and the Chief Medical Officer at the Endocrine Society in Washington, DC. On behalf of the European Society of Endocrinology and the Endocrine Society, I'm delighted to welcome you to the inaugural session of the Transatlantic Alliance webinar series. This series is a collaboration between our two societies and seeks to foster an international approach to presenting and discussing clinical practice guidelines and emerging topics of interest. We're excited to be co-hosting this webinar series and we hope you'll be joining us for future sessions. We're delighted to begin this series with a presentation of the 2020-23 International Evidence-Based Guideline on the Assessment and Management of Polycystic Ovarian Syndrome. ES and ESE are proud to have supported Monash University in the development of this guideline and we hope you enjoy today's presentation. Without further ado, it is my pleasure to turn it over to Rachel Mormon. Rachel is the Chair and Trustee of VERITY, a UK charitable society working to improve the lives of those with PCOS. Rachel, thank you for joining us today. Thank you so much for having me. It's truly an honor to be invited to come and speak to you all, so I really appreciate that. I'm just going to share my screen, one minute. Well, I don't seem to have a share screen option, so I will just talk to you. So I'll firstly introduce VERITY. We are the oldest PCOS organization globally. We were established in 1997. We are run by a team of volunteers. We have no paid staff, although we are very grateful at the moment to have a paid contractor helping us out with admin, which has been a life-changing experience. We are involved in a lot of things from kind of patient support, pointing people to evidence-based information. We do a lot of advocacy work with policy makers. We also assist a lot on research, either being co-applicants, co-writing, recruitment, dissemination. And we also are very honored and privileged to be invited to assist and represent the patient voice in projects like the Infectious Diseases Project, projects like the International-Based Guidelines, which we were involved in in 2018, and then most recently in 2023. And we've found over the last few years, our efforts have definitely moved from more kind of patient supporting roles to definitely more kind of advocacy and involvement in projects like this. And we're finding that that's having the biggest impact that we have. We work a lot with other patient organizations around the globe. And we have differences with each other, such as our healthcare and political systems, which kind of mean that we operate in different ways. We also have differences around how established we are as organizations, what access we might have to funding, and also opinions such as whether or not the name should be changed for PCOS. But we have a lot of commonalities, much more commonalities than differences. So predominantly we're all run by people living with PCOS. So we have passion really at the core of what we do. We're typically volunteer run. So we do this alongside having our own families and day jobs that pay the bills. So we have kind of challenges, very similar challenges around having PCOS taken more seriously, both in healthcare, in funding, in policymaking, awareness raising in public. And we also have this big common thread of funding and education, both for patient education, but also particularly in professional education. And we know that social media, which is actually how I, that is my day job. Social media is a global beast. So people are not just getting information from the countries that they're living in or their friends in that country, they're seeking and receiving information from people all across the globe. I think that's why it's so critical that initiatives such as the PCOS guidelines are truly international and that we have this consistent evidence-based information that is globally recognised and sought after. That is absolutely fundamental. We were thrilled and really privileged to be invited to represent the GD4 group of the guidelines in November last year in Prato. And we had a seat at the table, which is just a phenomenal honour really. And something really different that we've never had before since the last few years. So to have our voice recognised as patients, to be able to ask questions and say, well, what does that mean? Or a patient may not understand it in that way, or to even explain how we feel, for example, how information is presented and received by patients. And perhaps tweaking some words can mean a patient hears something and actually absorbs it because we are so often dismissed and told to go away and lose weight or to just not have our concerns heard properly. And the guidelines really shifted that and having that seat at the table and it being valued was really just an incredible opportunity and has, I think, made a big impact. And so I know that there were different countries' charity, sorry, different charity groups from around the world that got the same opportunity as Verity. And I just think that that is such an amazing thing because pointing back to what I said a moment ago about information being global, then we have that global voice of patients truly being reflected. Before I finish up, I just wanted to give you some information that we've found from some studies that we've worked on. So University College London and Verity, we did a Delphi study about a year ago. And what we found was that 60% of patients find it very difficult to get a diagnosis of PCOS, 95% can't access a specialised PCOS clinic or service, and 90% of patients in the UK feel that the NHS don't manage PCOS well. So the guidelines have an amazing ability to help us change those stats for the better. We found that patients said that 87% of patients that identified better education of healthcare professionals and consistent information that is evidence-based as being an absolute fundamental key that top of their wishlist for better healthcare for PCOS. And lastly, I'll just say that it's not uncommon, but in the UK, we found that when we asked patients in our 2023 patient consultation survey, how well they felt the country's healthcare system managed PCOS, it scored a 2.2 out of 10. And I think if you know the NHS, you will know that it's an amazing beast, but it's really failing PCOS patients. It's not treated seriously. We don't have any kind of guidelines accepted within the NHS. And so the international guidelines are really going to, we hope, change that for us. Yeah, I think I will end it there because I know I've only got a few minutes and there's a lot more exciting topics and speakers to come. So I thank you very much for your time and I'll hand you over to Professor Helene Attit. Thank you very much, Rachel, and good morning or good afternoon, depending where you are in the world. I'm in Australia, so it's 2.30 in the morning. It's my background. And just to highlight that this is the first transatlantic session, and it's fantastic to actually be involved in the opportunity to come to you all this evening. And I hope that you can all see the slides and everything clearly. So we are going to be talking tonight about the International Guideline in Polycystic Ovary Syndrome. And this will be a CME activity that all of you, I beg your pardon, a CME activity that all of you are able to be able to access your CME credits through the European Society for Endocrinology and through the Endocrine Society and we'll have the relevant information available to you all. So I'm going to speak to you, I'm speaking to you from Monash University as an endocrinologist and also as a Professor of Women's Health. But I've also been a long-term member of both the Endocrine Society and the European Society for Endocrinology. And I've had the true and fantastic pleasure of being involved in this process and being able to have the pleasure of bringing everyone together, including patient groups from the US, PCOS Challenge was involved in this as well as patient groups around the world. So with no further ado, to the speakers this evening in terms of disclosures will be Professor Dokris, Rachel Wilman, who you've just heard from, myself and also Professor Ilditz. And these are our disclosures. I have nothing of relevance to disclose. The guidelines were funded by the Australian government, by the Endocrine Society, the European Society of Endocrinology, the European Society for Human Reproduction and Embryology, and also the American Society for Reproductive Medicine. So this was truly an international enterprise. It's been such a pleasure to bring people together around the world and alongside our four sponsoring societies that I've just discussed alongside the Australian government there were actually a very large number of societies from across the world who came together patient groups, groups from obstetrics and gynecology, from endocrinology, from allied health, primary care, psychology, reproductive endocrinology, obstetric, midwifery, you name it, people were involved. And in terms of what we did in developing the guidelines, the really important, sorry, thank you, pardon. The important thing to note is the guidelines bring together not just systematic reviews which they are based on, but they go well beyond that. I'm sure all of you will know that a Cochrane review looks at the evidence, sometimes a really important clinical question doesn't actually have any evidence to answer. And the guidelines therefore go beyond just the evidence. We use the evidence, we grade it for certainty and that informs our recommendations, but we bring in multidisciplinary clinical expertise and every one of the five guideline groups had expertise from across multiple disciplines and from across the globe. All of them had European and North American representation and there were six continents involved. That is also brought in from the consumer perspective and all had consumer