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Hello, everyone. Uh Good evening. It's now half past seven with us. Uh Welcome to uh Metal Primary Care event. Uh Vikram is no stranger to medal, er, an incredible teacher and I've popped in the chat, er, a link that will take you to all of his other teachings. So there's teaching from both metal primary care and learn with nurses, which is another incredible organization on the platform and you can access that teaching and you are so welcome to access that teaching if you would like to. Um Bikram has incredible knowledge on women's reproductive. I don't know what you call it cos I'm not medical but all those bits and Bobs that women have. He is incredible about it and it's really practical teaching, really informative and really worth of you, to be honest with you. Um So what we're gonna do now is I'm gonna uh in a minute, I'm gonna hand you over to Vikram, but just so that, you know, if you can pop your questions in the chat, I will add them to AQ and A and Vikram will steam through them at the end. He will answer as many questions as he possibly can. Ok. So pop your questions in the chat, I'll add them to AQ and A and then he'll get through them at the end. Er, right at the end of this event in an hour's time, there will be a feedback form in your inbox. If you could fill that out, complete it. Um, once it's completed, it'll uh your attendance certificate will be on your med account for you to download. So without any further ado I'm going to pass you straight over to Vikram. OK, Vikram. Thank you. Thank you. Thank you, Medal. Thank you for providing a platform where we can do teaching like this. And thank you, everyone who has joined. Uh you're giving up a very important part of your time. Uh I to know more about testosterone today. So hopefully, I will be able to do justice to the topic. What we're going to talk about is testosterone as part of hormone replacement therapy for menopause. Where are we now? Uh And part of the reason for choosing this topic is you must have seen there is so much controversy out there every day. There are media headlines, there are programs, there are webinars talking about testosterone, the prescribing that has become more common prescribing that has exponentially risen in the last five or 10 years as part of menopausal age. RT. So we'll look at what evidence is out there. How can we approach testosterone prescribing? What are the indications what are the likely benefits and risks that we discuss with individuals and, and how can we uh monitor how long do we continue prescribing testosterone? My name is Vik. I work at UCL H which is my NHS Hospital. Uh and I do a little bit of research uh through women's Health Institute at UCL. Uh and I'm a BMS certified menopause specialist. So let's go for a little bit of background and introduction What is hormone replacement therapy? It is replacing the key female hormones that it includes estrogen progesterone or progesterone. And for some women also includes replacing testosterone. And we do that based on the symptom profile, what the main symptoms are when the individual is going through menopausal transition and based on the symptoms, hr still remains the most effective medical treatment for management of symptoms of menopause. Of course, it comes with its own set of benefits and risk, which is why we often say that HRT benefits should outweigh risk when we make a decision to prescribe HRT and it needs future reviews and monitoring so that we make sure that any time we prescribe HRT or testosterone, we are making sure benefits outweigh risk. Traditionally, testosterone has often been overlooked. So a lot of talk is always about estrogen and the progesterone or progesterone. And it's important estrogen progesterone are the most important components of HRT. But we haven't been talking enough about testosterone because some women do benefit from testosterone and it has not been brought to the uh discussion both by the healthcare professional and also not forthcoming from the women or individuals because they haven't been given that choice or information traditionally. But that's changing. More and more women or individuals are now getting aware about potential use of testosterone. And they're wanting to discuss that with health care professionals. And it's also important that health care professionals are up to date when they should be offering testosterone and coming to that sort of shared decision with the patient when they decide to prescribe it. What happens to testosterone in terms of physiology. Uh So both for men and for women, testosterone levels will decline somewhat after the age of 30. So from the third decade of life, gradually, the testosterone levels will go down both for men and women. But it's important that it's not just a male hormone. We know that healthy young women produce lots of testosterone every day. And it's important for lots of physiological functions. In fact, it's more than the amount of estrogen produced by the ovaries. Remember also that there is peripheral conversion of testosterone to estrogen. Uh and that's done by the aromatase enzyme. So it's important that the testosterone is recognized as one of the key female hormones alongside estrogen progesterone. Now, both ovaries and adrenals contribute. So, while menopause, what often happens is that the