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Good evening everyone. Thank you so much for joining us. Once again, we have grim with us again and we're talking about premature and surgical menopause. Um Not much to say really other than to, to let Vikram introduce himself, but also to say, thank you to medal for the platform, free education for healthcare professionals. Absolutely superb and a great initiative. So, thank you very much Vikram. I'm gonna pass over to you. We're gonna do questions at the end and there'll be a survey as well coming out to you as normal. OK, I'm gonna mute myself. Thanks. Thank you so much, Becky. Uh And so actually, uh this is going to be a little bit longer than usual, which means we'll finish at 740. But normally what I tend to do is about 10 to 15 minutes of slides and then go straight to quest. But we have two big topics today, the premature and the surgical menopause. So it's going to be a little bit fast. I'm gonna try and cover as many aspects of both poi and the surgical menopause may not be able to cover everything, but really to give you the important key themes and concepts and I'll try to save at least 10 to 15 minutes at the end for the questions. So I try to share my presentation. Uh There we go, uh entire screen share and you should be able to see uh slides from me in a second and let me know, Becky as soon as you need them. Yeah, I will do. We're not there yet. See them now. No. Could anyone else? It might be me. Ok, I'm sharing the screen. It says so you should ideally be seeing it. No, no, no. Ok. So let me try maybe share a window to know what's going on. Uh So maybe chair. Ok. Any, any progress, not at all. Nothing sharing. It doesn't like this web or now does it? So share a window. Let me try that. Yeah. Says don't share a window but if that works it works. Mm. The message. No, still not, still not. Uh I don't know what's going on then. Um I get the share option and I'm trying to, to share. Yeah, share entire screen thumbnail share. Uh but it does not share it, I guess. No. Well, I just uh it would have been nice to show the slides. I don't want to simply talk because there are some key important things there. Um I wonder what do I do? Do you? I'm just having a look, I'm just reading the instructions um from in the chat but me have put up just in case there's anything different to. What are you on? Are you on Chrome? I'm on Google Chrome. Yes. Yeah. OK. And you're using metal slide. Share to see there's a button at the bottom which says uh arrow. That's the one I'm using. Yeah. OK. Share entire screen and you're going to share entire screen. Yeah. Share entire screen best for full screen presentation. Yeah. And you're selecting the thumbnail of your. Yeah. Yeah. So here you go. Entire screen. I've selected it. It says share now, click the button and then nothing happens after that. No, nothing's happening at all for us. Uh Should I try share window or share tab? Share a tab? Maybe as long as you got nothing up there that people don't want to be no patient records or anything. Give it a go then. 00, yeah, that's working. Yeah. So if I go to and do you see the slides? No. Hang on. Mhm. Oh gosh. So it, let me, let me share this particular window but it wouldn't let me share what's on my desktop. That's a bit strange. Yeah. It's not all, all we're seen it. How bizarre. Uh, let me just, um, no, I'm just gonna see if there's something I can bring up that I can share just to see whoever it's. You. Let me just find something that isn't. Uh. Mhm. Right. Ok. Let me just try, try, try and sharing. I'm just gonna try and share my screen everyone. Not that this is anything to do with the presentation we're talking about, but just to see if it works. Sure. Can you see Parkinson's digital Home Care based care? No. What are you, what are you seeing? Uh Let me see. I'm trying to e-mail the presentation to you as suggested so I can see your Parkinson's digital Home based care now, right? So mine's working. Yeah. Do you want to share it to me? In which case I'm just sending you this the presentation now and you should see it in a you should receive it in a second. Um and there you go then we you can move the slides for me. Becky. I can do that. Yeah, cool. Let me just wait for this to come through. So sorry about this. Not exactly. Yeah, apologies. We don't normally have. I mean obviously had issues last time but we don't normally have issues so we do apologize for you. Ok? Send it to you and hopefully you'll get them in a second and we can get them live. Mm. Ok. Ok. Got it. Uh um No, hang on. No, no. Uh I that's the right li oh I haven't got my slide yet. I've only got the hang on, hang on, hang on presentation. Got the presentation. Ok. Here we go. Just like that, right? Ok, cool. So there very slick, isn't it a isn't it slick? Let me just see what I can do here a moment. So make it out of it. Ok, let's try this chat. I screen chat. Yeah, thank you. Right. OK, hang up here. Thank you, Becky. Thank you. Everyone who suggested solutions and sorry for the late start. But Becky, I'm gonna keep you on your toes. We're gonna run through this. So no relaxation for you. Ok. So we'll go for premature menopause, surgical menopause. Very important topics. And one of the reasons we thought of this webinar is because it's not much discussed about next slide, please. So