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Out. Thanks everyone. Um OK, this seems to be a really popular session um As VS Always Are tonight. So, um I'm gonna introduce Vikram. We're gonna be talking about cognition and mental health in menopause. Um And yeah, let, let's crack on with it, Vikram. We'll do questions at the end. Um So anything you've got either put in the chat or keep stored up and, and put into the chat once we, once we've finished, OK, over to you, Vikram. Thank you, Becky. Uh And thank you, everyone who's joined us. Uh As usual, the format will be, I will go through some slides, try and introduce the topic. Uh And we're looking at mental health and cognition uh during menopausal transition today. Once we've done that, we'll uh get the floor open for questions. So hopefully lots of questions uh from all of you. Uh I'll share my presentation in a minute. Uh So share your screen and let me get the presentation there. OK. Uh Becky Can you see my slides? Yes, perfect. Thank you. So, uh the topic for today is cognition and mental health in menopause. Uh Let's start with a bit of uh uh background information about menopause for those of you who may not have joined our previous sessions. Uh And why we are talking about the issue um that there are certain stages during journey towards menopause. Uh And the hormone changes happen in different stages until a woman or an individual stops their periods. Premenopause is before any hormonal changes have happened. Usually, the woman will be having regular periods, then comes the phase of perimenopause. This is when hormone fluctuations start, the periods tend to be uh irregular. So the menstrual cycles tend to be short in the beginning. And then as the transition progresses, the menstrual cycles will be longer, eventually, the periods will stop. Perimenopause usually will last between say 2 to 5 years for most individuals uh between age group of 45 to 50. However, it can go on longer for up to 10 years or more. Menopause is a technically defined as when the periods stop completely. Usually a retrospective diagnosis one year since the last menstrual period. So if 12 months have passed and there hasn't been a period that would be menopause. And finally, you have the post menopausal phase one year since the last period until the end of life, all that phase would be post menopause. And the reason to kind of go through the phases is because some symptoms may start very early during perimenopause when the hormones are fluctuating despite the individual continuing to have periods. Now, it's equally key to remember that. Although this is generalized information, uh the age of menopause depends on the ethnicity, socioeconomic status and many other variables, about 10% of women will have an early menopause. And that is usually between the age of 40 to 45 about 1 to 3% of women will have premature menopause or premature ovarian insufficiency that is under the age of 40. And of course, the ethnic variations are very important. Uh That's because say, for example, Asian women will have menopause five years earlier than the Caucasian counterpart. And so all those sort of subtle differences become important when clinically assessing women who are presenting with perimenopausal or postmenopausal symptoms. Why are we talking about this topic today? Of course, menopause, a lot of symptoms tend to be linked to the brain, menopausal transition in a way involves neurological transition. There are changes to brain and its functioning that will happen as the woman will progress from perimenopause to menopause to post menopause. Many menopausal symptoms are neurological in nature. They start in the brain. So for example, hot flashes, night sweats, the classical vasomotor symptoms, disturbed sleep, insomnia, mood changes, low mood anxiety, depression, forgetfulness, or brain fogging episodes, not being able to recollect something easily, uh not being able to find out why you're there or not being able to find the right word while having a conversation. Those sort of typical brain fogging episodes, headaches or migraines can increase or decrease or change at this point. And so also lower g of fatigue. All these tend to link together to indicate some sort of changes in the brain uh as the hormones change during the transition. Of course, it's equally important at this point in time in forties, fifties that there will be so many other lifestyle and other medical issues that may be causing similar uh symptoms. And there's a lot of overlap of the symptoms I mentioned with other conditions. Uh the typical one right now, the most relevant one being long COVID. So in the clinic, for example, we see women who have had both long COVID and have been perimenopausal and sometimes it's important to be aware of both because you can easily think that this is only long COVID or this is only perimenopause and not give due credence or importance to the other condition, which may be coexisting. If you look at the symptoms of long COVID. And if you look at the symptoms during perimenopause or menopause, you can see how many of them are similar or overlapping. So it's really important to be aware that is this down to hormones alone or could something else