Polycystic Ovary Syndrome (PCOS) Revisited: Diagnosis, Management, and Future Needs | Learn More

hello everyone my name is Aaron South and I would like to welcome you to the office of women's health scientific speaker series PCOS Revisited diagnosis management and future needs before we introduce our speaker I have a few announcements regarding continuing education credit for this activity all speakers are expected to use generic names if trade names are used those of several companies should be used rather than

that of a single company speakers attest that the content they contribute is supported by the best available knowledge or evidence and are reminded to disclose when products or procedures being discussed are off-label unlabeled or not FDA approved and any limitations on the information that is presented this activity May reference off-label use of FBA approved products our speaker has the following relationship to disclose May Health dsmb

member of clinical trial planning committee and CE team report nothing to disclose all of the relevant Financial relationships listed for these individuals have been mitigated the views expressed are those at the speaker and do not necessarily reflect official policy of the US FDA no official endorsement by the office of women's health or usfda is intended or should be inferred questions related to CE credit claiming should

be directed to Rachel bowetta all other inquiries for information should be directed to me Aaron South all registered participants will receive a CE claiming code and instructions by email within 24 hours after the seminar to claim CE credit all Physicians pharmacists nurses and those claiming non-physician CME must attest to their attendance and complete the final activity evaluation via the CE portal within two weeks after the

activity no exceptions Learners May then View and print a statement of credit Pharmacists and pharmacy technicians will need to enter their correct nabp e-profile ID number and date of birth in the required format failure to do so may result in loss of credit for the activity pharmacists should log into the CPE monitor eight weeks after the activity to ensure their credit is captured correctly closed captioning

is available by toggling the button at the bottom of the screen throughout the presentation you may type your questions for our speaker into the Q a box and we will address as many as time allowed and now please welcome our owh director and Associate commissioner for Women's Health Dr Kavita visish thank you so much Dr South and thank you everyone for joining us today happy National

Women's Health Week our theme for this year is no more about your health today and every day and this week we're bringing attention to a range of Health topics that are specific to females such as polycystic ovaries ovary syndrome and we're thrilled to have Dr hoger here today she is a professor of Obstetrics and Gynecology and the chief of the division of reproductive Endocrinology at the

University of Rochester she's a board-certified reproductive endocrinologist and completed a master's degree in public health with an emphasis in clinical investigation she has a research interest in the management of polycystic ovary syndrome this work has led to the establishment of the PCOS Lifestyle Center at the University of Rochester for which she is currently serving as the Director focusing on nutrition lifestyle change and medication in the

management of PCOS she is also an active clinical investigator and serves on the board of the aepcos society and maintains an active clinical practice in reproductive endocrinology I'd also like to invite our viewers to read our office of women's health blog for National Women's Health week which features a q a with Dr hoger and is focused on PCOS and I'd also like to thank my team

in the office of women's health for bringing today's seminar to you the blog and all of our other National Women's Health Week events uh Dr hogar thank you for being our speaker and we are very much looking forward to your talk today thank you very much and I want to extend my appreciation for the invitation and to Dr South who's been working with me to get

this ready so it is really a pleasure and an honor to be talking to you in women's health and obviously about this very important uh area so I think from the standpoint of the disclosures we are um already covered those so I will move on uh to our objectives for this talk so we want to understand the impact of PCOS really across the lifespan discuss the

options for management of PCOS at the different life stages and varying needs and recognize our limitations and gaps that are available in treatments for PCOS so I'm going to go back to when I first became a reproductive endocrinologist the only criteria for diagnosis was the NIH criteria so they were originally put forth in 1992 and there's basically two features you had to have some form of

irregular periods with oligo or anovulation and some evidence of clinical or biochemical hyperanginism after all the other endocrine assessments had been completed and then as technology improved and we recognized that this disease is not a single entity but rather traverses a spectrum of different presentations and with the introduction of ultrasound as a very formal part of our evaluation the Rotterdam criteria in 2003 so now 20

years old came up with three criteria and the idea was that it gives a little more flexibility to the diagnosis and now that Rotterdam criteria which adds the PCOS Imaging as an option will allow a better broader diagnostic criteria and is accepted by all the major endocrine societies across the world so the clinical features PCOS came from a reproductive history so as an OB GYN obviously

this is fundamental to sort of how we look at the world through our reproductive lenses but we recognize the disease is more than a reproductive disease even though the definition comes from its reproductive impact the metabolic and psychological factors that we now recognize to be intrinsic and fundamental underpinning of the disease itself have been recognized in fact there is a push to rename the syndrome because

it doesn't necessarily Encompass all of the the other aspects but important for us as Educators and clinicians to recognize that this is a disease that goes beyond the reproductive Arena so the lifespan of PCOS is really the same as all of the diseases that we talk about that Co that cover from adolescents to older age and while the reproductive disorders often are what bring people to

attention so in adolescence when I see adolescents it's because of their menstrual disorders or their concerns about Androgen excess as we care for women across their lifespan the other complications become more prominent as they age so first into pregnancy complications and then issues of type 2 diabetes and cardiovascular risk become more prominent and the reproductive issues become less so so in our multidisciplinary approach even though

