Are you referring your polycystic ovarian syndrome (PCOS) clients for exercise interventions? If so, are you familiar with the evidence around what exercise, movement and lifestyle interventions are of the most benefit for women with PCOS?
As a clinician and researcher Professor Nigel Stepto is an expert in this field and was part of the team developing the evidence-based Australian and the soon-to-release international guidelines for the treatment of PCOS.
In today's podcast we delve into the many drivers of PCOS, the role of exercise and diet, and how they can affect both the physical and biological markers, as well as psychological and psychosocial aspects of PCOS patients.
Professor Stepto is a key note speaker at the forthcoming ATMS Symposium on PCOS in September 2018 where he will share the new international treatment guidelines together with information aimed at helping more health professionals embrace exercise and lifestyle interventions as cost effective measures to improve quality of life outcomes for PCOS sufferers.
Covered in this episode
[00:50] Introducing Prof Nigel Stepto
[01:35] Getting into PCOS and exercise research
[02:51] What's causing the increase in PCOS diagnosis in Australia?
[04:59] Polycystic ovaries vs. the syndrome?
[07:45] Inflammation: cause, or effect?
[08:59] Exercise as medicine in PCOS
[14:18] Quality of life: the psychological or psychosocial aspects of PCOS
[16:43] What is the best exercise for PCOS?
[21:17] Dietary considerations for PCOS?
[23:47] Measuring blood glucose: clinical vs. research options
[27:07] PCOS requires a team-based approach to care
[29:50] Forthcoming ATMS PCOS Symposium - September 2018
SPECIAL THANKS TO:
Joining us on the line today is Professor Nigel Stepto who completed his studies at the University of Cape Town, South Africa before completing his PhD at RMIT in Melbourne in 2002. He joined Victoria University in 2007 after working at Monash University. His current research focuses on the role of exercise on health outcomes in people with chronic diseases. Including polycystic ovarian syndrome, looking at intermittent fasting and HIIT training, and caring for women with the ActiV4her© program. And I warmly welcome Nigel to FX Medicine today, how are you?
Nigel: Good, thank you. Thank you for chatting to me today, Andrew.
Andrew: Now, I think right from the top, I need to inform our listeners that you'll be speaking at the ATMS Symposium in September 2018, in Sydney.
So let's delve into polycystic ovarian syndrome and the physiology or pathophysiology that happens during that condition. But first of all, I'd like to delve a little bit into your career, what sparked your interest to study polycystic ovarian syndrome?
Nigel: This is probably a very unique situation. I happened to just finish off a lecture and was talking to one of the young students who was chatting about her challenges with a condition that I'd never heard of called polycystic ovarian syndrome. And was telling me that she believed it was all about her metabolism. So we got chatting. And from that we essentially or I essentially thought it was a very simple condition. And the simple answer would be to throw in some exercise and maybe to do some hard exercising in treating the condition.
And from that conversation stemmed a very long research career. So it's now been about 15 years since my first research project looking at exercising polycystic ovarian syndrome and also trying to understand the pathophysiology of the condition.
Andrew: I hear what you're saying about you’d never heard of it, because I can remember when I was nursing, it was so rare. It was something that you really rarely heard of. Indeed, I don't think I'd heard of it in nursing, I think was after? And then since then there's this explosion. So I've got to ask straight off the bat, is it an explosion of the condition with Australia becoming fatter? Or is it that we're more attuned to looking for it nowadays?
Nigel: I would say it's a combination of both. But I think it's more likely that we're starting to understand the condition better and understand the challenges that some women struggle to lose weight or having infertility concerns. So we start to look a little bit deeper. So I will preface this that I'm an Allied Health worker, so I'm not really into the diagnosis. But in my understanding of the experiences of many of these patients, is it can be a long and tedious process. Often general practitioners may not understand the condition or, as you say, may think it's a rare condition or something they've never heard of.
So in conjunction with some colleagues I'm working with, particularly at Monash University and Adelaide University. We embarked on, or I helped them embark on exploration into polycystic ovarian syndrome. And that resulted in the development of guidelines in about 2011. Which basically helped certainly in the Australian context, diagnosis and understanding the condition and recommended treatments as we understood them back in 2011.