be contributing to some of these symptoms? Now, let's look at first the low mood, heightened anxiety and depression. And some women will find that their periods may not change much in the beginning. They may not have any other classical vasomotor symptoms, hot flashes or night sweat, but they just have low mood or they just realize their anxiety levels hit uh the roof. A lot of anxiety, depression, depressive thoughts start happening around the time of perimenopause and post menopause. And it's usually the times of the hormonal changes that these symptoms happen. So for example, menopause is the one we are discussing now. But a lot of women will find that they have similar sort of mood changes or problems with emotions at the time of puberty after childbirth, postpartum or even when they have their monthly cycle, especially during the second half of monthly cycle, premenstrually or during the period or when they're taking contraceptive pills during a particular part of the contraceptive pill cycle. So, hormone changes do affect brain and emotions. It's the fluctuations in estrogen levels primarily which are thought to be the triggering factor for the low mood and the depressive thoughts. But as I said, it's not just the hormones, you have to always look at the bigger picture. And there are so many things happening during perimenopause menopausal transition. For example, some will have aging parents, others will have career pressures. There may be overlapping chronic health issues or problems. Uh kids leaving home empty nest as it is described, all these may be also having contribution besides the hormones that may all together contribute to the low mood and depression. If the woman has a history of depression, postpartum, depression, then those are the key risk factors that perimenopause or menopause may bring back the symptoms. Again. How do we manage and what do we advise if this happens? Because it's variable. Some women may not notice any low mood or anxiety. Others may have such increased anxiety and low mood that they will not be able to function. And it's really important to listen to women sometimes just listening, acknowledging symptoms and then giving different options that can be used to avoid these symptoms or suppress these symptoms is key. So there are lifestyle factors. So for example, making sure the diet is healthy, making sure there is regular physical exercise, uh mindfulness, stress relief, uh making sure that overall there is a healthy lifestyle such as no smoking, avoiding excess alcohol. Those will be the key lifestyle factors, cognitive behavioral therapy. CBT helps a lot of individuals and is one of the two go non hormonal options. Uh Again, either through the GP or self funded or there are so many options nowadays, online uh for accessing CBD psychological support counseling helps uh especially uh if this has helped previously, it is one of the options to always use and helps a lot hormone replacement therapy. If the low mood and anxiety has happened at a time that perimenopause or menopause is happening. Other symptoms of menopausal transition are present such as vasomotor symptoms or other vaginal symptoms at this point in time. The most likely reason why there is low mood and anxiety is the lack of estrogen or the fluctuation of estrogen levels. So, HRT tends to be the first line intervention when we think that the low mood and anxiety is happening because of the fluctuations or lack of hormones. Of course, there are effective non hormonal medications. For example, beta blockers for anxiety, antidepressants for major depression. And these will be useful if hormones are not the only cause of the depression. So remember that it's looking at the bigger picture and finding out how much contribution of low mood and anxiety is likely to be hormones that will determine which route you choose. Whether it's the a charity. That should be the first line, which is usually true if it's perimenopausal low mood or it's the non hormonal medication such as the beta blockers or antidepressants. Again, just a quick word to summarize the lifestyle intervention, it's stopping smoking, making sure there is no excess alcohol or caffeine, making sure the diet is healthy. The weight control is something that's being looked at regular physical exercise does wonders for mood. And it's really key any exercise that you enjoy, stress reduction, mindfulness and finally sleep hygiene, sleep is another key factor which is really important for avoiding brain related symptoms. Again, quick word about some of the apps and some of the internet resources one can use. For example, there are effective apps which one can use to help with sleep. And of course, there is so much advice out there. I won't go into details because we have restriction of time. There are plenty of resources online. Again, quick word about some of the antidepressants or anti anxiety agents. Uh This is Venlafaxine is supposed to be the best one if it's menopausal, uh low mood or anxiety and if the woman doesn't want to use HRT, of course, Venlafaxine 37.5 to 1 50 mg. You also have others, For example, classical SSRI citalopram, sertraline, which are also effective agents. And paroxetine is yet another one but be