estrogen level go down, remember that although the ovaries stop making testosterone and the testosterone levels also go down during menopause. The adrenal glands will continue to provide their share of testosterone. So that is one of the differences. We often say that happens when you look at estrogen decline, that happens during menopause. The testosterone decline that happens with age. So, testosterone will gradually come down with age in women. After the age of 30 it will keep coming down down, down down and sort of plateau after the menopausal age. But all this time as the ovaries make less and less of the testosterone, the adrenal glands will continue to produce some testosterone. It's about 5050 from each source. The levels of testosterone in women will decline between 20 to 40. Usually after 30 is when the real change happens. And by menopause, as I said, the levels have plateaued out. So they've come down gradually over the 3rd, 4th decade of life and then they are starting to plateau to a sort of low normal level. The profound and sudden loss is often typical with iatrogenic menopause. So if somebody has chemotherapy medical menopause, removal of ovaries, surgical menopause, that's when there is maximum impact because you're almost taking 50% source of testosterone from ovaries within 24 48 hours or within a period of few weeks or months. So this is when most individuals who had genic surgical or medical menopause often feel the maximum brunt of sudden lack of testosterone that should be kept in mind what are the functions of testosterone? There are testosterone receptors distributed throughout the body in different tissues and organs. And I might just mention the main important functions. There are many others which we possibly don't fully understand. The testosterone plays a very vital role in the brain function in cognition in the metabolism. How calories are utilized in the body, urogenital health, bone strength, uh muscle mass and muscle strength. So development of lean muscle mass and strength and these are all the main functions. But there are many others alongside the most crucial. One that we often talk about when we talk about testosterone therapy is of course the effect on women's libido or sex drive or desire, arousal, orgasm, all three aspects of sexual function. And this is where again, testosterone has a major function. So what can be the symptoms if a woman does experience low testosterone levels, uh often especially very marked symptoms after surgical menopause, for example. And the reason I've said they are not well characterized is because there are a lot of overlapping other causes which can cause similar symptoms. For example, lethargy, low mood headaches, brain fogging, these are very nonspecific symptoms and there might be other causes besides low hormone levels, which might cause these. So it's really important to correlate and make a clinical judgment. Are these symptoms really lack of estrogen, lack of testosterone or are these other factors which might contribute to these symptoms? But on an average if you suddenly removed, the ovaries, say surgical medical menopause, often the lack of estrogen and testosterone will usually contribute to some of these symptoms. The reduction in quality of life, tiredness, low mood headaches, brain fogging. And of course, the lack of testosterone will have some impact on the bone density and the muscle mass or and cause sarcopenia, loss of muscle mass. So, these are thought to be some of the problems which can be linked to low testosterone levels. Is it easy to assess testosterone levels in women for initiating testosterone treatment or monitoring it? The answer is no, unfortunately, we don't have a lot of help because the assessment and the interpretation of testosterone blood levels is not straightforward. Most of the essays which are used in the laboratory are often have been designed for studies in men. The techniques can differ, you have immunoassays, you have mass spectrometry and there are different other methods. Uh and often they may not be comparable or reliable. Uh When you do the blood matters, for example, on the day of using a testosterone product, you may get a higher level which may not be the same in a day or two or three. Uh you can get contamination from skin where you put the needle through to get blood. So there are lots of problems which can cause false positive or negative uh low or high results. It's not mandatory, but it would be useful to perform a total testosterone level prior to offering treatment with testosterone. And one of the reasons we often say it's good to do a baseline testosterone is to first correlate symptoms to what the level of testosterone is in the blood. Although we know it's not going to be very accurate and the symptoms may not always correlate with the blood level. But also you want to know that the woman is already not running very high levels of testosterone. In which case, you might rethink about prescribing testosterone, testosterone levels are advised for monitoring treatments. Most guidelines recommend uh six monthly or at least annual testosterone assay by measuring total testosterone. Some previous guidelines also mentioned the free androgen index, but we do recommend at least one annual measure to make sure that you're not giving too high levels. Generally testosterone levels in a normal