PCOS with Dr. Mark Trolice and Dr. Anuja Dokras

In this episode of the SART Fertility Experts podcast, Dr. Mark Trolice sits down with PCOS expert Dr. Anuja Dokras, who explains diagnosis, risks, fertility, lifestyle changes, and new treatments to empower women with PCOS in 2025 and beyond.

Hi, everyone. Welcome to another SART podcast. This week, I am thrilled to have our renowned PCOS expert, Dr. Anuja Dokras, who is the Executive Director of the Women's Health Center for Clinical Innovation and has her own PCOS Center at the University of Pennsylvania.

She has had extensive research experience in PCOS, focusing on the cardiometabolic risks and also the mental health issues in patients with PCOS. She is the past president and is the current Executive Director of the International Androgen Excess Society. Now, we're going to talk a little bit about diagnosing PCOS, and there's a little bit of a difference in that Androgen Excess Society versus the traditional criteria that we've used.

She's received a training in not only obstetrics and gynecology and reproductive endocrinology, but also is a Doctor of Philosophy from the University of Oxford. Oh, my gosh. Anuja, thank you so much for being with us today, and I'm really, really excited about talking PCOS with you.

Welcome. Thank you so much, Mark, for inviting me, and I'm excited that you are doing these podcasts to help our patients. Thank you.

Now, let's just dive into this. Now, traditionally, we've used the criteria from the Rotterdam Consensus Conference for over two decades, and that used patients that had ovulation dysfunction, elevated male hormone, either with hair growth or hormone levels, as well as the ultrasound appearance. So, they needed two out of those three criteria, but Androgen Excess gives a little bit of a different criteria.

Can you tell us about that? Yeah. I think today, in 2025, we are really using what you described, the Rotterdam criteria. They've been around for 20 years, and now we call them the modified Rotterdam criteria, and this is because we've had a number of different definitions floating around.

They're called either the NIH criteria, the Androgen Excess PCOS Society criteria, but I think for our listeners, let's make it simple. What we really need to use now in 2025 are these modified Rotterdam criteria, which is there's three of them, or like you described, and any two will make the diagnosis, but it's really important that your doctor tells you which of the two, and in general, it might be all three, which establishes the complete syndrome, and the reason why two out of three may be important is do you have something that's milder, right, or is going to have a lower long-term risk. So, always make sure to ask your doctor why do they think you have PCOS and what criteria do you satisfy.

Now, your Androgen Excess Society, out of those three, they require you to have some measure of elevated male hormone. What do you think of that in terms of PCOS? Because if you don't have that, PCOS could be confused with calorie deficit, the female athlete triad, you know, the criteria now declares the red syndrome for a lot of athletes and those that are energy expenditure. What do you think about meeting the male hormone issue for PCOS criteria? I think it's really important when we think about the pathophysiology, right, like what is the underlying mechanism for PCOS? It is an excess production of male hormones, typically from the ovaries, and then a little bit maybe from this gland that sits on top of the kidney called the adrenal gland.

But that combined male hormone in our circulation, if it's higher, nowhere in a male range, just a little higher than the female range, gives all of these manifestations that we talked about in the criteria. It is important to know if it's what we call it the hyperandrogenic phenotype or the phenotype where you have high male hormones, because a long-term risk related to cardiometabolic complications is very closely tied with those male hormones being high. So if you have, and that's what I refer to as the milder forms, where the male hormones are not as high or the blood test is just normal, then the discussion I'm having more is how do I make your periods more regular so you don't have a risk of cancer within the lining? You know, how do I help you with fertility if that's an issue? And that's where it stops.

I'm not really screening this patient every year for the cardiometabolic problems. So I do think it's a very important part of sort of trying to distinguish what type of PCOS our patient has. Why do you think it's taking still several years for patients to be diagnosed with PCOS, or at least have intervention about what they're going through? You know, when they go several years without a period or having irregular periods, particularly if their body mass index is elevated, they're putting themselves at risk and the OB-GYN or primary care physician needs to be aware that that increases the risk of preuterine cancer, right, not having periods regularly.

So why several years to diagnose and having to see multiple physicians? What are you seeing? Yeah, it is really unfortunate. You know, the data you're describing comes really from our paper and study that said between six months to two years for the diagnoses, and between, like for about 50% of the patients who responded to the survey. And then going from one physician to another, you know, three or four, and they may go from a primary care physician, an OB-GYN, an endocrinologist as well, because in our country, you don't need a referral to a subspecialist.

