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So, first of all, thank you ever so much for joining us today, everybody. Um It is great to have you here. It's great to, for you to be joining us again. This is the second um series in our women's health series of events. Um If you re if you joined us during the, just before the summer holidays and you'll know that um we discussed CBD cardiovascular disease and how that impacts women differently to, to men. And you would have also met Vikram, um who, who is our, who was our guest speaker today? Thank you Vikram for joining us. Now, this is going to be the first of nine webinars we're gonna be doing on women's health and in particular around menopause. So we're gonna be covering H RT bones and heart health. We're gonna be covering uh polycystic ovaries as well. So there's a massive agenda that we've got over the next nine months. So there's something to actually look at and tune into. It's going to be roughly every seven weeks and it will always be at seven o'clock in the evening on a Wednesday. So this is our slot that we've booked with with, with Michaela and, and the learn with nurses crew. So I'm Becky warns I um work with learn with nurses. I'm the er strategic partnership lead. I've joined the team over the last few months really. And, and I really kind of looking to bring some women's health agenda and topics on, onto the webinar platform. So that's me, I'm gonna let Vikram introduce himself. Um and I will then just let him carry on with, with tonight's presentation. We will do questions at the end, but if you want to put them in the chat as we're going so that they stay fresh in your head or that, you know, out of your head. Um That would be great, then we can get moving. Thank you ever so much for the positive comments as well. It's, it's really great to hear that this is, this is a popular topic to be discussing. So I'm gonna go on mute and then hopefully you won't get so much feedback on the, I'm gonna pass over to you. Thank you. Thank you so much, Becky. Uh First of all, thanks to Medal, thanks to law with nurses, Becky and Mikayla uh for uh organizing these webinars. Uh That was something we wanted to do for a long, long time. So thank you for the opportunity. Thank you to everyone who has joined uh given us your time today. Uh Today's topic is about what happens during menopause transition. The reason why I'm talking about it is because I do a menopause clinic at CLH. Uh that's where my uh NHS practice is. Uh And I'm uh also attached to the Institute of Women's Health at the University College London. Uh I also train GP S and doctors for uh menopause specialist certification. So 1st 2025 minutes, I'm going to spend really talking about what happens during menopausal transition. Why are we talking about it? What's the impact on long term health? Uh I'm looking forward to plenty of questions from you and hopefully it will take the next 20 minutes of the time. Uh trying to get as many questions answered as we can. Uh in those 20 minutes. What happens during transition? Um Menopausal transition um is a phase uh which is becoming more and more uh talked about now. And for that is the life expectancy for women is on the rise throughout the world. So as women are living longer, they're spending a significant number of years of their life in the menopausal phase. In fact, if you look at a lifespan of about 75 years, the last 25 years, which is one third will be in the postmenopausal menopausal phase. And so therefore, this may be the most productive time in a woman's life. This may also be the time when certain chronic conditions. Uh hormonal non hormonal may catch up. So menopausal issues uh need much more attention uh as the life expectancy increases, menopausal transition involves lots of changes. And we are going to look at what can be the physical changes. What can be the hormonal endocrine changes also look at some of the psychological changes that will happen. But important to remember that all these changes will be influenced by a number of other factors which are non medical. For example, the ethnicity of the woman, the geography, the country where the woman comes from, the socio cultural factors. All those are going to be pretty important because all will influence the symptoms or the onset of symptoms with menopause evolution of menopause. So there has been a lot of thought about why menopause happens, why human beings have menopause uh because there are only few animal species which actually experience menopause. So that would include the killer whales, the humans, the pilot whales, belugas, narwhals giraffes. And the thought is that the menopause is a phase where older females forgo the option to have Children because this is marked as the end of fertility. And that happens so that they can support the young ones, they can support their Children and grandchildren to survive thrive and pass on the genes. So that there is continuity of the passage of genes. Now, that's a theory which is called as grandmother theory. And the biologists are still trying to find out whether that is true. And are there any other reasons, any evolutionary advantages to having menopause in human beings? So there's plenty of research that is needed in the area. What we understand is that of course, the egg activity stops at menopause. And it may be that this is uh an evolutionary tactic