speak to me for three months. Absolutely not. You can’t be a psychologist, I don’t know why but she had this sense that I wouldn’t be a good one, I guess. But then when I started my Ph.D., I was studying nuclear medicine and neuroscience, and my grandmother started showing signs of cognitive impairment, which then progressed into dementia. So she had Alzheimer’s disease, which was very, very shocking and very frightening. And my grandmother was one of four siblings, three sisters and one brother, and all three sisters developed Alzheimer’s disease and died of it, whereas the brother did not. Yeah, so it was really quite, it was very scary. I’ll be honest, it was very scary. I was doing my Ph.D. at that time and I was asking, Is it just me? Is it just my family? Or is there a connection between Alzheimer’s disease and female sex? Does Alzheimer’s affect more women than men? And they would be like, yes, it does. Unfortunately, almost two thirds of all Alzheimer’s patients are women. And that was it. But why? What is the reason for that? What’s the cause? And the answer back then was, well, Alzheimer’s disease is a disease of old age and women live longer than men. So unfortunately, more women than men end up developing Alzheimer’s, are living with Alzheimer’s disease. And at the time, it was well, but the difference is not that wide. Right? So in the United States, I was in the States, I did my PhD at NYU Medical and in the United States, the gap is four and a half years. So women live four and a half years longer than men. But in the UK, for instance, the difference is two years. And Alzheimer’s disease… It’s the number one cause of death for women and not for men. And so then I did my work and other people’s work was really focused on showing that Alzheimer’s disease is not a disease of the old, is not a disease of old age. It’s actually a disease of midlife with symptoms that start in old age, but the pathology of Alzheimer’s disease, all the negative changes that take place in the brain are very slow, they’re very deliberate and they’re silent. You don’t know that you have them for decades until the symptoms become clear in the clinical workup. But it really takes a long time and we can find the red flags of Alzheimer’s disease. We can see the beginning of the Alzheimer’s plaque, the tangles and the neuronal loss in midlife. So that completely finally changed the question to, okay, so what happens to women and not men in midlife that could potentially increase the risk of Alzheimer’s disease in women? Right. And we show that menopause potentially plays a role and I think is becoming more and more active now that menopause is effectively a female specific risk factor for Alzheimer’s disease. So this has been that’s how I’m here talking to you about menopause. [00:08:41][282.4]

Dr Louise Newson: [00:08:42] Yeah. And it’s so interesting, I think, isn’t it, in lots of things in medicine and life is that it’s very obvious, but the obvious things are not thought of. And you’re absolutely right. When I was at medical school and I was taught this increased risk of Alzheimer’s is due to women living longer. And I then thought, Oh, but it’s not a sudden death. It’s not something they suddenly die overnight. That’s what’s really strange. And then I did a pathology degree, so I’ve got a BSE in pathology and we did a lot about all sorts of things, but we focused, one of our modules was about the brain, and we learned about tau protein, we learnt about amyloid. Then we learned a lot about inflammation as well and about how our immune cells can become very pro-inflammatory. And we learned a lot about mitochondrial function too. Things that we never had time to talk about when I was doing my basic medical training, but to dedicate a year in pathology and looking at the link even between atheroma and dementia and other inflammatory conditions and thinking about inflammation causing all sorts of diseases and then also learning many years ago that our hormones, oestradiol and testosterone can reduce tau protein, they can reduce amyloid deposition. And then thinking, oh, right, so midlife things that are more common in women, the things that start to be diagnosed. And then I went to a lecture seven years ago or maybe eight years ago now with Walter Rocca from the Mayo Institute. He’s done a lot of work with women who’ve had, I’m sure you know his work, women who’ve had oophorectomies, they’ve had both their ovaries removed at a young age for various medical reasons. And he’s followed them up and looked at their incidence of diseases. And he’s got this graph. And I remember looking and thinking, oh my goodness me, it’s all there. So women, as some of the listeners might know, if you’re younger and have an earlier menopause, then there’s this increased risk of all these inflammatory conditions. So heart disease, osteoporosis, type 2 diabetes, but also Alzheimer’s, but also Parkinson’s disease. Also multiple sclerosis and then even drug addiction, psychosis, bipolar, clinical depression. He’s shown it all. And then you think, well, why is it, is it a coincidence? Is it these women are grieving their ovaries? No, of course it’s not. Look at the biology. Look at the pattern. Their physiology. And so it’s all there. But I think often in medicine, we’re always, well, there’s so much, not we, I’m not, but there’s a lot of people who are trying to find this new drug. There’s a lot of sponsorship by pharma. There’s a lot of specially, obviously, and understandably, a lot of research going into cancer and sort of cutting-edge technology. So when we think about oh hormones, they’re generic, they’re off patent. They’re not… Really cheap. Like, why would someone invest in looking at that? But then my pushback is but it’s affecting 51% of the population and actually the 49% of the population who aren’t women have testosterone. And we know low testosterone in men increases risk of all the inflammatory conditions as well. So it’s sort of under our noses and we’re not really… So your work is starting to show because we need to demonstrate, but we don’t always need a randomised controlled study to show something works in science, do we? [00:11:57][194.9]

