Dr. Mike (Host): This is Pediatrics in Practice, a CME podcast. I'm Dr. Mike. And with me today is Dr. Tania Burgert from Children's Mercy. Today, we're going to be talking about Adolescent Polycystic Ovarian Syndrome: Rethinking Diagnosis, Care, and the Future. Welcome to the show, Dr. Burgert.

Tania Burgert, MD: Thank you for having me.

Host: I think maybe a good place to start is what's the current diagnostic criteria? And I know that's a big question for adolescents with maybe PCOS.

Tania Burgert, MD: Sure. It definitely is a big question. I'll try to answer it. Well, I think one of the keys is that PCOS can be diagnosed as early as one year post menarche. And as long as menstrual irregularity persists and there's evidence of clinical or biochemical hyperandrogenism, then the diagnosis of PCOS can be made as long, of course, you exclude other causes such as pregnancy, hyperprolactinemia, and thyroid dysfunction, adrenal disease, and all that. But that's kind of the basis of it.

Host: In adolescence, what is the average age that you see a patient with this?

Tania Burgert, MD: It's a spectrum of ages, but as young as 10. It depends on when they have menarche. So, some kids have menarche quite early at age eight. Sometimes we see them even as early as age nine. And then, at Children's Mercy, we see up to 18 for new patients. And then, follow-ups, we keep in the system longer.

Host: What are some of the biggest challenges that pediatricians face when trying to identify PCOS in teens? And I'm talking about the general pediatricians, maybe not the expert like you.

Tania Burgert, MD: Right. Traditionally or historically, it's been a challenge due to the difficulty in differentiating between what's physiologic puberty and what's PCOS. And people have always been kind of afraid to label something PCOS if it may just be menstrual irregularity due to puberty. So, that's been the biggest challenge. But I feel that with the new international PCOS guideline, there have been some specific recommendations which allow pediatricians to make firm decisions and move that process along.

Host: To help out maybe a general practitioner or a nurse practitioner in a community setting, Dr. Burgert, what are some of the key symptoms they should be watching out for that may make them go, "Ah, is this PCOS?"

Tania Burgert, MD: Yeah. So, the guidelines, as I mentioned before, state that you can diagnose PCOS as early as one year post-menarche. And at that time, if there is any skipped cycle of more than 90 days, then that patient should be evaluated for PCOS. Also, if cycles come more than every seven to eight weeks apart, patients should also be evaluated for PCOS. So, it's pretty clear if there are wildly skipped cycles or if you're not regular, only coming every two months, you should be evaluated for PCOS. That means we should examine the patient for signs of clinical hyperandrogenism and get blood work for biochemical hyperandrogenism, which would be total and free testosterone.

Host: Is PCOS increasing in prevalence?

Tania Burgert, MD: I think we are doing a better job diagnosing it, but also there are a lot of environmental factors that contribute to manifestations and expression of PCOS. So, it's a combination of better diagnostics and also maybe lifestyle and environment contributing to manifestations of PCOS.

Host: In adolescent females, is there a trend towards menarche in earlier ages in today's world?

Tania Burgert, MD: Certainly. That has been a trend, not necessarily related to PCOS, but it is certainly a trend and, again, whether that's endocrine disruptors or other environmental factors, insulin resistance. And maybe, if you'd like, we can talk a little bit about the pathophysiology of PCOS and contributing factors.

Host: The question I was going with was if there's early menarche, I was just curious if that's been correlated or associated with an increase in prevalence in PCOS. Is that the case or not?

Tania Burgert, MD: I think early menarche is different from premature adrenarche, which is early pubic hair. That certainly is a known association with PCOS because it's linked to insulin resistance. Early menarche may or may not be driven by premature adrenarche and, therefore, be an early sign of PCOS. But just the fact that early menarche doesn't mean necessarily that somebody is going to have PCOS.

Host: And so, something more like insulin sensitivity or insulin resistance, that's definitely more associated with PCOS. Correct?