range are anywhere between 0.4 up to two or 2.5 m moles per liter. And as long as you're kind of within that range, and the patient is noticing benefits and no side effects. That's how you continue testosterone safely. Uh And that's the part of the monitoring. What is the situation in UK for prescribing testosterone? Of course, you know, there are no licensed products for female use in the UK. We know that it's mostly the gels, the various kinds of testosterone gels, which are mainly have been tested and mainly produced for male indications, which are the ones we adopt on the NHS. Uh you can have gel cream implants in the private sector. Uh So you can get pallets of testosterone. A few NHS units do offer these, but the majority are in the private sector. Similarly, you have the cream, the Andro cream uh which is again, the Andro Cream was uh available from Australia. It's an imported version. Um It's not yet approved by the M HRA. So again, not licensed in the UK right now. Uh But we hope that it will be available on the NHS in future. What the guidelines say? Uh Nice guidelines do recommend that systemic HRT should ideally be prescribed before starting testosterone and testosterone should be considered mainly for the indication of low libido. So it's basically low sexual desire and that's the indication as per the guidelines. And of course, they often recommend starting the estrogen progesterone, optimizing estrogen levels because for many women, when you optimize estrogen that itself will cause improvement in libido cause improvement in most of the other symptoms such as the brain fog, the flushes, the mood changes and you might not need to add testosterone. But there are trial data which indicate that testosterone can be used alone without systemic estrogen and tends to be effective and safe. So it's not that you cannot offer a testosterone on its own. If the main indication is low libido and the woman may not want to consider estrogen progesterone before that you can potentially consider it as stand alone. The International Menopause Society has a very useful paper on testosterone as treatment for persistent low sexual desire. And it's important that it stresses but any other causes of low sexual desire should also be addressed. So it's not that all cases of sexual dysfunction or low libido may be just the lack of testosterone. There are so many other factors which can affect sex life. So relationship issues, medications like antidepressants or others, medical problems can heavily affect cancer care. For example, or post cancer recovery can heavily affect libido, urogenital atrophy. So, vulvovaginal dryness, pain can itself set a reflex and avoid uh and cause problems with libido. So it's important that these are addressed, these are ruled out before a testosterone uh is considered as a treatment because it may not be the source of low libido or or lack of sexual activity in the first place. This was a paper, uh a systematic review and meta analysis which was published uh around 2019, quite a useful paper to give us an overview of what was out there in terms of various trials that were published with testosterone. Um And again, 46 publications uh from 36 randomized controlled trials which were included in that meta analysis. There were 13 studies specifically recruiting women with low sexual function. One study uh based on the amount of testosterone in blood. Uh and it was testosterone was given orally in 15 trials. Uh but other trials used it as a patch cream gel spray. There are various formulations as part of the trials that were used. What were the results? Uh They did so many different studies combined together. So compared with the placebo, it did appear that testosterone did significantly increase satisfying sexual events and the frequency of satisfying sexual events. Uh So that was an interesting finding, an important finding which does suggest that testosterone is useful uh for sexual dysfunction during menopause, perimenopause testosterone increased, augmented sexual desire, but no benefit over placebo or comparator. Uh was found for frequency of satisfying sexual events, total score or any functional domain for which data were available. So again, you have to question the outcomes uh which were studied as well as what were the final results? Testosterone given orally was associated with an increase in LDL cholesterol and the reduction in total cholesterol HDL cholesterol triglyceride. What is even more important is that the data showed no effect of testosterone for any of the reported cognitive measures, bone density, body composition, muscle strength, psychological general well being index score. So again, this review mainly focused on the libido aspect showed that there was benefit for sexual dysfunction. But what it did not show of course, and many studies may not have measured the right outcomes did suggest that there was no obvious benefit for cognition, bone density, body composition, muscle or psychological wellbeing. What we need is better trials with proper outcomes and better study designs and better measurement tools to capture these data. So right now, therefore, we said that the evidence is mainly for sexual dysfunction. As long as other causes have been ruled out uh benefit for cognition, mood energy. We need a better randomized trial with better measurable outcomes so that we can