So these patients are really hopping around. It's because of a few things. So I think the factors that have contributed to this, one is we really haven't had as much research in PCOS in the beginning decades when it was described.

And then there were these varying criteria. So somebody says, maybe you have it, maybe you don't, I'm not sure, you don't meet all the criteria. So that's been part of it.

Part of it has been that the symptoms change with age. In the adolescent young girl, they're a little different, you know, in the 30s. But in the 40s, the periods become regular, male hormones are pretty much normal.

So depending on when the patient comes to the practice, and it may change a little bit based on your ethnicity and race in terms of like at least the hirsutism part, the obesity part, which is much more prevalent in our country. So these have been the challenges, I think. But I think we should take some ownership as the physicians and the educators to make sure that we get the message out now.

In 2025, there's no reason why there should be delays. Yeah. And just to follow up on that point, women from Asia will not have the degree of hair growth on their body because they have less hair follicles.

And so they are often missed with having PCOS. So let's talk about the metabolic problems. You know, there's always, we're all aware of the reproductive risks of PCOS that involve irregular cycles, abnormal bleeding.

They have more ovulation dysfunction, difficulty conceiving, diabetes and pregnancy risks, miscarriage. But the metabolic syndrome is not as discussed in circles with patients, at least when we see them. Talk to us about the metabolic syndrome and what are some ways that we diagnose but also can prevent complications of that? Yeah.

So let's start with even say, you know, talking about what is metabolic syndrome. So metabolic syndrome brings together five risk factors for heart disease. So the blood pressure, the cholesterol levels, the glucose levels and the weight or the waist circumference.

And it's just slight abnormalities or small abnormalities in each of these. Three out of five puts that patient at a higher risk for diabetes as they get older or even heart disease. So it's really a very important early marker.

And that's why we use it in PCOS because of course, if somebody has diabetes, you know, this is a risk factor. But we want to really catch it early. And why do we want to catch it early? Because again, our group and others have shown that even in the 20s, leave alone in the 30s or 40s, our patients with PCOS have a higher prevalence of metabolic syndrome.

So if you're going to pick it up that early, we can intervene. And that's why it really becomes important. There are racial differences, just like you described for hirsutism, differences, depending on if we have a European population, somebody from Southeast Asia, the risks are going to be different, maybe for diabetes, maybe for hypertension, but together that risk is overall elevated.

So we do need to first make the diagnoses, tell our patients what type of PCOS they have. And then we have to say, do you have any risks today? Or are you risk-free today? And then how do we follow you, right? So I think we need to not just do the diagnosis, but that next step, we need to go beyond and do an initial evaluation, which really isn't that hard, right? So it's height and weight, blood pressure, which we do for everybody. And then it's a cholesterol panel, which I think is the extra one that doesn't get done.

And with the glucose monitoring, we've made it much simpler now in terms of guidelines. We're not saying everybody needs a two-hour glucose tolerance test. That was hard, I think.

So if we can even do a fasting glucose or a hemoglobin A1C, that's going to give us information to start screening these patients. Yeah, or even just the fasting insulin and glucose to do the homeostatic model assessment of insulin resistance is a nice, simple calculation, although the cutoff values are not as well-defined. We know that they're significantly elevated, that high risk of insulin resistance.

So metabolic syndrome, two to four times higher in these patients. Now you mentioned the waist circumference. Let's talk about that a little bit.

It's not easy for patients to go there. We know that having an elevated body mass index worsens all the metabolic problems, unfortunately. Is it a chicken and egg type of situation? In other words, is obesity causing PCOS? Is PCOS causing the obesity, making it more difficult for them to lose, easy to gain? What is your understanding of the relationship between weight? And then, you know, this is also tying into the visceral adipose tissue, you know, the VAT, which are metabolically active and causing this metabolic issues with these patients.

Yeah, so we know that the high male hormone levels and the obesity goes hand in hand. So patients with PCOS have a tendency to gain weight more easily than those who don't. And that weight unfortunately settles sort of in the middle of the body, like a male pattern rather than the female pattern, which would typically be weight more on the thighs and the buttock area.

But the other way around as well, we know in populations as the weight goes up, and we've seen that across the world as the weight's gone up, even in Asia, Southeast Asia, the periods do become irregular, and the free testosterone goes up. So it mimics PCOS. Not everyone who is overweight or obese has PCOS, you have to have an underlying predisposition, which means genetically, you need to be at a higher risk.

