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Hello, everyone and welcome to Meal Primary Care. It's lovely to have you join us tonight. Um If you're new to medal, er and you're not sure who we are. We're in an online healthcare learning community who have a huge passion for global education. We have around 2000 organizations on our platform who host events regularly. We're passionate about fair medical education and partner with organizations who are hosting hybrid conferences to offer free tickets to those in lower middle income countries. We also run a series called Middle Education um primarily it began for those in Sudan. So if there's anyone from Sudan watching tonight, good, good, good evening to you. Um because I didn't actually know until they reached out to us that they actually are enduring war in their country since the spring. Anyway, we have uh delegates joining that from 99 countries. Um and they come along because we have incredible passionate consultants. Uh seeing how well this took off, we decided uh we'd put our resources behind hosting events for GPS and so middle primary care was birth and this is our second event tonight. We have 2084 people registered from 30 countries. Um, just a little bit of housekeeping. This event will probably will be recorded and shared probably tomorrow or the next day. Er, you'll receive a feedback form in your email. So fill it out. Once completed, your certificate of attendance will be on your profile. You can view a summary of your teaching that you've had on the platform by clicking on your profile and you, now that you're, er signed up to medal, you can view any events you like. Most of them are free. Er, they, most of them come with certificates. Um So please do make use of the platform. Now for our speaker tonight, Vicrom is no stranger to me. He has hosted uh with a few different organizations. He's actually done a talk on me education and he is uh he is frequently on learn with nurses. So if there's any nurses out there, hello to you all. We love to have you. Er, Vikram actually has another event coming up uh with learn with nurses. So please do um sign up for that. I'm gonna put their link in the chat for you if in case you want to um sign up and I'm also gonna put uh I think Vikram's link is already in the chat. So if you want to get any of his previous or future events, you can click sign up and come along to any of the events. So that's it for me. That was really quick. And I'm really sorry, I sped through that, but I know Vikram has got a lot to say and I know that you've all probably got a lot to ask. Ok. So over to you Vikram. Thank you so much, Sue for getting that all compressed within five or 10 minutes. So fantastic. Thank you always for the kind introduction and thank you to you and medal for this platform, which is so wonderful and it reaches all across the world. So I'm going to start sharing my slides in a minute. Uh Hopefully you'll be able to see that in next few seconds. Uh There we go and thank you. Um So are you seeing my flight? It's perfect. Yes, good. So let me start from before. So I'm Bikram. Uh I work at uh University College London Hospital uh and also for Institute of Women's Health UCL. Uh I'm a menopause specialist uh of the MS accredited menopause specialist. And my main interest is menopause and premature menopause. So today we are going to do a, a quick uh uh sort of rapid fire um course into menopause and H RT, what is the latest knowledge, what has changed in the last one or two decades? Uh How do we diagnose menopause and offer different forms of management options to women who come for health and support? Uh We have a lot to go through and we have about 40 45 minutes. So I may go through some of the slides quickly. Uh But hopefully, that will leave us with 1520 minutes at the end of the uh topic so that we can discuss and uh exchange lots of questions and answers. So starting with stages during the journey towards menopause, menopause has been in the talk in the media, in the social media as well as the uh electronic and print media. That's because uh people are getting aware that menopause uh basically covers a large number of years towards the end of reproductive phase. And after, for women, uh and women can spend up to one third of their life in menopausal stage. And so therefore, it's really important. We look after women, look after individuals in this phase uh and give them optimum health outcomes. So when we talk about stages during how the menopause happens or journey in menopause, there are mainly three stages that we talk about the perimenopause menopause and post menopause. But before perimenopause begins, what happens, it's the premenopause. This is where no hormonal changes have happened. A woman has regular menstrual cycles. Usually every month, FSH, LH, estrogen will be normal and that's the premenopausal phase. The first phase where changes start happening, the hormones will start fluctuating is the perimenopause. And this stage will usually last for 2 to 5 years. Between the age of 45 to 50. For majority of women, the hormones will fluctuate, the FSH, LH will gradually increase. The estrogen progesterone levels will drop, testosterone levels will gradually drop. And of course, some symptoms will appear whether it is mood fluctuations, some hot flashes, night sweats, uh sometimes it is just simply joint aches or bony pains. All those sort of subtle symptoms will start appearing during perimenopause then happens, menopause. This is an arbitrary time point. This is when periods stop completely. So while in perimenopause, there are some fluctuating periods happening, irregular menstrual cycles, happening, menopause happens when they stop completely. So this is a retrospective diagnosis. You can only diagnose menopause one year or 12 months after the last period has happened. And this is the time when symptoms will become more and more, there will be prominent symptoms, vasomotor symptoms and others finally, post menopause is a phase one year since the last period happened until the end of life. So from that 12 months, since the last period, until end of life, all that will be post menopausal phase, which may be 1020 3040 years of a woman's life. Two important reasons to highlight this slide as there has been change in thinking over the last 10 years. Of course, we now know that symptoms can present very early. So even in perimenopause, some women may have lots of significant symptoms and one can offer HRT as well as non HRT intervention. Even though the woman will still be having menstruation and menstrual cycle, you can offer management for symptoms similarly, symptoms can last longer than 10 or 15 years. So traditionally, we thought symptoms last for 2 to 5 years and then there will be resolution. That's not true for everyone. The majority of women, yes, symptoms may be 5 to 10 years. But for others, they can last 1015 years or even longer. And therefore they need attention and need some sort of management option given as they persist into later life. When does menopause happen? Uh So, of course, menopause can happen at different ages and by different ways, you can have vaginal menopause, uh you can have what we call as early menopause, you can have premature menopause. And so, of course, if it happens around the average age of 50 or 51 or above, that is the median