you know endocrinology and Gynecology sits in the middle we are constantly looking at other Specialties to assist so I work with pediatricians dermatologists endocrinologists diabetes doctors and Cardiology folks to really care for women so it is really a multi-disciplinary approach that's required for the toe Total Care in PCOS and we care about PCOS and we'll talk a lot about the prevalence it's a very prevalent condition

and the health and economic burden from this disorder is quite High recent Publications have indicated this is this is a really bleeding issue in women's health there's links to the rising burning obesity that affects a lot of diseases but also particularly PCOS and for many years this has been under recognized as a disorder there's long delays in diagnosis women often suffer for a long time before

someone gives them a diagnosis their diagnostic experiences often very un unhappy their emotional well-being is underappreciated and we don't recognize the metabolicus well and that leads to inadequate patient information and the ability to sort of intervene with lifestyle management somewhat limited so there's a lot of pressure for us to get this out there in the education sphere so the prevalence as I alluded to so when

we went back to 1992 and I said those were the first criteria that were formalized so that we could help make a diagnosis if we use only those criteria we have a relatively low prevalence although still fairly significant but now with the systematic review using Rotterdam criteria and all of the population-based studies were somewhere between around 10 percent to maybe 15 percent overall in the population

which is an enormous burden of disease we know that in health professional worlds our management is not consistent among Specialties and we make it a high priority for Education now amongst our health professionals and evidence-based guidelines are really what we were aiming for so we and 2017 led by the Monash group in Australia a multi-disciplinary collaborative approach was started to begin trying to pull all the

evidence get together to make guidelines and I was fortunate enough to sit on this International committee and we were able to sort of synthesize quite a bit of data and I'll share the current guidelines with you so we began with stakeholder participants so this was the researchers the clinicians the patients the consumers with framing the problem and trying to identify what are the priorities for the

group then there was knowledge synthesis systematic review International guidelines were put forth for public review and Amendment and then resource development translational activities as well as co-developed International awareness campaigns and and evaluation so after about I guess now five years of going through this cycle we restarted the stakeholder participant and have updated the guidelines for 2023 so they have now gone through the process and are

going to be published this summer but they are officially through the stakeholder assessments and again it's a collaborative approach we want to drive early diagnosis screening and management Across the Life side span we want to optimize the health resources and reduce unnecessary tests so people are not getting repeatedly done the same tests we want to have translational tools and resources for our patients and providers and

we want to promote research and translation into practice and policy and finally we want to upskill and Empower consumers so that they know what their options are and can advocate for themselves and we all talk about evidence-based practice in medicine as an academic physician this is sort of our lifeblood right evidence-based practice what does that really mean so it's not simply just taking a randomized controlled

trial and saying okay there's the answer everybody gets X for their treatment because it's really looking at the wheels of the consumer needs and preferences and clinical judgment that we have based on our own experiences integrating all of these and coming up with a treatment plan that is evidence-based but also consistent with patient values so the first thing we have to do with PCOS is diagnose

it it seems like that should be simple but in reality this is probably one of the most difficult areas it took a long time to get people to agree how to diagnose it and we still don't have a perfect diagnostic system which we'll talk a little bit about later but because we have the three pillars we have androgens irregular cycles and ovarian findings we can sort

of focus our topic on what is the the best way to measure hyperandroidism what is the best clinical way what is the best biochemical way and the key messages that came out of our investigation it were that clinical hyper-anergism is the first thing so the person complaining of what she perceives as hyperanginism is the person we look at and assess on a physical basis and we

use validated tools for that um using the distress index as a primary concern recognizing they're going to be a lot of ethnic differences in how people present and if we are unable to to sort of clarify that using biochemical measures can be supportive the real concern with biochemical measures there's a lot of variability in how the assays are done and all of the data now really

formally recommend the liquid chromatography mass spec for measuring androgens because these are relatively low levels in women compared to men and so we know that we want a very specific and high quality assay to really be able to differentiate at the lower levels so when I mentioned a visual scale we have traditionally used the Fairman Galway score there really aren't very many scores this is not

a perfect measure it's been modified from its original uh way back it was based in a single population of people so it doesn't have a lot of scaling to ethnic differences however a zero in any of the body areas would indicate there's no Androgen exposure Androgen exposure in areas where there are receptors can turn hair from vellus which is sort of a peach fuzz to a

darker hair and the darker hair is an androgenic hair and as we get more androgens those areas progress and so we we can put a number to this and we can measure it and we can follow it and then the other thing that's particularly distressing and one of the things that is probably underappreciated is that Androgen excess can also lead to hair loss from the scalp

and that can also be measured on a visual scale as well this is a very distressing component of PCOS and we do not generally use that in the diagnostic criteria but it just to be aware there are visual scales now the hard part of all of this is the normative cut off so when we say that something is abnormal compared to what right so we have

to think about most of our abnormals are okay if you're you've got a hundred percent and the top five percent is abnormal that's really sort of random it's not really based on any biology that could vary by ethnicity and by age which we know reproductive hormones definitely do that um so the idea is we've moved to Cluster analysis to try to accurately Define the natural distribution

