Menopause and the brain: why we need to bridge the gender gap in research

Regular listeners will know there is much more to the menopause than hot flushes – but how do hormone changes affect your memory, mood and cognition?

This week Dr Louise is joined by Dr Dan Reisel, Specialist Registrar in gynaecology at University College London and Newson Health Clinical Research Lead, to take a closer look at the relationship between hormones and brain health.

Dr Dan says awareness is improving, but researchers must up their game when it comes to studying the female brain. While mood and memory symptoms are common in menopause, too often, studies focus on male brains as they don’t want to deal with the complexity of female sex hormones, he adds.

Dr Dan’s three take home tips: 

1. If you’re going through the perimenopause or menopause and struggling with symptoms, don’t just accept how you feel. Seek out options for treatment such as HRT that can improve your symptoms.

2. Become an advocate for better care for women going through the menopause – speak to your friends, healthcare professionals and colleagues about your experiences.

3. If you are offered the chance to take part in research seize that opportunity to make your voice heard and improve the experience for women in the future.

You can follow Dr Dan on Twitter at @danreisel

Transcript

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. Today on the podcast, I’m really excited to introduce to you someone I’ve known for a little while but really respect his brain, his knowledge and his experience. So Dan Reisel is with me today, who is an academic, but also a senior registrar in gynaecology, but didn’t actually train in gynaecology initially. So we’re going to hear a bit about his background and a bit about what he knows about the menopause. So welcome to the podcast Dan.

Dr Dan Reisel: [00:01:27] Thanks for having me.

Dr Louise Newson: [00:01:28] So tell me a bit about your background because you didn’t actually start…your first degree wasn’t medicine, was it?

Dr Dan Reisel: [00:01:36] No, that’s right. I started life as a neuroscientist, actually. I like to say that when I was a kid, which is true, I wanted to be a magician. And instead of pulling rabbits out of hats, I pull habits out of rats. So I spent quite a few years doing basic research in neuroscience with a master’s and a PhD at Oxford in a really exciting lab looking at the building blocks of working memory in animal models. And that was work that was part of understanding the brain basis for dementia, but also for cognition, because working memory is that ability to engage in complex tasks and thus manage different things at the same time. So it takes this sort of bandwidth of the brain. And we looked at the particular neurotransmitter glutamate. But the thing about the brain is that it is an intersection of so many different systems and so many different neuromodulators and neurotransmitters. And so what we do in one area impacts in a very significant way so many other parts and in so many different ways. But it was really exciting time doing that work and going to conferences and being part of the academic community. But then in the final year of my PhD, I had a bit of a sort of career think and really felt that although the science and the academic research was really exciting, it would be even more exciting if I could do that work in a clinical role or as part of a clinical role. And so I went back to school essentially as a graduate entry medical student at UCL at the tender age of 28. And it was one of the hardest things I’ve ever done because really then you have to go from really advanced conversations about the function of various brain systems to learning basic physiology. But it was a really good thing for me to go through, I think, because I think it humbled me.

Dr Louise Newson: [00:03:30] So you’re with people that were ten years younger than you, essentially?

Dr Dan Reisel: [00:03:34] Yes, there was a group of graduates, but it was a was a humbling experience. But I think coming through it on the other side, now that I graduated out at UCL Medical School over ten years ago, it’s really shaped me and it’s caused me to really feel the impact that when you have patient exposure, when you really have the ability and the opportunity, the privilege to listen to people’s stories, then really that makes a big difference because it informs how you think about basic physiology and pathology and about your research priorities.

