Pape: Hi. I’m Joy Pape, Medical Editor for Diabetes in Control. And we’re here today at the American Diabetes Association 2018, Scientific Sessions. And well, I couldn’t be happier to be here with Dr. Dunaif because [of] my personal relationship with PCOS and she has taught me so much that I’m just so glad that we’re here, so she can teach the world more and tell more about it, so many people don’t know. You have a new position, so if you can tell us something about you and then I have some questions for you.
Dunaif: So, now I’m, for just about last year, System Chief of Endocrinology Diabetes and Bone Disease for the Icahn School of Medicine, Mount Sinai Health System. So, I not only have responsibilities at Mount Sinai Hospital and School of Medicine but throughout our very large network, one of the largest in the country.
Pape: Congratulations. Yes. From Chicago to New York which neither one of them weren’t too bad, but now you got the country. So, congratulations.
Dunaif: (Laughs) Thank you.
Pape: So, why is it important for diabetes care providers to diagnose PCOS? Well, first of all what is PCOS?
Dunaif: So, PCOS is an unfortunately named syndrome that’s diagnosed by its reproductive disturbances which are ovulatory disturbances. The symptom of that is irregular menstrual cycles, usually less frequent but occasionally prolonged frequent bleeding, male hormone or androgen excess, and the most common symptoms of that are increased hair growth but it can also lead to acne or occasionally to hair loss. And then there can be what are called polycystic ovarian changes, but they aren’t cysts in the ovaries. They are the normal structures that carry the eggs and they’re rested in development because of the hormone imbalance. And if we give them the appropriate stimulation, the follicles, which are what we’re calling the cysts, will mature and ovulate and there can be fertility but there is often decreased fertility with PCOS.
Pape: Is PCOS what they used to call Stein-Leventhal?
Dunaif: Yes. It was originally popularized by two gynecologists from Chicago in 1935, Stein and Leventhal. And it was a condition that surgeons really liked because they could do this surgical procedure called ovarian wedge resection where they took out pie-shaped wedges from each ovary and that would lead to improvement in the syndrome and ovulation, so it was a hormonal disorder imbalance that was correctable by a surgical procedure. And it really remained in the realm of gynecology until the early 1980s when it became recognized that women with PCOS had insulin resistance and an increased risk for diabetes. And that sort of goes to the question that you led off with, “Why should we know about PCOS as diabetes care professionals,” and it’s because it’s a major risk factor for type 2 diabetes.
Pape: And what’s the prevalence of diabetes related to PCOS?
Dunaif: Well, women with PCOS — and there have now been several very good population-based studies, one from Australia was just presented at this meeting, and they show that the increased risk is about four-fold and that it’s at a much younger age. So, in women 18 to 44 about 20% of type 2 diabetes is probably PCOS related if you do the math, then the population rate starts to increase. But I think what’s very, very important as we’re looking for ways to prevent diabetes is here’s a group of women with symptoms that can lead to diagnosis of PCOS just as they start to have their periods, so we could start diabetes prevention in young teenage girls and really improve outcomes. And I think that’s why it’s critically important to understand more about PCOS related diabetes.
Pape: And so, what causes PCOS?
Dunaif: What causes PCOS? Well, we know now that there’s an important genetic susceptibility. In fact, about — if you have a sister with PCOS, about 40% of women with a sister with PCOS have some form of the syndrome, about half of those sisters have the classic syndrome with the irregular periods and the high androgens, but the other half have high androgens. And so, 40% of sisters of women with PCOS having the syndrome is a really important risk that should lead to screening of families when we see a woman with PCOS. There have now been several big genome-wide association studies for mapping genes. And a number of genes have been found in PCOS of Chinese ancestry and of PCOS of European ancestry. And there’s a very interesting study where they use women who participated in 23andMe, who self reported PCOS and they have some of the same genes that cause PCOS in very well-diagnosed women. So, I think that women often by going on the internet are able to make an accurate self diagnosis with PCOS, which makes it all the more ridiculous that physicians say it’s difficult to diagnose and they can’t do it themselves.
Pape: Yeah. Which brings me — I remember something you taught me years ago was you said this could be a misnamed disease, if you want to call it that. And I remember asking, when you talk about the family and doing genetic testing, I remember asking you — because of learning that a lot of these symptoms were also in males in my family. And I remember you saying that you — I looked into studies and a lot of the men died early, we couldn’t really get the studies done, that was years ago. Now, I know we don’t have time to in this interview, but it’s something to look into. Is it insulin resistance in women? Is it — you were saying, is does it go beyond women. And when you’re talking about family, that brought that to mind.
Dunaif: Just briefly the men do have increased insulin resistance, increased risk of diabetes and metabolic syndrome, so it’s not for women only.
Pape: So, you can answer the question, is PCOS difficult to diagnose? I know a lot of people say it is. What do you say?