uh so that the genes are passed from one generation to the other. So stages during journey, a lot of people get confused about terms. What is premenopause, perimenopause menopause, post menopause. So it's important to actually know what these phases are before we talk about when symptoms will happen. If they happen, premenopause is before any hormonal changes start. So if a woman is having regular periods, her FSH LH estrogen levels are within normal range, then that's premenopause before any hormone changes, any symptoms have happened, that phase then goes into perimenopause. Perimenopause is the first stage where some changes are beginning to happen. So hormones will start fluctuating FSH LH estrogen, the three key hormones we talk about will be up and down. And this phase will usually last for 2 to 5 years in the UK, typically between 45 to 50 years of age. Once that phase is ending, that's when the periods will stop. And this is the phase where we say menopause has happened. So menopause is always a retrospective diagnosis. You can only say a woman has had menopause if she has been without a period for 12 months, one year's time. So all those fluctuations, irregularity of periods eventually will stop, the periods will stop. The hormones will go into one particular pattern and the menopause has happened. And finally, anytime, one year since the last period, onwards, until the end of life would be post menopause, that whole uh span of life would be considered as postmenopausal phase. The importance of this slide is that the symptoms may be present right from perimenopause. So a lot of times we find that women come and say my GP said I can't give you any help. I can't give you HRT or some other intervention because your periods are still happening. You can't be having menopausal symptoms. That's not strictly true because in perimenopause, the hormone levels will start going down. You may still be having a monthly bleed, but some symptoms may be starting to come up and you could benefit from either hormones or non hormonal intervention. Let's look at what happens with timing. So an average timing of onset of menopause in the UK, the median age is 51 anywhere between 45 to 55 is considered as normal range of onset of menopause. About 10% of women will have it between 40 to 45. So if you have menopause between 40 to 45 that's early menopause. If it happens below the age of 40 then that's premature menopause and only about one in 100 women will have menopause below 40. And it's very uncommon to have it even younger than that. So about one in 1000 women may have menopause even under the age of 30 or 20 that's very uncommon but can still happen. Now, the important bit is, again, there's a lot of influence of ethnicity, genes and geography. So if you look at India, for example, Southeast Asian women, they will have menopause at 46 on an average, that's five years earlier, that's a significant difference as compared to Western population. And so that's why the importance of talking about menopause is that these women who have menopause at 46 will need psychological or physical support, whether it's hormones, nonhormonal intervention. If they have difficult symptoms during this phase factors which affect onset and duration of transition. So age of menopause is influenced by a number of factors that includes diet includes exercise, level, smoking status, socioeconomic background, body mass index, ethnicity, cultural beliefs, your previous medical gynecological health all has impact on reject menopause. I won't go into too many details today because we have to keep it short. Uh But something that's uh that's being looked at more and more as uh we find out the differences between age of onset of menopause. High BMI usually is associated with a later onset of menopause. African American women have a longer duration of transition and is earlier onset of menopause in low or middle income countries. And smoking is associated with an earlier menopause, why does menopause happen at the uh physiological level? So if you look at the endocrine and what happens in the ovary. Uh Of course, we know ovary has lots of follicles or eggs. And every woman is born with a set reserve or a store of eggs. As the woman will grow old, the number of eggs will keep steadily coming down. And as you can see on the graph around the age of 37 there's a steep decline in the store of eggs. The number of follicles keeps decreasing. And by the time the woman reaches 50 the story is so small that there are no more eggs being released. No more egg activities happening and no more hormones coming from the ovary. So in the endocrine sort of basis, what happens is you will hear about three hormones being talked about with menopause. And again, I won't go into too much details of the diagram. But what happens essentially is that the ovaries produce less and less of estrogen and progesterone eventually stop producing estrogen progesterone. And that has an indirect effect on the brain and the pituitary which produces more and more FSH and LH, that's a reflex response to lack of estrogen. So when we diagnose menopause in women who need a blood test, usually they don't. But if you do a blood test, you will see low estrogen level and very high FSH and LH levels. A rise in FSH is typical and that causes something called as anovulatory menstrual cycle pattern. So the changes in hormones