we're gonna look at how poi is defined. What is premature ovarian insufficiency. What are the symptoms and signs of poi uh We're gonna look at how is it confirmed? What are the tests which are relevant? Then we look at surgical menopause. What are the implications for fertility and long term health and how to suppress unpleasant symptoms, improve quality of life with either condition and protect the long term health. Next slide, please. So, a quick recap of what happens during natural menopausal transition. We know that the first phase is premenopause. This is before any hormonal changes happen. This is when a woman would be having her natural menstrual cycles uh once every month. And of course, you have perimenopause, which is the first phase where hormones start fluctuating. Now, for majority of women that perimenopause will happen between 45 to 50. But of course, women may have shorter or longer perimenopause up to 10 years. And it can begin much earlier for some women and later for others hormones, fluctuate, FSH LH, estrogen progesterone, fluctuate up and down during perimenopause. And it could be a few months to few years, then comes the finality where menopause happens, the period stop and this is always a retrospective diagnosis, 12 months after the last period happened. And finally, anytime from that one year of last period, until the end of life would be, the whole phase would be postmenopause, which could be 2030 40 years or more. And that's a long period of time in postmenopause. The important bit is with natural menopause. Remember symptoms can happen right from perimenopause onwards. So even though the woman may be having some menstrual activity and periods, the estrogen levels may be dropping from time to time during the month and symptoms could be significant. So, offering HRT or non HRT interventions can start as early as perimenopause, right until postmenopause next, like please the age at menopause uh longitudinal studies uh show that average age of menopause is 51. Uh and the normal range is considered as 45 to 55. That is for majority of women based on caucasian population data. Early menopause is defined as 40 to 45 and 10% of women go through menopause at this age, premature ovarian insufficiency or premature menopause as a broad uh terminology happens when it happens below the age of 40 uh and 1 to 2% is supposed to be the prevalence. It varies in different ethnicities and population. For example, in Southeast Asian women, for example, it may happen very early. So the average age of menopause there being 46 or 47 5 years earlier than Caucasian population. And it is thought that incidence or prevalence of poi is bigger. It's higher in say against Southeast Asian women and certain other ethnicity up to 3 to 4% instead of 1 to 2% which is uh often quoted in based on the Caucasian population data. Next slide please. The terms can uh there are different terminologies which have been used. You might hear about primary ovarian insufficiency, premature ovarian failure or premature menopause or poi. We now stick to poi because it covers both natural and iatrogenic causes. And of course, there are multiple guidelines from BMS from I MS from different organizations which have provided a very useful clinical guidelines about how to approach and manage premature ovarian insufficiency. Next slide, please. So again, it's never too young to dismiss a diagnosis of poi. Although we say one in 100 women, 1% below the age of 40 will have poi it is less common. Uh the younger the woman is that it can happen, it can affect one in 1000 below the age of 31 in 10,000 below the age of 20 even before puberty has happened. So if there are symptoms, signs if there are biochemical uh indicators, never dismiss a diagnosis of poi because it could be that even at young age, the ovaries may have stopped functioning. Next slide please. Why, why are we worried about missing a diagnosis or a delayed diagnosis? Because diagnosis with poi is potentially life changing. There are lots of physical implication, emotional psychological consequences and those can be life-changing chronic hypoestrogenism, lack of estrogen at a early young age can cause lots of short term symptoms, impact quality of life. But also there are long term implication, poi or surgical menopause at an early age can have impact on bone health, cardiovascular health, cognition and fertility. Also important to keep in mind 25% 1 in five or one in four women will demonstrate some intermittent ovarian activity. So they may have occasional fluctuations with their ovarian activity. Despite having been diagnosed with premature men, menopause, they may have some periods at some point in time, they may have hormonal symptoms. They may have the occasional ovulations and fall pregnant naturally. So never say never. It's important to remember these things can happen. Next slide please cause for poi premature menopause unknown in almost 80%. Despite all the blood tests and scan, you never find the cause. It's likely unexplained and more likely genetic, but we haven't found the right gene yet. For others, there are known genes that can contribute. So 20% of women, we find a genetic cause or an immune cause infections can be responsible. Metabolic conditions can be responsible toxins or treatments such as chemotherapy, radiotherapy