of these hormones in a population and try to classify people into different groups that are based on these profiles and correlated features so we're still in the infancy really of looking at this but I want to bring forth one study that's applied to an adolescent population it's impressed should be published soon this is a adolescent population with a mean age of 15 years this is a

non-specialized group so this is community-based participation of adolescence since then they all underwent an exam and ultrasound and blood testing there was a hyper androgenic cluster that they defined by looking at the population and picking a number somewhat randomly and saying okay these features indicate the hyperanginism and then they looked at the other aspects that weren't part of the cluster to find cutoffs for those values

and when they did that they found a higher amh in the population that was listed as hyperandrogenic they found lower shbg and higher BMI and higher total testosterone so it really did correlate with actual disease process that they found and what was interesting in this population is when they looked at where did those cut points indicate they found they were not 95th percentile but in fact

were lower around 70th percentile so when they do this kind of analysis we're going to get more accurate numbers it's not going to be just a simple percentage situation so with respect to irregular Cycles that's it seems like that would be pretty easy to Define but in adolescence again we find that there is a difficulty because what happens over the period of puberty is that in

the first year post-menarchy over 80 percent of Cycles are going to be in ovulatory which means they're not going to be as predictable there's going to be a high degree of irregularity and none of that is abnormal so you wouldn't want to take a 12 year old and say okay you have irregular Cycles you have PCOS because that would be inaccurate and when we get to

three years post-menarchy we still see about 50 50 that some Cycles are in ovulatory still so somewhere between one and three years most people are starting to regulate and become ovulatory and by the time you get to the sixth post-menarchal year you have the majority of people with regular ovulatory cycles and that 20 remaining though that's where the pathology lies in terms of it not being

normal and if we look at what kinds of Cycles these individuals have as adolescents the majority are going to have very long Cycles so they're not going to have um you know sort of cycles that fall in between but they're going to have either very short Cycles or very long cycles and so we're going to find a particular pattern uh to Define irregularity so again when

we're looking at irregular Cycles we have to say in the first year post-menarchy we are not going to make a determination we are not going to make a diagnosis between the first year and the third year we're going to have a tendency to have very long Cycles or very short cycles and in those individuals we can start to classify them as abnormal and then once we

get past the third monarchical year we now have into adulthood we have less than 21 days being abnormal or greater than 35 days because the majority of people are going to fall that are normal are going to fall between there or we can Define it as less than eight cycles per year when you calculate that out because even in PCOS you're going to have some cycles

that may be ovulatory and normal and then they may stretch out so we look at the total number or the average number of days um but within that if someone has passed a year of post-menarchy and they have very very long Cycles more than three months that's clearly abnormal that's outside the normal range if they never have periods by the age of 15 or by three

years after they have breast development that's clearly abnormal and when you have a regular menstrual cycles you should consider the diagnosis of PCOS according to those guidelines so that's it is probably the most common cause of irregular Cycles obviously there are other things that can cause it but this is going to be one of your primary diagnosis should be popped right up there in your diagnostic

criteria and the third pillar so we went through androgens we went through his Cycles the third pillar is the ultrasound that was added um at the Rotterdam criteria so now it becomes a question of when is ultrasound indicated and what is the most effective criteria that we use for those of you used to seeing ultrasound you're going to notice this right away this is not a

normal ovary this is a larger ovary there's a large number of these very small two to nine millimeter follicles in this case they're lined up around the periphery which is a fairly classic pattern they don't have to be but the key is the size of the ovary and the number of follicles that you see so the recommendations that have come out of the guideline based on

evidence and I'm going to just clarify here so what you see here evidence-based recommendation is identified as EBR these are clinical recommendations identified as CR and then there's a third thing that will say practice Point as a PP I've tried to box the evidence base so as we go through the presentation if you see this box that's generally the evidence base and sometimes there are important

things below that all box as well so the evidence tells us what we should count as abnormal is the follicle number per ovary so those we count out those little Andrew follicles and that's the number we use and that's how we identify pcom if we have a three-dimensional view we're going to count all of them but you can use a single slice just like we saw

on the last slide and we're going to look at the follicle number in that cross section and the ovarian volume combined so ovarian volume greater than 10 CC's and follicle number greater than or equal to 20 anthropolicles would be consistent with a PCO ovary now this is based on transvaginal ultrasound and of course in adolescence that's problematic so unfortunately there are no definitive criteria to Define

pcom in adolescence we don't have a lot of evidence on this there are very few studies so these are really practice points but if you happen to do an ultrasound it's likely to be trans abdominal and then we're just going to be able to look at the volume and not so much the criteria of the morphology now in the current guidelines that's where the old guidelines

cut off because we have now a tool a anti-mullerian hormone or amh has been around for several years as a diagnostic tool for other conditions but what we wanted what we've noted in PCOS is everyone who takes care of them if you measure an amh it's like off the charts so why can't we use that as a diagnostic tool well up until recently we didn't really

have the data to tell us that that could be helpful but to remind those of you who are not familiar amh is a product of the early antroph follicles so from when they're morphing from primary follicles to pre-antral follicles they secrete amh and so amh is a measure of those follicles that are coming before we can physically see them on ultrasound FSH will stop the development