And the good news is, is that sometime later this year, there will be a new series of guidelines which are now international guidelines, which will now help practitioners and women and anyone interested in the condition to firstly understand it and secondly improve diagnosis and treatment of the condition.
So it is, as you say, traditionally rare. But if we do the figures now, we're looking particularly in Australia, around a million women in Australia will have polycystic ovarian syndrome. Be it a mild phenotype right through to the more extreme end, more clinically visible form of PCOS.
Andrew: Well, I’ve got to take first my hat off to you and the group that you've been researching with, for writing, firstly, Australian guidelines and having input to the international guidelines. Well done. That's good stuff.
Could you take our listeners through a brief recap of what happens in polycystic ovarian syndrome as opposed to polycystic ovaries? What's the dysfunctional physiology? Or are they just totally separate?
Nigel: Well, polycystic ovaries are actually a symptom of polycystic ovary syndrome and is often required as part of the diagnosis.
So women can have, and quite often do have, cysts on the ovary and maybe a couple of cysts and will get diagnosed with some form of polycystic ovaries rather than the syndrome. The syndrome is far more complex, involving a lot more hormonal imbalances. And currently we understand that it's mainly around the reproductive hormones, particularly androgens or testosterone. So you have an elevated level of testosterone and free testosterone which then ultimately obviously impacts fertility.
But underlying that, there is this complex interplay of insulin or insulin resistance which is often measured as a hyperinsulinemia. So very high insulin levels and they have an interplay which essentially creates this complex syndrome with a very complex, and I suppose heavy burden of disease on the people who actually suffer from PCOS and the people who are trying to help treat them. And that can be anything from subfertility, menstrual problems, through to high risk of type 2 diabetes, insulin resistance. And unfortunately, some of the clinian’s tend to classify them as having metabolic syndrome on top of polycystic ovarian syndrome. So, some of these poor girls actually end up with two syndromes when realistically they only have the polycystic ovary syndrome.
Andrew: Ahh, now that's something that I'd group together. So where are we going wrong there?
Nigel: Well, we don't have the exact evidence at the moment. But I think in the more extreme phenotypes of PCOS, there is an underlying metabolic condition that is specific to PCOS but similar in nature to metabolic syndrome.
Nigel: So some clinicians may actually say that PCOS is metabolic syndrome for women. But it is absolutely separate from that. And the interesting evidence is that there isn't this increased risk of cardiovascular disease that you would expect. Which is higher with PCOS...than you might expect if there was metabolic syndrome in PCOS. So I think the metabolic dysfunction that is classified as metabolic syndrome is more likely just a component of the disease.
Andrew: Is inflammation, like this unresolved inflammation, this background inflammation, this sort of evil emperor which blocks leptin and other brain signaling chemicals. Is that a reasonable target? Or is this artifact? Is this maybe a just a marker of what's going on, rather than a target to approach?
Nigel: This is very good question and obviously in some spaces when we can get fancy anti-inflammatories and purchase all the wonderful over-the-counter drugs tackling inflammation.
From our, or from my understanding within PCOS and certainly from the evidence that's out there that this inflammation that's associated with PCOS, like most chronic diseases, is potentially impacting the disease and making some of the burden of disease worse. But the reality is, it's probably more a marker of it, and having some impact, as inflammation would, on various metabolic markers and metabolic processes. But it's not the cause of PCOS. And it's often been found that resolving inflammation really doesn't change many of the clinical features of the disease.
Andrew: Got you.
Nigel: But certainly, it's something to monitor, and if it does get out of hand, does need to be treated.
Andrew: But then I guess you've got to tease apart, you know, what you're targeting, what you're actually going to intervene with. And traditionally, it's been, you always have to intervene at the weight part, if you like, of the cycle. But then there's a lot of ladies that don't have a weight problem. That maybe they're going to run into that issue in the future. But they don't, at least at this stage, have a weight issue.
So where then, if we've got a hormonally-driven issue, plus or minus a sugar metabolism issue, where do you tease that apart and where then do you intervene?
Nigel: That's a really good question and often it's a really hard component to tease apart. And I suppose as my background indicates, I'm a big advocate of ‘exercise is medicine’. I'm also a big advocate that we need to set health goals that aren't necessarily about weight loss. There needs to be about other health markers.