age for natural menopause, if menopause happens before the age of 45 so that's between 41 to 45 and that's called as early menopause. And if it happens below the age of 40 that's about 1% of women, then it will call as premature menopause or premature ovarian insufficiency. About one in 1000 women menopause will happen below even the age of 30. And so never too young to have menopause. If there are classic symptoms, if periods have stopped, even young individuals may be going through premature menopause. So never ignore the symptom, never, not say that you are too young uh to go through menopause. Now, of course, remember that ethnicity is important. Uh Different ethnic groups will experience menopause at different times. For example, in Indian women, it could be five years earlier at the age of 46.5. In Afro Caribbean population, you do see menopause usually happening between 47 to 49. So there's a lot of ethnic variation in menopause. Similarly. Uh if you look at the geography, if you look at the socioeconomic status, there are subtle differences in age of menopause because environment influences the gene. So this is again important because if you see somebody from a different ethnic group complaining of menopausal symptoms in your clinic, then it's important to recognize that these women may be going through menopause much earlier than what is traditionally thought to be that happens between 45 to 55. Now, let's look at diagnosis since the nice guidelines were published in 2015. And since we have had so much uh more studies and research into menopause, we now know this is a clinical diagnosis and blood tests are rarely needed. So if somebody is going through natural menopause after the age of 45 you do not need blood tests to offer them any form of management. It is purely a clinical diagnosis. There's no need to measure estrogen or FSH. If a woman presents to you with symptoms of menopause and she's about the age of 45. Now, you can do blood test, they may be of some value in 40 to 45 age. And that's also because sometimes the symptoms may not be classical. There may only be one or two symptoms. And therefore, you may want to know what the trend of FSHLH estrogen is. Or you may want to rule out thyroid or anemia or vitamin b12 deficiency, which may have overlapping symptom. So, there may be some value to blood testing between 4045 but certainly not about 45 for women who are younger than forties, they have to have blood tests. That's because you're making a diagnosis of premature menopause or premature ovarian insufficiency. This has fertility implication, lots of implications for future psychological and long term health. So we recommend that you do two sets of blood test, estrogen FSH. So that at least six weeks or eight weeks apart, you get two higher values for FSH, more than 25 and low estrogen. That would confirm and make sure the diagnosis is right. So what is the clinical diagnosis based on? It's the symptoms? So anybody with any of these menopausal symptoms, you could offer them HRT or non HRT intervention. 70 to 80% of all women will have some or other symptoms including the vasomotor symptom. The hot flashes, the night sweats or sleep issues. They may be having low mood anxiety, irritability, which are the typical psychological symptoms, fatigue, joint pains, headaches, palpitations, dryness of skin dryness of eyes, urinary symptoms, brain fogging difficulty concentrating, multitasking, low libido. These are again, other physical signs or symptoms of menopause, dryness of vagina, burning itching, vagina, painful intercourse. These are the local genitourinary symptoms. You could also have increased frequency of urinary tract infection, worsening, urinary frequency or incontinence and finally, periods of course, in perimenopause, the period will change, you will have change in the pattern. Sometimes it will be uh short menstrual cycles to start with and then gradually the gap between periods will increase. So you'll have longer and longer menstrual cycle, eventually they will stop. So, clinical diagnosis is the key here. It's also important that you know that symptoms overlap with other conditions. So sometimes it's not very straightforward to attribute symptoms to menopause because there are many symptoms which can overlap hot flushes or fatigue headaches, irritability, lack of sleep, brain fogging, joint pains, depression, they can overlap with other clinical condition. And that could include just clinical depression, chronic fatigue syndrome, fibromyalgia, rheumatological conditions which cause joint pains, anxiety, panic disorders. Long COVID to mention the recent one than thyroid adrenal dysfunction or vitamin deficiency. These can have overlapping feature. So your clinical history, the pattern of symptom. When did they start relation to period pattern, that becomes important when you are deciding whether this is down to menopause or whether this is down to some of the chronic conditions. We also know that women who have menopausal symptoms twice as likely to have chronic pain diagnosis. So managing this and offering HRT or not offering HRT. It's really important to get good history and correlate symptoms with periods. A quick word about genitourinary syndrome of menopause, previously known as the vaginal atrophy. This is an underdiagnosed undertreated condition. About 60% of postmenopausal women who do not take HRP will suffer from GSM and it takes a bit of a time of having the effects of lack of estrogen in the vaginal or pelvic tissues to manifest. So, it may take 3 to 5 years after menopause to have these effects of estrogen deficiency to become apparent women who are on HRT already. So they are using patches gels tablet, they still have vaginal atrophy or GSM symptom in about 25%. So you may have to add a vaginal estrogen alongside systemic HRP. And why does GSM happens? It's a classical lack of estrogen because in a healthy vagina, superficial mucosal cells of vagina are shared every four hours. There's lots of glycogen that are healthy lacto basil, but that changes. Once the estrogen deficiency happens, the skin becomes thin. There's a reduction in superficial cell, there's a reduction in glycogen, a rising ph and the change in the bacterial flora and that causes the dryness, the, the friable mucosa and the pain. Now, let's look at what we can do to help with symptoms and improve quality of life. So, when we talk about menopausal symptoms, if a woman has significant symptoms, which are getting her down, which are interfering with her day to day activities, which are making her quality of life poor. What we really want to do is help by giving something that would improve quality of life. But at the same time, we also want to improve the long term health. So what are the options we have? We have lifestyle modification, we have changes at workplace. We have nutritional or self-help intervention. We have alternative therapies, non HRT medications or HRT. Now, it's a lot to go through. I probably have another 2025 minutes. So we're going to try and uh and touch upon each of these uh subtopics a little bit to give you an idea of what are the main indications, main side effects but concentrate more on HRT because that's where a lot of things have changed in the last 10 years. So we look at each one in a, in a sort of brief uh manner. So what are the lifestyle