And then as the weight goes up, the balance shifts, and all of a sudden you have these symptoms, like the young girl who says, I went to college, and then I had my freshman 15, and I gained weight. Now my periods are irregular. It was not an issue before.

But so we know that weight is a very important modifier of this risk. And then it is a modifier of your metabolic risk, as you were referring to, the cholesterol levels, as well as diabetes. But independent of all of that, even if the weight's not up, our patients with PCOS who are sort of normal weight, or maybe overweight, do have a higher risk of cholesterol abnormalities and diabetes.

So that risk is independent of weight. It becomes worse as the weight goes up. So they're genetically predisposed, and the weight obviously worsens all of this.

How, where are we now with genetic markers? Are we any closer to being able to say this is the genetic pattern, if you will, for PCOS? Yeah. So we have a lot more information about the genetics. We understand that it's a little bit like diabetes.

We call this a complex genetic condition. There's no one gene. There's no one gene that has been altered, and now you have PCOS.

It's a number of genes that together are associated with PCOS. So there is no test right now, and hence we are left with our Rotterdam criteria, where we can just put five genes from this panel and say, okay, you have PCOS. So we're not close enough for that, but we have a lot more data, and I think the genetic data will help us also understand, are these just associations, or is it a real cause and effect? As you said, you know, does the obesity cause it? We haven't talked about the mental health, but, you know, there are genetics that show us higher prevalence of depression and PCOS, but it's an association.

It's not causal, but I think the genetic studies are closer in terms of letting us understand some of these questions that we have. Well, it's certainly a very, very frustrating problem for our patients, and they're sensitive to so much of this. They don't feel like a woman, not having regular cycles, and when they're trying to conceive, they feel like they're failing their partner.

It's just such a shame. I just wanted to touch on the fact that you mentioned about the waist circumference, and when we're looking at pregnancy outcomes, unfortunately, data is showing that elevated BMI do have lesser eggs retrieved, lesser egg quality, and embryo quality. So, what are some ways that you're advising patients to modify lifestyles to improve that, which could improve fertility, but also reduce pregnancy complications? So, how do you start these conversations, and what are you advising, including the new drugs that are out there, the GLP-1s? Exactly, yes.

So, I think, you know, the first part is we have to start these conversations early. When we make a diagnosis, we have to start those conversations to sort of say, lifestyle modification is not something you do over a week or over three months. It's a long-term lifestyle change, and hence, I think if the conversations are started early, and we talk about it can impact your long-term cardiometabolic risk, but also your pregnancy outcomes, I think that probably has more of an impression for some of these young patients when you talk about pregnancy outcomes.

The data, I do believe, is clear, even though in the IVF, non-PCOS field, weight loss doesn't necessarily improve IVF outcomes in some studies, but if you look at the subset of patients with PCOS, when they lose weight, their ovulation rates are better, their life birth rates are better, and I think it's sort of intuitive that you're going to have a lower risk for gestational diabetes, hypertension, because you are metabolically better when you start off. There's no one magic bullet for the improvement. There's no one diet that helps all, but in general, we have found that the diabetes diet, which is a higher protein, complex carb kind of diet, is better.

Caloric restriction is always hard, and if you start recommending that very early, our patients, unfortunately, are at a risk for disordered eating, so we don't want to be very restrictive. I would rather say, let's do it more sensibly. Reduce your carbs as much as you can, or eat the healthier carbs.

Push up your proteins. Exercise. And then for those, you know, who truly have obesity or even morbid obesity, we are in a much better place in this decade that we have weight loss medication.

In our field, unfortunately, we were using metformin, which really is not a weight loss medicine for so long. Did not do much for our patients at all, and so now that we have the GLP-1 receptor agonist that you're referring to, in those select patients who will benefit, we should be introducing these early, because again, you don't want to do it too close to pregnancy. That rapid weight loss, and then there's a rebound when you stop it.

So we still have some unanswered questions about the newer medications, but I am so glad that we have them as an option for our patients. Number one, should the reproductive endocrinologist, when they see these patients and they have markedly elevated body mass index, should the reproductive endocrinologist be prescribing the GLP-1s, you know, the ozempics and the mounjaros, or should they be sending them back to their primary care physician? But also, how long should our patients be on this? You know, they're concerned about their age, their ability to conceive, and they want to not really delay any longer than they absolutely have to. Yeah, I agree.

All of these are sort of very good questions and challenging ones, yeah. In terms of who should prescribe it, I think all the physicians who get comfortable prescribing it. It's only going to benefit our patients, because it's a long time getting into the medical endocrinologist.