means that there are no more ovulations happening and any periods that usually happen in perimenopause and menopause. As the menopause approaches, they will be usually an ovulate and the circulating levels of estrogen FSH LH can fluctuate. So, although we say that the blood test may be helpful, they're not mandatory because the levels of blood tests keep going up and down, up and down during the perimenopause. So at present, the nice guidelines say that if you have typical symptoms of menopause in a woman who is about 45 you don't need to have blood tests to diagnose menopause. You can be offered either HRT or non HRT interventions. If your symptoms happen to be severe, what happens to the androgen? So we've talked about estrogen going low. But what happens to the testosterone, the male pattern hormone, which is produced by the ovaries and the adrenals because testosterone is produced by ovaries, it does decline but not, not as much as the estrogen. So what happens here is that the estrogen goes down, the testosterone more or less remains similar, slightly lower, but there's an imbalance between estrogen and the testosterone or androgen. And that sometimes may cause typical symptoms during perimenopause. For example, there may be scalp hair thinning or there may be some hair on the chin hirsutism and that's typical androgen access that can happen during perimenopause coming to symptoms. So what will be the symptoms? Who will be affected? How severe will they be symptoms? Do affect almost 80% of women. So as we are studying more and more, we realize that almost 70 to 80% of women will have some or other perimenopausal or menopausal symptoms. And they will be severe in about one third, so mild to moderate in the rest. But one third of these women will have very severe symptoms which affect their quality of life. And it's thought that the earlier you have symptoms, it often signals the longer duration of symptoms in future. So you may have a longer transition as compared to uh symptoms that happened later on during the transition. Vasomotor symptoms are the commonest and we often hear about the hot flashes, the night sweats. Uh they are the most common, more than 80%. Other symptoms could be sleep fatigue, tiredness, depression, low mood, brain fogging, difficulty memorizing or multitasking joint pains or aches all over the body. Libido drops, vaginal dryness, painful sex, and sometimes things like heightened anxiety, palpitations may all be linked to declining estrogen progesterone levels. Hot flushes are typically described as a feeling of very warm or a flushing sensation that usually spreads along the upper part of the body. And this happens because there is a change in the thermoregulation in the brain. So the part of the brain that's regulating temperature and some women may have a very narrow zone, thermoregulatory zone that we describe in the brain and they will be more prone to have flushes one of the things that is critical to know is this flushing is linked to certain neurotransmitters, something called neurokinin B, which is produced in the brain. And the reason I'm mentioning that is because there is a new drug on the horizon which is going to be antagonizing certain receptors and neurokinin B which might be used for hot flashes in future, which will be a nonhormonal medication. So watch out for neurokinin B receptor modulators. Now, among various interventions at the moment, it looks like giving estrogen or HRT is the most effective treatment for hot flushes. But there are of course, other nonhormonal interventions. One can do another peculiar feature of flushes is that women who have severe flushes do tend to have a slightly increased risk of cardiovascular disease in later life. And it's thought that these women are very sensitive to lack of estrogen. So they also have an impact on their blood vessels and heart because of lack of estrogen that causes them to have this higher risk besides the systemic symptoms. And I've just described a few of them. There are apparently more than 35 symptoms that can happen during menopause. Let's look at the other common problem is the genitourinary syndrome of menopause. So, the genitourinary syndrome of menopause uh is is a chronic progressive condition. It causes the vaginal and the vulval dryness and atrophy. It also causes a number of bladder symptoms like leaking, frequency of bladder tract infection all because of lack of estrogen. And often the pelvic floor muscles also be effective. You see the picture on the left side and the right side, the loss of superficial cells that happen in the vaginal skin and then often exposes the skin to infections. And often the the diagnosis has to be by proactively asking question. Women may be embarrassed to come forward with problems affecting urogenital tissues. And often we have to find out actively if the woman is experiencing dryness or painful intercourse. In order to provide them with uh interventions that can help sexual function can be affected also at menopause and so, declining estrogen testosterone will cause uh I uh problems with dyspareunia, painful intercourse, reduced libido, there can be difficulties with arousal or orgasm. And of course, remember that this is multifactorial. So, besides the lack of hormones, this may be a time in the woman's life where there are lots of emotional fluctuations and there may be associated vaginal