Dr Lisa Mosconi: [00:11:57] I agree with you. We’re always caught in this loop that a lot of the research is observational and we need clinical trials. But it’s not feasible to do clinical trials for everything, and especially for something like hormone therapy that should be taken in midlife and then you’re trying to measure the impact on something that’s going to be measurable, like Alzheimer’s disease diagnose it 20 years later, 30 years later, you just can’t do trials like that. So what we’re trying to do now is to do like the Women’s Health Initiative, but do it right. [00:12:32][34.6]

Dr Louise Newson: [00:12:32] Yeah. [00:12:32][0.0]

Dr Lisa Mosconi: [00:12:33] So we’re testing hormones in perimenopausal women and early postmenopausal women who have the symptoms of menopause, the neurological symptoms of menopause, the hot flushes the night sweats, but especially the brain fog. It’s my thing, you know, just trying to avoid getting foggy brain and the memory lapses, and the forgetfulness. Can we avoid that? Can we reverse that? And we are not going to wait 20, 30 years until someone develops dementia. But what we’re doing now is that we’re doing brain scans, we’re doing brain imaging at the same time that the women are taking the hormones and then we repeat the brain scans over time to track the progression of changes. Just a much better way, in my opinion, of testing whether HRT is lowering the risk. Thank you. You know, you never know. So we’re doing brain scans that look at metabolic activity in the brain. We’re looking at mitochondria, ATP production in the brain. We are one of the very few centres in the United States that have these technologies, it’s called 31-Phosphorus MRS, magnetic resonance spectroscopy. And we have a very high resolution machine with a very nice coil that allows us to map the intracellular ratio of ATP to PCR to phosphocreatine. So it’s the amount of, the amount of energy, molecular energy, is being produced in the brain relative to your energy bank, if you will. How much of this ATP will you burn? How active is your brain? So we do that. We look at MRI scans, of course, we look at inflammation. We do everything that can happen in the brain. And then we’re measuring the markers of Alzheimer’s disease, not in brain, but in blood. We’re trying to make it easier on the participants when they’re young, they’re women in their 40s and 50s. So we’re looking at the amyloid beta fragments. We’re looking at the tau proteins in blood as well. And the trial, we still have three years to go, but we’re hoping that that would really help. [00:14:47][133.8]

Dr Louise Newson: [00:14:48] I think it’s going to be very, very revealing because so many women we see in the clinic, and we see thousands of women, are complaining of this brain fog that they cannot remember things. They’ve really thinking through treacle. And a lot of them are worried they have dementia. [00:15:02][14.7]

Dr Lisa Mosconi: [00:15:03] Yes. So many women who come to us and they’re like, I have a family history of dementia, which is the vast majority of the population these days, unfortunately. And as soon as you start forgetting things, you panic, which is perfectly legitimate and reasonable. So they come to us, we do cognitive testing, we do brain scans, and we make sure that everything’s clinically okay. But then we also… right so that ten years from now, if you actually have a problem, or if you feel that you have a problem, that your cognition is getting worse, that we can backtrack and compare data at that point with your own brain and cognitive performance when you were fine. I think it should be part of it. [00:15:46][42.8]