If your PCP or your OB-GYN can prescribe it, wouldn't that be wonderful? The reproductive endocrinologist, if they prescribe it, that would be great as well, and I do know some of our colleagues in our field, you know, have been trained to do that and have the resources to follow up on these patients. So, anybody, just like, I think, the psychiatric medications, right? Initially, it was you sent your patient to a psychiatrist, and now most OB-GYNs feel comfortable prescribing at least the first level sort of medications, if needed. So, it's more becoming comfortable with them.

The second part is harder. How long do you keep them on it? When do you stop? Because a lot of the initial studies did not include patients who are trying to get pregnant. So, we don't have that data.

We now have some data that tells us that birth defects are not increased. These come from registry studies, and so we need a little more information to reassure our patients. And then the real concern is the rebound.

If you say stop before you attempt pregnancy, you're not going to be pregnant necessarily in the next month. It may take a while, and if the weight comes back, that's a concern for our patients. So, there are some unanswered questions.

I'm still very optimistic. I'm so glad that our patients have this option, and we'll get the data over time. You know, we're all aware about the gaps in our knowledge, and are really pushing to get some of this information for our patients.

Yeah, the medication is very, very exciting. Since they cannot be on that forever, I think it's important that we emphasize the need for a healthy lifestyle, the Mediterranean diet, or the DASH diet, as well as regular exercise. You know, the cardio is important, but also, these patients at risk of prediabetes, insulin resistance, strength training improves that insulin resistance and can help blood sugar control as well.

I just wanted to touch on one other option for these patients when we talk about ovulation induction. They can go on often letrozole, which is that enzyme blocker that seems to be or has been shown to be superior to clomiphene citrate, particularly for patients with an elevated body mass index. But there's also the ovarian drilling.

In our experience, we have done probably about two-thirds of patients conceiving and half of them getting pregnant naturally after laparoscopic ovarian drilling. But we're participating in a study now that's doing a transvaginal ovarian drilling. Do you have much in the way of experience of knowing these options, and when would you consider giving these options to these patients? Yeah, yeah.

No, isn't it exciting that we can say there are more options for our patients now, you know, in this field? It's great. I want to answer this question by first saying that a large number of our patients get pregnant without our help, though. So I don't want every patient to think, oh my god, they're going to need to do some medication or some intervention.

There is a good number, because you're ovulating, you just don't know when you ovulate or you don't ovulate regularly. So a proportion will be pregnant on their own and without our help. A good proportion will respond to medications like you mentioned letrozole and clomid.

And then for the group that doesn't respond to those, it is exciting to have another intervention, which you refer to as ovarian drilling. We are part of that study now as well and have done our first case. And what it does is with radiofrequency ablation, we'll sort of reduce that volume of the ovary, decreasing androgens and maybe AMH just a notch to get the cycles going.

And that would be nice for patients who don't want to go onto something as invasive as in vitro fertilization or expensive as that. And so I think time will tell us if the, I'm hoping the data will be similar to what we saw with the laparoscopic approach. But again, we are a very conscious group of physicians who want all the data.

And so we are going to participate in these studies and get that information for our patients and reassure them. And I look forward to just giving our patients more options. Excellent.

Anuja, as we close, what would you say is the best advice to empower our patients to optimize their metabolic and reproductive health to prevent consequences? I want to leave our patients on a very high optimistic note. I think we are in a place with PCOS where we know a lot more. We understand that this is not just a gynecologic condition.

Here's your prescription for your birth control pill and come on back when you want to be pregnant, right? So we know this is a longer term endocrine condition, and I would encourage our patients also to be educated about it, like listening to podcasts like this, ask questions, ask your physicians, not just about the gynecologic issues, metabolic issues, psychological health. But for a vast majority of patients, we are able to help you guys. And so it's not as frustrating as it was in the prior decades.

We are in a much better place with more options, and we look forward to constantly getting you more information. Wonderful, Anuja. Thank you so much for your time.

This was just invaluable, and I'm sure our audience really appreciated all the expert advice. With me has been Dr. Anuja Dokras, who is a renowned researcher in PCOS and has a unique, comprehensive PCOS clinic where she is the executive director at the University of Pennsylvania. Thank you, Anuja, once again.

Until next time, everyone, this is Dr. Mark Trolice. Take care and good luck. Bye, everyone.

Thank you. do not necessarily reflect those of ASRM and its affiliates. These are provided as a source of general information and are not a substitute for consultation with a physician.