Thank you. So I'll be talking about PCOS and how to transition care across the lifespan from adolescence to adulthood. I have no relevant disclosures. I'll begin with how to make the diagnosis and how the diagnostic criteria has evolved over time, what the burden of disease is, the associated risk factors, and management across different age groups. So I'll start with a case, a 24-year-old woman who was concerned about facial hair, waxes every 10 days. She does not have any acne. Her menstrual history is that she had her first period at age 13. Cycles are irregular, and I encourage everyone, you know, when we ask our patients about irregular cycles, you'll get different answers. People mean different things and understand different things when they talk about irregular cycles. So always ask, like, do you have it once a month, you know, how many days? And she was having it every three to four months, often with skipping. So what would your next step be? My answer to that would be more history. And then I'll kind of go over this, because that's how, you know, for PCOS diagnosis, the history is very, very important as in other diagnosis. But the diagnosis of PCOS, the first time it was described in scientific literature was back in 1935 in Chicago. Stein and Leventhal discovered that a condition in which they described seven women with a combination of hirsutism, obesity, amenorrhea, and they had bilaterally enlarged polycystic appearing ovaries on both surgical and pathological evaluation. So that's on your left is normal ovary described, and then on the right side is polycystic ovaries formation. So diagnosis was redefined in 2003 by expert consensus, which is known as the Rotterdam Criteria, which is defined by the presence of two out of three of the following. So you don't need all three. You need two of the three. So oligo or anovulation, hyperandrogenism, which may be clinical or biochemical, and polycystic ovarian morphology. And sometimes with pelvic ultrasounds, I feel like the term may be used where like polycystic appearance seen, but we need to specifically see and clarify whether it means it meets this morphology criteria. But there is a caveat here that people who are on oral contraceptives, there is actually no criteria on how to define that polycystic morphology. So that's important to remember in people on OCPs. And this is, just to go into more detail, biochemical hyperandrogenism could be defined as elevated total or free testosterone or elevated DHEAS. High quality assays, remember the sensitivity as well as the accuracy of testosterone assays makes a difference. Clinical hyperandrogenism, so if they come in with significant hirsutism, high Ferrum and Galvez scores, a lot of acne, that meets criteria. You don't need biochemical and clinical. Either one counts. And then oligoammonoria, like I was saying, with the history actually defining how frequent, how often is it missed. And then the PCOS morphology. So we've had multiple diagnostic criteria for PCOS, and that actually has led to a lot of discrepancy in data because a lot of the recent studies, some have used one criteria, others have used the other criteria. So we've struggled with actually even defining PCOS through time. And I've kind of put this table on here which talks about the NIH criteria in 1919, then the Rotterdam criteria in 2003, and then 2012 International PCOS Guideline in 2018. So I'm going to focus more on the most recent one from the Endocrine Society, the 2023 International Evidence-Based Guidelines for Assessment and Management of PCOS. So they talk about an algorithm for diagnosing PCOS, and it's similar to the Rotterdam criteria because it's still used as the primary ways of diagnosing. So irregular cycles plus clinical hyperandrogenism. A patient comes in, you have this history. The most important thing is that PCOS is a diagnosis of exclusion. So you need to exclude other causes and then make the diagnosis. Step two, if there's no clinical hyperandrogenism, then you can do biochemical testing, and you can exclude other causes through biochemical testing. And if only irregular cycles or only hyperandrogenism, then you may consider an ultrasound. In Pakistan, where I also practiced for a few years, and probably in other countries, in young women, they may not consent and may not be comfortable with pelvic ultrasound and so forth. So that's there in transvaginal ultrasounds are usually avoided in that younger population. So that's a clinical consideration to keep in mind. So talking specifically for adolescents, sometimes PCOS is overdiagnosed, and in adult life feel like it may be underdiagnosed. So normal puberty, it may take a couple of years for the menstrual cycles to settle. That's one important thing to remember. And then acne, the menstrual irregularities and hyperinsulinemia could be seen in normal puberty without PCOS. So it's the immaturity until the HPA axis kind of develops and stabilizes. So the first two to three years post-menarche, it's premature to put a label of PCOS on a patient who may present to you with irregular cycles or acne. I would encourage people to kind of say, okay, you may have suspicion, and you can rule out secondary causes. But before you actually put that label on, just wait two to three years until things settle out. If there is persistent oligomonaria two to three years beyond menarche, that predicts that there will be ongoing menstrual irregularity, and there's a greater likelihood that there is some kind of underlying ovarian or adrenal dysfunction. So again, pointing out that multi-cystic ovaries could be seen in adolescent girls commonly, so ultrasound is not a first-line investigation in women less than 17 