interventions which we have so simple things in day to day life, for example, reducing caffeine intake, moderating alcohol intake, nutrition, eating healthy Mediterranean type of diet portion size management, exercising regularly at least five times a week, 30 minutes or so, uh things like yoga, Pilates, balance exercises, lifting weights is particularly useful for muscle building. Uh Again, uh bone healthy and heart healthy lifestyle is what we call exercise and diet that goes hand in hand that lays the foundation for good long term health, as well as trying to minimize the symptoms during menopause. Then there are practical tips at workplace. So workplace can be an issue when there are lots of symptoms and it can trigger symptoms. So several layers of light clothing, natural fabrics to try to minimize the hot flushes, access to cool water hydration, access to having temperature controlled cooling within the environment where you work flexible working patterns, having menopause champions or managers who understand difficulties that may happen due to menopausal symptom. Those will be the workplace issues that will help with symptoms, complementary therapies. Yes, some women choose to do acupuncture, access homeopathy, herbal treatments, hypnotherapy. These have all been recommended uh by certain um groups of uh authors or researchers at the moment. Though the evidence for all these techniques is limited, yes, there is better evidence for hypnotherapy. But if you look at the acupuncture or homeopathy, the long term safety is unknown if you compare the acupuncture sham acupuncture versus actual acupuncture. Currently, the recent randomized controlled trial suggested there was no benefit from acupuncture. So although there has been talk about these therapies and some women may benefit, we don't recommend them medically right now. So no therapy has got some randomized controlled trial evidence. So it is one of the techniques besides CBT, which has been recommended recently. So psychological therapies like relaxation, CBT, mindfulness certainly help CBT and hypnotherapy have been shown to be effective for vasomotor symptoms, effective for mood changes, uh effective for sleep. So certainly for women who may not wish to use hormone replacement or can't use hormone replacement, they may wish to use hypnotherapy and CBT herbal products like black cohosh or starflower oil or red Clover. Again, we don't have long term safety efficacy data. Many women use this over the counter, but again, one can't recommend them medically because they are city evidence for efficacy is limited and we certainly don't have long term safety data. What else is available? Medically? Of course, we have non HRT options, non hormonal pharmaceutical medical treatments for menopausal symptoms are Ssris and SNRIs. The most popular being venlafaxine. But you also have other Ssris like FLUoxetine or sertraline or citalopram. Then you have gabapentin, which is an anti epileptic and you have cloNIDine, which is an anti BP medication. You can use this to suppress hot flashes, night sweats. Uh Ssris improve mood but they can have side effects. They can have drowsiness, they can cause dry mouth or constipation. Gabapentin is associated with weight gain. CloNIDine can cause rebound hypertension when you stop it. So for all those reasons, it's important to look at the benefits for the patient and then uh compare that to the side effect profile and then have a discussion with your patient. If they don't want to use HRT or they can't use it, say they have got hormone dependent cancer. Then in those situations these drugs will be the first line, but otherwise they tend to be second line option to HRT for management of menopausal symptoms. So that brings us to what is HRT hormone replacement therapy, what has changed in the last 10 years? Of course, HRT is replacement of estrogen progesterone. And in modern times, we also say testosterone because it is used to improve libido uh when there is persistent lack of libido, which we attribute to menopausal transition. But remember, testosterone remains off license for this indication in the UK. So primarily HRT is estrogen progesterone and in some women, testosterone will help, it can be local HRT such as for example, vaginal estrogens or systemic HRT, which is patches, gels, tablet or sprays or implants, various forms of giving estrogen progestogen and systemic estrogen replacement therapy remains the most effective treatment for menopausal symptom. So it is more effective than any other intervention. What we need to do is balance the benefits versus the risk. Over the years. There have been lots of ups and downs with HRT. One could call it one of the most controversial medications over the last 2030 50 years. It was very popular before 19 seventies say fifties to seventies. And then of course, there was fear about estrogen use alone and endometrial cancer. That's when the combined HRT was introduced in 19 eighties with the progestogen cover. Then it again became quite popular between 19 eighties to 2000 and then came the two big studies, one from the US, the wh I study and the UK million women study both indicating higher risk of breast cancer and stroke. And so of course, there was sharp decline in use of HRT. It went into disrepute with a lot of negative headlines. There were more studies in the subsequent two decades. What we know now is that some of the um uh dangers of hr had been exaggerated at the time because the population that was studied was not representative of when women start HRT now. And so nice guidelines came in 2015 and we had subsequent few papers and studies since then, which suggests that for most women, if HRT started early benefits outweigh the risk and that's why it's gone back into popularity. Now, what's the choice of HRT that we do? Now, there are different hormones as part of HRT preparations. More than 3035 HRT preparations are available in the UK. The estrogen of choice we use is estrogen, 17 beta estradiol. This is a body identical, preferred estrogen because it's just like the natural ovarian estradiol. The progesterone, we either prefer the natural progesterone which is body identical or we have dydrogesterone which is body similar progesterone. And these are better tolerated than some of the old progesterones. Like the norethisterone, the Provera or levonorgestrel. We don't prefer them because the natural progesterone and the dydrogesterone have less thrombotic risk, less androgenic side effect. And less risk of breast cancer. About 10% of women remain sensitive to progestogen. And this can be very difficult for the patient as well as for the clinician challenging. And sometimes you have to try different types of progestogens in different doses and routes until you find the one that kind of gives you the balance of benefits and side effects. Why do we say this is a paper from a Pharmacology journal that actually say uh shows you, why do we say that the older progesterones could be a problem in HRT as compared to the newer ones. If you look at the action on different receptor, look at the Provera noretisterone, levonorgestrel, they have a strong progesteronic action but they also have an androgenic action. So they may cause oily skin or they may cause acne or hirsutism and of course, impact on the blood clotting in breast. Well, if you look at the