of will stop the production of FSH but will cause the development of the larger anthropolicles which no longer produce the amh so it comes in that window where it's very important to sort of say we we can see there's pathology there because there's a lot of follicles and in PCOS as we said they have high levels of amh now in a non-pcos follicle so this represents

a follicle FSH binds to the receptor produces a switch to estrogen production over Androgen production which then turns off the amh production in that follicle so that it grows and becomes an ovulatory follicle amh isn't really playing a role in the pathology but with PCOS we think not only is it a marker but it may have some pathology involved inside the ovary so as it goes

it's much higher so it's turning off that estrogen production and it's not allowing that follicle to go from an androgen producing follicle to an estrogen producing follicle and you get this follicular arrest and that follicular arrest is why we see a piling up of all those androph follicles so they're very the ultrasound image is really reflecting what we're seeing in the biochemistry with amh and the

data are now very very clear that we can use amh for assessing the anthropolical excess instead of using an ultrasound because ultrasound is not available everywhere in certain communities that's not whereas in my office I do 100 ultrasounds a week that's not clear in every other practice amh should be used in accordance with the diagnostic algorithm noting that people still have the assessments of The Irregular

cycles and the hyperandergonism and you don't need an amh to have the diagnosis so you don't have to order it it's really not a single test you don't want to say okay amh yes or no it's not meant to be a single test it's just like the idea of the ultrasound using it in conjunction and we do not have normative values for amh and Adolescence because

amh is going to be higher because their follicle counts as a whole are higher and we have to remember that amh is influenced by a lot of things so age someone 40 is different than someone 20. BMI amh is lower as BMI goes up serum amh may be influenced by the ethnicity of the individual birth control pills will suppress it menstrual cycle May Vary it so

those are things to keep in mind so the pillars of the diagnosis are now I think pretty clear from the document the guidelines we have a good way to describe androgens we have a good way to describe periods and now we have two tools to look at the ovary either amh or ultrasound so once you have the diagnosis again going back to our original discussion PCOS

is not just a reproductive disease even though that may be the presentation that the individual has there are lifelong consequences and how do we diagnose and manage those is the second tier the second part of our discussion and just to kind of summarize we are not going to talk about genetics in this talk but I will advise you there are several very well done g-was replicated

studies from many different populations both in Asia North America Europe that have indicated there are clear Pathways to genetic abnormalities it's linked often with overlap with obesity genes as well as diabetes genes but there is a pathway that genetics is playing a very prominent one um 50 of daughters of women with PCOS will have PCOS 50 of sisters will have it so it is a very

trackable genetic condition but equally important is the lifestyle component and they are both playing a role in the development of PCOS including antenatally as the individual is developing in utero so there are hormonal changes that are affecting the ovary in the individual if we layer on Obesity on top of that we are getting even more exacerbation so you have the leading um component leading to that

excess androgens that's resulting in our reproductive phenotype but when we look at the lifestyle issues and obesity you are talking about insulin resistance which is now felt to be sort of the major underpinning of the pathophysiology not part of the diagnosis but part of the pathophysiology increased insulin resistance leads to increase in diabetes cardiovascular risk and then of course underpinning it all is the psychosocial issues

and we believe that those aren't being driven to a large degree by the insulin resistance component so the first question we had at the guidelines is are women with PCOS at increased risk for cardiovascular disease and what is the most effective method to assess it and the evidence really is pretty clear about risk for cardiovascular disease what it is not clear about is cardiovascular mortality so

their data are still a little uncertain as to whether women with PCOS have an increased risk of dying from cardiovascular disease but they definitely have an increased morbidity and they have all the risk factors that we would associate with that so we would like help professionals to be aware that all women should be assessed for this so that is including any age and BMI so lipid

profiles would be indicated as well as blood pressure measurements so these are things that we think are fundamental as you're taking care of women with PCOS to at least get at the Baseline and we think that because of this recognition funding bodies should recognize that PCOS is highly prevalent with multi-system effects and should increase research to support that because one of the major findings of all

of this is that it's very under-researched underfunded compared to other diseases that are much less common from NIH funding for instance cardiovascular general population guidelines should include PCOS as a risk factor and we would want to have preventive strategies to reduce cardiovascular risk sort of talking about that in conjunction with the reproductive risks that we talk about as well and then when it gets to type

2 B diabetes this is actually pretty well known because again going back to the beginning this was one of the links that was found very early in the research of PCOS but PCOS regardless of age or BMI women do have an increased risk of impaired fasting glucose impaired glucose tolerance and type 2 diabetes you see this quite often every day in the clinic I'm diagnosing diabetes