representation. And we do also consider value-based care and alongside the evidence and a very rigorous transparent process, we come up with the recommendations. So the recommendations, the guideline itself uses world's best practice with what's called the agree to tool around a guideline quality. And, but also that gives us the opportunity to grade the evidence, which is graded as high certainty, moderate, low or very low. And then to make recommendations that are either evidence-based, consensus-based or practice points, which are more about how you interpret or put into practice the recommendations. And we use what's called grade, which is the guideline recommendations are graded. So we don't just take the evidence, we start with that. But on top of that, we consider the feasibility of a recommendation, whether it's acceptable to patients and indeed to practitioners and health systems globally, what the cost might be, whether it impacts equity, how we're going to implement it and then give a strength of recommendation. So we may have something that's strongly evidence-based that nobody can ever implement and that will not necessarily result in a strong recommendation, but that's all very transparent. And if anyone who wishes to look at the detail behind this, if you actually search up Monash PCOS, this is actually the full guideline document, which is much shorter than the, sorry, much longer, I beg your pardon, than the published summary. The guideline is freely available online. The summary of the recommendations are published both in JCM and the Appearance Journal of Endocrinology. And the actual guideline itself is in multiple languages online. But accompanying that, if anyone wishes to look at it, is a 6,000 page evidence summary and each one of those grade tables where we went through the process collectively of what the recommendation was going to be. So if you wish to look through that and the evidence, it's there, I don't expect anyone to read it, but it's an important resource. Alongside the guideline is a number of translation resources, which Professor Yildiz will speak about, but probably the key one is the Ask PCOS app. It is currently used in 195 countries. It has resources in multiple languages. And as Rachel has said, one of the critical things is getting patient information out that's evidence-based. So I would encourage you to consider referring your patients onto this. It's freely available and is government funded. So what are we talking about today? Polycystic ovary syndrome is a complex condition. As Rachel mentioned, the name is a problem because it is neither a primary ovarian disease, nor actually do they have true epithelial line cysts. So we are looking at how we might evolve from there. But the problem with the name is really doesn't reflect the nature of the condition. So this is caused by genetics, epigenetics, and also environmental and metabolic factors with our rising increased weight. This is also driving the condition. The endocrine changes that occur underneath that are exacerbated by BMI and our hyperandrogenism, which we're all familiar with. Hypothalamic pituitary, gonadotropin changes, and insulin resistance. Those endocrine, and I'm going to emphasize again, this is an endocrine condition. It's often put in the gynecology or infertility box alone. And in fact, we've done some mapping recently, and at most medical schools at the top universities, this condition, which affects one in eight women around the world, or 12%, or 140 million women, is usually in the medical curriculum for one to two hours in the entire course, and it's usually under infertility or gynecology only. So we really need to make sure as endocrinologists that we're actually familiar with the condition and assist populations in terms of overcoming that delayed diagnosis, under diagnosis, and inadequate opportunities for care outside their infertility. The clinical features are reproductive with infertility, significant pregnancy complications, and increased endometrial cancer, metabolic with higher weight, much higher diabetes rates at a younger age, as well as other cardiovascular risk factors and cardiovascular disease, and then significant dermatological features, which often as clinicians, we may not realize the very profound effects they can have, especially at adolescence on body image. And then finally, all of that comes together in quite pronounced psychological features. The psychological features don't appear to be genetically related, unlike the metabolic and reproductive, but there is a very high prevalence, 80% have anxiety and depressive symptoms, and significant anxiety and depression in about 30 to 40%, which Professor Dockriss will talk about. So we really do need to recognize this is not about the ovaries alone, this is a much broader condition with impacts across the lifespan. So in terms of diagnosis, we've transitioned from what was a historical consensus. We had originally had the diagnosis from the NIH in 1990, that transitioned to a consensus diagnosis with the Rotterdam criteria in 2003. And in 2018, those Rotterdam criteria transitioned to evidence-based guidelines for the first time. And so they are now the International Evidence-Based Diagnostic Criteria. And in that, the guidelines are by definition, as good practice guidelines, updated every five years, and we're presenting the 2023 guideline. And with that, it's important to note that that international guideline criteria then can evolve without changing its name, can evolve every five years as evidence does. And indeed, that's actually what's happened. So in the diagnostic features, we have now defined each one of them, and I'll go through those with you. And we've also expanded the criteria to include anti-malaria in homeland. So in terms of diagnosis, the first of the diagnostic criteria is actually irregular cycles and I was the one who had the pleasure of crawling through the rather significant dearth of evidence actually around what is a normal menstrual cycle and indeed what is therefore defined as abnormal that we need to consider PCOS diagnosis. And so this is changes postmenarche. So essentially we know that in the first year postmenarche it's very common as part of the normal pubertal transition to have irregular cycles. From one to three years postmenarche it's normal for those cycles to be up to 45 days but any more than that on a regular basis then we would define that as irregular. After three years and onwards through to perimenopause the normal cycle is usually 21 to 35 days or less than eight cycles per year then becomes abnormal. If there's more than 90 days with no cycle then that is an irregular cycle or if there's primary amenorrhoea by the age of 15. And so that does then need further investigation and PCOS should be considered. It's obviously, it may be other causes and we'll go on to causes of exclusion but those are the criteria in adolescence and this is very important because what our patients tell us and Rachel's given you some of their data but we have global data including from the US and Europe and very consistent including actually through Asia and Australia is that often these young women when they present in adolescence with hirsutism, acne, irregular cycles they put on the oral contraceptive pill and they simply stay on it until they're planning a family which means they don't have a diagnosis and we know in itself that diagnosis is therapy in this condition. As long as we get the accurate diagnosis it is very important to make it because otherwise we take away the opportunity for explaining symptoms for screening, prevention and family planning. Otherwise the particular women may come out in their early 30s, decide they want to have a family and then are very limited in the treatment options they've got and are much more likely to require assistance and then have advanced maternal age and have a lower family size than they aspire to. So really important we get a prompt diagnosis in adolescence. In terms of clinical hyperandrogenism, essentially the cardinal sign which is in 70 to 80 percent of women with this condition is the presence of hirsutism alone and so that should really be considered as reflecting biochemical hyperandrogenism and when we're making that diagnosis we also need to be aware of the negative psychological impact. In terms of biochemical hyperandrogenism we only need to test for this if we think there are secondary causes on which I'll come back to in a moment but if we don't have clinical hyperandrogenism. If we do have clinical hyperandrogenism we do not need to then look for biochemical but if we're looking for biochemical hyperandrogenism the news is good. The evidence is better for total and free testosterone or bioavailable testosterone. We could consider measuring androstenedione or DHEAS however they have a poorer specificity and they're not associated as strongly so they're not routinely recommended in the diagnostic process and we do need to use accurate assays. In terms of assessing polycystic ovarian morphology, so the primary diagnosis requires two out of three criteria which I'll come to in a moment. So if you have hirsutism and irregular cycles by definition with exclusion of other common causes you have the diagnosis. If you have only one of those features and then you can go on to check ovarian morphology. So 70 percent of patients who have this condition will not require progressing to an ultrasound but if they do follicle number per ovary on either ovary at greater than or equal to 20 with modern ultrasound technology is the diagnostic cutoff. This is really important because the original Rotterdam criteria were 12 per ovary but the ultrasounds were far less sensitive back then and currently it is actually at 20 or it can be an increased ovarian volume. Now the new thing in the guideline now is the serum AMH level and this you'll see has reasonable certainty and fairly strong recommendations