careful in women with breast cancer because it can affect the efficacy of tamoxifen. A quick word about migraines. Uh estrogen and headaches is a bit of a complex relationship. Sometimes it's the lack of estrogen which can trigger headaches and make migraines worse at perimenopause. At other times. You find that excess estrogen, too much HRT itself can trigger migraines. There are effective online resources available. Uh I can point out to the National Migraine Center or the migraine trust, which can again help and provide very useful information for individuals suffering with migraines. From HRT point of view, if the hormone fluctuations are causing migraines, HRT does help and you will find that giving a continuous combined bleed free HRT that avoids cyclical pattern of hormones is the one that's most likely to help. So, keeping somebody on a continuous bleed free, HRT and transdermal patch gel or spray form of estrogen is likely to help with migraines rather than oral forms or cyclical forms of HRT. Now, let's look at the other bit which is the menopause and cognition. There is so much out there in the press right now about this dementia is of course, emerging as one of the uh biggest health care problems we have. It's the biggest uh health threats for the world. Uh And of course, number of people living with the condition is set to nearly triple to more than 1 50 million by 2050 two. In three people with Alzheimer's, which is just one form of dementia are female and about a quarter of women in UK, they carry a gene called EPO four, which is a strong risk factor. A genetic risk for the disease. So it's really important to address uh cognition and menopause because we really want to find out something that could help with prevention of the condition. It is, of course, a global pandemic. There are huge global financial costs of caring for individuals with dementia and the human cost is even worse. It's not just for the person, it's a major cause of disability or dependency, but the people around that person, the team that cares the relatives, they have so much physical, psychological, social, economic impact. Alzheimer's disease, of course, is one of the types of dementia which accounts for 70% and one in 10 people will develop Alzheimer's after 65. And as you can see, it's 16 women for every 10 men. And that is the statistic that's important. It's more for women at risk than men. There's no one who is immune and currently there remains no proven preventive intervention. It's very complex to study the link between hormone changes at menopause and dementia because brain is affected by so many variables, the lifestyle, the other hormones, medical conditions, and then you have, of course, the estrogen progesterone is at menopause. And if you look at everything, you have to often summarize the effect of each individual variable when looking at a complex condition like dementia. A lot of women present with brain fogging during the menopausal transition. And the question is, is this dementia, how do we know this is not dementia? Is the brain fake fogging telling us that in future that person will develop dementia. Can we treat brain fogging? So the one thing is that we currently do not know if you experience brain fogging during the perimenopause or menopause, does it mean you're going to have dementia in the future? We don't have research to suggest that it may be that it's one of the warning signs, but we simply haven't studied enough to say that brain fogging is a symptom that could indicate future risk. We need much more research on this brain fogging often responds to HRT. So replacing estrogen progesterone as part of the HRT often improves brain fogging makes the brain function better whether it's a temporary effect or something that is always required in future. Again, we don't have enough evidence to suggest. Right now, there are subtle differences in how dementia presents and the brain fogging of menopause presents. And again, these are subtle, there is so much overlap and sometimes it may be very difficult to know which one. But remember that dementia is usually memory loss, it's mainly the short term memory and other issues while the brain fogging can affect not only memory but often the thinking process. So trying to find a word, trying to find I'm here in a room trying to make sense of uh things which are being uh done at the same time, multitasking, that sort of brain fogging pattern is more towards hormonal deficiency or hormonal changes that happen as part of transition. While dementia is mainly the lapses in memory. Currently, we know that dementia is thought to be multifactorial. There are so many body changes that happen that eventually contribute to the risk of dementia. One of the ways estrogen could also be affecting dementia risk is not just on its own as function on the brain, but remember that estrogen is very good for heart and blood vessels. So if it if it keeps your heart and blood blood vessels supple for a longer period of time, it's likely that that itself may have an impact on future risk of dementia. And that's why it may be protective to some extent but despite studying all these variable, what comes out from research right now is that lifestyle