embolization, surgical menopause removal of ovaries. They are the genic premature menopause. Next slide please. In the those who have unexplained poi, why does it happen? There are two theories which are known. So women are born with a set number of eggs which is millions of oocytes in the ovary at the time of birth. What happens then is that those ocys are used up over the next 3040 years, 50 years. And by the time natural menopause happens only about 1000 eggs, ocys are left in the ovary in the background. All this time for 4050 years, the number of oocytes are being uh used up in the ovaries and destroyed. Now, it is thought that women who have unexplained poi may have a less number to start with or they have an accelerated destruction of the ocys because of some problem with how the oocytes mature. So they use of the ocys earlier in life because of low number to start with or accelerated depletion. And therefore, poi happens uh ovaries stop working early. Next slide, please. So poi could be a reduction in the pool of follicles at birth or some problem with uh recruitment and maturation of how the eggs are used up month after month. There's also a theory about epigenetic aging which means this may have started even in utero when the woman was a baby in her mother's womb. Already, the aging process and the aging of the oocytes may have started for genetic reasons. And that means that they are born with less number of eggs or finish them early in their life. Next slide, please. Genetic causes. So to pinpoint a little bit about the ones where we know a cause of poi overall, we know that genetic causes will affect 10 to 20% of poi and often those who are unexplained, there is usually a family history suggesting a genetic uh uh in the uh uh cause mainly it's X chromosome which is affected when poi happens or it could be a genetic variation. Several genetic mutations have been discovered and are being discovered every year. So we get more genetic uh causes as we move along chromosomal karyotyping and fragile x screening are the two tests that we recommend for women. Now. So any woman who presents for the first time with premature menopause, we offer two tests for genes. One is a karyotyping to rule out Turner Syndrome and a fragile x testing that is mainly to make sure there is no fragile x premutation. Next slide please. Turner syndrome, of course. Uh As you may have heard is the commonest genetic reason for poi. It affects about one in 2500 female births as loss of X chromosome, either complete or partial women who have Turner syndrome should be offered multidisciplinary care. So there are specialized clinics in big hospitals which look after women with Turner syndrome. Right? From uh pediatric age adolescence up to adult clinics. That's because there can be multiple health issues with Turner Syndrome, hearing or learning difficulties, risk for diabetes, uh loss of bone density osteopenia, celiac disease, thyroid problems, aortic problems, or cardiovascular disease, hepatic liver dysfunction, uh problems with cholesterol and lipids. And of course, if they do go down at donation IVF, then there are pregnancy risk. And so for all those reasons, they really need a multidisciplinary care uh throughout life. Next slide please. This is a quick slide that women who have Turner syndrome, not all may be having ovarian insufficiency right from birth. There will be a small proportion of women about 20% who may have some ovarian activity, that's because of partial affection of X chromosome. And so they may continue to have uh uh what we call is mosaic karyotype and they may have cycles, ovarian function, menstrual cycles for certain length of time in their life into their twenties and thirties and even longer. Sometimes if that happens, if there is some ovarian activity, we tried to freeze eggs for a set of women and we did actually find that this can be successfully done. It's one of the options for fertility preservation. One can offer at, at a young age uh where you can freeze some of the eggs. So they may be used in future. It's early stages, it may not apply to all but certainly an option that some women they turn us can consider if they have some menstrual function. Next, like please genetic causes. The other one I talked about is a fragile x syndrome. This is a pre mutation in the X chromosome that may cause poi. And if you do find this, then it's important that the patient has genetic counseling. He's a clinical geneticist because other members in the family may be affected. Like, like please, let's look at the second common cause which is autoimmune. It is found that women with poi uh often have other immune conditions. For example, arthritis, thyroiditis, diabetes, adrenal insufficiency, bowel inflammatory disease or multiple sclerosis, myasthenia that suggests that there may be an immune pathology which destroys both ovarian function as well as causes an immune disease. And commonly used tests which we do in the clinic is we test for antibodies for ovaries. Uh We test for celiac screen thyroid autoantibodies and adrenal antibodies. These are the four tests we will do at the initial consultation. Next slide, please. Iatrogenic. We talk about surgical menopause and why do we talk about it because it's sudden menopause. You don't have the time that happens with natural menopause. Number of years of hormone