Tania Burgert, MD: For sure. That is the root of the problem in many cases.

Host: So, how should pediatricians approach the concept then of who's at risk for PCOS in adolescent patients?

Tania Burgert, MD: We used to either diagnose somebody with PCOS or say they didn't have PCOS. But we now know that is still a little tricky in adolescence. So, a new category was created, the at-risk category. So if a patient has menstrual irregularity but doesn't have hyperandrogenism or vice versa if they have hyperandrogenism, but regular menstrual cycles, they are considered at risk for PCOS. Because we don't want to over-diagnose and we don't want to miss a diagnosis. And so, these patients are treated clinically symptomatically, and they are followed until that diagnosis can be confirmed or refuted.

And also because ultrasound examination is not part of the diagnostic criteria anymore as these patients age. And if we still don't know if they have PCOS or not, that diagnostic method can be added in to the repertoire and then, they might be able to get that diagnosis or have that diagnosis refuted later on in life when an ultrasound can be done as well.

Host: So, early on, in how doctors would diagnose PCOS, ultrasound was one of the first things they would go to, right? But what you're saying is that's not part of that initial workup anymore. You're looking more at those insulin factors, lifestyle risk factors for insulin sensitivity. Is that correct?

Tania Burgert, MD: In terms of making the diagnosis, hyperandrogenism and menstrual irregularity are the only two factors that you need for diagnosis. Insulin resistance is not part of the diagnostic criteria, but it is certainly part of the condition. Ultrasound used to be part of the diagnostic criteria, but we didn't have enough data on normal ovarian morphology in adolescence, and there was a lot of confusion in terms of what constitutes a normal ovary or PCOS ovary in adolescence, because again, there was a lot of overlap, just like menstrual irregularity overlaps. So, it was taken out of the diagnostic criteria. But eight years post-menarche, the ovaries are matured and you can start looking. So if a girl starts menstruating at age 10, at age 18, she could have an ultrasound if it's still not clear whether she has PCOS or not.

Host: Let's move into treatment now. What are the most effective first line treatment options for managing PCOS symptoms in teens?

Tania Burgert, MD: I personally think that education is the most important treatment. And in our clinic, we spend a lot of time going over the pathophysiology of PCOS, how menstrual irregularity and hormone imbalance ties into high insulin levels and insulin resistance. So once the patients understand that as the root of the problem, as the root of the cycle irregularity in the hormone imbalance, we talk about the different targeted treatments for insulin resistance. And we usually start with exercise. We know that cardiovascular exercise decreases insulin resistance and will lower insulin levels. We talk about a diet that's rich in fiber and low in refined carbohydrates, which also will reduce insulin resistance.

And then, of course, we have metformin, which is an insulin sensitizer. And it will pharmacologically reduce insulin resistance. But it also-- many don't know-- has an additional benefit of directly affecting ovarian androgen production. So in addition to reducing insulin resistance, it also just reduces ovarian androgen production. So, it has that double benefit in terms of PCOS treatment.

The other options, there's many treatments and other options. So, if there is prolonged amenorrhea, patients with PCOS are at risk for endometrial hyperplasia, endometrial buildup. And so, we wouldn't want that to happen. So, we often give a 10-day course of medroxyprogesterone to make sure that we don't have endometrial buildup.

 The other option if there's concern for endometrial buildup and if you want uterine protection is the oral contraceptive pill. And it has the additional benefit in terms of hirsutism and acne. So, some patients prefer that. But I do want to note that the pill is not necessary to create cycle regularity. Studies have shown, and in our practice, we also see it all the time that 90% of girls will start cycling regularly once insulin resistance is treated. So if they're on metformin and having lifestyle changes, they will have regular menstrual cycles. So, the pill is an option, but it's not necessary. But it can have many other benefits and, certainly, if there's a contraceptive need, that is above everything else.