progesterone, natural micronized progesterone or dydrogesterone, right on top, look at they have the progesteronic action, but they don't seem to have the androgenic action. And that's why we prefer them in the modern HRT as far as possible. How do we give HRT, do we give oral tablets or capsules or do we give transdermal to everyone? Gel, spray, implant patches. Of course, you choose based on individual preferences and medical history. Oral tablets can still be used if there are no risk factors for thrombosis, any healthy woman below the age of 60 with no medical risks can have oral HRT patient preference plays a role. Young women often choose to have oral preparations because it's easy to stick to compliance and adherence is better. They tend to have less breakthrough bleeding because they tend to adhere to oral tablets better, aesthetically non visible. Of course, if you look at the transdermal preparation that's gel spray implant or patch, of course, this is a first line use in anybody with a thrombotic risk. Anybody taking a liver enzyme inducing drug, for example, anticonvulsants for epilepsy. Anybody where liver disorder is a problem, bowel absorption is a problem. Lacto sensitivity exist, migraines are happening. They're about the age of 60 or BMI is high. All these are risks for thrombosis and therefore one would prefer to go first line transdermal. But for the others, you can still use oral HRT, low dose vaginal estrogen such as cream pity or ring. You can use for urogenital symptoms alone and can be used in conjunction with systemic H RT. What are the contraindications and caution where we should not be using HRP. Of course, we individualize this because in many of these situations which I have listed on the slide, you could individualize and in specialist clinic, these women may still be offered HRT if they take on board the risks of HRT but generally to make it simple in the primary care, what we don't prescribe HRT for is any current past or suspected breast cancer, known estrogen dependent cancer, undiagnosed, vaginal bleeding or untreated endometrial hyperplasia. One doesn't want to start HRT until it's treated any idiopathic or current venous thromboembolism or active arterial thromboembolic disease. We don't want to start HRT, active liver disease with abnormal liver functions until it's diagnosed and treated and pregnancy. All these are contraindications and of course, one has to be cautious when offering HRT and porphyria complicated diabetes. Uh recurrent thromboembolism migraine with aura and increased risk of breast cancer due to BRCA gene or family history. In this situation. One is to counsel patients appropriately and offer the most uh suitable or body identical HRP for most of these conditions. Some of the practical prescribing tips in the clinic is that one size fits all approach does not work. You have to try maybe two or three preparations in different doses and routes until you get the HRT that works best for that particular individual and always start with the lowest dose and try to increase based on the symptoms, how well they are controlled and any side effects which are of uh happening. We try to avoid as far as possible, any off license prescribing. Unless you have an individual who may not absorb any form of licensed dose. Blood tests usually will never be required unless you have a problem with poor absorption. So even if using the highest dose of a licensed HRT does not cause him to relief, you may want to test in the blood and his sterol level to see how much absorption is happening. Women who have poi are usually younger women need more estrogen. They may need 4 mg, oral estrogen or the 100 patch or four pumps of gel. That's more as compared to an average dose that you will need after the age of 50. Let's compare pill and H RT for women with poi premature menopause. One can give the contraceptive pill unless there are any contraindications. One can use the pill as a form of estrogen replacement. Uh versus you can have natural HRT which can be replaced. There have been very few small studies comparing pill versus HRP and generally, it appears that the HRP is better for bone and the heart outcomes. However, there's a big trial happening now, which is the co study at U uh which will be a two year study which will give us, give us much more information about this uh comparison. Anybody who's just been through menopause in the last one year or is still having some menstrual activity, some periods we tend to give cyclical HRT so that you still continue to give some bleeds for the individual. And after a year or two, you can switch to non bleed. HRT. Younger women with poi tend to prefer a cyclical HRT, especially if they want to have a donation d in future. It's better to continue giving cyclical HRP. Those with heavy menstrual bleeds, heavy withdrawal, bleeds on HRT having preexisting endometriosis or premenstrual symptoms where fluctuation should be avoided. You may want to give either the pill or no bleed form of HRT, quick word about treatment of GSM. Uh Of course, the first line is vaginal estrogen which can be used as long as needed indefinitely. It enhances the blood flow improves the bacterial flora, keeps the ph low and of course, it helps with urinary symptoms. Besides vaginal symptom, urgency incontinence frequency will be better. Estradiol can be given as tablet ring or you have pessaries creams gels, you have a loading dose followed by maintenance dose. And of course, women with breast cancer treatment can use vaginal estrogen if they are on tamoxifen, then that's straightforward. If they are on letrozole or aromatase inhibitor, then one has to liaise with the oncologist because there is some observational data regarding slightly higher risk of recurrence of cancer. But if the symptoms are severe, then benefits would still outweigh the risk. So it's a joint decision with you patient and the oncologist. Vaginal DHEA is a new drug that's available in the last couple of years. Uh It's basically a pessary for a daily use and the DHEA is converted into estrogen androgens within the vagina and helps with the GSM symptoms. Again, limited use in women with breast cancer, but there are some clinicians who use it now following breast cancer treatment. So we'll have more experience in the next few years. Amien is an oral selective estrogen receptor modulator, 60 mg daily used as an oral tablet and again, can be used for women who don't want to use vaginal preparations for vaginal atrophy symptom and may be used in women with history of breast endometrial cancer. However, clinical data are limited. So the decision should be individualized. A quick word about what is body identical and bioidentical HRT body identical or biosimilar uh is what we use on the uh NHS. It's estrogen and progesterone, which is well studied. Uh 17 beta estradiol and the natural micronized progesterone. And we use this in combinations of different types. These are well studied and regulated forms of HRT. The ones that we don't recommend are the bioidentical or the compounded preparation which are unique to each high street clinic. They do combinations of plant estrogens and progesterones and other hormones which are unique combinations. They haven't been put through rigorous randomized trials over five or 10 years. Periods haven't been studied for that long. And therefore we say