fluctuations that a woman gets with natural menopause may not happen with surgical because you just go from hormones to no hormones within 24 hours. And so surgical menopause can be quite severe, quite debilitating symptoms can happen and the symptoms may persist longer damage to ovaries, varies if it's because of chemotherapy, that's cause medically induced menopause. Again, different chemotherapy agents cause different uh extent of damage to ovaries. More common with alkylating agent chemotherapy. And of course, any risk with chemotherapy or radiotherapy will depend on how much dose and what medications are used. And what is the age of the woman at the time of treatment? Younger the woman less the impact of chemotherapy on the ovaries. We're also seeing increasing number of women having risk reducing surgery such as bilateral removal of tubes and ovaries. That's for BRCA uh breast cancer gene carrier status. And so these women will go into surgical menopause because they are removing ovaries for risk of uh ovarian cancer. Again, they need good support after surgical menopause. Next slide, please. What are the signs and symptoms and how we diagnose poi? So to keep it simple, lack of periods for more than four months. So if somebody is having periods regularly before or notices that there is sudden gap of more than four months, there are some symptoms of estrogen deficiency, hot flashes, night sweat problems with sleep energy, mood vaginal dryness, those sort of symptoms. And of course blood test, we do two levels of FSH blood test and if it's more than 25 4 to 6 weeks apart, on two occasions, that would confirm your diagnosis of poi symptoms are sudden and severe with surgical menopause. So if, if you know that a woman is going to go through surgery and surgical menopause planning before uh for the actual plan after surgical menopause, the treatment and management is really critical. Unfortunately, most women who have surgery to remove ovaries don't have this plan in place and struggle quite a lot after because the initiation of HRT or other forms of management options is delayed. A H is not a diagnostic test for poi because it can vary and it's actually not a good marker. It can only suggest the egg store or egg reserve level. So it can be used for fertility counseling, but it's not a diagnostic test. Next slide, please. Now let's look at the long term impact of this condition, whether it's uh poi or early menopause, possibly due to surgical intervention. So women with poi are at increased risk of osteoporosis because estrogen is key for bones and once the estrogen is no, no longer coming from the ovary, the bones will tend to lose their mineral density and strength. So it's important to recommend lifestyle interventions to women with poi that would include good calcium through diet and only supplement if needed. Vitamin D supplement, especially in winters is very useful. Weight bearing exercises are go for bones and really important to do them. Bone density scans are offered to women on HRT every 3 to 4 years or otherwise. And then specialist advise when HRT is contraindicated, but the gold standard will be HRT. So anybody with poi, you're worried about osteopenia because of lack of estrogen, HRT is the gold standard treatment besides lifestyle indications. And a specialist advice may be needed if HRT is not able to improve the bone density. Next, like please again, impact on heart is significant because estrogen is heart friendly, keeps the BP low, keeps the heart and the blood vessels supple. So there is increased risk of heart disease. Once poi happens, lifestyle changes are key, improving the lifestyle diet, exercise, stopping smoking, good body weight, critical estrogen deficiency should not be allowed. So generous, HRT tends to lower the risk of long term heart disease because estrogen does improve heart profile. So it's recommended until the age of 50. Again, HRT tends to be the gold standard. Next slide please. Then observational studies for cognition. Again, for young women below 40 having poi certainly lack of estrogen can have cognitive uh impact uh impairment of cognition and risk of dementia. A window of opportunity here is to start HRT early so that you prevent any long term cognitive issues. Now, this situation is different from women going through natural menopause after 50 where we don't have confirming data about impact on dementia. I'm mainly talking about the poi early menopause but certainly HRT or estrogen replacement will help. Next slide, please. What about fertility? What happens when somebody has poi. Of course, there are no proven treatments to increase the rate of pregnancy with autologous ci uh if the amh is less than 0.2 if the poi is confirmed, we don't have any uh treatments right now that could reverse the pro the po poi 5 to 10% of women will have spontaneous pregnancy. So those with unexplained or autoimmune causes, we do see about 10% of women can have spontaneous natural pregnancy with some ovulations. HRT can be safely taken. It's not contraceptive. In fact, it will help with the womb lining and actually is recommended. But that also means that if a pregnancy is not wanted or to be avoided, contraception becomes very important because there can be natural pregnancies. For most women with poi, the most recommended treatment will be a donation, donation