Dr Louise Newson: [00:04:05] It’s very interesting, isn’t it? I, as you know, did some research on a very small scale compared to you, but I did a BSc (Hons) in pathology and I was looking at the skin of women who had something called systemic sclerosis, which is probably a condition you know about. And I was looking at type IV collagen in the skin in the basement membrane, which is so minute, and I was doing the technique called in situ hybridization where we used radioactivity labels until, you know, it says to mark the different types of collagen. And I got very excited when there was a signal, you wait two weeks for a result. The first time I did it, I forgot to put the right chemical in the right thing. And then two weeks later there was no results. And I realised that I just because I am a bit cack-handed and it made me realise how frustrating research was. But then also I got a paper, I got a publication. I was really pleased. I was working with laboratory people. But then towards the end of my year, I thought, do you know what, I’ve never seen a patient with systemic sclerosis. Got no idea what they’re like. And I’d read about the disease, of course I had. So I went up to north Manchester where there was a clinic. And then I realised these poor women, the skin gets very, very tight, as you know. So the women I saw in the clinic couldn’t open their mouth. They couldn’t actually pick up cutlery to eat because they had such bad scarring and sort of retraction of their digits. And I thought, goodness me, I’m excited because I found one thing, that’s never going to make a difference to their life. How are they ever going to pick up their children? How are they going to be able to… it’s quite a progressive disease, they …all sorts of things. And I just thought oh Louise what are you doing? Actually, what I really want to do is sit down and talk to them and work out what it is like and how they can adapt their life and how…and it is like that with sometimes with research, isn’t it Dan, that you, you forget the context of what you’re doing it for?

Dr Dan Reisel: [00:05:49] I think that’s right. I think life in general, but also clinical medicine is humility school, where you really learn from those encounters with people who are experts on their symptoms, their symptomatology and their condition. And so one of the things that I love about gynecology, just when I’m clinically at the moment, is the fact that we can make a difference in women, often because it’s a sort of hands on specialty, whether it’s surgical or medical. And that is clearly the only way to make a difference is to really work on understanding where people come from. And so I was recently asked, actually, I teach a bit. That’s the UCL medical school now, and we were asked to summarise in five words advice to qualifying doctors. My suggestion was tune into your patient. I don’t know if that’s five words, but it is essentially, what I think is the most important thing. You have to tune in to where they’re at. And it’s sometimes really hard. It’s hard for me as a man to sometimes understand the impacts that gynaecological disease and pathology and even life stages have on women having experienced it, let alone birth. But that’s where really we have to work hard, I think.

Dr Louise Newson: [00:06:59] Is so important, isn’t it? And, you know, when I was younger about ten years ago, I was teaching graduate entry…a graduate entry course in Birmingham University. And I was teaching medical students then. And the attitude is very different compared to undergraduates who had just come straight from school. And what I realised more when I taught them was this life skill that they have, which is just it just takes time, doesn’t it? And experience. And I think having the ability to talk to patients and understand where they’re coming from is the most important thing. I think it’s, well I know, it’s such a privilege being a medic and the stories that I’ve heard, the way people will tell you things that they’ve never even told their partner or their best friend or a member of their family and they have utmost confidence in you. But it’s also having that confidence that we can share every decision and make sure they’re comfortable with it. And the art of communication. But also changing your communication according to the patient is really powerful. And I know when I changed and pivoted into general practice, my trainer said to me, Louise you’re going to be a terrible GP because physicians in hospital are too robotic. They’ll never talk to patients properly. I said, What do you mean, John? I’ve, you know, I’ve always done really well. He said, No, you’re going to fail this exam. You’re going to be really bad. And obviously when someone says you’ll do bad, you do better. Which worked of course, but it’s that ability of being able to ask the patient what’s worrying you, which it seems really silly when at medical school, of course all you want to get is a diagnosis and you want to make the best diagnosis the quickest compared to your peers. But actually the patients often aren’t so bothered about the diagnosis. It’s more about how it’s going to affect them and what does it mean? And that’s something that takes quite a long time, doesn’t it, to realise, I think?

Dr Dan Reisel: [00:08:51] No, I think that’s right. And sometimes the diagnosis can be a gift. We worry sometimes that patients will be really disappointed if you give them a name for their condition. But in some ways it can be liberating because then a whole host of things might happen. There might be a treatment option. There might be information that they can access.