prove whether testosterone does have a long term benefit for these. And hopefully we'll get that trial in the near future so that we may be able to expand the indications for use of testosterone. What is available right now. Uh in terms of preparation, we have Testogel Toran test one test and, and testosterone implants. And as I said, what is the aim of the dose is about 5 mg daily. So we try to achieve five mgs by keeping changing the various preparations. Uh say, for example, if it's Toran gel 2% then we'll do one pump every other day or half a pump every day. If it's testogel, if it's a 50 mg preparation, then it's about 1/10 every day. If it's a 40 mg sachet, then it's 1/8 of a sachet every day. Uh And so we try to adapt the dose to make it about 5 mg daily. And when you reassess the patient in say six months or a year, if you're noticing that the testosterone blood level is high, or if they're getting side effects such as acne or hair growth, you reduce the dose. If they don't have side effects, they're seeing symptomatic benefit, then you continue. The treatment is usually should be minimum for 3 to 4 months before a review and then six months and then you can do annual reviews thereafter. What can be the possible side effects of testosterone. So, increased body hair, uh sort of increase generalized hirsutism, uh male pattern hair loss, scalp hair thinning can be affect acne or greasy skin can be an another side effect. So these are the more common ones, the excess hair growth, scalp, hair thinning or acne greasy skin, usually with the 5 mg dose. This doesn't happen often if women self medicate and increase their dose, that's when it's usually a problem. So it's good to bring the dose down, deepening of voice or enlarged clitoris. These are with very high doses for a long period of time. More than 69, 12 months. If women take very large doses, much more than five mg, that's when such uh effects can happen. So we don't see them fortunately clinically so commonly potential risk. Uh So far whatever evidence we have from the randomized trials and from the observational data that we have, it doesn't show an increased risk of cardiovascular disease or breast cancer. Although what we need is good long term trials because we've only been prescribing testosterone in the last 1015 years. We need long term follow ups. Uh Unlike HRT that is welt of data for 4050 years. Testosterone has been new. And so therefore, we want long term trials to confirm these benefits and these lack of risks continues evidence about the long term efficacy safety remains limited. So we have to counsel patients that yes, we've started you on testosterone and if you want to stay on this so far, so good, the evidence does suggest there are no big potential long term risk, but the data is limited, we have limited evidence and hopefully there'll be more larger observational and randomized trials, which will give us much more clearer answer both about the non libido effects, which women are noting but also about the long term safety. A quick word about the DH A because this often comes up whenever we talk about testosterone. Can you use oral uh DH A during perimenopause and menopause? Remember it's a hormone precursor, it's a precursor of androgen and gets converted to testosterone and estrogens. So again, there was a very good systematic review with 28 trials and thousands of menopausal women and data extracted from 16 trials and overall quality of the studies was moderate to low, but there was no evidence there that giving DHEA improves quality of life. Uh Some evidence that it also caused androgenic side effects. Uh And there's uncertainty whether DHEA increa decreases the menopausal symptom. Uh but it may slightly improve sexual function compared with placebo. And this probably again, is a effect such as androgenic effect that it does improve sexual function. So at the moment, we don't recommend dhe as part of treatment for menopause testosterone mainly for low libido. But hopefully, in future, if we can demonstrate long term evidence of benefits for bone muscle cognition, brain and other symptoms, then hopefully we'll be able to expand the uh indications for testosterone. So that in a nutshell is the summary about how we use testosterone in the UK. Uh and, and the, and the physiology behind it and the evidence so far. So I'm going to stop sharing my screen now and then we are going to take questions from you. So if you have question, then uh I will hopefully run through the chat now and take them from there. Oh, we actually don't have many yet, which is uh surprising, isn't it? We have one that's just there. OK. So it says is there an optimal time to apply? So again, there is no optimal time during the day. What is important is consistency. Uh So often if you have a regime of testosterone that will be daily basis, then that's the best one to follow. So people can sometimes say to 10 mg pump every other day, I tend to often favor uh a daily regime rather than an every other day. And that's come through experience. I used to also recommend every other day, but now I'm going to every day because you don't want the fluctuations in the testosterone levels on a every other day basis. So you can use a sachet every day or you can use a pump, half pump every day. As long as you've done one in 24 hours, you should get a consistency in terms of the