Dr Louise Newson: [00:15:47] It is so interesting. And I remember sort of eight or nine years ago, I started to get more interested in the menopause and thought, I really want to start a clinic. So I went and sat in some other people’s clinics because you learn as a clinician so much more sort of on the job. You learn how to talk to people. How to prescribe, which tests, all sorts of things. So it’s great. And I remember sitting there with one of the doctors and saying, When do you know how to start HRT? When do you know when people are perimenopausal? How do you know? And he said oh Louise, it can be quite obvious. And I was thinking, I was 45 then, and I thought, Really, really, hmm don’t know. And then I decided to develop a website, write a website, and I just opened my clinic and I work a lot in the evening when my children are generally in bed. And I remember going to, going to my husband and going to the study and going, Oh my gosh, I can’t, I just can’t think. I can’t function. I feel like I’ve been drugged. It was not just a tiredness that you can go to sleep and you’ll be okay the next day. I felt just awful. I just could not think. And my brain is quite fast and I’m used to just like I’m not very good at names, but otherwise I’m quite good at thinking about three or four things at once. And it’s just it’s something I’ve always done and I just thought I can’t even. And he said, yeah, you look dreadful and I, it was really scary, like petrifying. And then I’d be with patients and I think, I just don’t even know what they’ve just told me. Have they got a cough or have they got a runny nose or have they got? And I thought, I can’t ask them again. And then I think, oh yeah, no they had you urinary symptoms. I think they’ve got a urinary tract infection. Right, which antibiotics? Oh my goodness, I can’t remember. And I can really see why people give up their work and it’s it’s horrible. And most things in life, you know, if you cut yourself, you know, it’s going to improve with time. If you’ve got a bruise, you know… Or if you’re overtired, just have a weekend and just relax and then you’ll recharge. This was completely different to anything I’d experienced before. And I was just absolutely mortified. But even then, I didn’t think it was my hormones. I thought it was because I was trying to set up a clinic and do a website and look after my three children and la la la. And even when I started my HRT because I suddenly, after a few months realised I had other symptoms, it helped a bit, but not much and my mother-in-law kept saying, Are you feeling better now? No, I just can’t think. And then it was actually adding in testosterone and having the right dose of oestrogen and waiting because it took a few months, actually. And then suddenly I’m like, Gosh, my brain is back, but it’s back to how it should have been or how it was like eight or ten years ago. It’s really it’s not just a little bit better. It’s so much better. And you just wonder like, is it because I’m using my brain more, because it’s got less inflammation, it’s got more blood flow, it’s using, you know, the glucose metabolism, everything’s better because I’ve got the hormones. What else is it going on in my brain? And actually this is a problem. Often with dementia, it’s quite hard to make a diagnosis as well. And like you say, it’s not actually about dementia. It’s about memory loss. Like having a diagnosis of dementia sometimes we would try and delay in general practice because it’s such a big diagnosis without an available treatment often. [00:18:45][178.8]

Dr Lisa Mosconi: [00:18:46] That’s right. [00:18:46][0.3]

Dr Louise Newson: [00:18:46] But actually it’s that journey to that diagnosis that can be really, really disabling not just for the person, but those around them as well. So anything that affects our brain, especially our memory, is it’s really petrifying. [00:18:59][12.4]

Dr Lisa Mosconi: [00:19:00] I completely agree with you. I spent most of my life really trying to understand what leads to dementia and what leads away from it. And the way we live in my household, in my family, is very brain health conscious and my husband thinks I’m mad but there’s so many things that I do for myself and for my family that are really based on the research and we’ve changed many things in our lifestyle based on science, because I just don’t want that to happen to me if I can. Anything I can do that would take me away from that kind of outcome, I’m on, I’m doing it. Yes, my husband’s the same way. Even our daughter, she’s eight now, Lily’s eight, and she knows everything about the brain. She can talk to you about menopause for, like, forever, for hours and hours. She knows everything about puberty, she’s ready. And what I think is very important as women also, is to realise the menopause is not an alien event, but there’s a rational biological basis for it, which doesn’t make it any easier or any better, but I think it helps to know that you’re not being possessed by an evil spirit. [00:20:14][74.1]

Dr Louise Newson: [00:20:14] I absolutely agree. And just having knowledge, actually people going, Oh gosh, I haven’t got dementia then, or so, it’s related to my hormones. I really thought there was something else. So having that knowledge is crucially important. But I spoke to someone last week who was telling me that she’s only 38, so she’s younger, she hasn’t had many periods. She’s had two this year and she had three the year before. And her sister had an early menopause. And she said, I just can’t think and concentrate. But she’d only been given antidepressants and trazodone, which is a really quite horrible drug. And she said every time they give it to me, I feel worse. And I really can’t think and I can’t sleep and I’m getting flushes and sweats. And I was a real mess. And I think, well, actually, why are we giving these people other drugs as well? There’s one thing not having anything. But there’s another thing having drugs that actually are going to impair cognition even more. And that can be really difficult for many people can’t it? [00:21:10][56.1]