is the most important variable and it's thought that at least one in every three Alzheimer's could be prevented by improving lifestyle choices. Uh diet exercise, intellectual stimulation, reducing risk of vascular disease, heart disease or BP, making sure hearing loss is attended to uh social interaction is preserved. All these remain the key aspects of trying to reduce the risk of dementia. I will just cite a couple of papers from Doctor Lisa Mosconi. You many of you would have been um would be familiar with her work and would have seen her uh podcasts and, and some of the publication, you can just look at this picture and see the effect of Mediterranean diet, a healthy Mediterranean diet versus largely meat based and uh Western diet. And you often find the fullness of the brain more of the brain tissue uh in a woman at around 50 years of age who's had Mediterranean diet throughout her life. And you see lots of black or dark areas with less brain tissue in and around the hippocampus in and around the ventricles suggesting that Mediterranean diet, healthy diet is key to preserving brain function and tissue. The neuroimaging also suggests similar situation in that the brain does change the structure, the connectivity, the metabolism in the brain changes across premenopause, perimenopause post menopause. And you find that the amyloid deposition, which is the key aspect of the dementia risk is more pronounced in perimenopausal and postmenopausal women who carry the epo four genotype. If you do the same to the same gene, males, you find that women are at more of a risk. So there is some link, there is no doubt that uh menopause brings in in terms of the changes to hormones and women who carry the epo four gene may be particularly at more risk. This is yet another paper from Mosconi group which showed the energy metabolism in the brain and how it changes with menopause. Overall. With menopause, there was a 30% drop in the energy metabolism uh from before to after. But the change appears to be temporary because five years into menopause, it looked like the changes in the metabolism had plateaued with many of the symptoms like brain fog or fatigue trying to resolve it may be that this is just a physiology and action and this doesn't have any long term consequences. But it's in interesting to see how the brain changes as the hormones change in the body. So again, what about HRT for dementia prevention? Uh There are lots of media reports about HRT but they lack scientific rigor. Lots of paper headlines saying HRT may be good for preventing dementia. Uh lots of headlines about animal or experimental studies, but we're not there yet. So mostly we have experimental animal observational studies which suggest that maybe perimenopausal hormone therapy may preserve the brain tissue. Uh as compared to somebody not taking hormone therapy at perimenopause. It could be that estrogen does produce more neuronal connections or the changes the way the chemicals act, the serotonin, the choline and the dopamine. But we have no conclusive evidence for this from human trials. So it's really important to know that right now, we cannot say HRT prevents dementia. We need much more good quality human based research. Observational studies show efficacy for brain fogging. You can certainly treat brain fogging with HRT. But the effect of HRT on the risk of dementia is unclear. Uh The study findings do not show causality and there appears to be a timing effect. In fact, if you look at some of the early observational studies from who and a few others, they showed that if you started HRT, especially later after the age of 60 it increased the risk of dementia. Um So you can see that there was some increase in the risk of dementia in women who initiated combined HRT between 65 to 79 years of age. But those who were young and started HRT did not have any difference in risk of dementia. Another study which was the keep study had about 693 women again showed no difference uh or worsening of cognitive outcomes. Uh There was a big Finnish study that came from Finland. It was observational with more than 80,000 women comparing Alzheimer's to controls and found that estrogen or combined estrogen progesterone increased the risk of dementia. Now, there are lots of new studies as well. One of the more important one is the observational one that came from University of East Anglia and University of Edinburgh, which actually analyzed data from more than 1000 women. And what they looked at is uh those who carried the epo four genes versus those who didn't and did find that some women who had the EPO four carrier uh gene status had some benefit from HRT. So HRT did seem to have benefits for brain volume and better cognition uh parameters. So there seems to be some role from observational studies for starting HRT early, which may benefit some women who have the, the risk of EPO four gene. But overall, the studies are conflicting, some still showing a higher risk versus others which show uh uh no risk or slight benefit. So at the moment, the BM S position is that we should uh just start HRT for symptom benefit and women do have the heart and the bone benefits of HRT. HRT is unlikely to increase the risk of dementia. But HRT