symptom relief or symptom benefit, which one is available to prescribe on the NHS, you've got almost option of all. Uh So most formularies will usually have testogel or Toran or Testim or test one. Uh you can use any of these as long as you titrate to 5 mg per day dose, just work out 5 mg every day dose for testosterone. Uh and you should be fine. Is breast cancer a contraindication. Yes. Uh testosterone when it's applied does get converted to estrogen in the body. The uh the aromatase enzyme will convert some of that testosterone to estrogen. So, as a as a in the primary care setting, certainly, we wouldn't recommend testosterone just like we wouldn't recommend estrogen uh as a management for menopausal symptoms after breast cancer. Now, sometimes you may have to refer patients to specialist centers if they insist they would like to use testosterone after breast cancer and then often in very severe situations when the symptoms are severe and no other non hormonal treatments work. There may be a combined decision between the specialist menopause clinic and the oncologist where they might consider uh in some women prescribing HRT or prescribing testosterone that happens as an exception and will usually be an MDT or a combined decision. Uh but as a, as a rule, it would be contraindicated in breast cancer patients or move on top again. Um Then the next question is, am I correct? It is an unlicensed drug? Absolutely right. Testosterone is not licensed in the UK uh for indication uh of any menopausal symptoms. So, it's an off license medication that is prescribed by each doctor. Uh and they have a discussion with their patient and reach a shared decision. What does 5 mg daily translate to with Testogel, one sachet or one pump. Testogel usually is now available in a 40 mg sachet. So five mg would be 1/8 of a sachet. So if you divide the sachet into eight parts, it's 1/8 of a sachet daily and it's usually applied to the inner aspect of both thighs. Please. Would you advise prescribing testosterone for a patient with low libido with normal estrogen and normal total testosterone patient is perimenopausal? Again, uh I'm not giving in individual medical advice. That's not the uh sort of uh aim of this webinar. And so you have to look at other parts of the patient's history. But pertaining to the question, we don't usually look at the serum levels of estrogen testosterone, it's the symptoms that we treat. So if the woman is perimenopausal, she's suffering from a sexual dysfunction or low libido. Uh and you have addressed any other causes and it looks like testosterone will be the only bit that might help you. You've kind of removed any other uh cau cau causative factors. Then yes, you can prescribe testosterone. You don't have to really go by monitoring of bloods for symptom. As long as you know that the normal total testosterone at baseline is there, you will then repeat another testosterone in six months time to make sure it's not too high. It's within the physiological range on the testosterone treatment. But you can offer it just based on her symptom history, safe to take alongside HRT. Yes. In fact, HRT is usually recommended first for the reasons. I said estrogen itself can improve libido and take care of most menopausal symptoms and you may not have to add a testosterone only if you've addressed that. And there are still persistent low libido. That's when usually when we recommend adding in the testosterone alongside estrogen progesterone, HRT. Any other contraindications, not as such. The the dose used for female use is so little that one would be quite um uh it's quite safe to prescribe that dose as long as you're doing it for the right reasons and you've checked with the patient and there's nothing else in terms of the cost for the low libido. Um You can, you can usually prescribe it uh safely. Uh What is important is to tell the patient that once they've used it, they should be washing their hands properly because it can be transferred to uh say partner or Children or pets. So it's important that they should not be exposed to testosterone. Also, uh the contraindications will be similar to systemic HRT. So somebody who has estrogen dependent or hormone dependent malignancy, somebody who's already running very high baseline testosterone, you might not want to prescribe the uh testosterone. Those will be the contraindications. Can you please repeat target ranges for bloods when monitoring? So remember that an average uh assay uh any sort of uh testosterone assay in the UK. In most labs, the normal levels will be anywhere 0.4 or less up to 2 to 2.5 animals per liter. That's the normal variation of the normal range in the UK. And as long as you are within that limit, even if it's high, normal or low normal, but it's within less than 2.5 that would be generally considered clinically acceptable level as and if you do that once in a year or once every six months, when you're monitoring the patient and you're not exceeding those physiological ranges, then that's fine to continue. The other way to monitor. Of course, is clinical signs. As long as the patient doesn't have acne hirsutism clinically uh showing you that the testosterone is too much, you should not be continuing with it and trying to reduce the dose or come off if it's not benefiting, usually make that decision around six months. If the patient has not had