I am not a diabetologist I'm a reproductive endocrinologist but it's because I'm seeing women with PCOS even in young ages that we're seeing a high prevalence of this and so glycemic status should be assessed a diagnosis in both adolescents and adults how do we do that so we have an algorithm now that I think is helpful we want to assess weight in BMI at each visit

or at least you know month or six months or yearly um and it's a coordinated and agreed to uh between the health professional and the individual because it will talk a little bit about weight stigma down the road but glucose screening should be a part of every initial assessment and at least every three years if someone does not have any other risk factors for diabetes we

do an A1C or a fasting glucose if there are other diabetes risk factors and most of that is yes in our PCOS population either family history obesity then we do an oral glucose challenge test and certainly in preconception planning and early in pregnancy it is recommended we would recommend blood pressure checks on an annual basis because there is evidence of increased hypertension in this population and

then lipid screening generally is is recommended based on risk obstructive sleep apnea should be considered we find that at a very high rate in PCOS and treated if symptomatic and then with respect to endometrial cancer this is something that's often overlooked by our non-gynecologic colleagues and it is an important component pre-menopausal women with PCOS do have a much higher risk of this I think I have

had personally several young women in their 20s who have developed endometrial cancer particularly because they're being untreated so they have you know even though they're 22 they might have had 10 years of not having their menstrual problems assessed or treated they have higher weight and they may develop early diabetes so if those are conditions you see we want to make sure that we are assessing the

endometrial cancer risk as well then obesity I would say of all the things that we see the main reason that people are driven to come into my PCOS Clinic is they're concerned about wheat and it's uh trajectory in PCOS this is a very common concern right now the data do not tell us there is a consistent evidence that links a certain type of physiology to weight

in PCOS however even though we don't understand those mechanisms based on evidence It is Well recognized that most if not all women with PCOS have underlying mechanisms that drive greater longitudinal weight gain and higher BMI so these these kinds of mechanisms are making it harder to manage weight greater challenges healthy lifestyle is important and the prevention of excess weight gain should be addressed at the early

onset and we should be prepared to assist women in forming realistic and tailored lifestyle goals weight stigma I mentioned that earlier so weight stigma is something that basically indicates that that individual is seen first for her weight and second for her condition and that is very problematic in terms of helping individuals because weight doesn't explain all the pathology appease to us it does improve if you

lose weight to a large degree but it is not the only concern and I think it has very negative psychosocial impact if we don't recognize that bias as we're caring for people so what does it mean to recognize it is that we have acceptance and respect for the body size of the people who present to us that includes saying that while it's a risk factor it's

only one indicator of Health we should ask permission about weight recognizing some of the terms we use and we continue to use because it's part of our literature may be stigmatizing and try to be careful with that we want to ensure we have appropriate equipment offering weight-centric care for those that want to lose weight or weight inclusive care if people are not ready to have that

discussion and then focusing on quality of life so quality of life is a constellation of things but in PCOS the things that we know to be out of sorts are anxiety and depression which we'll talk about but also poor body image psychosocial dysfunction and eating disorders all of which are more common in women with PCOS But anxiety and depression is particularly underappreciated in this population so

this is a systematic review that was done and we looked at this again there was really been no updates to it so I think it still holds that the overall population of PCOS versus women without PCOS there's more than double the rate of depression that we see and if we look at the degree of depression it's much more likely to be moderate or severe so this

is clearly something of concern the same is true with anxiety as far as prevalence it's it's you know quite a bit higher in one with PCOS anxiety is is one of the more common traits that we see it's very dramatic it's even seen in animal populations with PCOS when they induce a prenatal androgenized Mouse and they put it in a in a maze it will never

go out in the open because it has such high anxiety so we think it's one of these things that does have some fundamental pathology from the outset and when we look at who's more likely to have continued depression and PCOS this data comes to us from the University of California San Francisco in their multi-disciplinary PCOS Clinic they measured the findings at 29 years of age and

seven years later and they had a very high prevalence not surprising as we just said of depression and it was very consistent over the seven years but there was a variability some women treated for depression got better others did not and so the predictors for the long-term depression risk was really driven by BMI so every time BMI increased it increased the risk of an enduring depression

so there's a very tight link between obesity and depression there's also a metabolic link so we see abnormal metabolic parameters also predicting higher rates of diabetes and then when we look at the impact of race and depress on anxiety and depression we do see some differences between the races in the U.S we see higher anxiety in white women compared to black women and perhaps a trend

towards higher rates of depression in black women and taking this from the consumer perspective so this was a very important part of our work in the international guidelines is having the consumer perspective on every single committee and they presented from all over the world so this is um the president of the PCOS Association of Australia and she said that PCOS is very distressing to women who

are living with a condition and presents differently from person to person there's no one treatment or medication that treats PCOS holistically and there's a lot of frustration with the lack of Headway in pcos-specific treatments and this is the message we're getting over and over from the consumer is that we don't have any treatments that are specifically designed for PCOS there's a lot of dissatisfaction how slow

it takes to get diagnosis and what kind of care there is so we still have a long way to go so the key points in treatment planning is that you need to tailor the treatment lifestyle we think is critical for everyone because of the the pathophysiology of insulin resistance which lifestyle can address but we also need to Target therapy for the primary concern if patients want

to get pregnant if they have concerns about their menstrual cycles if their hair growth is is distressing and we also want to look at a chronic illness and what is the long-term treatment and what pharmacotherapy do we have so this is what I would consider some of the ideal workflow of the multidisciplinary clinic which I had mentioned at the beginning we started at our clinic in