which are the symbols on the right. So antimalarian hormone can be used for defining PCOM so you can either do an antimalarian hormone level or an ultrasound. It's important you don't do both because we will be then prone to overdiagnosis but for a woman who may not want the inconvenience, who may not yet be sexually active, who may not wish to pay for an ultrasound or who doesn't have other indications, for example presentation with infertility, an AMH level could be an alternative. Very important we do it with the diagnostic algorithm which I'll come to in a moment and it should not be used ever as a single test for the diagnosis of PCOS and the same goes for an ultrasound. So many women will get an ultrasound which is abnormal and the result will be PCOS which is not possible on ultrasound or AMH alone, it requires the other clinical features. It should not be used in adolescence nor should ultrasound, so either of them should be used. So if we come back to the diagnostic criteria which have evolved from Rotterdam to the international guideline criteria, when we're looking at adults we require two of oligoanovulation and clinical or biochemical hyperandrogenism, remembering that up to 70 percent will be met by those first two criteria which require nothing other than history and examination and potentially a biochemical analysis but it's not mandatory if they have clinical features and then if they only have one of those polycystic ovaries on ultrasound or an anti-malarian hormone and I'll come back to the exclusions in a moment. In adolescence this is different and this is where the guideline has evolved. Adolescent criteria require both irregular cycles and hyperandrogenism and the reason for that is that polycystic ovarian morphology and anti-malarian hormone are commonly increased as part of normal pubertal transition and will over-diagnose up to double the prevalence of this condition which does not do anyone any favours. So it's really important we have both of those in the adolescent but if you have an adolescent that has irregular cycles or hyperandrogenic features and they don't have other causes then it's important to designate them as at risk and make sure we reassess them in their early 20s with an ultrasound or an AMH if necessary because otherwise we miss up to 20 percent to 30 percent of them. So we don't want to over-diagnose by doing those tests early but we also don't want to miss it. In terms of the diagnostic algorithm and this is really important in the order we do those tests. So first it's around your history with irregular cycles and clinical hyperandrogenism. If you have those other than the tests for exclusion at the bottom so that's thyroid stimulating hormone, prolactin, 17-hydroxyprogesterone for non-classic CAH and an FSH level then as well as clinically excluding Cushing's or other rare causes and also clinically excluding hypogonadotrophic hypogonadism then you have the diagnosis and that is around 12 to 13 percent of women. If you don't have both of those features the next thing to do is a free free androgen index or free bioavailable testosterone and you don't need to do additional androgens for diagnosis. If that is negative only then which is about 20 to 30 percent of participants or patients will need an ultrasound or if they're an adult ultrasound or an AMH if they're an adolescent they do not get those tests they've only got one feature and they're deemed at risk and re-evaluated. It's that algorithm order that's really important and has simplified the diagnosis. The other thing that came out in the guideline is that women should be considered at increased risk of cardiovascular disease and potentially cardiovascular mortality. So up until now the evidence has not been strong enough despite all of the cardiovascular risk factors that this condition has but it was now deemed the evidence is adequate. You'll see that there's only one star of certainty there but that's largely in part because none of this is randomized controlled trial data so it's automatically downgraded but the strength of the recommendation reflects the fact that there's now enough evidence across the board and there is therefore a recommendation that these women should be assessed for cardiovascular risk factors and I'm sure you've all seen adolescents with type 2 diabetes who otherwise would be undiagnosed if they were not aware of the condition and were not being screened. So the other issue is how we screen for dysglycemia. I'd love to tell you that a simple fasting glucose or HbA1c is adequate but it's not. In terms of accuracy there isn't a comparator to the 75 gram or depending on where you are and what dose you use of glucose but there is an alternative to that test in terms of accuracy. You can use a fasting plasma glucose if you really need to. HbA1c is even less accurate but they're not as good as picking up the dysglycemia in this condition largely because of the effect of estrogen on the hepatic glucose pathways. So the other thing is that we do not recommend the measurement of insulin resistance. It's just too highly variable in terms of the assay and whilst we know it's there in around 80 to 95 percent of these women, measurement on a clinical available assay is not recommended. So what do we recommend in terms of cardiovascular risk prevention? We recommend regular weighing, very careful we avoid weight stigma. It's very clear that weight is not a choice, it's not an individual behavioural failure, it's essentially a very obesogenic environment we're living in and it is a physiological predisposition in this condition to increase weight and then weight obviously increases the severity of the condition. As clinicians the very important message for us is to not stigmatise or blame the individual who has the condition but at the same time encourage them to be the healthiest they can be and at a very minimum to use lifestyle for prevention of weight gain lifelong. So asking permission to weigh, informing about why we're weighing which is to reflect risk and to optimise prevention is really important and making sure that there's not an issue around eating disorders when we're doing that. Informing women on the risks of diabetes and heart disease and the opportunity for prevention. Implementing the oral glucose tolerance test screening around three yearly and if they have other risk factors more often especially if they're considering infertility treatment or pregnancy as so many of these women go into pregnancy with dysglycemia that's not diagnosed. Annual blood pressure measurements and if they have other risk factors such as higher weight that we then do their baseline and ongoing lipids. Noting the prevalence of obstructive sleep apnea is very high in this population so if your women do have symptoms please do screen and then consider a sleep study if needed. They also have increased risk of endometrial cancer. The awareness of that risk is important but routine screening is not recommended because of the low absolute risk. So it is actually important that women are aware of the fact that they are at risk of increased weight gain, that that weight gain has implications for pretty much all of the features of the condition and that we're there to partner and support them to prevent that as much as possible and to give them the opportunity to be as healthy as they can be no matter what the starting BMI scenario is. Therefore that includes the fact that over their life plan and as doctors will talk about the reproductive plan we recommend that increasing awareness around the fact that increasing weight not only causes PCOS and makes it worse, it causes infertility and makes it worse and it also has adverse impact in pregnancy and that needs to be very carefully conveyed but it doesn't emphasise the reason we need to keep people as healthy as we can. Routine preconception care is really important because the cardiometabolic impacts these women often will go into pregnancy with. Really important outcome of the guideline, very poorly appreciated. Women with PCOS make up one in eight pregnant women and they have really high pregnancy risks. They're often at advanced maternal age because of their infertility and treatment and they also often have a dysglycemia going into pregnancy and yet we know in the States and in Europe and in Australia that PCOS status is very rarely recognised, identified, captured or alters risk stratification or pathways for treatment in pregnancy and yet we know they have much higher gestational weight gain, higher rates of miscarriage, much higher rates of gestational diabetes that are already astronomical, higher hypertension in pregnancy and preeclampsia, higher IUGR, small for gestational age, low birth weight, preterm delivery and caesarean section and these are quite high odds ratios. So these are absolutely very high risk in terms of their pregnancy outcomes and despite having a higher BMI and often GDM they don't have large for gestational age babies because this is a vascular condition and they often have placental insufficiency. They're not at risk of LGA and increased instrumental delivery in that context. So one of the important messages for all of you is to think about preconception care and about how we make sure that these risks are addressed when our patients go on to pregnancy. So really important that we don't necessarily just think they're going to have big babies but actually recognise they're at risk for other complications. Really important therefore that we think about early lifestyle intervention before and according to many guidelines including the US Prevention Taskforce actually look at lifestyle intervention in pregnancy given their risk, measuring their blood pressure and also doing the post-trial test ideally before but if not early in the pregnancy. I'm just going to touch very quickly on metformin here because we're talking about pregnancy. There's a lot of interest in