atrophy and pain that's contributing to it. Chronic illnesses may be contributing to the brain function and and libido. So one has to address these aspects and not just the like of his, when they are looking through this function, p mood changes are typical. A lot of women find that they have overall low mood and menopausal transition. And after and again, that's linked to lack of estrogen. Uh there's a risk of depression, especially if there has been depression in the past, there's association between the poor sleep, the flushes, anxiety and the depressive symptoms. And again, it's important to remember that some of these may be multifactorial with personal and psychosocial factors playing a role besides the hormonal factors, sleep and cognition. Um many women do report problems with sleep, sleep, difficulty, sleep, apnea, insomnia and often cognitive functioning declines. The good news is that most studies show that although there may be some dip in cognitive functioning during the transition, perimenopause early menopause, often brain function tends to return to baseline towards the end of that process. So the body adapts to the lack of hormones and the changing hormones after a few years. That's what we know right now. But that area is still being studied. So we'll have much more information in the coming few years on cognition and estrogen lack. Finally, what about other tissues? Uh the the bones, the muscles and the connective tissue. So for all individuals, uh the peak bone density happens around the age of 20 to 30. And as we grow older, we tend to lose our bone mass gradually. So that's the mineral content of calcium and other minerals. But see what happens for women, for women at the time of menopause because estrogen is the hormone that's required to build bones. And there's a sharp drop at menopause. Unlike men who have a very steady decline in testosterone, there is a risk that some women with additional risk factors can become osteoporotic, which means they have a risk of fractures, which is significantly high. And so therefore, exercise Vitamin D calcium through diet all becomes important more. So, in perimenopause and menopause, because what we want to avoid is osteoporosis, which is a very significant costly and and um painful condition uh which predisposes women to fractures and increases risks because of the lack of estrogen, hormone, heart and blood vessels. Uh besides bones besides muscles, estrogen is key for heart and blood vessels. So, before menopause, women have a lower risk of heart disease, coronary artery disease. After menopause, once estrogen is gone, women's risk will then start coming close to men's risk. And of course, estrogen is heart friendly. It keeps the bad cholesterol low prevents atherosclerosis. So, loss of hormone will then increase the risk of plaques and hypertension. So, uh estrogen is usually the the hormone that prevents that you can maintain heart health with healthy lifestyle diet exercise. There are lots of non HRT interventions to maintain heart health. But of course, for women who have symptoms, HRT might be one of the options. So to summarize every woman's experience of menopausal transition is unique. Although majority will have symptoms, some women may not need any extra support, may be able to cope with mild symptoms very well. 30% will have severe symptoms and may need extra help with HRT as well as other non hormonal intervention. And one size fits all doesn't work, everybody is different. What is important is to, to have a positive approach to the menopause rather than taking a negative message that everyone is going to go through a very difficult stage. It doesn't have to be that way. Some women may be affected more severely, but there are interventions that can help go through the transition uh in a much more positive and, and better way than uh in a negative way. Thank you. Thank you for listening. Thank you, Becky. Thank you very much. Indeed, Vikram. Um And let's open the floor up to some questions, please. If you can put your questions in the chat, um Vikram will be here to, to answer them for the next, for the next 10 minutes or so. So take the opportunity whilst we're, whilst we have him here. OK, whilst we're waiting. Um Vikram, I guess I'll, I'll, I'll ask a, a question then with regard to um to, to H RT at the moment. Um and the supply we, we obviously very short lived had a, had a H RTR that was, that was, you know, appointed by the government. They've since left that post. What are you experiencing with regard to H RT supply? And how is that impacting patients and, and and wellness generally? Well, um Thank you for raising that, Becky. First of all, we should not be in this situation. Let me be very clear that it's unfortunate that we are in a situation that we are in now because in a way, we had a long time to predict that there would be an increase in HRT usage as menopause became widely talked about. So in a way we weren't prepared, but unfortunately, we are where we are. The HRT shortage was very acute a couple of months ago, it's still there, but things are becoming better. I don't know what happened with the appointment of the HRT are and, and that will be some political uh uh issue behind why she was again moved back to COVID and other uh departments. But I think from my point of view, the the shortage is improving. Uh it's mainly the gel, the estrogen gel