years of age. So ovarian dysfunction in adolescents should be based on oligomonaria and or biochemical evidence of oligo or anovulation, but major limitations, especially because of sensitivity of testosterone assays in ranges which are applicable to younger women. Now let's talk about burden of disease, and this is where the struggle is because through the last many decades, the definition and the diagnostic criteria of PCOS has been so variable that we are under-diagnosing or are unable to define the actual burden of disease depending on which definition was used. The estimate is that about 8 to 13%, and in some studies in South Asia, in the MENA region, up to 20% have been described. Up to 70% of affected women remain undiagnosed worldwide. It is the commonest cause of anovulation and a major cause of infertility, and it is associated with a variety of other long-term chronic diseases which I'll go into in a little bit of detail. PCOS does run in families, but there are some ethnic variations in which which symptoms will be more prominent and how it manifests itself and how it affects people with PCOS. Prevalence-wise, a 2019 study shows age-standardized point prevalence could be about 77.2 per 100,000 people respectively, which is much higher than the prevalence described previously and up to 37.9%, and a 33.7% increase since 1990. So it is increasing, and that is where there's a lot of debate about what is the environmental contribution and why are we seeing an increasing incidence and prevalence of PCOS, and we don't really have a very good answer for that so far. This is from the US. And in the United States, there is quite a bit of variability in different regions and the prevalence seen more so in the south at 47.5% as well. So these are some studies of across South Asia, different parts of the world, China, in Caucasian women as well, so you see quite a bit of disparity in the prevalence, and so I think having focus studies and region-specific recommendations are very important. So let's now talk about associated risk factors and the chronic diseases that I want to talk about. And there are two different factors I will go over. One is associated conditions medically, which we need to focus on, and then the second is what is important to your patient, which may seem like, as Dr. Kirmani was talking about, like even with thalassemia, with other complications, if to the patient their height is the most important thing, you do need to address what is important to the patient as well within reason. So associated conditions, most women with PCOS will have insulin resistance, not everybody. Hypertension and hyperlipidemia rates are higher, obesity and infertility, and there is a higher risk of developing endometrial hyperplasia and endometrial cancer. Increased risk of mental health issues and obstructive sleep apnea associated. Now patient concerns, weight gain, fatigue, unwanted hair growth, and that's also relative because there will be some women with PCOS with significant clinically apparent hirsutism and some may be bothered by relatively lesser hirsutism, but that is important to the patient. Thinning hair on the head, infertility, acne, darkening of the skin, mood changes, pelvic pain, headaches, sleep problems, depression, and anxiety. And there have been different papers where it's been described as a leading cause of increased depression in adolescents and reason for people skipping school, and that can have long-term consequences on overall health and social well-being. So for management, I always tell my patients with PCOS that we have to work as a team. It's not one person that will be managing, but they need to be established with endo, GYN, and dermatology. Not necessarily at the same time, but depending on what their focus and concern is, at different times in their lifetime, they may feel one is more important than the other, and we will then address that issue as their first priority. For example, if a woman comes in who has no plans for fertility but is bothered by irregular cycles, then we would focus on that primarily, or you have somebody else coming in and their main focus is fertility and the facial hair does not really concern them, you would focus on the fertility aspect of it. So it's an individualized approach based on the patient's presentation and their desire for pregnancy or not, and then what's really important is that we still consistently monitor their weight, BMI, blood pressure, metabolic parameters, and also always ask about mental health in our visits. So the management, like I was alluding to, is mostly symptom-focused, cycles, fertility, and then manifestations of hyperandrogenism, which would be acne and facial hair or thinning of hair. Associated risk reduction, if they have high blood pressure, you would treat, hyperlipidemia, you would treat according to cardiovascular risk, obesity, one would manage, and yesterday's talks, you know, we've gone, there were some excellent speakers about GLP-1 agonist and how that could actually help with infertility with PCOS women and decrease the risk of gestational diabetes and onset of diabetes later. So that's insulin resistance. So management in adolescents, as per the ACE guidelines, metformin is first-line monotherapy or in combination with OCPs and anti-androgen medications. There is controversy about using metformin in women with PCOS who do not have manifestations of insulin resistance. So in lean adolescent girls, a dose as low as 850 milligram daily may be effective at reducing PCOS symptoms. And overweight and obese adolescents, we can go up on the dose. The recommendations here is up to 2.5 gram dailies. In my own clinical practice, I do not exceed