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Melanie Cole (Host): Welcome. Our topic today is polycystic ovarian syndrome in adolescence. My guest is Dr. Holly Hoefgen. She’s a Washington University Pediatric and Adolescent Gynecologist at St. Louis Children’s Hospital. Dr. Hoefgen, explain a little bit about polycystic ovarian syndrome.

Holly Hoefgen, MD (Guest): Yes, so polycystic ovarian syndrome, what’s commonly referred to as PCOS is really a spectrum of clinical disorders that’s associated with the increase in androgen production from the ovaries.

Melanie: Is it common in young girls?

Dr. Hoefgen: It’s actually pretty common. It’s one of the most common endocrinopathies in all reproductive aged women but we do see it a lot in adolescence and depending on a number of different diagnostic criteria that are out there; it’s anywhere between about six to almost up to twenty six percent of the population and just due to a number of different kind of concerns and medical issues that come off of the diagnosis; it can actually be a pretty high cost burden as well. Some studies have it up to being about four million dollars of cost burden in the US per year. So, it is something that is pretty common and something that we see in our clinics at least on a weekly if not daily basis.

Melanie: Wow. So, do we know what causes it and is there a genetic component?

Dr. Hoefgen: So, we know a little bit about what causes it. There’s not a single cause that has been identified and the exact pathophysiology isn’t clear. But we think that there is sort of a multifaceted trait with lots of different factors. So, there are over 100 different genetic components that are being studied both in steroid synthesis, looking at different metabolism components and inflammatory markers. There are some people who are looking at intrauterine effects such as if increased prenatal exposure to androgens can have an effect on giving you a predisposition to PCOS. Some environmental components are being looked at. Mostly that’s looking at things like plasticizers and BPA in our food packaging but also certain medical devices. But really the things that we look most at are is there an overexpression of our steroidogenic enzymes in the ovary or an overexpression in LH receptors that are then leading to this overproduction of steroids that causes PCOS. So, some play in all of these is likely what the cause is. But we can’t really pinpoint one exact thing that leads to PCOS.

Melanie: Dr. Hoefgen what is the clinical presentation in adolescence? What are some of the first signs and symptoms?

Dr. Hoefgen: So, classically PCOS has been thought of as this characterization of hyperandrogenism, so elevated steroid hormones, some type of ovulatory dysfunction or irregularities in the menstrual cycle and then polycystic ovarian morphology. So, a large amount of follicles in the ovary. But the exact pathophysiology like we said, the diagnostic criteria and how to treat patients with PCOS; every aspect of PCOS pretty much remains controversial and that is especially true in adolescence where all of those things are even more controversial than they are in our adult population.

Melanie: Well while you are mentioning controversial; what are the diagnostic criteria and why are they controversial?

Dr. Hoefgen: Yeah so, I mean that’s actually a very interesting story that can probably be our entire talk. But over the years, there has sort of been an evolution of a lot of different criteria for diagnosing PCOS in the adult population and currently we are utilizing a system where we look at these three symptoms that patients can have. So, ovulatory dysfunction or abnormal periods, hyperandrogenism which clinically is usually looking at abnormal hair growth, but also things like acne or virilization or you can look at it biochemically looking at like elevated testosterone levels and then the third thing is polycystic appearing ovaries on ultrasound. So, do patients have an increased number of enlarged follicles? And in the adult populations patients need to have two of those three criteria and depending on which two or all three; we put them into one of four different phenotypes and we can use those different phenotypes to assist us clinically on how we think the patients are going to do throughout their lifetime.

The difficulty in adolescence is that a number of those things, if not all of those things can be normal in an adolescent, right. It’s pretty common knowledge that in the first few years after patients start their periods, they can be very anovulatory and irregular periods are common. And then when we look at the criteria for adult hyperandrogenism; we just don’t know how reliable that is in adolescence, right. So, there’s this maturing of the HPO axis from the hypothalamic and pituitary gland down to the ovaries and when that happens you have increases in androgen levels and so how should we be evaluating adolescents and what does that mean; it’s hard to tell and things like acne are very common in adolescence, right. So, some of those criteria are hard to use and then that third criteria especially the polycystic appearing ovary is actually very normal in an adolescent and even up to half of adolescents, that can just be how their ovary look and there are studies that show that half of girls who never go on to have PCOS actually meet the diagnostic criteria for a polycystic appearing ovary. So, it can just be very difficult to then make that diagnosis in a patient who is in their adolescent years.

Melanie: Once you have diagnosed this, speak about treatment a little bit and the risks and benefits associated with certain treatments.

Dr. Hoefgen: Yeah well, I think the first thing would be – first we have to kind of make that diagnosis in adolescence and so we have made some strides to be able to do that. So, even though it is challenging; over the last few years there have been some strides in that and there was a recent international consortium where some of the pediatric experts in the field so from endocrinology and gynecology and adolescent medicine came together and really have put out some guidelines to help. So, there are some guidelines that you can look at now that say well in the adolescents let’s look at the just their menstrual cycle abnormalities and hyperandrogenism and focus down on those things, not looking at the ovaries or acne or these types of problems and try to wait until patients are two years out from their menarche to do that. So, there are some criteria that we can use. And then if we are thinking that a patient either has PCOS or we are going to not give them that diagnosis yet, but they are heading in that direction; then we can treat them as a patient who is at risk for PCOS, right.