and the spray uh which was affected, the patches and the oral tablets were not affected, things are getting better and hopefully in the next couple of months, I think we'll have more and more uh stocks coming back in the meantime, for those women who are struggling, all I would say is try and speak to your GP or a specialist so that you can maybe transition from one form of transdermal therapy to another just for the next 23 months and then come back to your original preparation once you get your stocks back in the pharmacy. Great, great. Thank you ever so much. And let's move on to, to questions from the audience then. So um what's the first question? What are your thoughts on testosterone replacement for peri or menopausal women vra so, testosterone replacement at the moment is really for the indication of low libido. I know there has been a lot of talk in the media about it helping with energy, mood, uh stabilizing mood as well as uh things like muscle mass, bone. Yes, testosterone may have action on these areas as well, but we don't have good quality data to say that it certainly benefits. The one thing that it does benefit is if your libido is low. So if you're in perimenopause, you're having symptoms, the first thing to try is HRT a good form of estrogen replacement. And as long as you're absorbing good estrogen and if that doesn't improve libido, it's an ongoing problem. The testosterone can definitely be added as the next step. Great. Thank you very much. Next question. What indications does a hysterectomy have with the ovary removal on menopause? So when you look at hysterectomy, uh it can be done either on its own or you can have hysterectomy with removal of ovaries that would bring you into something like surgical menopause. I guess you're asking me the second one with removal of ovaries, right? So if it's hysterectomy on its own, I'll, I'll tell you both aspects of it, then ovaries usually will stop working slightly earlier in life. So in three or five years time, we see that the you may become menopausal if your ovaries were left behind. If however your ovaries were removed at the time of operation. Surgical menopause can happen and that is supposed to be one of the most severe forms of menopause, especially if you were not menopausal before that. Because if you suddenly remove the ovary, all hormones are gone together. And that can be a profound like of hormone in a short time for your body. The same principle will apply if you're symptomatic and if you're younger than 50 you've got to go on to HRT, that would be the best option. But there are non hormonal interventions which you might also want to do side by side HRT. If you're above 50 then it depends on your symptoms. Whether you consider HRT with all its benefits versus risk. I think we'll cover that hopefully in some of the future. Uh by what HRT is, what are the benefits and risks, et cetera. Brill. Okie Doke. Moving on to the next question. Do you think there will be a role for hit as a primary prevention for bone health, heart uh brain uh with no significant menopausal symptoms? It's a very good question, something that you can debate on hours and hours at a time. Uh My personal view is yes, estrogen has a potential to be a very good primary prevention uh modality for preventing osteoporosis heart disease as well as preserving brain health in in later life. The difficulty is that at the moment, use of HRT is associated with increased risk of say blood clotting and increased risk of breast cancer. And so therefore, balancing the two right now, the data are insufficient to say use this as a primary prevention method as we're trying to improve a charity. For example, you are using transdermal products which don't have risk of blood clotting. We might find certain combinations of estrogen progesterone are very low risk for breast cancer and it might come to a stage in a few years. We find a combination that has very low risk. So, primary prevention uh with estrogen becomes a reality, it's certainly good. But right now the data are missing to justify its use for primary prevention. Great. Thank you. Um Beverley's asking, is it ever too late to start? H RT? Um The answer to that is no, it depends on why you're taking it and what your benefits from it will be. So most women below the age of 60. If you're healthy, if you have significant symptoms, your benefits outweigh risk, you should consider HRT as one of the options. If you're about 60 then the the the benefits for bone and heart will be less because some of the changes with menopause have already happened. They won't be zero, but they won't be as much as if you had started HRT early during transition. So you could still consider it, but it's mainly for symptoms. So if your symptoms are bothering you, you can still consider it. Uh the balance of benefit versus risk is a bit less as compared to before, but it could still mean that it could be useful for you. So there are no arbitrary ages for starting or stopping according to me. Great. OK. Next question, then um someone said the slide timing of menopause relating to ages affecting women. So your slide on, on ages of, of menopause, is there more recent information because the slide is dated in 1986. What is it that, that hasn't changed? Well, it hasn't changed really. There have been plenty of studies. So if you, uh I might just quote one of our recent books or