Dr Lisa Mosconi: [00:21:12] The thing is at least here, the guidelines are professional societies have been updated to not only recommend, but also really encourage women who are going through an early menopause, a premature menopause, to take advantage of hormone therapy if they’re eligible for it, which is a whole other, you know, can of worms. [00:21:34][22.4]

Dr Louise Newson: [00:21:34] Yeah, I mean, our guidelines are the same, but it’s really hard for actually women to be listened to. And some studies have shown it takes seven years for people to actually receive the treatment or the diagnosis as well. So I want to talk about the paper that you produced recently. I was very excited. [00:21:50][16.0]

Dr Lisa Mosconi: [00:21:51] Let’s do it. It was a good study. There was so much work and then people were like, Oh, there’s this review paper and I’m like, no, excuse me. It’s not a review paper it’s an actual statistical evaluation of 50-plus, 52 studies, which is a real other work, in my opinion. [00:22:08][16.6]

Dr Louise Newson: [00:22:09] Yes, so it came out and actually, well, there’s lots of things that excited me but saddened me as well actually about your paper, because there was a review that was put in the British Medical Journal, the BMJ, a few months before your paper came out. And it reached the headlines and it was saying HRT increases the risk of Alzheimer’s. And I read it. And as you always do with the papers, you don’t read the top line, you read the actual paper and you realise this paper was putting together older types of HRT, different sort of studies. Even the conclusion said it’s probably an association, not a cause, and we can’t really interpret the study very much. So it should never really have been published. And I remember putting a little video on my Instagram to say, actually it doesn’t tell us anything. It’s not very helpful. And there are different types of hormones. We know the synthetic progestogens have a risk of clot and stroke with them, so that can affect the vascularture. And certainly when we think about vascular dementia probably has a role as well. So it was a really awful… But it went to the front page of the news. I was on national telly talking about it, and then your study came out. I thought, Great, this is going to be front page of the news. Everyone will talk about it. But there was some media pick up, but not in the UK to the extent. [00:23:23][73.8]

Dr Lisa Mosconi: [00:23:24] Oh no probably not in the UK. But here the study was picked up by CNN. There was more now, and the New York Times, so that was great part for us. [00:23:33][9.3]

Dr Louise Newson: [00:23:33] Which is brilliant. In the UK we only report about bad news because that sounds like… [00:23:39][5.6]

Dr Lisa Mosconi: [00:23:40] Yeah, it sounds like it. [00:23:40][0.1]

Dr Louise Newson: [00:23:40] So tell us about it. [00:23:41][1.0]

Dr Lisa Mosconi: [00:23:42] So that started, and you and I talked about, the BMJ study is really what kind of, not prompted our analysis but was really like the last straw I think because it was so… It’s been years and years that people would ask, so can I take hormones? When do I take hormones? Do they increase the risk of dementia? Do they reduce the risk of dementia? Is it protective? Is it not? And every couple of months there’s a new study that makes the headline and people are really confused. Right? So one month you’re told that you should go on hormones immediately and stay on hormones for life because that would reduce every problem under the sun. And then you get hit by headlines like the BMJ study that say exactly the opposite. And it’s very scary. It’s really frightening. And people don’t necessarily know how to read the paper like you do either… to read the fine print. And I just want to say one thing about that study, that if you look at their own figures, the outcomes they reported were for dementia. Dementia is a little bit of a mixed bag. It’s an umbrella term that includes many possible disorders that impact brain health and cognition. But when you look about Alzheimer’s disease, specifically in their own study, the estimates were actually not significant. So that was irregular. Why is that not being a knowledge? Why is the headline so different than the actual results of the study? But so many women just wanted to stop, the few women who do take hormones for menopause, in this country at least, wanted to go off because of that study. And of course, and no, we’re not doing that. We’re not, obviously the North American Menopause Society stepped up and said, no, no, no, this is not what we’re doing. But I thought we need numbers here. Right. Because we can’t look at each isolated study and overdo it or underdo it. We need to get a sense of the full picture because there have been many, many studies published that looked at HRT and the risk of Alzheimer’s and dementia. So there is a statistical technique that one can use that’s called meta analysis or, one step up, you can do a multilevel major regression analysis, which is what we did, we did both, just for clarity, where you pull the data from all these different stuff. First, you need to identify all the good studies because some, you know, maybe not worth it, but the really good studies, you pull them all together. We were able to rank about 52 that provided all the information that we needed for statistical analysis. And then you combine them all together. And the results, I think, were very clear. And we can look at them, the figures from the paper, which I think are quite clear. This is what we find is my keynote talk. [00:26:42][180.3]