Dr Louise Newson: [00:09:08] Yeah, and it is interesting, when I was in Manchester and as you know, I wanted to do oncology, we had some amazing training with someone called Peter Maguire, who was a psychiatrist who worked at the Christie Hospital, and this was many, many years ago. So it’s quite unusual actually. Where people didn’t really talk about cancer then and there was a lot of collusion going on, and certainly when my dad cancer in the 1970s, no one told him at all he had cancer. And it just wasn’t the done thing, which is I know now is so wrong. So we had a lot of training about breaking bad news and giving someone a cancer diagnosis. And I thought, this is going to be awful, so terrible. But actually when you get it right, people are so relieved. Actually, if you say it in the right way and prepare them in the right way and like you say, then, oh, well, that’s why I’ve been feeling this, this and this. And then they can move on to the next step to try and decide where to go, what to do. But it does take quite a lot of skill, that’s for sure.

Dr Dan Reisel: [00:10:03] We’re all still learning.

Dr Louise Newson: [00:10:04] Absolutely. So you did all your neuroscience and you did your medicine and you’ve done gynaecology. How much until we met did you know about the menopause? I’m putting you on the spot here Dan.

Dr Dan Reisel: [00:10:17] Well, the truth is, I was…I’ve always been interested in in hormones. And previous to now, spending every waking hour thinking about ways in which we can study the impact of hormones on lifelong health. I spent ten years at UCL working at the Institute for Women’s Health there, part of a team, really pioneering team, looking at the impact of hormones on cancer. So women’s cancers, specifically womb cancer, but also ovarian cancer, breast cancer. And one of the big learning points from that was that hormones are ungovernable. They go everywhere, they impact every body system. They go to places where other chemicals and bioactive substances in the body don’t go because of brain barrier. I don’t think there’s a body system that isn’t impacted by hormones. And so one of the interesting paradoxes, a lot of paradoxes in this area, one of the paradoxes is if you give contraception to women who are at risk of breast and ovarian cancers or women, for example, with a BRCA mutation, BRCA mutation, you decrease the risk. And we don’t quite know why that is, but we think it might have something to do with avoiding the peaks and troughs of the menstrual cycle. And that was really interesting to me. Why is it that hormones sometimes are the bad guys and sometimes the good guys? Why is it that, for example, progesterone is considered a risk factor for breast cancer? Depends on how it is given. But it’s protective for womb cancer. Those two cancers are hormone driven, but there are contradictory effects of hormones. So we give a small amounts of progesterone. So we want to protect the endometrial the lining of the womb. We don’t want to give too much progesterone because then that can have an impact on the breast. So women are much more complex than men in that regard.

Dr Louise Newson: [00:12:14] And hormones are interesting, aren’t they? So they’re just chemical messengers, really, aren’t they, that just go in the bloodstream and go to all our organs. And we’ve got many, many different hormones in our bodies. A lot of you would have heard of, obviously, insulin, thyroxine. And then, you know, the ones that we always talk about are estrogen and progesterone and testosterone as well, actually, which mainly get produced from our ovaries when they’re working, when we’re younger. And, you know, our hormones, sex hormones, it’s very interesting when you when you look back in time when the hormones were discovered, you know, when insulin was discovered, then it was associated with a disease, diabetes. When Thyroxine was discovered, it was associated with a condition hypothyroidism. When estrogen was discovered, it was associated with symptoms, vasomotor symptoms and hot flushes. Which was such a shame actually, because if it had been associated with a condition, we would be in a very different stage now. And obviously they defined it as meno-pause. So stopping the menstrual cycle. So the menopause has always been associated with periods, with fertility, with hot flushes. And we you know, you’ve been to conferences, I’ve been to many conferences, and a lot of that conversation is about menstruation and vasomotor the symptoms. Yet we know that hormones go all over our body. We know they affect everywhere. But they also, like you say, they go through the blood brain barrier. So when you were learning and doing your amazing research, looking at cognition and memory, did you do anything about hormones then?