metformin in pregnancy. We'd love to tell you what prevents gestational diabetes, miscarriage, hypertension, preeclampsia and macrosomia but the evidence is not there. In fact the evidence quite surprisingly is that it does not do that and that doesn't seem to depend on when they started the therapy even if they became pregnant on metformin. It can reduce early miscarriage slightly and also potentially preterm birth. So if you have someone who's at high risk that's important and it also can limit excess gestational weight gain. So there may be some indications, there's not too contra indications really, but we shouldn't be using it because of potential long-term offspring risk unless there's a reason to do so. So on that note I'm going to stop sharing my slides and actually hand over to my colleagues. There we go and so I'm going to hand over to Professor Anuja Dockers who's from the US. Anuja I'll ask you to introduce yourself. Thank you so much Helena, that was fantastic. Good morning from Philadelphia in USA and good afternoon or evening to you wherever you've logged in from. I want to start by just congratulating Helena on her leadership for just another fantastic round of bringing together the 2023 guidelines. It was quite an effort in 2018 but as I was listening to her presentation it just blows my mind away each time the amount of work that's gone on behind the scenes. So I applaud her for her leadership. I am the Director of the Penn PCOS Center in Philadelphia and also the Executive Director of the Androgen Excess PCOS Society and we have worked very closely both with Endocrine Society and now we'll be working with the European Society of Endocrinology for our upcoming update meeting. So it's my pleasure to be part of this first webinar that's being held jointly with both of these societies. Let me share my screen with you and all right I hope you can see my screen here. Are we good? Yes we can Anuja. Perfect, thank you so much. So I'm going to be talking to you on assessment and management of psychological well-being, the models of care, as well as lifestyle management and this was addressed through GDG2 which I chaired the prevalent screening management of psychological issues and models of care. Here is our picture of the team when we met in Prato, Italy. And emotional wellbeing is vital because manifestations of PCOS really challenge feminine identity and body image. And as you heard, you know, within the diagnostic criteria features of PCOS such as the higher weight, versatilism and acne, they can adversely affect mood and self-efficacy. They can compromise quality of life. And I'll show you evidence for that and the recommendations. And more importantly, they can also impact effectiveness of lifestyle interventions, which is our first line treatment. And as a result of this, psychological screening and treatment has been integral aspect of PCOS care. We'd included this in 2018 and have continued to do so in the 2023 update. So these were the priorities and the components that we looked at within the GDG. And the quality of life assessment, again, as you heard, there was initially assessment based on the systematic reviews and then recommendations made downstream. And here we have the forest plots based on the SF-36 as well as the WHO quality of life surveys. And the evidence-based recommendations say that the healthcare professionals and women should recognize the adverse impact of PCOS, the diagnosis, as well as features on quality of life. And women with PCOS should be asked about their perception of PCOS-related symptoms and really their key concerns so that we can prioritize management. The limitations here are that we do not have adequate studies in adolescents and we do not have a PCOS-specific quality of life tool that is comprehensive. So there is a certain tool called PCOS-Q, but really we need a little more data with respect to assessment of quality of life. Moving on to depression and anxiety, there's robust data. And I just put in a couple of slides to show you that the current forest plots that were generated through the 2023 evidence synthesis was an odds ratio of about 2.6 for depression scores being higher in adults. And now we have data to show that there's an increase in the similar sort of extent, 2.2 odds ratios for adolescents. And again, more data compared to 2018, looking at anxiety scores and disorders with an odds ratio of about 2.9, but not adequate data in adolescents for anxiety outcomes. So the current guidelines have been updated a little bit from 2018, where we want healthcare professionals to be aware of this high prevalence. And it's for moderate and severe depressive symptoms. I do want to highlight that. And both in adults as well as adolescents. And we recommend screening for depression in both these groups. With respect to anxiety, there's a high prevalence of moderate and severe anxiety symptoms, but primarily in adults. And we've restricted the recommendation to say that we should screen for anxiety in all adults. What we don't know is the optimal interval for anxiety and depression screening. So definitely recommending screening at the time of diagnosis, but then using a more pragmatic approach and repeating the screening when there are new risk factors, comorbidities, or even life events, such as the perinatal postpartum period. The next priority area was psychosexual dysfunction. And the manuscript that has now been written based on the evidence synthesis generated from the 2023 guidelines is in the final stages of review for publication. And what it shows is and summarizes is that women with PCOS do report lower sexual function and lower sexual satisfaction. Sexual distress, however, if it's not associated or if it is not being surveyed, it becomes a little hard to get the overall prevalence of sexual dysfunction in this population. And multiple screens need to be used to determine one, the level of sexual, the decrease in sexual satisfaction and function, but secondly, also whether there's distress associated with it. So keeping that in mind, then it's a clinical recommendation that healthcare professionals should consider the multiple factors that could influence psychosexual function in PCOS. And these include higher weight, versatilism, so the body image, mood disorders, infertility, and also maybe some of our PCOS medications. And we should seek permission to discuss psychosexual health and then if detected, make the appropriate referrals. Body image is a way a person may feel, think, and view their body, including their appearance. And a number of factors that impact body image are prevalent in PCOS, such as the physical factors, the psychological factors, and also social, cultural, maybe related to PCOS, infertility, et cetera. So the evidence-based recommendation here, again, asks healthcare professionals to be aware of the features of PCOS that can have a negative impact on body image. The evidence for an increased prevalence of eating disorders is also robust now with an odds ratio of 1.5. A number of studies across the globe supported this evidence to say that eating disorders and disordered eating should be considered in PCOS, regardless of weight, and especially in context of weight management and lifestyle interventions. And we'll talk a little bit about this when I talk about lifestyle intervention in terms of the appropriate counseling for patients who might have a history of disordered eating. And women with PCOS who are diagnosed with any of the conditions we've talked about, namely depression, anxiety, and eating disorders, should be offered psychological therapy that's really guided by regional general population guidelines and also the preference of the woman with PCOS. And then those who may also have the body image distress, low self-esteem, or psychosexual dysfunction should be offered appropriate evidence-based treatments depending upon the condition. Now, in terms of treatment, the data is more limited specifically for the PCOS population, and we were able to derive some of these recommendations from the general population. But using the evidence, psychological therapy can be considered as first-line treatment and followed by antidepressant medications where mental health disorders are clearly documented or persistent. But we wanted to call out the fact that lifestyle intervention and other treatments for PCOS, namely birth control pills, metformin, laser, that target the PCOS features should really be considered in these patients because they do have the potential to improve the psychological symptoms. So simultaneously managing PCOS and its features and then also escalating to other health providers who are more proficient in management of anxiety and depression should be considered. So moving on to the second aspect, which was the models of care and information sources and needs for our patient. It is very clear through a number of surveys that we have all conducted collaboratively with Helena's group and ours that the patients really are asking us for more tailored information, education, and resources that are high quality. And this really needs to be provided to all our patients and should be provided in a respectful as well as empathetic manner. And it should really be embedded at all levels of healthcare professional training as well. And Helena alluded to the fact that not enough time is spent in our medical education talking about PCOS and the updates such that the professionals can offer high quality data to the patients. What are the models of care that could be offered? And it could be an accessible care model which is either interdisciplinary, it could be primary care focused and then escalation to specialists or a centered care where you have a PCOS center like we do at Penn. It could or needs to be patient centered where we offer the patient the empowerment, education, and prioritize their key concerns. And finally, we really need to change this