Host: Going back to the idea of first line, right? So, you laid out some lifestyle suggestions, right? Exercise, fiber and you even then went into metformin can come next. Is that how you do it: you first start with the lifestyle changes, you make sure they're getting more fiber, more exercise, overall a low glycemic diet, and then, you see how they do and go to metformin? Or does lifestyle and metformin happen all at once?

Tania Burgert, MD: It's very individualized. We really try to spend 90% of our time on education, and then have the patient make an informed decision. And so, we go over and we offer everything. We offer lifestyle alone, lifestyle in combination with metformin, lifestyle in combination with OCPs, metformin in combination with OCPs. We also have spironolactone as another option. So, we go through all the stress pathophysiology, and then we describe which medication targets, which aspect of the pathophysiology and, once they're informed, what they think is important to them, and then, we start there. And of course, we guide them, but in general, we leave it up to them.

Host: Is there any clinical data just looking at lifestyle alone? Like, we're going to exercise four times a week and we're going to do cardio and resistance training. And then, we're going to add fiber, a certain amount. Is there any data that shows just those changes can make a difference?

Tania Burgert, MD: Yes, definitely. The problem is that those are, you know, in this experimental setting. And so, it's easier if patients are able to keep it up. It's very effective. It's very effective.

Host: Yeah. Yeah. It's one of the problems we have with clinical research, right? It's so controlled that when you get out your real life, it didn't always work out that same way, right?

Tania Burgert, MD: Yeah. But as a proof of concept, yes, it works.

Host: Mental health is a big part of this as well. Mental health is often intertwined with chronic conditions. How should pediatricians address the psychological aspects of PCOS in adolescence?

Tania Burgert, MD: So, an interesting fact is adolescents with PCOS have three times higher risk of depression than adolescents with type 2 diabetes. We don't know exactly what specifically it is about PCOS. Is it the hormone dysregulation? Is it the added aspect of hirsutism and body shape? We don't know exactly what it is, but we know for a fact that anxiety and depression are really high. PCOS creates a really high risk for this comorbidity. And so, it would be important for pediatricians to know that if they diagnose somebody with PCOS, to make that patient aware that depression and anxiety really are strongly linked. And it's generally recommended if you diagnose somebody with PCOS that you screen them, at least for depression and anxiety.

Host: And you mentioned before, education's so important. I'm sure this is something you bring up early on. If it's a teen, you speak with the parents, recognizing those possible symptoms, right? I'm sure all that's going on.

Tania Burgert, MD: Yes. We screen everybody for anxiety and depression. And in our clinic, we have Adolescent Medicine who's very skilled in having these conversations.

Host: So, let's look into the future. Dr. Burgert, you're the expert, you're the one who studied all this, you know what you're doing. What most excites you about the future of adolescent PCOS care?

Tania Burgert, MD: In general, I am pleased with the advocacy groups that have come up around PCOS with the self-advocacy that patients are conducting. I am pleased with the knowledge that they now have and how they can demand proper care for themselves and how they demand to be taken seriously. So, I really kind of like the movement that's going on in that way from a patient perspective.

In terms of research, obviously, I'm biased in terms of the research that I do. So, I am lucky to be in on a collaboration with Adolescent Medicine. We are co-investigators in this study, an NIH trial that's spearheaded by Cornell, where we look at daughters of women with PCOS and we look at the first two and a half years post-menarche. And we look at all factors, environmental, hormonal, metabolic. We actually do ovarian ultrasounds, and we trying to see if we can predict who's going to develop PCOS and who's not going to develop PCOS in this high risk group. Is it more environmental? Is it more hormonal? Is it more biological? Is it ovarian features? So, we are just about to launch this study and I'm super excited about it.

Host: That sounds like a great future research topic for us for sure. This has been great, Dr. Burgert. Great job. This has been great information.

Tania Burgert, MD: Thank you. Thank you.

Host: For more information, you can go to cmkc.link/cmepodcast. If you enjoyed this one, please share it on your social channels and check out the entire podcast library for topics of interest to you. This is Pediatrics in Practice, a CME podcast. I'm Dr. Mike. Thanks for listening.