more than two gram daily. I do not see the benefit in insulin resistance beyond that. And anti-androgen therapy in adolescents can affect bone mass, so I generally would avoid that in adolescents, although there is some short-term data would suggest that it might be safe. So recommendations from the 2023 International Evidence-Based Guidelines from the Endocrine Society. I'll go over each because this is a busy slide. So the fasting blood glucose in A1c may not be the most reliable test for evaluating for insulin resistance, and they recommend the 75 gram oral glucose tolerance test as the most accurate test to assess glycemic status in PCOS women, regardless of the BMI. Now because it is a multi-step test, some people may just screen with the fasting blood glucose in A1c. If you find a positive, then that's easy, but if it's negative, it is not the most accurate. Lifestyle intervention always to improve metabolic health. So I tell my patients with PCOS that, you know, at different stages of your life, different things will matter to you, and we'll address that specifically, but if there's one thing that you should be doing for your entire lifespan, that is like exercise, cardiometabolic, it's really important, and not just cardio, but you need to do strength training. So the habit of at least two to three times a week of strength training and muscle building has been shown to help with decreasing insulin resistance. Now combined OCPs could be recommended in reproductive age adults with PCOS for both management of irregular cycles and hirsutism. Metformin alone can be considered in women who are overweight with PCOS for metabolic outcomes including insulin resistance, glucose, and lipid profiles, hyperlipidemia. Anti-UBCD medications, as I alluded to, and then in combination with effective contraception, it's very important that their own, you know, ironclad contraception, anti-androgens like spironolactone could be used to treat hirsutism in women with PCOS. And I've seen this being used more by dermatologists rather than us endocrinologists, but you may see women, you know, presenting first with hirsutism to their dermatologist, and they've already been started on OCPs and spironolactone. But I usually would wait for OCPs, and then if after six months, then add on if needed. Similarly for hair, mechanical laser and light therapies like trollises and laser is better used. It's important to tell the patients that, you know, the general laser packages that a lot of women will buy and say, well, I had six treatments and they said it would go away, but it didn't. So it's proven that women with PCOS will require long-term, and they don't fit in the same category as women without PCOS for management of hirsutism. So it's important for them to have that expectation because a lot of times they come in very disappointed that it didn't work. The hair does decrease, but they may need prolonged, and maybe for the rest of their lives they might need once a year or twice a year touch-ups as well. So that's a practical tip to give them. Inositol has had a lot of media, social media attention, so in any form, it could be considered women with PCOS. It can cause headache, dizziness, stomach pain, and digestive discomfort. So they can tolerate it. You know, there is limited harm, possible potential for improvement in some studies, but limited clinical benefits for weight and ovulation and hirsutism. So it's preferable to consider metformin over inositol for hirsutism and central adiposity. But you know, metformin also has GI side effects, as we know of. Bariatric and metabolic surgery could be considered, especially in women with, you know, in whom anti-obesity medications have not been able to help achieve a BMI under 27. And they do have other obesity-related complications, such as sleep apnea, hyperlipidemia, osteoarthritis, diabetes. And women with PCOS will have, most women have higher risk of pregnancies. There are some women with PCOS who have no issues with fertility, but that's a minority. And we should, it's important to kind of counsel them beforehand about risk of gestational diabetes and so forth as well. So infertility, this is something that, you know, usually reproductive endocrinologists or gynecology would manage, but I just wanted to kind of show you that that is included in the guidelines, the 2023 guidelines. And they do talk about, you know, the diagnosis based on Rotterdam criteria, and then health and lifestyle, and then they talk about first-line medical treatment as letrozole, and second-line medical treatment with gonadotropins with ultrasound monitoring. This is not something that I do in my clinical practice, but I just wanted to be aware of, because sometimes a patient may have questions about, you know, what are my options, and you can kind of discuss that before making a referral if they would like. So that concludes my talk, but what I want to mention here is I've put in a bunch of websites, which if you'd like to go on, we talked about mental health. So there are a lot of PCOS support groups and foundations, because of the different criteria over the last decades, there's a lot of questions and mistrust by PCOS, women with PCOS about their care. So I find this a good resource. I kind of point them to, you know, the evidence-based resources online, rather than them just Googling stuff which may or may not be scientifically sound. So these are some good, reliable websites, and the TEAL ribbon is actually used, and September is PCOS Awareness Month, so if you would like to do education sessions, it's a good resource. Thank you.

PCOS

diagnostic criteria

management strategies

multidisciplinary approach

pharmacological treatments