focus from it being either a gynecologic condition or cardiometabolic with really thinking about this as a chronic disease and focusing on prevention and chronic disease management across the lifespan. So the models of care should be prioritized for equitable access and to evidence-based primary care pathways and then escalation to integrated specialists or multidisciplinary services as required. And the support in terms of managing PCOS, we as a society really need to recognize that there has to be greater awareness and education on PCOS and that would be the first step to reduce stigma as well as marginalization. And we need to prepare culturally appropriate resources and education on PCOS, again, across the lifespan and not really focused on the reproductive time period. And Helena showed you some of the PCOS Ask app which is available for patients. And I wanted to also show you that on that same Monash website, there are very beautifully created, easy to understand PCOS information on emotional wellness, fertility, lifestyle, that you could click into each of these. They can be downloaded. They are freely available for our patients. And I would encourage you to use some of these resources or all of these resources that have been prepared. And then moving on to the lifestyle, which was GDG3. And here is a list of the team members as well as the picture they met in Melbourne, Australia in November of last year. And so the first aspect of lifestyle includes the effectiveness of lifestyle interventions. And what we're talking about here is either exercise alone or a multi-component diet combined with exercise and behavioral strategies. So the entire encompassing exercise, diet and behavioral strategies should be recommended for all patients with PCOS. And this is to improve their metabolic health, central adiposity, lipid profile, but also the clinical recommendation point talks about recommending these healthy behaviors in all patients to optimize their general health, not just cardiometabolic, but to improve the quality of life, prevent weight gain. And I'll go into some of those details. A couple of the other practice points that have been included, talk about lifestyle management being a core focus in PCOS management. It should be co-developed in partnership with your patient. And the discussion should also focus on that the benefits of a healthy lifestyle exist even in the absence of any weight loss achieved. Helena focused a little bit or mentioned a bit about awareness of weight stigma, and I'll talk about it in the next couple of slides, but this is really front and center of our discussions for lifestyle interventions. And in patients who are not overweight, specifically in adolescents and at other key time points, the focus should still be on healthy lifestyle to prevent the excess weight. And again, insulin resistance that came up in the previous talk, although part of the pathophysiology, we are not recommending that as a screen in routine care. Moving on to the behavioral strategies, we do believe that the behavior and the evidence sort of shows that the behavioral strategies combined with the other lifestyle interventions is going to be critical because it will prevent relapse. It'll increase engagement and will overall allow a more healthy lifestyle and emotional wellbeing. The behavioral support can be given in different ways, and one of them being utilization of the SMART goals where one has to be specific, use measurable outcomes, those that are achievable, realistic, and within some sort of a timely manner. And then also using and incorporating cognitive behavioral therapies and interventions has been shown to improve engagement, retention, as well as adherence. So this is sort of a summary of the lifestyle interventions where this is the core and a first-line therapy that's been recommended, not only for weight management, weight loss, but weight prevention, and permission to offer weight-centric care aiming for about a 5% to 10% weight loss over a six-month period. More specifically, looking at the dietary intervention, there is really no evidence to support one type of diet over another or one type of composition over another. And healthcare professionals should really advise sustainable healthy eating, which is tailored to an individual's preference and goal so that they can then follow this through over a longer period of time. And really that's the focus of co-developing this approach. Coming back to the higher risk of disordered eating, the recommendation is to avoid unduly restrictive and nutritionally unbalanced diets, specifically in this population. And then a referral to suitably trained allied health professionals like a clinical nutritionist or dietitian should also be considered very early on as we offer this comprehensive care to our patients. So here is sort of the summary of the dietary intervention aspect of the guidelines. And then finally, moving on to the exercise interventions, there's lack of evidence supporting one particular type or intensity of exercise as being better than another. And once again, just like the dietary intervention, healthcare professionals should advise sustainable physical activity based on the individual's preferences as well as goals. Here is a summary of what is recommended in terms of for adults when we talk about prevention of weight gain, about 150 minutes of moderate exercise per week or 75 minutes of vigorous exercise per week. In adolescents, that translates into about 60 minutes of moderate to vigorous exercise three times a week. Now, when we talk about weight loss or prevention of weight regain, the numbers are a little higher at 250 minutes of moderate exercise per week and 150 minutes of vigorous exercise per week. And we're really encouraging movement and even in spurts and bouts of movement and avoiding the sedentary behavior. You've heard us talk about weight stigma and many women with PCOS experience weight stigma in healthcare and other settings and the negative bio-psychosocial impact of this really should be recognized. And healthcare professionals should be aware of their own weight biases and then the impact that this might be on their professional practice and the impact on their patients. As you can see again from these slides, this was an important aspect that was discussed. Rachel brought it up in her talk as well. And one of the things that I do want to highlight is that we need to discuss that the higher weight, yes, it's a risk factor for PCOS and its complications, but it is not the only one indicator of health and broader factors really should be assessed as we engage in this comprehensive discussion. So I'm gonna conclude here and hand it off to Professor Ildiz. Let me stop sharing. Thank you so much. Professor Ildiz, you can turn on your camera. Thank you. Thank you, Anuja. And it's a pleasure to participate in this first of the series of transatlantic webinars, and I'm happy that the first one is about PCOS. It's also a pleasure to be part of this international guidelines, the previous one and the new one. So I will try to cover the management of chronic management, management of non-fertility issues. As we heard already, lifestyle is the first line for prevention and therapy, and we need to target women's primary concerns and consider the impact of any intervention on quality of life. So when we talk about pharmacological management, combined oral contraceptives, metformin, the combination of those two, anti-androgens, anti-obesity agents, and inositol, that's a new one, was the topics that covered in the new guideline. So we need to emphasize at the beginning that almost all of the medications being used in PCOS are off-label, but evidence-based. So that's important to share this information and discuss the evidence, possible concerns and side effects of any treatments with our patients. So here is the pharmacological treatment for non-fertility indications. We had the diagnosis first, we said education, lifestyle is important, and the first line pharmacological intervention for androgen excess and irregular cycles would be combined oral contraceptives. And the evidence-based recommendation is general population guidelines should be considered when prescribing OCs both for adults and adolescents with PCOS. And the specific types or doses of progestins, oestrogens are combinations, cannot currently be recommended. This was the case with 2018 guideline, and it is still the case for this new guideline, meaning that we really need further research in this area. So using lowest effective oestrogen dose is recommended, and when we say low, we're talking about lower than 35, so 20 to 30 micrograms of ethanol oestradiol or equivalent. Natural oestrogen preparations, balancing efficacy, metabolic risk profile, side effects, cost and availability could be considered. For the absolute and relative contraindications and risks, we follow the WHO guidelines for the use of oral contraceptives in general population. We do not have specific data in such large populations of women with PCOS. The 35 microgram ethanol oestradiol plus cyprothorone acetate is not the first line in PCOS due to increased adverse effects reported in general population. So even though any OC could be prescribed first line, we avoid 35 microgram ethanol oestradiol plus cyprothorone. When we deal with herpetism, we need to know from the beginning that herpetism requires oral contraceptives and additional cosmetic therapy for at least six months. So the expected outcome will not appear before six months, and even it could take more. And when we prescribe oral contraceptives, we need to consider additional PCOS-specific risk factors, including high BMI, hyperlipidemia, and hypertension. As we said already, no combined oral contraceptive preparation is superior in PCOS. What is new in this 2023 version of the guideline, again, coming from extrapolating from the general population, is that