Dr Dan Reisel: [00:13:52] Well, the truth is neuroscientists, at least in my experience, are they always try to make things the systems that they use to understand disease, the models, as simple as possible. And often they avoid actually using female rats and mice, for example, in experiments, because things that could become a lot more complicated once you have an estrus cycle and changes that are hormone dependent. So they sort of cut out all of that by just studying disease in male animals. There are also ways in which you can manipulate cycles in experimental animals, and certainly most experimental animals are not kept alive long enough to have a natural menopause and that’s not a thing. So it’s I would say it’s worse than not being on their radar. They sort of actively cut out some of that variance and some of that complexity because they want to keep their confounding factors as low as possible. That’s in some ways good in order to progress research, it has quite significant side effects, that our understanding is actually quite male based in certain areas and certain ways, and also that we don’t really study female specific physiology. And that’s true for clinical medicine as well. Trials, for example, are commonly not conducted with pregnant people in mind. That was a big problem with the COVID vaccination that they just didn’t know what to do with these people, kept having babies. And so this is a big problem in how do you conduct and carry out research. So it wasn’t really on the radar at all, no, to answer your question.

Dr Louise Newson: [00:15:23] Well it’s been a problem for many decades. Lack of research in women, that lack of research in menopause as well. And certainly when you look at a lot of the studies, they are focusing on symptoms. And as many people listening know, I, of course I’m interested in symptoms, but I’m more interested in the immune modulating effects of our hormones and also the disease preventative effects of our hormones as well, which has been neglected largely for many years. But the more work I do and the more papers that I read, I’m so interested in the brain, and I’m also interested because I know how I felt when I didn’t have hormones. And it’s the most crippling feeling ever to… always… you know, my brain is always active. I’m always thinking. I’m always trying to read. I’m always, you know, I get up and I think, I’m in the shower and I think I use my brain a lot. And I felt like some zombie, you know, this whole thing that people talk about the brain fog or the thinking through treacle and…very hard to describe, you know, when people say, my zest for life has gone and I’m just existing, I’m not living. And I don’t know how you measure that in studies. I just went into someone that just, you know…my 18 year old sometimes keeps texting me ‘CBA’ – can’t be arsed. And it’s you know it’s that sort of feeling where you just really, everything is an effort. You know I used to look at the pile of washing and think that’s probably two loads of washing. I don’t even want to put one load on. Now actually it takes a second. I’m very lucky. I have a washing machine, I can put it in and press the button and it doesn’t take long but everything was overwhelming and my memory was bad, my temper was awful. But all this is brain, you know, obviously I was frustrated because I physically wasn’t feeling as well, especially having migraines and joint pains when I was perimenopausal. But it’s without your brain, you’re nothing. It’s really difficult. And I see it and hear it time and time again in the clinic of these poor women who say, I think I’ve got dementia. I can’t remember the words for that yellow thing that I’m eating that I see in the fruit bowl. And you say banana? Yes, of course it is. And it can be amusing, but it’s really scary. But you talked at the beginning about neurotransmitters to explain what a neurotransmitter is, if you don’t mind.