symptomatic benefit. Despite giving testosterone, then testosterone is not the cause for low libido. And you can take the patient off the treatment if it's not beneficial with regard to pui. Is there any research or guidelines or thoughts on the role of testosterone? Well, generally from experience, clinically, younger women tend to not need so much testosterone on an average, it's individual though some women may but the majority won't. Uh And usually it's thought that the adrenal keeps giving out the testosterone so often compensates. But you will find 10 20% of women where the libido uh will be affected and testosterone will help. So again, the same guy lines that you would apply to after 50 would be important for poi estrogen progesterone replacement should always happen first and then testosterone should be added depending on the symptoms uh and important again for surgical menopause which can again cause poi or early menopause. That's when testosterone should be added much more earlier because they tend to experience majority of symptoms of lack of testosterone. Think Andro is not available for NHS prescribing. Yes, as I mentioned on my slide, uh remember that in the NHS, we only have the gels and in the private sector, it's mainly the gels. You have the cream, which is the andro and of course, you have the implants which are done in many private clinics. But on the NHS, we use the gels as a transdermal testosterone therapy. What is the major use of testosterone in the female body systems? I think I again, put this on the slide. Uh It's mainly what we think are the uh the main uh sort of functions of testosterone are bone health, muscle health cognition, brain function. Uh uh Again, urogenital function, uh those are the really main important bits besides the sexual function and libido, can you elaborate on monitoring requirements? What exactly do we need to check? So it's mainly total testosterone. Uh Most of the guidelines now say you only need to check the serum, total testosterone. And again, as I said, the lab range is usually between 0.4 to 2.5 MLS per liter. And as long as you get a reading within that, then you're not overdosing the patient, you mentioned uh there are more types of testosterone available in the private sector. Do you know what the cost of prescription is? No, II don't know the exact cost of the prescriptions. Uh And you'd probably have to find that out individually with the clinics. I mainly prescribe testosterone in the, in the NHS. And so that's something I can't answer. Uh No says if the levels return high during treatment and should be symptomatic with Herut how long typically until we recheck the testosterone and it's safe to restart once the levels have returned to normal despite ongoing hirsutism, so if you've started testosterone that's caused clinical side effects and the level is high, certainly take a break or reduce the level. It does take about 3 to 4 months or even sometimes longer for the hirsutism to completely go away or reverse and it may take some while. But in the meantime, you can certainly go to half the dose or quarter the dose and repeat the level. If the patient wishes to continue. If the patient's patient is happy to stop, give herself another 3 to 6 months until the clinical side effects reverse. Then you can start with a lower dose, a half dose or a quarter dose because that patient may be sensitive to the five mg dose. The next one is mhm is that precaution with PCOS? Well, we generally don't see much of a difference. Uh So women with PCOS in the past who go through menopause, perimenopause continue to experience some of the hyperandrogenic symptom. In fact, in menopause, they can start noticing chin hair, they may start noticing acne return. That's typically because the estrogen levels drop, but the testosterone levels are generally higher than the drop in the estrogen. But again, the the main indication here will be low libido. So if women tend to experience that despite replacing estrogen progesterone, persistent lack of libido, then yes, you will still offer them testosterone and you will follow the same rules in terms of starting and monitoring the patient. I know this talk is regarding testosterone. What about testosterone in male in low libido with low testosterone. I wouldn't recommend that for this particular talk. We'll hopefully have more talks about male hypogonadism testosterone in future. Let's focus mainly on the use of testosterone HRP for menopause. Today is total testosterone, the only test required. And what should we aim for any time gap that is needed between testosterone and blood test? Yes. So at the moment, we are not looking for any free androgen index, we are concentrating on serum total testosterone. The essays are not very accurate. So you really correlate clinical side effects and symptoms alongside the blood test and look at the whole picture. What should we aim for? As I said, as long as your readings are coming within the physiological range, then that's fine up to 2.5 mL. So later any time gap that's needed, always try and not do it on the day of application or try and do it quite late after application. So you could actually test the next day after the application or on the day. But quite late. For example, if the morning application of testosterone is done, you can test later, also try and avoid the arm where the actual