progestin-only oral contraceptives may be considered for endometrial protection with limited evidence in PCOS. After the OCs, the second line pharmacological therapies would include OC plus metformin, OC plus antiandrogens, and metformin and lifestyle. A few words about metformin. Evidence-based recommendation, metformin alone should be considered in adults with PCOS who has a BMI over 25 for anthropometric and metabolic outcomes, including insulin resistance, glucose, and lipid profiles. And metformin alone could be considered in adolescents at risk of or with PCOS for cycle regulation, although there is limited evidence. Antiandrogens alone or in combination are used to treat hirsutism, so the guideline recommends, based on limited evidence with very low certainty, that the addition of antiandrogens should be considered after seeing no response to oral contraceptives alone for the treatment of hirsutism. And given the negative psychological impact of female pattern halos, antiandrogen OC combination could be trialed, again, acknowledging the lack of evidence in PCOS population. One important issue to emphasize, that's a practice point, whenever pregnancy is possible, the healthcare professionals must educate and counsel women and adolescents regarding the risks of incomplete development of external genital structures of male fetuses, namely underviralization. So in other words, if you are giving an antiandrogen, there should be an effective contraception alongside. How about the other medications and treatments? Anti-obesity pharmacological agents. Those that were covered in the guideline are liraglutide, semaglutide, both GLP-1 receptor agonists, and orlistat. They could be considered in addition to active lifestyle intervention for the management of higher weight in adults with PCOS per general population guidelines. So this is a consensus recommendation. Unfortunately, our group was unable to make an evidence-based recommendation since there was absence of useful evidence for this specific question. And when the pregnancy is possible, it's important to use effective contraception since we do not have pregnancy safety data for GLP-1 receptor agonists. And the other practice points are, I mean, endocrinologists are already familiar with the dose escalation of GLP-1 receptor agonists and shared decision-making regarding use of this medication. Inositol is covered for the first time. So in 2018, there was not a part on that. So the evidence-based recommendation, inositol in any form could be considered in women with PCOS based on individual preferences and values, noting limited harm and limited clinical benefits, including ovulation, herpetism, or weight. And again, another evidence-based recommendation, metformin should be considered over inositol for metabolic measures. Herpetism and central adiposity, noting that metformin has more GI side effects than inositol. So if you look at, again, the level of evidence for both, it is very low quality or certainty of evidence to make these recommendations. How about the mechanical laser and light therapies for hair reduction? So they should be considered for reducing facial hirsutism and for related, as we heard from Professor Dokras, that depression, anxiety, and impaired quality of life are important for women with PCOS. So these laser therapies are helpful reducing facial hirsutism and these psychological comorbidities as well. Women with PCOS might require a greater number of laser treatment sessions compared to women with other causes, including idiopathic hirsutism. And adverse effects appear to be limited in the hands of experienced and suitably qualified providers. How about the bariatric metabolic surgery? This type of surgery could be considered to improve weight loss, hypertension, diabetes, hirsutism, irregular menstrual cycles, ovulation, and pregnancy rates in women with PCOS. This is a consensus recommendation. So the bariatric metabolic surgery in women with PCOS should be informed by general population guidelines. PCOS is a metabolic condition and could be considered an indication at a lower BMI threshold for bariatric and metabolic surgery, similar to other metabolic conditions, including diabetes. Here, this is a high priority area for clinicians and women with PCOS and also high priority area for future research. So we were not able to come up with an evidence-based recommendation, but further research is needed. One important issue, if the patient undergoes bariatric surgery, then they should be strongly counseled on the likelihood of return of fertility. So contraception should be continued until a stable weight is achieved. And this is usually after one year to avoid significantly increased risk of growth restriction, prematurity, small for gestational age, pregnancy complications, and prolonged hospitalization of the infant. How about the reproductive life plan infertility? So this is GDG5. The first-line medical treatment for infertility for women with PCOS is letrozole. An alternative to letrozole could be CC plus metformin, CC alone, or metformin alone. Metformin alone has low cost, low efficacy, and it does not require monitoring. You might prefer an alternative, gonadotropins, with different protocols, but they would have high cost, high efficacy, and they would require monitoring. And if there is no response to the first-line medical treatment letrozole, then gonadotropins with the ultrasound monitoring is an option. An alternative would be laparoscopic ovarian surgery. And finally, if there is no clinical response to the second-line, the third-line medical treatment would be IVF. So we already heard the huge amount of work to come up with these guidelines. So how about the translation of these guidelines? Here are the tools for healthcare professionals and consumers. So there is a primary care tool, PCOS Care Plan, and there are five algorithms. One for screening, one for emotional well-being, one for lifestyle, you already have seen that slide, one for pharmacological treatment for non-fertility, so long-term medical management, which I have shown in my presentation, and also the last one I showed a minute ago, management of infertility in PCOS. There are infographics available, both for the definition and comorbidities and treatment of PCOS. There is this website, including podcasts, webinars, and narratives, and there are also a lot of written resources. Here you see the PCOS GP tool that is available from the Monash University website. And there is this Ask PCOS app, which could be downloaded to handheld devices and helpful for self-assessment of women with PCOS. So with that, I would like to thank all our participants on behalf of the International PCOS Network, and just want to invite my co-panelists to the screen. Thanks, we've had some really good questions in the chat, which I have been answering as we go through. I might just take the opportunity to just respond to one that was common on the first talk, which was about AMH cut-offs. There's not a level given specifically because it varies by assay and also in population context. So the cut-off provided by your local laboratory, which could be anywhere between about 3 and 5, is usually what we recommend rather than giving you a specific cut-off, and that's quite important to note. But there were a few questions in the chat if you wanted to know. One of them was about alternative treatments to combine oral contraceptive pill if there are side effects or risks you've got. What else besides metformin? So I don't know whether you want to discuss intermittent progestin or not. Yeah, sure. Maybe, I don't know if any more questions from the audience regarding these diagnostic tools, because when you present AMH as a tool, everybody is excited. So everybody wants to use it instead of ultrasound. So I don't know. It might take time for every population to develop the age and BMI-adjusted normal values with accurate assays. Hopefully, we could have it in practice soon. And regarding the chat screen, I don't know. So there was another one in there about alternatives to, or treating hepatitis and for those who desire pregnancy, around the efficacy of laser and these recommendations in the guideline around that, if you want to comment on that. Yeah. Well, first of all, it's still, I mean, unfortunately, when it comes to evidence to inform the guidelines from 2018 to 2023, both for OCs and for metformin and for combinations, the recommendations are still similar, meaning that in five years, we still don't have large studies asking questions about these old medications. But what we know is oral contraceptives are good for androgen excess. Metformin is good for metabolic features. Then you might think the combination would be good for addressing both issues at the same time. But the systematic reviews of the guideline tells us making this combination wouldn't add much to using these agents alone. So we still, unfortunately, we are still stuck with the OCs to address clinical androgen excess. And for metabolic features, still the best available option appears to be metformin. Although we can use mechanical laser, I think. So that was one of the new recommendations in the guideline, not only over the last six years has there been quite a few studies, but those studies have showed that with the appropriate skin and hair colour, making caveats around that, laser therapy is effective. We recommended appropriately trained providers. And also note there is an improvement in mood and quality of life with the use of those agents. So just if you have someone who can't be treated with the medical therapies, then that is important. And so I don't know if you can see the chat as well as I can moderate here, but there's one there's a question on scalp hair loss and what would we recommend? I've highlighted that it does the ring or never ring or patchwork. I'm making the point in here that about the fact that needs to be first passed. Hepatic