So things like feelings of wellbeing are obviously a good marker. Rather than going for huge weight loss on the scale, rather go for and changes in waist circumference. So if people's pants start to get...particularly in these girls and from our experience, if they start to lose...they don't necessarily lose body weight, but they do tend to lose a lot of girth around their waists and their pants start to fit them better or start to get loose if they're doing exercise for a long period of time. So that is obviously one way to look at it. In exercise, irrespective of the state of weight or whether you are able to lose weight easily or not, will always have major health benefits for the person.
But I will preface that in saying that someone with PCOS may indeed need weight loss targets.
Nigel: And I would suggest that it's an integrated approach. So it's not just about either doing lots of exercise or just doing diets. It’s about doing do a combination of both. That's going to be probably the most effective form of treatment.
Yes, obviously there's some medications that people can take, but I certainly would say that in our current guidelines from 2011 and I think our international guidelines which I’m on embargo to say anything about, have similar recommendations around pharmacotherapy being sort of second line if the lifestyle therapy isn't targeting those areas.
So I wouldn't be able to tease out a specific mechanism of why they have such high weight gain or whether that weight gain can be stopped. But certainly through appropriate lifestyle, we can have major, major impacts for these girls.
Andrew: Okay. So I just want to clear this up in my mind. So you're saying that they won't always have a reduction in the metabolic, or let's say, hormonal disruption, even if they lose weight, there needs to be some other intervention. Is that what you're saying?
Nigel: That's one way of interpreting it. But from our experience that if they lose some weight, or undertake exercise, they do have a change in their hormonal structure but it's not something that they may see on the scale or measurable unless they're doing some sort of clinical marker measure.
So the androgens do go down. Some of the reproductive markers...there's a hormone called anti-mullerian hormone which is a marker of reproductive capacity. Does actually change with exercise, in a favorable direction, to help with fertility. And then obviously insulin resistance does actually...particularly in the overweight girls, does actually improved quite substantially. Just with lifestyle and definitely with exercise.
Andrew: And what about the cyclical mode, if you like, of hormones. You know, like hormones aren't static. So we've got the periods in this instance to think of. Are you talking about a normalisation overall, of their periods?
Nigel: I would be hesitant to use the word ‘normalisation.’ But I would say we do improve menstrual cyclicity. So those hormones, the progesterones, estrogens, follicular stimulating hormone, luteinizing hormone… will go back or return to a more normal phase or pulsatile activity. We don't necessarily normalise it to someone who doesn't have a PCOS, but we do improve it to the extent that it can help induce fertility and allow conception as well.
Andrew: And then obviously I guess you've always got to bring this back to, you know, practically assessing this on an ongoing basis. You can do blood tests and things like that. But do you often use things like, for instance, women using their ovulatory diary and things like that just to track potential benefits? And then you might concern them with biochemical markers and more, you know, let's say, invasive investigations.
Nigel: Certainly from a research perspective, we definitely would head for the clinical markers. But from a practical clinical standpoint, a menstrual diary would be very, very useful. Because many of these women can maybe potentially only have four cycles a year. Maybe even two, depending on how bad the condition is.
So if the menstrual cycles improves, that definitely helps. Obviously, there are some over-the-counter type measures that people can use for ovulation these days as well. So that that's another way of monitoring. And certainly I think monitoring waist circumference either using a tape measure or just how clothes are fitting definitely helps.
And the one factor that probably we don't talk about, is… it’s not necessarily consider pathophysiological, is quality of life. So how you're feeling or how depressed are you and things like that. You can start looking at some of those or the questionnaires or tools to see how women are actually feeling. It's not just about the physiology as well.
So probably shouldn't separate out the psychological, or psychosocial issues with PCOS. Because these women do tend to have higher levels of depression and anxiety. So things like...certainly exercise through various mechanisms across a whole lot of conditions, really improves that feeling or improves depression scores and anxiety to some extent as well. So very, very great interventions.
Andrew: There's obviously things like the DASS assessment scale, which is more psychological in its focus, but you've also got quality of life scales. Which ones do you prefer? Which are more maybe appropriate to women?