uh testosterone was applied. For example. Uh So if you, if for example, they've applied testosterone, some, some women will do it on the arm. So that should, that should be avoided. Others, for example, I often say uh use only one arm on the day that you apply testosterone and draw the blood from the other arm. These are all crude methods but often help to get the right reading without any contamination as far as possible because you might get a false high reading when you try to do it. On the same arm that was used to apply testosterone and soon after application within say one or two hours PCO S patients. Uh again, any thoughts about data research, do they fare better or worse as they would naturally run high testosterone? Uh and it says drop levels. Therefore, if wanting to initiate, does the baseline look different? Again, you should uh you should concentrate on symptom, as I said. So the, the baseline testosterone with the PCOS, although it may be high, it won't be more than four or five, which is then considered quite pathological. The the PCOS patients either run a normal testosterone or it's slightly higher between 2 to 4 animals. In that situation, you'll go by symptoms because all the PCOS women may have high testosterone over a 2030 40 year period. The sensitivity to that raise testosterone may not be the same. Some may be less sensitive despite the high blood testosterone level. So for example, some women don't have any hyperandrogenic symptoms despite having PCOS. And that's because they might have quite good production of testosterone, but the hair follicles in skin is not sensitive. And so again, the rule is about the symptom if they have sexual dysfunction, low libido despite good replacement of HRP and there is an indication for testosterone. You can use it even though the baseline testosterone may be slightly high normal. And then as long as you're monitoring it and it doesn't become more than three or four nanomoles in that situation, one would be happy to continue if the patient is noticing symptom benefit and is not noticing any obvious side effects. Next one is sorry. Uh Last week, there were you can use headlines reporting of epidemic uh of women, sorry. The question is where I lost the question. Uh So last week, there were UK news headlines reporting epidemic of women in the UK prescribed testosterone with little evidence suggesting it's grossly over prescribed. What are your thoughts on this? I haven't read those reports in details what they were referring to in terms of the rates of prescription, who they are prescribed for and how women may be getting hold of them. So I can't comment on the article at the moment. I think testosterone has a role in HRT, it should be prescribed carefully for the right indication. It certainly helps many women, especially with regards to libido, other women do not other benefits for cognition, mood and for brain function and energy. Just that we don't have good scientific evidence because whatever evidence we have so far was mainly concentrated on sexual function. And we did not note any other benefits other than maybe a placebo effect. But hopefully now that we have more intensity and focus on testosterone. We can use the right essays, right, questionnaires, right. Outcome measures. And we might be able to demonstrate difference on many other aspects in future. But right now there is a group of women who will benefit from it. And as long as we have the discussion about benefits and risks and prescribe it, then I think it should be fine. Do you go straight to five mg or titrate based on symptom, the levels are high or low. What sort of percentage alteration? Yes, we start with the standard dose, the one recommended dose which is five mg and then we assess the patient for symptoms side effects and then do a blood test at six months. And based on that, you can lower the dose, half the dose. Sometimes you may need a bit more, but that's individualized based on symptoms signs as well as the uh blood levels from what you are saying, you're not routinely checking SHBG or FAI. No, not right now. So this used to be commonly part of prescribing and monitoring in the past doing SHBG and trying to work out the free androgen index. We're not doing that. Now, they're monitoring patient based on their symptom response. Any clinical side effects, acne hirsutism, scalp, hair thinning and then do a total serum testosterone level. How do you uh you can or can you continue the testosterone for again, this is like HRT, you have to have that annual review and have continued discussions with the women. And if you feel the benefits are there, there are no side effects. And as we go along, we'll get more and more observational data and evidence about long term safety and we continue with the benefits outweigh risk. There is no one a time or a deadline where you should come off. Uh Hopefully, as more data is gathered, we'll have more confidence about the long term safety of testosterone. So it's every time you see a patient and review have that discussion is the treatment benefiting you. Do you see a difference? And at the moment, the long term data are fine but the evidence is limited. Would you be happy to continue and make sure there are no clinical side effects like the hair growth, the acne or the scalp hair thinning. I'm just checking. You're not routinely checking fa or