Dr Dan Reisel: [00:17:41] So I’m happy to. But I wonder if if it’s worth taking a sort of a bit of a zoom out for a second and just reflect on language before we go into neurotransmitters, because you mentioned brain fog, which I think is a bit of a… well, it’s a term that we hear a lot and it’s often something that patients describe. But in a way patients also describe, we’re given this sort of terminology often and we use it. And it’s interesting to look at different cultures describe menopause transitions in different ways, so spoken to people in the Indian subcontinent, and often they go to their local doctors and talk about all of the body pain. And that’s a sort of cardinal feature. If you look up menopause on the internet, often hot flushes come up with sort of a top, top thing. But there was a study that came out before Christmas by the Fawcett Society, and it listed the most common symptoms in women, it was a large group of women, 4,000 people, I think, a representative sample with due concern to different ethnicities etc. And it was called a panel survey. So a really good study. And what they found was that in the top ten, in fact, the top five of symptoms were all brain based. And that’s really interesting to me because I think it’s possible that one of the reasons why this field is underfunded and under-researched and under prioritised and has been for so long is that it sort of happens in the corners. It is the gonadal bit, the gonadal bit of the pituitary hypothalamic pituitary gonadal axis. And so it happens sort of down there in the ovaries, I guess, in the adrenal system. And actually to reconceive the menopause as a cognitive disorder would answer both the kind of symptoms portrayed that patients come with. They often talk about, describe, and sometimes the terminology we use isn’t precise enough. So people say, well, you know, why do we talk about brain fog in the menopause and why isn’t there proper nomenclature set of terms to be used? You know, there’s no reason why psychiatrists and general practitioners and gynaecologists can’t get together and decide, well, this is a kind of hyperactive working memory state, or to actually begin to describe it in scientific terms because once you name something then you can study it, then you can apply for funding for it and then you see it everywhere. So I think that’s one of the myths that the menopause really happens down there in terms of hot flushes, of course, that’s part of it. Sometimes the symptoms that relate to genitourinary tract symptoms are very, very common, too. But the brain, cognitive, moods side of the menopause, I think, is not prioritised enough and studied enough. And that’s also one of the kind of exciting areas coming on to your question about neurotransmitters. So I guess one way to attack that question, because there’s a big question and I want to go into some detail, but I want to keep focused on the relevant parts of neurophysiology. And I guess the thing to say is that there are, broadly speaking, three or four or five neuromodulation systems, so you’ve got your cholinergic. So that’s a lot of these symptoms happen across the brain, but especially maybe brainstem and basal part of the brain cholinergic activity. You’ve got your serotonergic, so serotonin, which is the predominant neurotransmitter in the amygdala and what we used to call the limbic system, again, also has brain wide effects. Then you have the dopaminergic. Dopamine is one of the major classes of families of nerve transmitters. And that’s obviously a big part of hypothalamic working memory, reward, also arousal and anticipation of reward features predominantly in terms of dopamine and then noradrenaline, which is again, one of the big workhorses of the central nervous system. And then there are others: glutamate, which I spent a lot of time working on in my research. But all of these neurotransmitter systems operate across several different huge highways of information across different brain areas. But what is completely off the beaten path is the impact on all of those systems of estrogen and testosterone. And that’s really, I think, one of the white patches on these maps, completely unexplored territories. And really it is not just that it’s not you know, we can’t find many papers, aren’t many groups working if you speak to neuroscientists. They’re sort of vaguely aware that estrogen and androgens have neuromodulatary effects on activation and metabolism and grey matter density and all these things, but they don’t spend a lot of time studying it. You know, I think one of the reasons, sadly, is because it happens in women, certainly estrogen. And it’s just, you know, at least traditionally the community of brain researchers have been men. So we can only hope that that will change by engaging with people, patients coming together and advocating and people like you putting the word out.

Dr Louise Newson:[00:22:47] I think it is changing because as women, we’re realising more and, you know, sometimes it’s not until you treat something, you see the response, because as you know with the perimenopause and menopause, there’s no biochemical test and there’s lots of reasons why our memory might not be as good as it was before. And I know when I was struggling in my husband used to say, yeah but Louise you’ve just got too much going on. You’re working too hard, you need to slow down and then your memory will be better. And I said, I just can’t remember anything. I really can’t really struggling and I’m so tired and what’s going on? And it was just because I remember once I was writing for the website that I had launched and it was obviously a menopause website, clearly didn’t know I was perimenopausal. And I remember my mum came into the study and she said, Louise, would you stop working so hard? And I said, but I’m really trying. It’s just taken me twice as long to do anything. And it was only when I replaced my hormones by being prescribed HRT that then I thought, wow, that must be the effect. And there’s obviously a lot of talk are hormones placebos, but I don’t think they are because we know that we’ve got receptors for cells in our brains that respond to estrogen and testosterone. There’s a reason that they’re responding to hormones when we have them. But like you say, it’s so crucial that we can move this conversation forward with proper research, isn’t it?