Dr Louise Newson: [00:26:44] Ver good, look at that. [00:26:44][0.3]

Dr Lisa Mosconi: [00:26:44] Do you like, isn’t it pretty, I made it? [00:26:46][1.9]

Dr Louise Newson: [00:26:47] Yeah, I love that picture. We were WhatsApping it around various people when it came out. So talk us through it Lisa. [00:26:54][7.1]

Dr Lisa Mosconi: [00:26:54] So this is oestrogen only therapy. So we were able, this meta analysis was the first study that was able to look not just at any type of HRT together, but we were able to really look at oestrogen-only therapy and oestrogen and progestogen therapy. And then we were able to look at each therapy initiated in midlife or more than ten years after menopause. And we were able to find differential effects on the risk of Alzheimer’s disease and all-cause dementia. I would like to have a lot more studies. But this is what we have, right? So this is the best we can do with the data we have at this point. So with oestrogen-only therapy started in midlife, there was a significant 32% reduced risk of Alzheimer’s disease and dementia later in life. And that was very significant and it was very consistent. So the variability was very small. The error was very small, which means then the vast majority of studies consistently reported a protective effect, which is what you want to hear. [00:28:04][69.8]

Dr Louise Newson: [00:28:05] Yes, course. [00:28:05][0.4]

Dr Lisa Mosconi: [00:28:05] Yes, exactly. Now, if you start oestrogen-only therapy more than ten years after surgery, or after menopause in this case it’s for women with hysterectomies, then the effect was neutral. There was no protection, there was no increase in risk. For oestrogen progestogen, which is important. [00:28:25][19.9]

Dr Louise Newson: [00:28:26] So that’s the synthetic progestogen. [00:28:28][1.6]

Dr Lisa Mosconi: [00:28:28] Yes, that’s so the vast majority of studies, except for maybe one or two, were using progestins. Only a couple were using, were looking at bioidentical progesterone, but not in isolation, mixed with another. And so it’s hard to, we couldn’t possibly tell them apart. You know, good things to take away. However, even then, this combined therapy initiated in midlife or within ten years of the onset of menopause, was associated with a 23% reduced risk of Alzheimer’s disease and dementia. Now, this was a trend. Why? Because, unfortunately, there are a few studies that were driving up this curve and made it only borderline significant. However, most studies were showing a protective effect, which is what is driving this little cone downward, right. Now over here is combined therapy started more than ten years after menopause. And I have to tell you, this increase risk is not significant. Number one, again, is a trend, which means that there are studies to show protective effects and studies to show a harmful effect, an increased risk of Alzheimer’s. But this is really the Women’s Health Initiative is driving the effect. If you take out the Women’s Health Initiative, then the effect is neutral again. [00:29:55][86.5]

Dr Louise Newson: [00:29:55] Yeah. Which is really interesting. And as we know, there’s a lot of women in the Women’s Health Initiative study were actually women who were overweight, they had cardiovascular disease. And they’d also had oral oestrogen and the synthetic progestogen. And so there were lots of things that weren’t right. You know, I would never prescribe that type of HRT to someone in their 60s. So I think it’s comparing apples with pears. But I think what is really reassuring is certainly the first picture to show that oestrogen-only HRT, so oestrogen without a synthetic progestogen, has got a lower risk certainly started early. So we know from other studies the earlier people who start HRT, the better. And actually that’s very comparable to the reduction risk people have of breast cancer if they have oestrogen-only HRT as well. [00:30:42][46.6]

Dr Lisa Mosconi: [00:30:44] And cardiovascular disease right? [00:30:44][0.2]