metabolism may be what you might want to speak to the impact on SHBG and the importance of having the oral route of estrogen administration. Yeah. Do I see the question in the chat screen, by the way? Yes, you can go down to Q&A. So it's not chat, it's the Q&A button next to it. OK. So the question was about female pattern hair loss, right? Yes. And can we use the CRCPs first line, but does the never ring or the topical contraceptives work? I mean, that's just certainly good to discuss the fact that they don't impact SHBG. Yeah. I mean, female pattern hair loss is quite a challenge for the clinician. Even using oral OC alone is not helpful. And you really need to add an antiandrogen to an OC. So other than the oral route, the transdermal route would not help when we are talking about this problem. And this is unfortunately not only androgen related. So it's quite challenging, but I could tell a single agent oral OC would not be helpful. The transdermal would not help at all. But the combinations, I mean, adding antiandrogens have some reasonable results in the long run. Anuj, did you want to make any other comments just on going through the questions there? No, I think the one that you had asked earlier was it about using progesterone options when OCPs were not indicated. I'm trying to look for where that question went. Yes, it's in the answered one. Did you address it? What exactly were they asking? There was a question about alternatives to combined oral contraceptive pills if there was a high risk. And in the context of was there anything else other than that formant for endometrial protection? And so you might want to cover, Anuj, maybe you want to discuss intermittent progesterone use. Right, right. So, you know, there is unfortunately a fair proportion of PCOS patients who may not be good candidates for the combined oral contraceptive pills, either given dyslipidemia, hypertension, BMI, smoking, just as Bulent reviewed. And in those patients, it's either the options are then the progesterone only pill, which could be used in a continuous form, at least in the US, the norathendrone is the popular one, or one could do cyclic progesterone, which could vary anywhere between the 10 to 14 days. And these are more practice points, I think Willem can correct me, but I don't think this was under the evidence-based recommendation just because we are extrapolating the data from the general population to the PCOS population here. And then the third option, which would be, again, an equally good option, is an IUD form of delivering the progestin, so in very low doses, but locally, and really with the target being protection of endometrial hypoplasia. I don't think metformin really comes high there, it's both combined oral contraceptives followed by progestin only, and then very weak for metformin if you're really looking for endometrial hyperplasia. And I think I did see somewhere in terms of measuring endometrial thickness as well, right? Did I go past a question? And really, in the reproductive age group, we don't have guidance to track endometrial thickness as a way of screening for endometrial hyperplasia, so we really need to be treating these patients and preventing the hyperplasia with medications. There's just another question here just about insulin levels. I might just respond to that. So the challenge is if we could do a simple test that was accurate to measure insulin resistance, that would probably be advisable, but we know that for the vast majority of these women who do have a higher BMI, that 95% of them have insulin resistance. The diagnosis of PCOS is in fact a diagnosis of insulin resistance. For lean women, it's about 85%. And so essentially, if they have PCOS, for the vast majority, they're insulin resistant. The problem with the assay is that if they sit and wait in the waiting room at the pathology collection service versus walking a few hundred metres before they actually have the test, you'll get widely varying levels. So it's not a reproducible assay, and for that reason, at this time, we don't recommend it. Essentially, you should consider your patient, especially if they have a higher BMI, as being insulin resistant and treat them as such. The other reason why we don't recommend using it is it doesn't alter your treatment. Interestingly, your insulin level doesn't predict your response to metformin or indeed to other therapies, and it doesn't even necessarily accurately predict what's going to happen in terms of complications. So important to note that. Also, just to highlight, there's a comment in the chat if you're wanting to collect your CMA points from either society. So in terms of other questions, there was a question about GLP. I don't know if you wanted to just discuss that a little bit further, but in terms of the evidence from the broader population, given that we don't have a lot of data in this population, but we know that they are increasingly being used. Yeah, yeah, it's very exciting. I mean, we really look forward to see the results of this group's studies in PCOS, not only GLP-1 receptor agonists, but also twin creatins. I mean, they have promising results from obesity and diabetes, but at this time, the evidence base is quite limited, both for adults and adolescents. I'm aware at least one randomized control trials on adolescents are coming up soon. There are a few studies from Europe as well, but we are not able to make any evidence-based recommendations, but they look quite promising, I would say, once we see data in women with PCOS. Yes, it is quite promising. The challenge, of course, is that with these agents, everyone's certainly going to be chronic long-term treatment. And the biggest challenge for this group, for all of us, actually, as clinicians, is when women stop these treatments, especially for pregnancy, the astronomical escalation in gestational weight gain during pregnancy is a real challenge. So I think in this condition, one of the big things is going to be, what do we do transitioning? And I might actually ask, on that point, Anuja, our study, I don't know if you want to give us a little bit of insight, because one of the challenges here is lifestyle and weight loss for improving fertility in our patients. And then reciprocally, what happens as they go into pregnancy, do you want to make a comment about that? Yeah, and I also, if I might add, there's a question on when a woman conceives on Metformin, when would you stop it along the same lines of the, when do you stop the GLP-1s? And I don't know if this was specifically addressed in the guidelines bulletin in your section, but the general practice pattern is that with a positive pregnancy test, if the Metformin was used just as an adjunct for ovulation induction, we stop that. But coming back to Helena's point, we really do not know, and there's a lot of sort of conflicting recommendations right now as to when to stop GLP-1 agonists in a patient who is attempting pregnancy. And it's, I've heard it anywhere between two months prior to attempting conception to, with a positive pregnancy test. The challenge with stopping these medications prior to, are that, you know, patients don't get pregnant the first month they attempt pregnancy. And the success rate per month and per cycle varies depending on the modality used, but with oral ovulation induction agents like Letrozole or Clomiphene, it's anywhere between 15, 17, 18% per cycle. And hence it might be six or more months before your patient's pregnant. And that weight regain in that time period can be significant so that the advantage of the weight loss preceding might be totally negated. And that becomes quite a significant challenge. What Helena was referring to was we conducted the OWL-PCOS study looking at weight loss for four months with an intensive lifestyle management group followed by Clomiphene, and certainly had higher live birth rates in the group that engaged in a lifestyle modification program. However, for those who did not get pregnant or got pregnant later, there was significant weight regain as well. So I think more to come and more that needs to be done in terms of optimally counseling our patients for the GLP-1s. But for metformin with a positive pregnancy test, I think most people feel comfortable keeping the patient on it during the ovulation induction process. Yes, and so I'm just noting there are some questions here about DHEAS and isolated elevations of DHEAS. So one of the reasons that we made the recommendations we did in the guideline about diagnosis was that you can often get marginal elevations of DHEAS that are nonspecific. And indeed, they often result in ongoing significant endocrine testing. And as endocrinologists, we're all very familiar with the merry-go-round we get on when we get one abnormal test and then have to keep checking, for example, when we get incident lomas on imaging or nodules on thyroid ultrasound imaging. Likewise, one of the reasons we're discouraging doing DHEAS and androstenedione in the diagnostic test is that often you will get an isolated marginal elevation of those agents, and they're not necessarily reflective of pathology that has long-term impact. So in terms of the diagnosis, we are just recommending the testosterone-level or bioavailable, not measuring DHEAS and androstenedione. Having said that, often people are referred to us with those minor abnormalities. Personally, I use my clinical acumen as to whether or not I think there is anything else going on, any features of bushings, especially watching them over time. But if not, and if it's only a mild aberration, I don't act on it based on the fact that it doesn't usually reflect clinical pathology. These are the marginal elevations, obviously. The other areas is that there is a few questions about which antiandrogen, but I don't know if you wish to, most of the focus was on spironolactone, but did you want to discuss that? Yeah, again, there's a very limited data, but as a