University of Rochester there are many around the country that do this we have a team approach so we have the provider nutritionist Behavioral Health nursing support including the patient on the team and then we have outside discipline Specialists like dermatologists GI and endocrine to sort of complement prior to the appointment we bring in patient engagement so they bring their goals on a screening form we provide

assessment including blood work and ultrasound that they've had before so we can look at that and assess whether they need to do it again we screen everyone for depression and anxiety and whether they're ready to have that conversation at their first visit we do the multidisciplinary intakes we order additional assessments and then we come together as a team and set the treatment plan and then follow-ups

are based on progress on those goals we said at the first visit and we make adjustments as we go sometimes people come in because they're worried about their periods but then two years later they want to get pregnant so we have to adjust kinda of what we're doing but fundamentally as I said we're looking at lifestyle so lifestyle Intervention which is defined as either exercise alone

or a multi-component diet combined with exercise and behavior strategy is really recommended for all women to improve metabolic Health including Central adiposity and lipid profile and these data have shown over and over that lifestyle will improve those things in PCOS it should be recommended that they all try to optimize General Health it will improve quality of life and body composition but at minimum maintaining weight and

preventing weight gains should be part of the discussion there's no evidence that there's one type of diet that is better than other I think that's probably the most common question we get at the lifestyle Clinic okay should I be on a low carb should I be gluten-free should I and you know there is no evidence so whatever diet that is considered a balanced and healthy diet

that works for that individual has been tried probably in some study and has benefited the patient so we know that there is no one diet anyone that says that is probably trying to sell you something it is not appropriate to say that's the only way but each person needs support for the decisions and choices that they're making we consider lifestyle change to be first line therapy

healthy lifestyle for excess weight gain prevention is really important even if they're normal waste so I see a lot of normal weight women with PCOS we talk about how to prevent weight gain we want to aim for five to ten percent weight loss over a six-month period if they indicate they wish to lose weight energy deficits around 30 percent exercise we don't prescribe in a specific

way the data are not enough to tell us there's a specific exercise that's better but not being sedentary which is true for all of us as I've been sitting here all morning we need to move in 10 minute intervals and we want to try to have realistic specific measurable goals that we can follow with the patient but in addition to Lifestyle there are going to be

needs for pharmacologic therapy and we're going to talk about the main ones here which are the birth control pill and Metformin and some of the others that we can add in so the medication options as we've been saying all along we need to address medications to the condition the person is concerned about so if you are coming in with irregular Cycles or hirsatism the treatment of

therapy as well there's not as much data on that alone those that continue to have worsening hair growth we do have data on anti-androgen therapies that are listed there it is not something that we start with generally in most people and don't treat a majority of people with that and Metformin therapy which is obviously treated used for type 2 diabetes by off-label we use it um

because of insulin resistance and glucose intolerance and we do see Improvement there and then more recently there's a big push on weight loss drugs these do actually work very well in the piece to a sphere again at this point I'm still a little early to say what the impact on the diseases but they certainly are very effective for weight loss so I want to bring your

attention to a study that was completed out of the University of Pennsylvania and what they did was they randomly assigned people to either an oral contraceptive or a lifestyle intervention this was nih-funded study and what they looked at was after four months of treatment with either a birth control pill or lifestyle in both groups they saw a reduction in the rate of depression which I think

is very telling because a lot of times people say oh the birth control pill I don't want to get depressed because I take it in general like this is not the finding we see in PCOS and as well with anxiety symptoms they both improve the rates of anxiety so reducing androgens regular Cycles either through lifestyle birth control pill does seem to address some of those issues

as well and with any pharmacologic therapy it's going to be shared decision making and you need to talk with a patient their family if there's adolescents involved with their cultural values are we need to understand those before we can make a recommendation but we generally don't want to sort of say there's only one way to go and recognizing as we said it's all off label we

don't have a specific pill for PCOS but we need to inform people about the side effects and the concerns and we do think that eventually we would like Regulatory Agencies like the FDA to to consider some treatments that are specific for PCOS now the evidence bar here is really big because everything about birth control pills has been well documented in PCOS um we there's good evidence

that it should be recommended as First Line agent to control menstrual cycles it's very helpful in adolescence um they're one point we would make is that does not need to be a high-dose birth control pill it can be any dose of estrogen in the pill that can be effective there's not a specific pill type that one needs to be on that's that's common misconception that there's

only one type of pill that is simply not the case in any of the literature there's not any real evidence on the progestin only pills in PCOS but it does have in the general population benefit for endometrial protection and so those are all evidence-based recommendations and finally I'm going to talk about metformin because this is really I go back to this partly because when I was

a young fellow I was starting my fellowship and right that very uh year a little paper came out about using Metformin for PCOS it was just a small little case series and at that point the data were just coming out saying that there was a connection between insulin resistance and diabetes and PCOS so somebody uh in South America actually tried this and I was in Virginia

at the time and there was a group that um Medical College of Virginia as well that decided to try this and it became really a hot commodity and everybody wanted to study it so this was my first research in PCOS was looking at the impact of Metformin lifestyle and birth control pills and Adolescent women with PCOS so over the 20 plus years since that original interest