Dunaif: It’s really very easy to diagnose. The symptom of infrequent menstrual periods, eight or fewer per year, six or fewer per year. Women are aware of that. It’s a big deal when you miss a period. And so, women can really accurately self record their menstrual frequency. And 80% of women with that symptom, six or eight or fewer menses per year turn out to have PCOS just on a single blood test. So, it’s not that you have to repeat blood tests or there’s any difficulty and that’s just an elevation of testosterone or free testosterone, so in that group it’s very easy to make the diagnosis. Most women who have increased hair will turn out to have PCOS 80% or 90%. So, it’s not difficult at all. I think what’s happened is physicians say, “Oh, it’s such a complicated and heterogeneous disorder,” I say that’s the dark and stormy night of the field — PCOS as a complex and heterogeneous disorder that, oh, no, they can’t diagnose it, and yet the women are going online and reading the symptom online and saying, “Gee, I think that’s what I have.” And they’re right most of the time.
Pape: Mm-hmm. So, what other tests are needed to diagnose? What you’d mentioned? Do you do any other testing?
Dunaif: So, we do the testosterone, the total, and what we call, the best one is the bioavailable. And it makes a difference how that’s done, there’s now a wider standardization of the high quality method which is liquid chromatography, Tandem Mass Spec. And that the CDC is now requiring laboratories to do that and providing standards. And then, we mainly have to rule out other conditions. And the conditions that we rule out are pituitary conditions, though they’re really very uncommon, but high prolactin, thyroid conditions, again, very uncommon presenting as PCOS but inexpensive to exclude. We make sure that the ovaries are functioning normally, that there’s no premature ovarian failure, and we make sure that there’s not an inherited condition of the adrenal gland production of male hormones, 21 hydroxylase deficiency, but again that’s uncommon except in certain ethnic groups. So, most of the time it’s PCOS.
Pape: And so, what’s the best test to screen if you were random screening?
Dunaif: So, well done testosterone, a total, and a free, because 90% of the time it will be some measure of the free testosterone. And by that we mean the testosterone that’s not bound to sex hormone-binding globulin, it’s either circulating free or it’s weakly associated with albumin. And that’s very easy to do if you measure the total testosterone and the sex hormone-binding globulin. You can Google free testosterone calculator, and you plug your numbers in, and it just by the equations and mass action laws will calculate for you what’s free.
Pape: So, I think you’ve answered this question, but does someone need to obtain an ovarian ultrasound to make the diagnosis of PCOS?
Dunaif: Absolutely not. What I call the endocrinologist form of PCOS , the old NIH criteria, and that’s the women with the irregular, infrequent menstrual cycle and the high androgen levels, and that’s the form that’s associated with the increased metabolic risk. The women who fall into the other diagnostic criteria, the so-called Rotterdam Criteria, which include women with polycystic ovarian changes on ultrasound and high androgen levels or polycystic ovarian changes on ultrasound and irregular periods. Both those other groups don’t have increased metabolic risk or if they do it’s very slight. So, when we’re talking as diabetes health care providers about the form of PCOS that we should be worried about, it’s the old classic NIH PCOS that’s easy to diagnose without an ultrasound.
Pape: So, if women with PCOS don’t have ovarian cysts why hasn’t the name changed?
Dunaif: Well, there was a conference at NIH in 2012, very similar to a consensus conference where all the scientific evidence is presented to an expert panel of individuals who know the topic area, like Bob Rizza was the Chair of the Panel for diabetes, OBGYN, cardiology, general internal medicine. But they can’t be doing research in the field, so they’re not biased. They heard the evidence and their statement was, “The name PCOS is a distraction and should be changed because there aren’t cysts. And that people fighting over what the ovaries look like keep them from addressing the important parts of the syndrome.” And it also keeps kind of mainstream health care providers, internists, primary care doctors, they think, “Oh, this is just an ovarian disorder. It’s not something I should care about.” So, I think it’s really a disincentive to physicians being interested in the field. There’s been an international effort to try to change the name. And interestingly we got pushback from patient advocates who felt they wanted to participate and we have polled them and it’s about 50/50. They don’t like the name but they’re not sure what new name they want, but I think they don’t quite understand some of the other aspects that we as physicians understand, that who’s going to be interested in a condition is very much determined by what it’s called and how it’s going to be coded, where it’s going to go for funding at NIH is determined by the name. So, I think if they had a more appreciation of that they’d be more supportive of names that kind of carried the metabolic implications in the name and one of the names that’s very popular as an alternative is Metabolic Reproductive Syndrome or MRS, which does sort of encapsulate what is going on.
Pape: Interesting. Well, I feel like we could go on and on talking about treatment, identification, so I’ll ask you this one thing and maybe next year we can get back together with more. And that is, so what would you tell clinicians? You got someone come in their office, what should they be aware of? What happens if they do think the woman does have PCOS? What’s the next step?
Dunaif: So, I think the message to get out to all physicians is that menses are a vital sign and they should be doing a menstrual history in any reproductive aged woman because if the menses are absent or irregular that’s a sign of an underlying hormonal disorder, usually PCOS, but it occasionally can be ovarian failure or hypothalamic amenorrhea, and both the latter two are characterized by insufficient estrogen which can put you at risk for bone loss. So, they need to take that history. They can absolutely do the evaluation for PCOS. They can send the testosterone. But if they’re not comfortable, they can refer to their colleagues who are endocrinologists to have the individual further evaluated and screened for diabetes. And I think there’s growing awareness that we really need to do the two-hour post-challenge glucose, not just the hemoglobin A1C. So, absolutely easy for any health care provider to do the testing themselves, but certainly if they have an index of suspicion and they don’t feel comfortable, they can refer.