IVF but it needs to be done with proper counseling because there are some risks of high BP, low birth weight during pregnancy. There are some research therapies such as stem cell treatments, platelet rich plasma injections into ovary or primordial follicle activation. They're all being tried and researched at the moment, but the evidence is short of recommending them for clinical practice. So one doesn't recommend any of these treatments because there is no strong evidence of efficacy and we don't know about long term safety. Next slide, please. What about symptoms? Quality of life? Yes. 80% of women who have poi surgical menopause as we talked about will have unpleasant menopausal symptoms and 30% can have it quite severe and debilitating symptom. Next slide, please. So here HRT plays a major role. I'm not going to go through all the symptoms because these are typical classical symptoms of lack of estrogen, whether it's the hot flushes, the night sweats, the dryness or the low energy uh libido brain fogging mood issues. Uh Next slide, please. So psychological support and medical treatments such as HRT non HRT options become the most important. And this is one thing we are not good as medical health professionals are doing is offering psychological support. It's such a life-changing diagnosis. So I encourage patients to seek help, offer counseling. Life planning is needed with a diagnosis like poi or a surgical menopause at an early age. The care is best offered through specialist clinics. So these women need referral to specialist clinics where there is support available with annual reviews of their health. These are the two organizations uh we have been lucky to be uh involved with, with our patients. One is the Internist Support society and of course, we have the Daisy Network for Poi and these are fantastic support systems for patients. Next slide please. Addressing symptoms. Uh how do we improve quality of life and address the symptoms which are unpleasant. Of course, lifestyle modification changes at workplace, uh nutrition, self-help interventions, alternative therapies have some role, non HRT medications. NHRT HRT being the gold standard, I'm not going to talk about others a lot because of course, HRT becomes the most recommended treatment for early or premature menopause. And of course, if surgical menopause below 45 next, like please, what is available with lifestyle is reducing caffeine, avoid excess alcohol, a good diet, exercise several layers of light clothing. That's the practical tip for hot flashes. These are small, small lifestyle changes which may make a difference to symptoms. Some women prefer complementary therapies, acupuncture, homeopathy, not much scientific evidence, but may help psychological therapies such as CBD mindfulness are very useful for vasomotor symptoms, mood changes and sleep. And finally, you have herbal products which are not recommended because of lack of long term evidence for safety. Next slide please. The SNRIs, Venlafaxine and the antidepressants such as Ssris have now become popular option for vasomotor symptoms or sleep. For those who can't take HRP such as breast cancer, bone cancer, which is estrogen sensitive or few other conditions where HRT may be high risk SSRI or SNRI S may work. Some women may prefer gabapentin or cloNIDine but often these nonhormonal medications have significant side effects, drowsiness, dry mouth, constipation. So, HRT might be the best option unless there is a contraindication. Next slide please. Estrogen is the key hormone in HRT. It prevents symptoms, protects bone, heart muscle joints, protects against high cholesterol diabetes and can cause some minor side effects in the initial stage. But that's the key part of HRT. Next slide please, whether you give a pill or HRT. Uh so some women with poi may be prescribed the pill because it gives contraception and hormones. Others may be given HRT, not contraceptive but gives estrogen progesterone. Which one to prefer. Of course, the main one here being whatever little evidence we have from small study favors the HRT natural estrogen progesterone better for long term health and bone health. However, if contraception is is must is important and the pill can be used as effective form of estrogen replacement for young women. Next slide please, progesterone is mainly used to protect the womb lining. It's given alongside estrogen and I won't talk more about what, what sort of progesterone sensitivity can cause that's a topic for another day, but it can cause some side effects and they can be minimized. Next slide, please. Testosterone can be used for some women who have persistent lack of libido, lack of energy and in those situations, especially after surgical menopause. When there is sudden loss of testosterone coming from ovary, it tends to help with symptoms alongside estrogen and progesterone. Next slide, please. Finally, for those with vaginal symptoms. In addition to the systemic HRT you can have vaginal estrogen for dryness, bladder problems or painful sex. This can also be used as long as required because it doesn't have the systemic risks that sometimes the estrogen has been taken orally. Next slide, please. What are the risks associated with HRT. So we talked about the good bits, the symptoms, the bone, the heart and the metabolism. What about the risk? Now