in metformin we now have quite a bit of data and we can see that BMI is impacted when you give metformin but it's not a huge impact you can see the red box there it's a small impact but it does have an impact on BMI and when we look at androgens there is an impact on testosterone all the studies indicate but it's not very powerful to

be honest so the recommendations that metformin should be considered in women with PCOS with a BMI greater than 25 because it does improve insulin resistance glucose lipid profiles and androgens you can consider it in adolescence at risk for PCOS as well because there's good data in in early data anyway in adolescence and if we compare the birth control pill to metformin we can see with respect

to testosterone so to the left is ocp favored to the right is metformin favorite if you look at the Red Box it goes to the left so birth control pills are going to be much more powerful than metformin for control of androgens and if we look at the metabolic aspects however the right now becomes more prominent so metformin is much more valuable for control of metabolic

Associated problems in PCOS so there's a role for each of them and then finally there's a combination of birth control pills and anti-androgen therapy again off label that indicates that anti-androgens are best in used in combination with effective contraception and they can be used in women if there's a sub-optimal response to androgens they can be pretty powerful to suppress new hair growth and again quite distressing

for some individuals so in summary um we didn't cover every area but those are the main areas that we see every day in practice but PCOS is the most common endocrine disorder in reproduction impacts at least 10 percent of reproductive aged women it's a complex disease that has both genetic and environmental impacts as well as antenatal contributions to its pathophysiology and it's underpinned by insulin resistance

neuroendocrine disruption and ovarian abnormalities in addition to the reproductive disruption there are lifelong metabolic risks in PCOS that we cannot ignore and must follow carefully we believe it's an independent risk factor for cardiovascular disease and diabetes there is currently no single medication that's approved for management of PCOS the treatment we direct is that underlying concern such as menstrual regularity infertility Androgen excess and glucose intolerance the

main things that we're seeing in the younger women as the etiology is further defined in PCOS we are hopeful there will be development of targeted therapies that will be able to mitigate this symptoms that women have more broadly and reduce the overall long-term lifetime risk so with that I will close and be happy to take any questions and I really thank you for your attention and

again for the invitation thank you Dr hooker that was wonderful um and we do have a lot of questions that have been coming in and continue to come in so folks can submit their questions into the Q a pod um our first question for you Dr hoger how do you approach these assessments and preventative plan in women with lean PCOS meaning they are not overweight or

pre-diabetic or have high blood pressure yeah so generally in those individuals again you're making the diagnosis based on not their body type but their irregular Cycles Androgen excess presumably so whatever their symptoms are you're going to address that so you you will I still have a discussion about lifestyle with thin women because when we study those and there's a number of studies out of Sweden and

the UK that look at body fat distribution and even in these individuals that are lean they have some abnormal fat depositions and they're certainly at risk should they have an injury because sedentary their weight can increase quite rapidly so we do talk about lifestyle but we don't focus our efforts on that so much as we go we really direct to either birth control pills if that's

appropriate or anti-androgen therapy there's some evidence in thin women that metformin can still play a role in Psycho regulation at least based on the data but it's not usually my first line therapy if there's no metabolic disease great thank you uh the next question is it possible to reduce the risk of developing PCOS if someone is diagnosed with PCOS and is able to make Lifestyle Changes

like losing weight is it possible to reverse the symptoms or risk of PCOS yeah that's that is the excellent question and the data don't support entirely that weight loss alone will erase PCOS but it does definitely improve the symptoms of PCOS certain number of bariatric surgery studies where there's dramatic weight loss and you see the symptoms of PCOS pretty much reversing but they're still there if

you look at ovaries if you look at their response to ovulation therapy they still have problems so there's some still fundamental issues you're not correcting with weight loss as far as prevention that is really key we do not have any any way right now to know what is prevented for PCOS preventing weight gain we all sort of believe and when we look at the data um

out of Spain where they have a very specific adolescent population they've been they've been using Metformin for prevention that I don't think that's universally accepted but it does seem to be that controlling insulin resistance early on in life does seem to help the symptoms from progressing thank you our next question from the audience what is the impact of PCOS on fertility slash ovulation induction can you

have a healthy pregnancy with PCOS yeah that's great we didn't have a chance to talk about pregnancy and that's an important question um so ovulation induction this is something that obviously this is my bread and butter kind of work that I do clinically it is very successful in PCOS so there are two agents that have been tried uh one off label one on label ploma Bean

citrate is approved for this indication letrozole is actually a better drug there's a great quite a bit of data and the guidelines will recommend letrozole Kamara as a excuse me letrozole as the main drug that you would use in PCOS but as far as a healthy pregnancy there is significant risk we know of gestational diabetes and pregnancy we know there's increased risk of pregnancy loss potentially

preeclampsia and so careful monitoring the pregnancy as I indicated earlier you want know ahead of time if someone has glucose intolerance prior to becoming pregnant there's a very large trial out of the Scandinavian countries Norway that looked at providing metformin during pregnancy it did not show a benefit to prevent these complications unfortunately although it had slight reduction in miscarriage it wasn't sustainable as a recommendation in