long term safety efficacy is unknown. Uh And therefore we don't recommend it. This is a quick chart about hormone replacement therapy as a guide for somebody who's new to prescribing HRT. And I won't be going through too many details here because you'll have the slides after the event. It basically says that if someone has had a hysterectomy, they only need estrogen, no endometrial protection needed, but somebody has uterus intact. They will either have sequential combined or continuous combined. HRT, depending on when was their last period, less than one year or more than one year. So, caveat for hysterectomy is if somebody has had a hysterectomy for severe, moderate to severe endometriosis or endometrial cancer, sometimes we still recommend that the woman has progesterone along with estrogen despite hysterectomy to try and prevent recurrence of pelvic endometriosis or endometrial cancer. So, how long do we continue with HRT? What we know is not all women need or wish to take HRT. But if someone wants to use it for the significant symptoms, then it should not be denied. You can commence a charity during perimenopause or menopause and there is no arbitrary limit to the duration of use. So you can use it for 2 to 5 years or longer even for 1015 years. And some women are prefer preferring to take it until end of life. So we don't have a lot of data in women after 65 or 70. And that will come with experience. But certainly there should not be an arbitrary limit. If the individual thinks their benefits outweigh the risk, then they can continue benefits for bones benefit for heart benefit, for metabolism symptoms has to be balanced against thrombosis, breast and endometrial cancer. Women who have premature menopause or early menopause at least 50 is the minimum, the natural age of menopause that's recommended they have HRT so that they don't have deficiency of estrogen after 50 they can choose to continue or they may wish to come off if they don't wish to continue with. The HRT testosterone is a recently more commonly used hormone with HRT. The assessment interpretation can be tricky but the main indication is low libido. Yes, it can help with a few other symptoms such as brain fogging or energy or mood. But we don't have good quality RCT evidence for those. And that's why we stick to low libido for now. And hopefully we'll have more trial evidence to expand the indications of testosterone in future. There are no testosterone products for female use licensed in the UK. So we try and use the male products and try to make sure that the dose is about five mg daily. What monitoring is required? We tend to do a total testosterone at the beginning at six months and then once every year to make sure it's not far above the upper limit of normal range side effects with testosterone are uncommon. The main side effect being a bit of uh hair growth at the application site, sometimes a bit oily skin or increased body hair. In which case, we reduce the dose. But any generalized hirsutism or alopecia or deepening of voice or enlarged to it is rare unless too much dose is used in excess of 5 mg. The long term trials don't show any increased risk of breast cancer or cardiovascular disease. Although longer term trials are still desirable. But so far, the evidence is reassuring. The final bit about the talk is about side effects of HRT and the risk because we've seen a lot of good bits of HRT for symptoms, for bone, for heart, for metabolism. But what about the side effects that we need to balance it? So, of course, the transdermal HRT has changed everything in the last 10 years. It's very safe in terms of blood clotting risk. And we'll look at that in the next few slides before we finish. The commonest side effect of HRT is breakthrough bleeding. It's very common in the first six months. And unless there are any other clinical features, if it's just the breakthrough bleeding with HRT, you can reassure the patient and evaluate at six months for most women, it will stop by six months. But if this breakthrough still continues, then what do we do? So we check compliance, make sure the patient is not missing the dose. We change the dose or type of progestogen, increase it slightly or change it. If persisting bleeding beyond six months, we do a scan to make sure the endometrium looks healthy. There's no polyp or fibroid. The chance of finding endometrial pathology is very low with bleeding on HRT, unlike post menopausal bleeding where HRT is not the cause. So remember the chance is less than 1%. That's why it's important to avoid over intervention and unnecessary investigations other common side effects of HRT are breast tenderness, bloating, nausea or headaches. And these tend to wear off in the 234 weeks of using the HRT. If they continue beyond 4 to 6 weeks, then slightly reduce the estrogen and start again and usually they will be gone. There are four main areas of risks. We talk with HRT one is stroke or thrombosis, endometrial cancer, breast cancer and heart disease. If you look at the stroke or the blood clotting stroke risk, then of course, the absolute risk is very small in women under 60. If you give oral HRT, that is associated with a small increase in risk of stroke or in general, it's 2 to 4 times the risk of blood clotting. But the overall numbers are extremely small transdermal estrogen Aspas gel spray is not associated with any increase in risk. This is the mmr estimate about how many Ks per 1000 women over five years. But remember for healthy women, below 60 oral HRT still remains an option for those with definite risk factors. For thrombosis. Definitely the transdermal will be first line choice. This was a nice study published in BMJ in 2019. And if you look at the effect of different forms of HRP, transdermal HRP, uh certainly doesn't seem to have any thrombotic effect. The progestogens which are new, for example, dydrogesterone, which we talked about is a very body friendly progestogen combined with estradiol. It doesn't seem to be having any effect there. It's the old progesterone like Provera or the norethisterone, they are the ones that seem to give the blood clotting effect. And of course, oral estrogen seems to give the effect. What about endometrial safety? So we know that we don't give unopposed estrogen for a woman who has a womb, that's because unopposed estrogen can increase the risk of endometrial cancer. So, for anybody who is taking a cyclical HRT, it's important to give minimum of 12 to 14 days of progestogen every month, every cycle, 12 to 14 days of progestogen is really key. If it's less than 10 days, that will increase the risk of endometrial hyperplasia and cancer. So we don't shortcut on the progesterone up to five years of use. It's fine to continue doing cyclical if the patient wishes. But after that, any cyclical HRT will slightly increase risk of endometrial hyperplasia. That is why after five years, it should definitely be a combined continuous HRT. So what we recommend is continuous, combined HRT after five years rather than cyclical HRT to try and minimize the risk of any uh endometrial hyperplasia or cancer. And this is really key because often what is noted is uh people can keep increasing the dose of estrogen from one pump to two pumps to four pumps or the patch from 50 to 100. And often the progestogen is not enough to cover the uh the cover for the endometrium. So