practice point, spironolactone is the preferred one, usually with the doses of 25 to 100 in European populations. But I know in US, when obesity is there, even 200, 300 milligrams are being used. The others, the, I mean, finasteride, flutamide, I mean, there are concerns for the liver dysfunction, but we don't have head-to-head large RCTs to answer this question. The practice point, spironolactone number one, the others are options. For the new guideline, which was written for the first time, is the concerns with the cyprocterone acetate with high doses. So even, I mean, especially over 25 milligram, there is this risk of meningioma reported in general population. That's why there's one reason to avoid this medication in addition to oral contraceptives. Great. There's quite a few questions in the chat about different cutoffs for androgens or for AMH. And just to say, you know, much like we have a variety of cutoffs for different diagnostic tests in endocrinology, this really does depend on the assays and the lab. So we haven't provided cutoffs deliberately. This really is about what your lab will present to you based on what assays they're using and what's the normal range in your population. So just to emphasize, that's why there's not specific cutoffs. Could I just take the opportunity, Rachel, if you're still on, any reflections from you from a patient perspective? You may not still be there. Hello, I am. Yes, you are. Good. Yes, is there anything you wanted to offer? Yeah, I've been also reading the question box really attentively as well and learning a lot myself, but I'd just, yeah, I'd like to echo the thoughts particularly shared during your session, Anuja, around weight stigma and language and just really being mindful of the impact that can have on the receptiveness and willingness of a patient with PCOS to follow, I guess, an agreed healthcare plan. You get bombarded with, you know, obviously weight stigmatizing language so often as someone that is overweight, and I can speak from first-hand experience there, that you may then not take on the information. So we're so grateful that this has made such an important kind of role within the guidelines as well. And I think that that will really be one of the big barriers that women have in terms of adopting the changes that are needed to help manage their condition is addressed within the guidelines. So, yeah, it's really, really appreciative. Thanks, Rachel. And we might also want to say that Anuja, well, Antoinette and myself and all of our members from the Endocrine Society, the European Society, but also around the world with our consumers didn't just make clinical recommendations because this is such a common, underappreciated and diverse chronic disease, as Anuja has pointed out. We made specific recommendations about improving education at undergraduate level, at postgraduate level. So thank you all for joining and do spread the word because I believe this will be recorded and hopefully be available to members more broadly. But also that we made recommendations about policymaker awareness. And as Anuja alluded to about the need to have more models of care, our scoping has showed that there are very few dedicated services other than in fertility care, which is usually not PCS specific. And that that is a real challenge for women and those affected by the condition. Anuja, perhaps, and then Bullet, do you want to make just a comment on models of care and anything we particularly as endocrinologists need to think about how we might step up in this space as well? So perhaps Bullet first in the European setting. Yeah, I mean, I think this guideline is emphasising this very much and it's very important. This is an under-appreciated, under-recognised, underfunded disorder affecting millions of women and not even having a drug with an indication. I mean, everything we use is off-label. So we really need to raise our voices as endocrinologists. And I hope the policymakers will hear us around the world and this will make change for the better lives of women with PCOS. Yes, actually on that point, Bullet, I am aware that there are now multiple, actually in the context of the guideline translation, there are multiple pharma companies who will be putting metformin forward for approval for PCOS specifically, which is great. Anuja, any comments in the US context? Yeah, I think that the main take-home message is that we need to view this, yes, we need to view it as an endocrine disease, but the people who are managing it are the endocrinologists, they're the gynaecologists, they're primary care physicians, and we need to partner with everybody. How does one do that in the context of all our healthcare systems can be hard, especially in the US, it's fragmented. But I think just having that awareness that we need to seek help beyond what each of us siloed can offer these patients. There are very few multidisciplinary centers, and it takes a lot of resources to bring that together. So till we have those models or till we have many of those, we need to be aware that our patients might need that referral for mental health, might need the referral to a trained clinical nutritionist. And ideally, we want our primary care physicians to be able to coordinate that. But till that happens, I think each of us, as we see these patients, should be aware of their additional needs. Great, thank you. And I think the other thing to note here is that empathy is really important. These women have often struggled, we know around the world, that it takes two to three doctors often to get a diagnosis. Often, especially our pediatric endocrine colleagues, one of the big things we've learned on this guideline journey is that often the pediatricians were reluctant to make the diagnosis. And one of the reasons was with ultrasound and AMH, there was a significant over-diagnosis that was occurring because it is normal pubertal transition. And in that context, they often were not making the diagnosis. And the message loud and clear when we put our reproductive adult endocrinologists in the room, who then were dealing with the infertility without any planning or insight towards the latter part of the woman's reproductive life and the patients themselves, who knew that whole time that they had something and weren't aware of what it was and didn't have an explanation. It's important that respecting that diagnosis is therapy. If someone is aware of their condition, they are much more empowered to be able to do something about it. And it's incredibly paternalistic and presumptive of us to assume that we might harm our patients if we make a diagnosis when they're the ones that are actually living with a condition. So just to reiterate, we should be as accurate as we could, but wherever possible, we should advocate for making sure women or people with PCOS are empowered with their diagnosis and then with adequate evidence-based information. But once they have that diagnosis, then respecting the fact that they then can access, hopefully, care that is empathetic and that understands and doesn't dismiss the very significant problems that Anuja described so eloquently around the fact that an adolescent girl who is putting on weight at a rate that she cannot control, has hirsutism, has a different body habitus, isn't getting regular cycles like her friends, has acne and potentially hair thinning. There's psychosocial implications of that. The anxiety, depression and isolation and often the disharmony in the household the number of mother-daughter pairs that I have seen in my office and I'm sure we all have, where often the parents are well-intended, the lifestyle practices are getting more and more restrictive, the tension between the adolescent daughter and family is often escalating and there's usually anxiety and depression in the background and often eating disorders emerge. So our job is really to make sure that we are empathetic, that we do consider weight stigma, we're not judgmental and we explain all the features of the condition. And I don't think there's any condition I manage as an endocrinologist where I have more flooded relief of tears on being able to be empathetic and discuss these then with this condition. So I think as an endocrinologist I would just on behalf of patients implore us all to think about that. Anuja, any other key... I can see Rachel nodding her head vigorously. Anuja, any thoughts or comments that you wanted to add? No, I think we're good. We might be at time, it's 12.34 here. Okay, great. All right, and so we can probably conclude there. And Rachel, any final words? No, just thank you for everything that you just said. You saw me nodding my head. I'm like, yes, yes, yes. And I can speak to everything that you've just said firsthand from personal experience. So yeah, empathy goes a long way. Great, thank you very much. And thank you for joining the inaugural session of the Endocrine Society and the European Society for Endocrinology. And we hope you found it useful. Back to you, Rob. Yes, I wanted to thank all our participants on a great first session. I can't thank you enough for getting up at bizarre hours of the night and for Helena and for the rest of our participants. A really interesting group of people really interesting conference. I learned a lot and will be claiming my CME credit. Don't forget to claim yours as well. There are instructions in the chat on how to do that. So thank you again to everybody. I hope you all have a pleasant day or evening or whatever time it is in your part of the world. And we'll see you soon for the next installment of this combined transatlantic webinar series. Take care, everybody. Thank you very much. Thank you, bye-bye.

polycystic ovarian syndrome

PCOS

assessment

management

diagnostic criteria

cardiovascular risk assessment

psychological well-being

screening

treatment

multidisciplinary approach

lifestyle interventions

chronic disease

evidence-based care