sh PG no, I don't. In my own practice, most of us just take just the serum total testosterone. The guidelines suggest to use and optimize a charity before considering testosterone, sometimes estrogen levels are checked to ensure patient is absorbing. Can you please advise what would be the appropriate range to expect? There's no one range because remember, estrogen levels vary from women to women. Most people think that getting estrogen, estradiol levels of 2 to 400 picomoles per liter is considered as a physiological range of replacing the estrogen but it varies. Some women may have a lower estrogen level, less than 200 be completely asymptomatic. Others may have a very high estrogen level but still have lots of symptoms. So the blood testing is not very useful other than just to make sure they're absorbing. In which case, it should be more than 200 to 250 picomoles per liter. And that shows you that the product is getting absorbed after that. It's all about symptom. The HRT dose will be determined by what the symptoms are and you keep increasing within the licensed dose of the product until you get to the highest licensed dose of the HRT. And then of course, if sexual dysfunction is still an issue with a good dose of estrogen, that's when one would recommend testosterone from what you're saying, you're not repeatedly checking. Uh I think that question was repeated again. Yeah. And then you mentioned optimizing HRT. First, can I check with what minimum levels of blood estrogen if we are to check these again, optimizing HRT based on symptoms would be more important than checking for blood. So as long as most of the hot flushes or other typical menopausal symptoms are taken care of, then then you know that the estrogen has done its job. And then of course, if there is persistent low libido, that's when testosterone would be indicated. So, optimizing HRP is more clinical rather than just blood tests or SH PG, not checked routinely. That's again, another question repeated again. FPG, not checked routinely. Remember that it's the serum total testosterone that we go for. SHBG may be checked in certain situations but not routinely. Which body parts do you apply? The testosterone gel? When and like, uh, what time I think I've already said it's usually preferred to be applied to the inner thighs. Uh, and again, it depends, as long as you do one application every 24 hours, you should get a steady state in terms of symptoms. Uh and the uh levels of testosterone in the blood. Would you optimize a charity dose? I think these questions are getting repeated. So I titrate down if any side effects or elevated bloods, but would you titrate up after six months? Uh No. So again, it depends on patient's response if you've given a standard dose of 5 mg and you've not noticed any side effects. Uh But you've also not noticed any benefits, then of course, it's important to know are the symptoms going to be treated by testosterone. So you may have to review your whole therapy rather than going up because usually if the lack of testosterone is causing sexual dysfunction, you should see some improvement by six months. So I would be skeptic whether you continue if you've given the standard dose and they haven't noticed any um significant benefits, reevaluate your treatment before you commit to increasing the levels or going up, I titrate down if any side effects or elevated bloods. Yes, that's a good strategy. Uh reducing the dose if you have side effects or elevated testosterone in the blood is always a good strategy and you can then go up again. If you think that the patient is now starting to reverse the original side effects, you can try going up back to the standard dose, but it may not work. In which case you can stay on the lower dose as long as it gives benefits for the patient. Ok? I think we've covered all those questions there. That's us. That's it. So I I'm gonna put in the chat again, the link to all your other teaching. This teaching will get on either tomorrow or the next day. So this will be available for catch up too if you want to go back over this and listen again. Um Vikram, thank you so much. There's always so many questions in the chat. I think it's a really, it was like mental health back in the day, wasn't it that it wasn't spoken about? And now it is spoken about thankfully and it's actually helping women and GPS and doctors actually communicate better. So this is just fantastic. There is another one, another message from Pria, any other contra interdictions apart from breast cancer? No. So as I said, mainly the hormone sensitive cancers again, evaluate role of testosterone in women with say uh multiple metabolic risk factors, heart disease, established heart disease, not that you cannot prescribe it, but always weigh the benefits and risks. Are you really thinking this is testosterone driven, low libido and it will help versus the risks such as metabolic changes or long term safety because we don't have a lot of data beyond five years for testosterone. So you can always prescribe other than for breast cancer or hormone dependent cancer, but weigh the benefits risk because in some situation, the risks may still be high with lots of comorbidities medically. And you might think testosterone may not be the only solution for low libido. So, weighing that balance and making a clinical judgment, that's very important.