Nigel: That's a very interesting one. It sort of depends on the context. Now, we've certainly used a DASS scale in our research. It is something that can be used in a clinical setting relatively easily. So it's definitely a good measure of, at least stress, anxiety, and depression. But there are other quality of life scales out there. There's a plethora of them. I think the trick would be, is to make sure if you choose one, that you're using one that's easy to interpret and is meaningful to the patients.
So anything from, let's say, SF-36 right through to the DASS, I think there's a few others and my psychology colleagues will probably not be too happy with me forgetting them. But they're out there and my advice would be is if you do use them, they're really useful but just make sure you stick to the same one with the same client and monitor their changes.
Also, there are specific tools for PCOS. There is PCOS health writer quality of life questionnaire out there as well. It's probably a bit more of burden for a clinical tool. But certainly in research it's been quite useful to actually tease out some of the PCOS-specific health-related quality of life issues.
So for me to recommend a specific tool would be really difficult, but certainly very useful and very helpful if that's a major concern for a client that you're treating with PCOS.
Andrew: Now, you mentioned you're a fan of exercise and there's so much controversy over which exercise. So you've got HIIT, you've got cardio, you've got your circuits and everything like that, strength training, which is best?
Nigel: That is the million dollar question. And all jokes aside, I'll say that we're looking for research funding to actually answer some of those questions in a big, national, randomised control trial over the next few years.
But the answer really is at this point in time, and the evidence is certainly backing us up, is that any exercise for any duration, is better than nothing. It might be...I'd rather recommend an exercise that someone will enjoy, they find enjoyable, will go back to, it will be challenging for them. And more importantly, if they get bored of that exercise to try something else. And it doesn't matter whether people decide they want to go swimming, whether they want to start jogging and running, joining a walking club or an outdoor exercise group or anything really, just to keep them moving.
But in terms of what would be really great? Is could we find the most appropriate exercise program for women with PCOS. And certainly from the clinical data and from some of our earlier research, we do find that women with PCOS in the context of exercise-only, do need to work a lot harder than, say, a woman without PCOS, to get any sort of clinical benefits on PCOS. But even if they're not getting big, huge changes in those clinical benefits, just undertaking some exercise has huge health benefits. And particularly around health-related, quality of life and depression and anxiety.
Andrew: There's a real link here between what I'm seeing between polycystic ovarian syndrome and let's say, prostate cancer. In that once you're dealing with the androgens, you really must incorporate some brisk exercise. Whatever that be, it seems like you're really pushing uphill.
So I guess where I go here, like, I'm so glad that you mentioned enjoyment. Because we know from all the trials that people very commonly embark on this sort of New Year's resolution and very quickly fall off the wagon. Same with weight gain, they quickly lose it, they'll get into their dress size, but then a year later or two years later, they’ve regain that weight plus some.
I was also very interested in reading a paper a few weeks ago, and it spoke of athletes… basically not an addiction, but that the opioids that were released from high intensity exercise was short-lived and so it required another ‘hit,’ if you like, of exercise.
So, you know, I'm wondering if you see a difference in women that may be embark on the more socially-orientated exercise like walking in a group, versus the hardcore weight training, gym, meat-head type lifting-like exercise...forgive me, not lifting, necessarily.
Nigel: That's actually an interesting question and it's one I hadn't really considered before. But certainly from the women that we see particularly in our exercise trials, they do really enjoy sort of, the higher-intensity exercise. A little bit more than your standard cardio exercise.
But I think it's really hard, particularly at this point, without the evidence to say, you know, please always women will respond differently or have different enjoyments. I still think it's very much an individual and personal choice. And I think there's not an underlying, dare I go there, genetic background that might predispose people to enjoy and respond better to different types of exercises. And I think that's probably where we need to go at the end of the day. I think, just doing something. So then going back to the mantra of exercise is medicine or movement is medicine, really is probably the best way to go at this stage without that really clear evidence to say which exercise is better.
And the most important thing, and to go back to it, really is find something people enjoy. Don't just recommend them to go the gym and lose weight. I think that a lot of GPs do that and I think that really is not helpful in treating patients. Because it's not just simply go and exercise and lose weight. It's a very complex condition that's an interplay between the pathophysiology and the psychology. So we really need to think about what we say to people before we recommend things like that.
Andrew: Very wise words. Not just...I’ve got to say I'm going to steal that mantra, "movement is medicine." I love it. What about various diets? Is there any evidence or what do patients report?