Dr Dan Reisel: [00:24:07] I think it’s a really exciting time, actually, because we’ve had sort of two decades now since the major studies came out and people got very afraid of hormones. And that didn’t only have the impact on prescriptions. So worldwide prescriptions dropped precipitously in the mid to late 90s. In many countries, certainly in the West, 20, 30% of women who needed it were on hormone replacement therapy. Then it dropped to zero in many places. And we’re sort of coming out of that two decades of lost time now. But the other thing that we don’t talk enough about is that that actually caused also a massive drop in funding for research and massive, you know, there’s two decades of research that we need to catch up on, too. One of the exciting and fascinating areas that I don’t think we talk enough about that are around the preventive effects of hormone therapy. And so clearly, many women are helped by hormone replacement when they’re premenopausal postmenopausal. But there’s also significant effects on long term cognition and the preventive effects in terms of avoiding or minimizing the effects of dementia in women who don’t go through and have years and years of low hormones in their 50s and 60s. I did a small study of my local hospital recently of women who had an oophorectomy, so women who have had surgical removal of their ovaries if they were under the age of 45, did they have a conversation or any documentation or a prescription of hormones? And there was less than 10%. And that’s, you know, in many cases, you know, you go overnight essentially from having your hormones to not having them. So it’s a sort of overnight menopause and it will have huge symptomatic effects in those women in terms of the mood and cognition and a host of other things. But the bigger worry for me looking at that is what is the effect of that long term in terms of the risk of Alzheimer’s disease, Parkinson’s disease. And we know those risks are at least doubled. And so that’s an area where research and clinical practice really need to work together to find better answers.

Dr Louise Newson: [00:26:18] Absolutely. And for those of you that haven’t listened to the podcast I did with Walter Rocca talking about this with women who, especially when they’re young, have their ovaries removed, how important it is to consider hormones to reduce the risk of diseases. It’s worth having a listen. So there’s a lot of work we need to do. There’s a lot of research. I’m very grateful for your time today, Dan, and I hope you’ll be able to come back and tell us some of the studies that you’ve been involved in going forward, because everyone, I’m sure, listening will agree that the need for proper research in perimenopause and menopause and disease, preventative effects, especially in the brain, is really overdue and really needed. So before I finish, I’m not going to let you off the hook. It’s three take home tips. So three reasons why the menopause should be thought of as more than just affecting our ovaries. So what are the three things that you, if you are talking to a stranger and telling them about the menopause, what are the three things that you would say?

Dr Dan Reisel: [00:27:20] Well, I think the first thing I would say if I was a woman who either is contemplating going through the perimenopause, menopause, woman in the midst of the perimenopause, which by the way, it stretches out to seven years on average, or if you’re a woman who’s menopausal, having gone through to the other side, I think don’t accept the status quo of well, how you’re feeling is how you how it has to be. I think there’s a, what we need are women and men to advocate for choice, for the ability to have the treatment, not to accept that this is how it’s going to be now. My cognition is just reduced or my ability to function in my workplace is reduced, and we have to guard against that sort of fatalistic mindset. That’s number one. And number two that flows from that is speak to your doctor or your girlfriend or your group of friends or your workplace to really become an advocate as a patient,because we need that external pressure both as clinicians and as researchers. And the third, again, flowing from that is if you are in a position to participate in research and to contribute, you know, we can’t design studies or write up papers without the input from the women who are facing this or have been helped by this. And that voice is really important. So this is a partnership, an alliance really, between doctors and researchers and patients. And that’s 100% necessary in order to make progress in this area.

Dr Louise Newson: [00:28:58] And progress we are definitely going to make. So thank you ever so much for your time today, Dan, I really appreciate it.

Dr Dan Reisel: [00:29:04] Pleasure.

Dr Louise Newson: [00:29:09] You can find out more about Newson Health group by visiting www.newsonhealth.co.uk and you can download the free balance app on the App store or Google Play.

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