the guidelines thank you um our next question is there any correlation with tcos and premenstrual dysphoric disorder and thyroid dysfunction okay both very good questions um partly this it's a challenge to answer the first part of that question uh the pmdd because most women with PCOS are you know that you have to be in the ludial phase for that to be a formal diagnosis and since

most of them are not ovulating regularly it's not something you can make a diagnosis of easily in the condition and it's not felt to be higher I think what we sort of misinterpret a little bit is that with hormone dysfunction in irregular Cycles there's all kinds of psychological impacts of not having regular Cycles so it's not specific to the luteal phase the way pmdd is but

it is very much a part of that irregular cycle so there is some dysfunction associated with irregular Cycles but not in the same manner as pmdd with respect to thyroid disease there is quite a bit of evidence now that women with PCOS have higher rates of thyroid disease and it's not entirely clear why but it is part of the diagnostic evaluation when we're doing for irregular

Cycles as well so we're able to pick that up pretty quickly I would say thank you do I need to worry about menopause and additional symptoms of PCOS to evolve from menopause yeah another great question and when we have almost no information about we are gathering more I mean what we know what we've what we have so far in the data suggests that menopause does seem

to occur a little bit later in women with PCOS we're not entirely clear why but it may have to do with the follicle pool that seems to be higher so it is probably a year or two later than the average without PCOS what we also see is there is a surge of Androgen hormones in most women with PCOS at men are without PCOS sorry at menopause

and that is not um abated in PCOS so you do see a slight worsening of Androgen but that you sort of become like the normal population so what we actually see is this reversal whereas women with PCOS as they get closer to menopause their periods get more regular as women without PCOS get close to menopause their periods get more irregular so you're sort of having this

role reversal and so it kind of balances out when we look at the population data we don't see abnormalities because everybody's kind of washing each other out but we do know that you know insulin resistance may get a little bit worse with menopause and that's certainly something to be considered um but in in reality we don't have a lot of data post menopause in women with

PCOS because they stop basically going to their endocrinologists or gynecologists because they're not having periods anymore so we do need more information on that well to follow that up we've got a related question if you have your ovaries removed will this help with PCOS so yes that's a great question I probably get that question quite a bit people who are very frustrated I would say you

are going to correct one problem your Androgen levels will fall very dramatically but you will not affect the insulin resistance and the dismetabolic aspects of PCOS and you're probably going to make your cardiovascular disease worse so we do not recommend ovarian removal for women with PCOS thank you okay our next question is there any association between PCOS and pre-term deliveries yes so I mentioned it briefly

but kind of flew over that in the end so preterm delivery is higher in moment PCOS it is again not clear why some of that may relate to body weight we do see a higher rate in obesity in general but women with PCOS do have higher stillbirth and preterm delivery rates that have been shown in several studies but most women to be assured most people that

is not the case I mean most people have very healthy pregnancies and the better we are going into pregnancy the healthier we are in terms of managing our glucose abnormalities and our weight the more likely we are to have a healthy pregnancy great um are you concerned about prescribing estrogen containing birth control for PCOS patients since they might be at risk for hypertension so yes with

anybody who has hypertensive disease we don't want to use birth control pills but if they don't have hypertensive disease we do not see a worsening of that condition developing with the use of birth control pills and that's been studied in a lot of long-term studies so we're always combining everything with lifestyle change and treated hypertension is still a you know it's not a contraindication to using

birth control pills but it is absolutely a great thing to pay attention to and we do monitor when we're treating people with with birth control pills but it's it is very powerful drug and it does have such good effects in people who don't have hypertension that we don't worry about inducing hypertension right at what point in the menstrual cycle do you recommend checking amh yeah so

the the highest levels are seen in the early follicular phase so in the first few days of the menstrual cycle so typically in our practice if we can if we have a normally cycling person that's when we would measure it because we want to see the maximum amount with PCOS it really probably doesn't matter because they don't cycle normally so then it's just more of a

random thank you and then I think this will be our last question where do you think research for PCOS is most needed oh boy that's a big question to answer at the last one so I mean I think obviously from the standpoint of understanding the pathophysiology at the at the basic level is still very needed so we need funding for that because that's where our drug

development is going to come from um with PCOS obviously um we still have a lot of work in the genetics aspect of it because we don't understand its fundamental etiologies I think looking at it in its origins in the antenatal area as well because we have quite a bit of data coming out um that this is a disease that probably is intergenerational so we need to

sort of understand that a little bit better in terms of prevention but so the basic Sciences need to be funded for PCOS so that we can have a pathway that we might be able to address with medications well wonderful thank you so much Dr hoger we can't thank you enough for this wonderful presentation and for answering all of our questions uh this was so informative um

and we want to thank our audience for joining us today uh just a bit of housekeeping the CE code and claiming instructions will be emailed to all registered participants and the recording will be shared in the next two weeks just a reminder that this is National Women's Health week you can follow fda's office of Women's Health on social media and on our YouTube channel this week

and throughout the year for information and resources to promote the health of women again thank you Dr hooker thank you all for joining us today and this concludes today's presentation goodbye bye-bye thank you so much I really enjoyed it thank you