this was a safety alert that was issued some time back by different bodies related to menopause. Uh And therefore, it's important that estrogen should not be prescribed in doses higher than upper limit. And if high doses of estrogen are used, it's important that enough progestogen cover is ensured, then we come to the big one, which is the breast cancer risk from HRT. This is one problem which puts off women as well as the health care providers from giving HRT to women. So far from all the evidence we have estrogen alone is associated with little or no change in risk of breast cancer. It appears safe estrogen combined with progesterone, the combined HRT that leads to an increase in the risk of breast cancer, but it's very small increase. Absolute risk is very small risk of breast cancer relates of course to the treatment duration and it will reduce after hr stopped. So, and even in the worst case scenario, if we go by the observational data and if you're explaining to a woman in your clinic, how much is the excess risk? Even in the papers that suggest the maximum risk. Three out of 50 women who are not taking any HRT for five years will develop a diagnosis of breast cancer in the background. Extra, one person that's four out of 50 will get a diagnosis of breast cancer taking HRT for five years. So it's a very, very tiny extra risk uh as compared to the benefits of HRP. There have been two important papers in 2019 and 2021 was an observational study which suggested that even estrogen alone could increase the risk of breast cancer. And it was detectable much earlier in the younger age group. While the randomized trial study, which was the w trial long term follow up suggested that estrogen alone reduced the risk of breast cancer and mortality. And it's the combined HRT which slightly increase the risk but not mortality. So this is really important. Again, that estrogen alone seems to actually lower the risk or doesn't increase the risk of breast cancer. The combined HRT slightly increases the risk but not mortality. If you look at the influence on heart disease, we know that heart disease risk is not increased when HRT started below the age of 60. In fact, if you start HRT below age of 60 or within 10 years of menopause, it is cardioprotective. It, it reduces risk of heart disease later on in life. And it's important that the BP, diabetes are well controlled side by side. HRT can be used if they are optimally managed. But even if a woman comes to you and ask for HRT after 60 or after 10 years, as long as you balance the benefits and risks you can still offer HRT, it's not shown to increase any major cardiac events just because you have offered HRT. So you can safely use it even after that, as long as you've had a discussion about the lack of benefits but no increase in risk with the woman. So since publication of the study and the results and the million women study where HRT got quite a negative press, there were lots of scare stories. A lot has changed in the last 20 years. Uh We know that there are modern HRT preparations which are body identical, which are transdermal, avoiding the blood clotting, risk, minimizing the impact on the breast. And the benefits have been shown to be all across the body from head to toe. So we believe that many more women will benefit from HRT for symptoms and there are side benefits for long term health. A lot has changed. Therefore, in the last two decades, but every woman's experience of menopause is unique. So some may wish to take HRT, others may not, some may do very well on non HRT and alternative treatments. Others may do very well on HRT. And so individualizing HRT recommendation or treatment recommendation remains the key. And that's really very important when you have the patient in front of you who is asking you for what options there are trying to manage their menopause uh successfully. Thank you for listening. Uh I think I've stuck to 45 minutes the best I had to cram a lot of information within the 45 minutes. So hopefully I've done justice to that. I'll be happy to take questions from you. Now. Uh We'll deep dive into questions straight away. Thank you. Oh Wow, that was a lot. So Vikram, we have lots and lots of questions in the Q and A. So if you want Vicrom, if you can click on the Q and A, what I'm gonna do first is just show people where they can find. So we've put these Q and A into a thread so that this conversation can continue externally of this event. So after this event, er bit can go to the thread, he can answer the questions that he doesn't get answered. Cos I think he has about 50 odd questions. So I'm just gonna quickly share my screen and show everyone in the audience how you can find our thread for this event. So if you um if you go to middle primary care, um if you go to me and then search for primary care um and then click on threads, this is our thread right here. After today. After we've got it sorted, then we will have um the video and the catch up and the slides on this two. But for now we don't have that. So this is this event and on here we've got actually got 62 questions for Vikram to answer, to be honest, I don't think we all want to stay here probably till what 1011 o'clock tonight with Vikram answering those. So we have this now what we can do here is actually um uh you can comment on the questions. So here are the questions here. So if I wanted to comment on um Katie's question, if I knew the answer to this, I'm gonna click this and I will just reply here and I'll post my comments. OK? So this enables all of us to help each other with answers as well as Vikram. I'm gonna send this link to Vikram as well so that he can answer these questions too. So I just wanted to let you all know where you can find some of the answers. OK. Now, over to Vikram for his uh we'll start the questions. OK. So Ali has a question here, how to differentiate between menopause symptoms from long term long COVID symptoms. So again, I'll be very, very brief here because we want to go through as many as possible. So how to differentiate menopause symptoms from long COVID? Sometimes it's very difficult because they overlap. There are lots of similar symptoms, pay attention to what is happening to periods. What phase of life the woman is going through? What is the age? Some of them will be more classical for menopause such as hot flashes, night sweats, sleep issue. Uh the more of fatigue and other sort of symptoms will be more for the viral postviral long COVID symptom. So although it's impossible to completely differentiate the two, you will more or less get an idea on your clinical history. Which one is the main problem, is it the hormones or the lung COVID? If it's very difficult to distinguish, sometimes based on the symptoms you can offer, HRT we call it as a trial of hormone replacement therapy with transdermal preparation in a very low dose. And often if it's the hormonal symptoms, they will go away. So that will give you a clinical diagnosis that this was more likely hormones rather than the long COVID. What happens if patients are on pills and they feel they are menopausal and younger than 45 or do you test again? Somebody who is on a combined uh estrogen progesterone pill, of course, you will not be able to rely on blood tests. So one would take them off their combined contraception for a month or two and then look at