And the mainstay of treatment for any of those patients is going to be a lifestyle modification and we are going to try to counsel them and all patients who either have PCOS or are at risk of good diet and exercise management. That’s always going to be key. Above that it’s really kind of based on what type of symptoms the patient has. So, if we are worried about their menstrual related concerns; we want to make sure that all patients are trying to have regular menstrual cycles or cycles that are not bothersome to them. At the very least, to make sure they are having periods more often than 90 days to provide protection to them. And then from there, it’s more about what’s bothering the patient, if they are bothered by their acne or their hair growth. In most of their scenarios, we can treat them with hormonal medication to bring down their steroid levels and to help with all of those things. And then in patients who are not able to be treated with hormone medication, there are a number of other options that we have for them and we can kind of talk through them with the risks and benefits of what those treatments might be.

Melanie: Well, before we do that, tell us about some of the long-term effects of PCOS and complications if left untreated such as metabolic risk in adolescence.

Dr. Hoefgen: Yeah, so that’s really some of the biggest concerns with PCOS is there is a long-term implication in a number of different areas. So, the main metabolic risks would be things like hyperinsulinism, they can have the long-term risk of hypertension, diabetes as they grow into their adult life. From a gynecological concern; if patients are going undiagnosed or untreated and they are having prolonged times without a menstrual cycle then we really are putting them at risk for things like endometrial hyperplasia and eventual uterine cancer. And then there’s also the thing that kind of goes unnoticed a lot in patients with PCOS is there is a concern for long-term psychologic health problems. A lot of these women have issues with depression and anxiety and some body image dysfunction as they go through both adolescence and their adult life. And these are all things that as even patients who are diagnosed, that we have to continue to work with them not only through their adolescence but also through their adulthood to assure that we are managing properly.

Melanie: Dr. Hoefgen tell us some of the warning signs that a pediatrician should look out for and when should that pediatrician refer to a specialist.

Dr. Hoefgen: So, I think the biggest thing that we want to make sure of is that we are catching all of these red flags for patients with abnormal menstrual cycles. I think most pediatricians are very familiar with the basic diagnosis of amenorrhea which is usually a patient who is not having menstrual cycles by age 15 or a patient who is 13 but might not be having their signs of secondary sexual characteristics such as breast development, right. But there are other diagnoses for amenorrhea that are less commonly thought of such as a patient who is 14 and doesn’t have their period yet but might have signs of hirsutism because that is giving us concerns for PCOS, right. Also, if a patient started breast development earlier like at nine or ten and is now three years past that and doesn’t have a menstrual cycle yet, that is technically still a diagnostic criteria for amenorrhea and that patient would require a workup. And then the other is that even though adolescent patients should have – have an expectation that they can have irregular menstrual cycles. There is a caveat to that that they shouldn’t be going more than 90 days without a period regardless of where they are, even if they are in their first year past their menarche. We would not expect them to have that much irregularity. So, we still want to be looking at those things and not just chalking it up to the fact that they are kind of newly having periods. So, those are things we want to look for and make sure that those patients are seeing a specialist.

Melanie: And Dr. Hoefgen in summary, what can a pediatrician expect after referring a patient to the pediatric and adolescent gynecology team at St. Louis Children’s Hospital and what else would you like them to know about PCOS?

Dr. Hoefgen: I think the things would be to just expect that the patients will get a very well-rounded discussion about the things that we know, and we don’t know about PCOS. And that we will be very frank with them about the fact that they may not leave our office with a diagnosis that day because of the limitations on being able to do that diagnosis and often we maybe giving them a transitional diagnosis of possible PCOS. But that doesn’t mean that we cannot treat the patients or provide them with management for the things that bother them. We don’t have to have a diagnosis of PCOS to be able to help patients with their menstrual cycles, or their acne or their hair growth related concerns. We just don’t want to label them with a diagnosis that could mean that they would have lifelong concerns, if that’s not a diagnosis that they truly have. And then also, if patients do end up having concerns for PCOS in the future; that this is an ongoing concern and it does end up being a more multidisciplinary approach that we would like to have throughout their lifetime to help them with all of these things from both the metabolic side, the gynecologic side and that sort of psychosocial aspect that needs to be done. So, it is something that would be between both the specialty care aspect and the primary care aspect to make sure that patients are taken care of in a very well-rounded nature.

Melanie: Thank you so much for being on with us today Dr. Hoefgen and sharing your expertise explaining to other physicians when it’s important to refer, when it regards to PCOS. And please note that Dr. Hoefgen will be presenting PCOS in more detail during the October 26^th and 27^th Fall Clinical Pediatric Update for CME credits. To register, call Children’s Direct Physician Access Line at 1-800-678-HELP, that’s 1-800-678-4357. This is also the same number that a referring physician can use to refer a patient. You’re listening to Radio Rounds with St. Louis Children’s Hospital. For more information on resources available at St. Louis Children’s Hospital please visit www.stlouischildrens.org, that’s www.stlouischildrens.org. This is Melanie Cole. Thanks so much for listening.