Nigel: That's a good question and I will preface my response in that I'm not a dietitian. I have published with a couple of really good dietitians the evidence-based guidelines from 2011. And the bottom line from that evidence really was that it doesn't matter what diet you actually go onto. You can do the Mediterranean diet, you can do whatever you want that you can sustain, as long as there's caloric restriction.
So jumping on fad diets is probably not the best way. I'd almost recommend getting advice from a nutritionist or dietitian who will engage with the client, who understands what they're about and is not trying to put them on some fancy drink or diet that they need to do. I think it's a slow process and it's...again it's another individual process and at this stage there's no one diet that's better than another.
Andrew: And what about those drivers of hunger? You know, I mentioned earlier that sort of the brain signaling chemicals. We're all quite versed in leptin but there's leptin resistance in obese people.
I shouldn't categorise all PCOS as being obese. But people with weight problems very often have this sort of leptin resistance but there's a myriad of other chemicals as well. And there's a lot of drivers of hunger, not the least of which are physical. So how do you overcome that issue of hunger particularly when you're looking at dietary interventions?
Nigel: Again that is a very good point. And I think there is a little bit of evidence that women, particularly overweight women with PCOS, do have more hunger drivers. And they do tend to eat more healthfully but they will tend to eat greater quantities.
So you do raise an interesting question around those hunger drivers and the current information I have, in my understanding of it, is there isn't really an answer for that at the moment. But certainly, those very low-calorie diet where you have hunger suppression going in there can be quite useful if that is a major driver of the actual nutritional excess caloric intake. But it doesn't seem to be, from my experience and from my understanding of the literature, seem to be the main driver of weight gain within PCOS. There are a myriad of interesting and complex physiological processes going on there, not just from the hormones.
Andrew: Yeah. And you've been studying the euglycemic clamp, which is obviously only really available in a research setting. But can you explain this to me? I remember Dr Mark Houston explaining this with regards to, you know, pre-diabetes and diabetes. But can you explain this and the relevance to glycemic control and even cardiovascular risk for our listeners please?
Nigel: Oh, certainly. So the clamp you're talking about, the euglycemic hyperinsulinemic clamp is considered the gold standard to estimate what we call insulin sensitivity. So how well the body will respond to a particular insulin dose.
So it's quite a slow and relatively simple procedure but it does take about two to three hours. Where essentially we take an insulin dose normally anywhere from 40 milliunits of insulin to anywhere up to 80 milliunits of insulin. And we infuse it at a constant rate to get the insulin levels nice and high. So that's around about the insulin level you might expect after a meal. And then at the same time, what we do is we do what all a variable infusion of glucose solution or a blood sugar solution. And that we manually adjust that so that we keep the blood sugar at around about 5 millimoles of glucose.
Andrew: Right, so at the upper limit.
Nigel: Yep, so I tend to call that "middle healthy limit."
Andrew: Oh, "Middle healthy" is it? Right. The 5.5 is the upper... Is that right?
Nigel: Six millimoles is normally around your pre-diabetes. Six, six and a half is normally where you start to look at... certainly at the fasting level, start to look at the clinical pre-diabetes and things like that.
So we do that over a few hours and the more glucose that we have to infuse over that insulin clamp, the more insulin-sensitive you are. So someone...and to put that into reverse. Someone who has a high glucose infusion rate will be more insulin-sensitive and not have insulin resistance, and their body will be sensitive to that hormone. And the predominant tissues would be...so predominant organs will be your liver, your muscle, and maybe some of your fat that respond to that insulin that we infuse.
From a clinical perspective, the next-best way to assess that and where you actually assess more an insulin resistance is using the oral glucose tolerance test. Where you see how much insulin and how high the glucose goes in response to a 75 gram dose that you drink, which is a more clinical way of measuring that.
Nigel: And that then, I think too...there's some set clinical values around a two-hour glucose levels that will define whether you have insulin resistance, or normal glycemic control or type two diabetes.
And the oral glucose tolerance test is probably a better measure in women with PCOS. At least it seems to unveil any form of insulin resistance which might not be present at rest.
Nigel: So that's why we tend to use the clamp or the oral glucose tolerance test, more in a research setting.