their symptoms as as well as consider blood tests. If you want to make the diagnosis of menopause and then consider different options. Those who are on progesterone only forms of contraception, you may still be able to do their blood test and look at their FSH levels because they will not be as suppressed as combined oral contraceptive pill. And you may be able to still make a diagnosis while they continue the progesterone only pill. If you have a lady with symptoms who is less than 40 with one raised FSH, but a 6 to 8 week repeat is normal. How long do you keep going with repeats. Given FSH may fluctuate. This is again your clinical acumen. So a lot of women before they have full blown poi will have fluctuating ovarian function. If they're having symptoms of low estrogen levels and their FSH has been raised intermittently, you can still offer them HRT or other forms of symptom treatment. One would often then consider a bit of long term monitoring over six months to a year to see how the FSH pattern emerges, how the estrogen pattern emerges, what their periods are doing because the fluctuations will be there but usually will phase out over six months to 12 months as you continue to monitor the woman. So again, clinical individualization, more than a fixed tool for anybody can a patient with history of E RPR positive breast cancer have vaginal estrogen. Yes. Uh significant vaginal symptoms. Of course, you can offer non hormonal treatments as first line. And if they are not successful, you can offer vaginal estrogen. Uh If as I said, if they are on endocrine treatment, then tamoxifen is fine. If you're using it with letrozole or aromatase inhibitor of some other kind, then involve the oncologist and let the patient know that there is small observational data to suggest small possibility of increased recurrence. However, if the symptoms are severe, then benefits still outweigh that small risk. How about those who have transitioned from female to male? Maybe hormonal surgical transition? Do they experience menopause? Of course, menopause in transgender individuals is a whole area of specialization itself. I don't have time to go through the differences there and the kind of hormone replacement preparations which are used. It's probably a topic for another day. But yes, certainly it's a neglected area of medicine. Very little research about transgender individuals having hormonal treatments for menopause. Uh Hopefully a topic in future, please. Can you reference the comment for women with menopausal symptoms are nearly twice as likely to have chronic pain. Yes, it's available on PUBMED or Google. If you, if you actually Google that sentence, you will get the papers that will come through and I will share my slides. I'll try to make sure I give you the reference for the same with regards to differentiating between other conditions or menopause. You mentioned good period history. How do we do that for women who have had amenorrhea due to pop? Again? I think I answered this previously. Somebody on contraception, you may have to take them off contraception. If they are on a strong combined oral contraceptive pill, those who are on progesterone only, you may still be able to check their FSH levels. But of course, if you can't get FSH levels that correlate with the clinical history that are menopausal symptoms, you can then take a break for a month or two on the kind of preparation you're using and then do the levels. If someone is having menopausal symptoms, they have a Mirena coil or they have some form of poop they are taking, I wouldn't really even do blood tests. I would offer them cyclical or combined HRT alongside the Mirena or alongside their poop because actually you're treating the symptoms and not the blood test. Uh What are the true uh c uh yes, adding to bulges. Uh What are the true contraindication? I guess that's the question. It's not clear contraindications, as I said, are mainly breast cancer for systemic HRT, especially if it's a hormone receptor positive cancer, then one should not be using systemic HRT vaginal estrogens are fine. As long as you've lied with the oncologist, especially if they are on the letrozole or aromatase inhibitor of any other type women with no vasomotor symptoms but other symptoms of mood swing, brain fog arthralgia is trial of HRT beneficial. Yes, the answer is yes. Some women may not have classical vasomotor symptoms and may only present with brain fogging mood swings or joint pains. And often a trial of HRT will show benefit for women where hormones is the only cause and they'll usually come for a follow up. You'll be able to see the change in their symptom profile. Contraindication to vaginal cream and length of use. Again, there are no contraindication. Just caution. If somebody has had breast cancer in the past and is on aromatase inhibitor, then it's the liaison and careful counseling. But you can still use vaginal estrogen as long as the symptoms will continue. How early can you start HRT for perimenopause? Would the side effect be cumulative? No, if somebody is symptomatic during perimenopause, you can start using HRT straight away and you apply the same rule after the age of 45 which is the same sort of statistics I gave every five years, the increased risk of breast cancer would be something like five in 1000. And so that's the same statistics that you apply. Even if you start HRT at 50 the same one will be if you start HRT in the perimenopause. Does menopause occur in young age? Yes, of course, it can happen even before puberty happens. Uh And the, the the girl may never experience a period because already the uh FSHLH will be high and the premature menopause has happened. Uh Poi itself is a separate topic and hopefully we will deal with it in one of the future sessions. Can HRT patches be given if someone has had a prior stroke. Yes. Any previous history of stroke or previous history of thrombosis or blood clotting one can use transdermal HRT. There are very few studies looking at this particular question. So although we know that patches or gels are safe in healthy women, there are very limited trial data in women who have already had a blood clot or have had a stroke. So what we do is we liaise with the neurologist. Look if there are any other risk factor for stroke still there, whether they need anticoagulation and then of course, consider transdermal charity on an individualized basis. So you may want to do it in conjunction with the hematologist or a neurologist. Can HRT be given when there are uh symptoms of perimenopause but still regular periods. The short answer is yes. If someone under the age of 40 or nearly 40 comes with perimenopausal symptoms, uh Can we start on OCP instead of HRP if no contraindication? Yes. OCP is one of the uh sort of uh management options for women who wish to use OCP long term. Uh Some women continue to use the combined pill later in life into their forties, early or even late forties. This is individual decision. We tend to always recommend HRT, which is more natural rather than a combined pill if it is for menopause and it's not for contraception, but the pill has the advantage of giving contraception. So it's individual choice and some women may still continue to choose to stay on the pill rather than HRT. As long as you've counseled the patient about the risk and the benefits. That's completely