remember that the blood clotting risk with HRT only is associated with oral form of HRT. If your woman doesn't have, if your patient doesn't have any risk factors, then up to the age of 60 they can safely take oral HRT. After 16, transdermal is the best because transdermal has no increased risk of blood clots at all. Breast cancer risk does not apply to women with poi or early menopause because they are under the age of 45 they are replacing their hormones. They're not taking any extra hormone. So no increased risk of breast cancer with HRT in women with poi. This is really important to note because many women are scared with poi not to take HRT. It should be reinforced that the data for women above 50 does not apply to them. The benefits far outweigh any potential risk. Next slide, please. Again, this is a bit of technical maybe not required in too much detail. Is that generally the aim with oral HRT is 2 to 4 mg of estrogen and you might need the higher dose of the patch of the pump 100 mcg or four pumps for young women, they tend to need slightly more estrogen than the women. After 50. Next slide, please. So how long to take a charity? Uh We recommend it at least until 50 for women with uh premature menopause or early menopause. But you can continue after 50. If there are symptomatic benefits and its benefits out the risk, then you can continue. But we'll have to discuss the risk of breast cancer after the age of 50. So as long as the benefits are outweighing risk, these women after 50 could continue to take it long term with surgical menopause. Similarly, as long as benefits out the risk and HRT can be continued long term. Next slide, please. So as a summary, po and surgical menopause care should include specialist input. But more so because there are lots of physical and psychological implication, psychological support is really crucial. Early diagnosis, quick referral is important. So not dismissing symptom doing blood test. If the symptoms suggest possibility of poi if it's surgical menopause surgery being planned on ovary, getting that plan in place with the team before the surgery happens is key for po or early menopause. We recommend hr till 50. But if HRT is contraindicated, then there are lifestyle nonhormonal options. And finally, we need to understand much more, especially with other ethnicities and other backgrounds. It's really important that we try and do research to find out more about which women may benefit from what treatments as well as get data for other ethnicities besides Caucasian population for these two conditions. Thank you so much for listening. Uh And happy to take any questions. I've tried to go through this really fast. So we have 10 minutes for questions. Thank you. Let me just have a look at chat a minute. Right? And I just go back to the top. Oh, here we go. Ok. Uh So Kayleigh, when do you run bloods in cycle when there's no period? So this question, sorry, you run blood the cycle and no period. There is no particular time. If someone has been amen and has not had period for more than 3 to 4 months and you want to do the bloods, then you don't have to time it in any way. Just do the bloods on the day that's available because you will get the picture of what is happening in the background with the hormones when somebody is having cycles and you want to know their ovarian reserve bloods. That's when we say in the early part of the cycle in the first seven days. Thank you. And um would you run a baseline bone density and then repeat it in four years? Yes. So ideally do a baseline bone density. And then if the woman is doing something for their bones lifestyle, non HRT HRT, every four years would be ideal if the bone density is not responding or is already osteopenia or osteoporosis, you might have to do it a little bit frequently initially every 23 years until it gets stable on form of treatment. And then again, every four or five years. Ok. And uh my understanding is transdermal patches with nova. So carry clot risks. Yeah. So that's not true if you have a patch or a form of a combination of estradiol and norethisterone, which is the C or ever conti patches, it does not carry any increased risk of blood clotting. You can safely prescribe this. It's the oral norethisterone that increases the clot risk. So in the patch, it doesn't increase the clot risk. Brilliant. Ok. Um I'm just having a look back up. Are there any more questions any more questions from anybody at all? Becky's just had fantastic potted information. Just what I needed. Brilliant, Becky. Thank you. That's good to know. Give you a smiley face. Um Any more questions for thick crumbs. It was a really, really informative presentation to be honest, Vikram, I think it was uh thank you. So again, we may not have covered every bit, but we've tried to touch on the main aspects. Um And hopefully you will have got the gist of what is important with the topics. Uh and hopefully we'll cover more content like this in future. So do give us a feed back and we'll try to uh refine it every time we come back to you. Thank you. Yeah, definitely. Is there anything else? No brilliant. Lots of. Thank you. You've seen the feedback, as Vikram said, give us some feedback. Thank you so much. Indeed. Have a lovely evening, Vikram speak to you soon. Same here. Thank you for your time, Vicky. Thank you, take care. Goodbye.