Dr Louise Newson: [00:30:44] And cardiovascular disease. So we know that oestrogen actually isn’t the enemy in our bodies and it’s not the enemy in our brains. And I know that’s fuelling you to do even more research, which you can come and talk about in the future. But it’s really important that we know that. And even looking at that curve, which could look scary, firstly, we don’t usually prescribe those types of hormones to older women. And secondly, it wasn’t statistically significant. So it doesn’t mean that older people can’t start taking HRT, but we give the body identical hormones and know that there are definitely benefits to our bones as well and probably for symptoms as well. So there’s lots of reasons to consider HRT, but this paper is really important to have a look at and take away the top tips really to help us catapult into doing more research in this area as well. We can’t keep ignoring the role of hormones in our brains. So, so I’m very grateful for your time, Lisa. But before we finish, I always ask for three take home tips. So three reasons why you think female hormones, especially oestradiol, but also progesterone and maybe testosterone, but especially oestradiol, three reasons why it’s beneficial on the brain. [00:32:00][75.2]

Dr Lisa Mosconi: [00:32:00] In my field of neuroscience, we like to say that oestrogen and oestradiol in particular is the master regulator of women’s brains. And that, I think, is an important concept because it really is like saying that oestrogen is to your brain what fuel is for an engine. It keeps your brain running. So I think that more research is needed because it’s really there isn’t that much research. A lot of the work that we have is preclinical. You know, what happens in mice very often stays in mice. We need to make sure that it translates to women and we need more options. We need better options, and we need more data to really be able to counsel women appropriately. And we were talking about that before. The standard care for some women, a low dose is enough. For some women, a high dose is better. How do you even make the call that we need to have better measurements? We want to measure oestrogen in the brain. Like you and I were talking about that we’re trying to do it now. Yeah. So that would be my first take home message, is that oestrogen is important for the brain and there’s no denying that. Number two is that endogenous oestrogen is different from exogenous oestrogen. So when we say oestrogen is the master regulator, oestrogen is so important for brain health, we’re talking about the oestrogen that our bodies make. There are many other forms of oestrogen that have been used pharmaceutically for women. And I think at this point in time, most people agree the bioidentical oestradiol is probably the best one to use because it really maps on the same circuits for your own endogenous oestrogen, oestradiol does. So that’s another important thing. And number three, I would love for all women to be able to make an informed decision about whether or not hormone therapy is a viable option for them. And what I mean is that we know that there are women who are not offered HRT, and there has to be more education about the risks. I think of some updates maybe. But there are so many women who are eligible and do not go on HRT out of fear and the fear comes from outdated information, mislabelling on some of the packages or you know what I mean? The black label warning on vaginal oestrogen for one. So I think it’s very important that all women have access to more information, to more updated information, so that if you choose not to take hormones for menopause, is your own personal choice based on preference and not misinformation or fear? [00:34:51][170.8]

Dr Louise Newson: [00:34:52] Yeah that’s so important. [00:34:52][0.2]

Dr Lisa Mosconi: [00:34:53] So we’re here to provide the information. And then this is America, everybody makes up their mind on their own, for sure. [00:35:00][7.6]

Dr Louise Newson: [00:35:00] Absolutely. Absolutely. And the choice has been taken away from too many women for too long. So it is absolutely having an informed choice. Knowing benefits, knowing risks and knowing uncertainties as well, because we’ll never have the answer for everything, not just with hormones, but with everything. [00:35:17][16.6]

Dr Lisa Mosconi: [00:35:18] And then you’re own individual risk tolerance, I think is something that needs to be included in the conversation. You can’t go to your provider and the answer is no, you’re not going on hormones because of this, this and that. There has to be a little bit more of a conversation about what are my priorities, what am I optimising, what am I scared off and less scared of, and what do I want for myself right now and in the future? And this doesn’t, I don’t hear that happening very often when you go to your doctor for a menopause consultation. So I think that should be, if possible. [00:35:53][35.8]

Dr Louise Newson: [00:35:54] Absolutely. So there’s a lot we need to change, but certainly all your work we’re very grateful for and we’re watching with interest from the UK. So thank you ever so much for your time today. Lisa, it’s been great. [00:36:04][9.8]

Dr Lisa Mosconi: [00:36:04] Thank you. [00:36:05][0.3]

Dr Louise Newson: [00:36:09] You can find out more about Newson Health group by visiting and you can download the free balance app on the App Store or Google Play. [00:36:09][0.0]


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