Nigel: Because they're obviously quite...giving the oral glucose tolerance test is quite cumbersome, a cumbersome clinical assessment.
Andrew: Now, you mentioned a few red flags that practitioners need to be aware of. Like for instance, just passing people off to say, "Go and lose some weight, go and do some weight training" and things like that. It's really not giving full appreciation of the complexity of polycystic ovarian syndrome.
What red flags do you really...would you please urge people, practitioners out there to be aware of, that you see people are doing wrong?
Nigel: Basically, it's probably very hard for me to make a call on diagnosis and the practices of general practitioners as I’m only an allied health professional.
But certainly, there's a few things that are quite important, particularly if young women, particularly those going into puberty are having weight loss problems and they're not losing weight via the usual treatments or approaches that maybe there should be some investigations into polycystic ovarian syndrome. But appreciate that it's quite difficult to diagnose at that pre-pubescent or puberty phase. Understand that the diagnosis may only occur post-puberty.
I really think...there are really no flags, I think each particular patient needs to be treated as an individual and go through the most appropriate steps.
And I do know that there is still a lot of education needed around...an engagement with general practitioners to really understand PCOS. And also other allied health practitioners as well to actually understand it and make recommendations that are appropriate to each particular client.
If it's weight loss that's needed, then the approaches around that. If it's fertility, again, approaches around fertility really should be done. And it should be done in a team-based approach with a patient-centered focus. So in other words, the patient really...what their needs are, guides, how that treatment goes. It really is a team effort. So it's everything from their general practitioner, their allied health practitioners, nurses, psychologists, exercise physiologists, gynecologists, endocrinologists. Whomever's the most appropriate for them in the team.
So in terms of red flags, I probably don't have any just that if you do have a difficult client and it does look like a weight issue or metabolic issue and potentially some irregular cycles. Or in some cases, there may be some inappropriate hair growth and associated psychological distress with that. They should be treated accordingly. And hopefully work with the patient as best they can. And obviously take an opportunity to engage in as much education as one can around what polycystic ovarian syndrome is, and the fact that it's not a rare condition, it is actually quite common.
Andrew: Nigel, without giving too much away, you'll be speaking at the ATMS Symposium in September in Sydney. What do you hope the delegates will take away from your talk? What are you hoping to concentrate on there?
Nigel: I'm hoping to obviously enlighten the delegates about the role of exercise as a therapy for PCOS. Provide some information around the evidence-based guidelines which I will be able to share the latest version of them with the delegation. And hopefully enlighten the delegation to engage in team-based treatment plans around PCOS. And to think… to acknowledge and embrace lifestyle as a really good and probably a cost-effective therapy for people with PCOS.
Andrew: I've got to say, for our listeners, everybody please, go and look up Nigel Stepto at University of Victoria. Sorry, Victorian University, that's the correct vernacular, isn't it?
Because your references that I've looked at previously, there's a couple of great ones like, What Doesn't Kill You Makes You Fitter, and also the Physical activity and mental health in women with Polycystic Ovarian Syndrome. And there's some really great articles there, so we'll done.
Nigel: I'm glad someone enjoys them. I'm pretty sure people read it.
Andrew: Well, look, I think one of the best things as well is that they're often full versions of those so that people can actually learn from them, rather than just a little abstract, which doesn't give you really insight into what the research is really doing.
Nigel: Thank you.
Andrew: Professor Nigel Stepto, I cannot thank you enough for, I’ve got to say, enlightening me. You know, there's a few things I need to really look into further, you know, to educate myself about polycystic ovarian syndrome. Because I think my mind is way back about 10, 15 years ago, and I really need to catch up. I'll certainly be at the ATMS event, and I'll hope to catch up with you there.
Nigel: Look forward to that Andrew.
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook.
|Professor Nigel Stepto|
|CRE PCOS: Evidence-based Guideline for the assessment and management of polycystic ovary syndrome (PCOS)|
|The DASS assessment questionnaire|
|ATMS Event: PCOS Symposium|
Levinger I, Shaw CS, Stepto NK, et al. What doesn't kill you makes you fitter: A systematic review of high intensity interval exercise for patients with cardiovascular and metabolic diseases. Clinical Medicine Insights: Cardiology. (2015):9 53-63.