chapters which we wrote for one of the uh best practice issues, maybe we summarize the data of what has happened over the last many years. Essentially, the information hasn't changed, which is why we go back to the Gold Standard studies which were done in eighties and seventies and nineties. The only thing that's different is that we know that the ethnic ethnicity and the geography will then change that information. So that study which has been quoted is for UK, it's based on Caucasian European population for in individual populations, say from Asia or Africa or South America, you will have to look at individual papers. Some of them are summarized in, in, in a couple of publication. I can easily give you the references if you're interested to look into those. Great. Thank you. Next question, what is the maximum level of estrogen that a Mirena coil will cover? Well, the Mirena coil is a very good form of progesterone for HRT. Um and as long as you use estrogen within the recommended doses of the manufacturer, so that would mean you're using either a maximum of 100 patch twice a week or four pumps of gel a day or three sprays a day or oral, 2 to 4 mg a day. That's the maximum estrogen we recommend the Mirena is taught to protect the womb lining with those doses. If you go outside of those doses, which is unlicensed doses of HRT, then there are very limited studies. So you would have to be monitored for your womb lining if you're crossing the manufacturer's recommendations. Great. Thank you. Um And OK, stay with, with the HRT thing. What are your thoughts on bio identical? HRT versus Standard H RT? Ok. So again, this is the two are the body identical regulated HRT, which most of us use in clinics on the NHS versus the Bioidentical, which is the nonregulated and individual clinic HRT often done by high street clinics uh which have their plant estrogens, progesterones combined together, both are effective and both give symptom relief. The body identical are well regulated. We know what happens with them in 5, 1015, 20 years. What are the exact risks with blood clotting of breast cancer? The problem with bioidentical individual clinics is that we don't have such studies for 5, 1015 years in a randomized trial fashion. We don't have gold standard evidence. How much is the risk with these medications? Over the next 1015 years? I have occasionally come across women on bioidentical, unregulated HRT who have had problems, say with thickened womb lining had to have hysteroscopy, et cetera, et cetera. So I tend to recommend only body identical just like most of the BMS and the I MS bodies. Uh The bioidentical, we simply need more data before we can recommend it. Great. Thank you. And one other question we got here, please, can you repeat what you said about neurokinin and what to look out for in the future? So, Neurokinin B is one of the receptors in the brain, which actually is involved in triggering of the hot flashes. So there is a medication that is being developed which is neurokinin three receptor modulator uh which basically acts on the receptors to prevent the generation of hot flashes. Uh Again, that's well covered. So if you Google Neurokinin B receptor antagonists in the, in the, in the Google, you will come through lots of trials that are happening now with the medication, if that comes through uh and passes the trials with safety and efficacy, I think it's almost there in the next year. It will be a very good addition. Uh which means you don't have to necessarily take HRT but you could take the new medication? Great. Thank you Bigram. And are there any more questions at all? I've just sent the feedback uh questionnaire out um in the link. But are there any more questions for bit? No? OK. What I will say is our next session? Thank you, Regel. Our next session, our next webinar will actually, I did say seven weeks. It's actually gonna be on the second of November and it's on PCO S and that's something I know that I'm very passionate about. So um yeah, I've, I've, that's something really to look forward to and hopefully get, get in your diaries. Um Sorry, something from uh not a question but a suggestion I can recommend on a personal level cold water swimming rather you than me. But yeah, absolutely sounds good. Vikram is that uh obviously you, you're not suffering menopausal symptoms, but have you, have you um come across patients that are using that to relieve symptoms? Well, yes, some patients do actually use different forms of non HRT intervention. And I think if cold swimming works for you to at least get the worse symptoms down and works for you. That's great. We just have to have scientific studies before we recommend it, but it's uh there are lots of such interventions which individual patients find useful. Yes. Thank you ever so much. Everyone. I think it's been a really successful evening. Thank you for joining us. Do fill in the feedback forms and keep that feedback coming so that we know what else we can plan for in the future. We would like to really expand the women's health side of things. So do feed that through victor anything you want to say before we sign off. Thank you everyone for giving you a valuable time. Uh and do give us feedback because that keeps us improving our presentations every time. But thank you so much for, for joining today. Thank you. Have a great evening. Thank you ever so much, everyone. Bye bye bye.