fine. What type of HRT does one use? One has no proper periods, very light stain on wiping but has symptoms of brain engorgement. Of course, you may not get all the tick boxes done in one preparation of HRT. So you will have to usually try different forms of cyclical HRT. The fact that this woman is having some light staining, some light bleed, still happening. There's some ovarian activity still there. So you might want to use a cyclical HRT for one or two years and then switch on to continuous combined HRT. You'll have to use low doses if she has sensitive breasts. So very low dose uh and estradiol and micronized progesterone might be the best ones when can be prescribed testosterone. If you, if you have a patient who has persistent low libido, uh she's already has had estrogen progesterone for menopause and it's been more than six months or a year and still continues to have low libido. Despite good stable HRT, there's no other cause like antidepressant or vaginal atrophy or relationship issues that can account for the low libido. That's when we would offer testosterone as an option. Can ladies with history of breast cancer receive testosterone? This is a controversial question. The general answer in primary care would be no. There are some women who do consider testosterone. Now, after counseling in menopause, specialist clinics, especially involving the oncologist, there's very little data on use of testosterone after breast cancer. Most of the data comes from clinics in America. Uh very little uh a long term study about use of testosterone. Generally, the answer would be contraindicated because part of testosterone converts into estrogen in the body. And that's why we don't recommend it if there's been estrogen receptor positive cancer. Some women are, are taking testosterone alongside letrozole or an estra as a combination to prevent conversion of testosterone to estrogen. However, these treatments uh remain not recommended currently until we have more information and better data. Can you prescribe HRT with previous history of non Hodgkin's lymphoma? Yes. Uh It's a non hormone sensitive cancer and you can prescribe HRT with history of lymphoma regarding diet. What about diets rich in phytoestrogen, Japanese versus Mediterranean? What is the current thinking about suggesting this for women who and who do not want a chart or have a contraindication? Certainly, you can always recommend both Mediterranean and phytoestrogen rich diet to women who may not want to take a chart or manage menopause naturally, the Mediterranean diet has the maximum evidence for long term good health outcomes for bone heart brain phytoestrogens. They are very, very weak. Estrogens may not be enough to take care of all symptoms but certainly have some impact on symptoms. For many women. Many women find it useful as part of their diet. Certainly there are no contraindication. Dietary estrogen is not shown to have any adverse outcomes. Also, remember, not all women will break down phytoestrogens in their gut in the same way. So if they get benefits from that diet and they do see noticed benefit for symptom, certainly they can continue with both phytoestrogen as well as for the Mediterranean diet. Does HRT cause dementia or prevent it? I have read mixed things. We don't have any evidence to suggest HRT causes dementia, neither. We don't have good human trial evidence to suggest that HRT can prevent dementia. There are observational data which have suggested increased risk of dementia with old forms of HRT. Similarly, there are observational data that in some women who have the echo gene, HRT may prevent cognitive decline. But unless we have good human randomized trials, we will never be able to confirm HRT causes dementia or prevents it who can initiate testosterone therapy. And I think I've just said that it's a question in GP surgeries because of course, it's difficult as there are no licensed products, but it's persistent low libido and a woman who's already tried estrogen progesterone, HRT, then one can think of testosterone and some women will really find it useful. It needs monitoring with total testosterone levels at least once a year. So we are reaching 8 p.m. now. So, so you might want to let me know if we continue or I can certainly answer the questions over the next few weeks from the third uh whichever is preferred. You tell me how much longer you want to go for because actually I want to highlight a comment and where is it? Somebody put in Amri Kundrat said, what a legend, loving the way er, the doctor is smashing all the questions with so much ease, a sign of a true expert, very knowledgeable. Thank you for sharing your knowledge. So we have lots of questions. It's entirely up to you Vikram. I don't want to take up your evening. Um However long you want to go, I'll stay. So I think so. We might call you today. Uh And what we'll do is we have all the questions in you will have. I'm te te technically, I'm terrible. So you'll have to remind me by an email how I access the questions and for all those questions still in the chat, what I will do is I'll try to go through them every evening, little by little. So by the weekend, I'll try to catch up with those questions and keep putting the answers in the third. So hopefully we'll go through all those questions in time. So you have an answer to what you've asked. Uh And then of course, I'll be sharing my slide so you might be able to go back and look at some of the statements or anything that you could not catch up because we have a rapid fire today. Uh But yes, I will answer all of them. Uh But maybe time for close today. That's perfect. I'm trying to keep up and add them to the questions as well. So yes, I will share with you Vikram the er the threads, everyone in the chat. You er if you follow me primary care, you would have gotten notified to say that er there's threads, it is in this chat, the link is in this chat too. Um So you can get a hold of it. If you just go to primary care on metal, you can find it. There, catch up will come to you within the next couple of days, slides will come to you within the next couple of days. And as Vikram has said, he will get those questions answered as soon as he can. We have without that big flurry that we just had. There, there are 100 and seven questions which is just and there's more on the chat. So it's incredible, you know, on behalf of all the delegates that have come along. Vik Thank you so much. Thank you. My pleasure. It's been really good. Um So you should all get a feedback form in your inbox, please fill it out and I will pass all that feedback on to Vikram as well. So please be honest. Um And, and if there's any further topics you want within uh menopause, if there's something that you want Vikram to come back and give another talk on Vikram is very passionate about this incredibly passionate. If you followed him on Twitter, you would see how passionate he is. Um So please pop in the er feedback form, other topics that you might want VM to speak on and we can get him back again. I'm sure he would be happy to come back and speak. All right, but for now, I think we should let Vra go and get a cup of tea. So fill out your form and your attendance certificate will be on your medal profile. Ok, everyone. Thank you, everyone. Take care. Thank you so much and thank you. So thank you. All right, take care.