should not be initiated for simply for the sole purpose of reducing or preventing dementia. So we did much more research before we can say it's uh something that can prevent dementia. So that's in, in nutshell, a summary. Uh And again, I'm gonna stop with this slide. So we can take some questions from you. Uh But overall the message would be uh it's about concentrating on lifestyle, eating, well, ensuring good sleep, exercising, uh keeping mind active and consider HRT especially if menopausal symptoms are severe but not for the sole purpose of preventing dementia. Thank you. Great. Thank you ever so much. Uh Vi Right. Let's just have a look. There was a question up here about cloNIDine. Uh Sarah's asked, um re cloNIDine please. This appears to be helpful at reducing, reducing hot flushes but seems it can cause sedation effects. Could you explain further, please, Vikram. So cloNIDine has been uh it's been included as one of the non hormonal options for for treating vasomotor symptoms such as hot flashes or night sweats, uh which are part of menopausal transition. Uh It is one of the only licensed medication for this indication actually and used often in dose of 50 to 1 50 mg a day. CloNIDine is an alpha two agonist. Uh So it has action on the same part of the brain that actually triggers the flushes. So many women find that the flushes are better. The trouble with cloNIDine is it can cause hypotension and it can cause a lot of dizziness and sometimes the sedation that you're describing is because of the dizziness that the cloNIDine causes. For most patients I ever started cloNIDine. The ones that had have to come off even with the lowest dose is because of that dizziness or a bit of, uh, brain fog that happens. It's purely because of its antihypertensive or hypotensive effects and that's what causes the sedation like or dizziness like effect. So, if the woman can tolerate it well, doesn't have these effects and gets rid of flushes, it's a good medication. Uh, but you have to be careful when you come off it to prevent rebound, BP increase. Otherwise, in my own experience, cloNIDine works for very few. Um and it has not been a very effective treatment option. So uh I tend to reserve it for those who really can't take HRT. Great. Thanks V very much. That's a really, really informative er response there. Um Alison's asking what age is it too late to start? H RT, there's no uh arbitrary limit as to starting HRT or stopping HRT. Uh the general consensus from the knowledge we have so far and it keeps evolving, keeps changing. So always watch the space. But what we have right now, we think that majority of benefits of HRT for symptoms as well as for bones, for heart, for long term health metabolism tend to be under the age of 60. So we tend to encourage somebody starting HRP early in perimenopause if you're symptomatic or between 50 to 60 to get try and get the maximum benefits. After 60 the benefits will be there but relatively little and the risk in terms of aging, the risk of stroke, risk of cancers like breast cancer gradually will go up the longer you use HRT. So the balance of benefit versus risk, the benefits tend to be low and the risks keep going up. Having said that it's individualization. I do have women who will choose based on evidence that yes, they would still like to have that little benefit from a charity and be careful about preventing the risks in any way possible. So it's an individualized decision. Overall, one would say starting below 60 is ideal. Great. Thank you. Um Zoe's asking will there be retrospective or prospective studies uh to look at reported brain fogging? Um and and dementia. Well, I think both uh retrospectively uh we are very poor. Generally. Traditionally, we've been very poor at recording symptoms. I'm personally guilty sometimes of not recording symptoms in a systematic way to go back. And 100s of thousands of women we see across different clinics to then actually see what happened retrospectively. What's the response to HRT other interventions? So if you have good record keeping and all the symptoms are recorded right from word go, then you can go retrospectively from the onset of symptoms and the response to HRT or non HRT intervention. That would be a good series to look at the uh how brain fogging responds otherwise, prospectively designing a study to record symptoms in future. And then actually trying to have a set of women who use intervention, A like HRT versus intervention B non HRT versus those who don't choose to address the symptom or decide to just monitor symptom. That sort of a prospective study will be equally useful. Whatever research, little research that comes through is really key because for a long period of time, we have neglected these symptoms, thinking it's something multifactorial and the hormones may not be at the root cause of this. Brilliant. Thank you. And Sarah is asking how can women find out if they carry the potential dementia gene? Who screens? Well, I don't think there is a routine screening. Uh This might be a question for neurologist or dementia specialist as to whether EPO four screening is routinely uh hopefully offered in future, given that it has some implications for dementia risk now or whether this is a screen, I have certainly come across women in my own practice who have done it on their own. Sometimes they access genetic kits online, for example, 23 and me and others, but sometimes they have been identified to carry these genes. Uh I don't know to the NHS, what criteria or uh you would need to satisfy what boxes you would need to take to get this, uh to be screened. I guess it would be based on your family history. Uh But again, something that uh is more of a neurologist or a dementia specialist. I it, I guess Brill, thanks Vikram. Um And Sarah, I know Sarah's asking how frequently, how frequently even should po I ladies have the bone scans, please. So general recommendation is if you're on, on HRT hormone replacement therapy for poi, you would have a scan once every four years. Uh sometimes three years, if you've already had established severe osteopenia or osteoporosis, and then you're taking HRT to try and reverse that bone loss. But the general recommendation would be somewhere between 3 to 4 years. If your levels are of the, of the T scores are looking stable or improving, then you just stick to that frequency. If the T scores drop, which means your bone density is dropping, you might need more frequent scan because then you will need to either change the HRT or consider non HRT intervention to make sure your bone density doesn't keep dropping. In which case, you might need a bit frequent scanning. OK. And Stephanie, I've seen your question but as we are on the poi thing, I'm just gonna jump across down to Sarah's next question. Should poi ladies have regular mammograms? So, outside of the usual mammogram regime, in your opinion, no. Um So again, remember you're only replacing estrogen progesterone as part of poi HRT regime. That means you're only replacing what's missing, you're not taking excess hormone unless you have had a specific family history of breast cancer. So you yourself have had breast lesions and you've been advised by the breast clinic or specialist to have more frequent mammograms or you've had other forms of cancer treatment, radiotherapy for which then you have to have mammograms as poi with HRT. You don't need any extra breast surveillance. Just make sure you check your breasts regularly. And if you report uh make sure you report to your GP, if you see any abnormality, lump discharge or any unusual findings. Great. Thank you. And Stephanie saying, uh I don't know whether this is, is, is herself or, or a patient, but since starting H RT, she's having restless legs. Is there any suggestion for that? It's something I have come across before but not commonly. Uh restless legs can just be a standalone issue on its own, not linked to the hormones or HRT, but it can sometimes come up during perimenopause and after introduction of HRT, um one of the things that has sometimes helped is to try and vary the estrogen dose, uh estrogen uh and the muscles and calcium. Those are the three factors that are often interlinked and sometimes trying to choose an alternative route or dose of estrogen may help with the restless legs or muscle cramps in the legs. Uh Those are the two conditions that tend to be linked. Uh You might still want to see your GP if after changing the route or dose of estrogen or form of HRT things don't improve. This might be unlinked to the hormones uh or the HRT brill. Thank you. And Lena is asking um is anyone having any knowledge about stem cell specifically crystal cell. It's one of the best products that help menopause anxiety and everything involved in hormonal issues. Um I certainly haven't heard of stem cells or crystal cells in my practice. Uh It's something that I haven't come across. Uh I uh one would have to be uh more familiar with it. Read the research behind it before one can recommend it. Thank you. OK. Have we got any more questions at all? For Vikram? I just keep the, keep the line open for, for sort of 30 seconds or so. Um I'd sent everybody the uh feedback. Please. Please give us some feedback. Let us know what you thought of tonight's session. Is there any other topics you want to be uh want us to discuss? Um Are there any other women's health specific uh speakers that you want us to get in? Get in? And yeah, my, my sort of role here in this menopause session has very much been about facilitating and bringing vra on board. So for me, what I want to try and do is expand this session if we can to include other speakers on different topics, let us know, let us feedback. I think that when we are actually done with questions. So if there's anything else you want want to add, then then then please do. Thank you, Becky. Uh again for the opportunity to present today. I hope that people who have joined, found it useful and I guess you do have access to recording. Am I right, Becky? If they, if you want to go back and watch? Yes. Uh, any questions? Of course, uh, you can, you can get in touch with us if you have any questions, um, and give us feedback. We like to keep improving on topics and sessions as Becky said, uh, so we'll try to keep bringing on new topics in women's health and try and present a short bite size data as we can within the 30 minutes. Uh, thank you so much for your valuable time today. I much appreciate it.