The Root Causes And Treatment For PCOS

Mark Hyman, MD

Full Transcript

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Introduction: Coming up on this episode of The Doctor's Farmacy. Dr. Heather Huddleston: I think a lot of patients with PCOS sort of end up getting bounced around to different doctors, never really getting great explanations about what's going on with them and what are sort of some appropriate treatment pathways for them. Dr. Mark Hyman: Welcome to The Doctor's Farmacy. I'm Dr. Mark Hyman. That's Farmacy with an F, a place for conversations that matter. If you struggle with hormones, if you've had something called PCOS, or known someone with it, or know anybody with infertility, or acne, or irregular periods, this podcast might be quite interesting for you because we're going to discuss polycystic ovarian syndrome, a really common problem that affects so many women, maybe 5% to 10% of women in America and around the world. And we're talking to an expert in PCOS, Dr. Heather Huddleston. She's a professor of OB/GYN and reproductive sciences. She's a specialist in reproductive endocrinology and fertility and cares for people with a whole bunch of reproductive and fertility issues. She's really interested in PCOS, polycystic ovarian syndrome, and other things like recurrent pregnancy loss, uterine disorders. She is the founder of the USCF Multidisciplinary PCOS Clinic and Research Center. That clinic provides care with an integrated group of doctors and providers with expertise in reproductive endocrinology, dermatology, nutrition, I love that, and psychology. She also does a lot of research. She has programs on how we can understand exercise, depression, cognition, sleep, metabolic health, and how all that affects PCOS. She's taught all over the place. She's published in major journals. And she's a graduate of Harvard Medical School. She's done her OB/GYN and fellowship in reproductive endocrinology at Brigham Women's Hospital in Boston, and she's worked at UCSF since finishing her training in 2005. And I actually did a UCSF residency at Santa Rosa in family practice, so we have that in common. So welcome, Heather. Dr. Heather Huddleston: Thank you so much for having me. Dr. Mark Hyman: All right. So I did a little bit of a clip on PCOS on my podcast, and it caused a lot of discussion and a lot of controversy. And everybody's got opinions. And like many things in medicine and in life, it's not black and white. There's many layers to this conversation, which we couldn't really address in that short clip. And I discussed something that is a huge factor in women's health, which is insulin resistance and weight gain, which often interfere with hormonal function. And yet, that's only one piece of the puzzle. It's not all about diet. And we're going to talk about PCOS in general. We're going to talk about what factors cause it, how to treat it, and how obviously also nutrition plays a role. But I'm really, really excited to talk to you about it. And let's just get started by talking about how common this is. About 5% to 10% of women who are of childbearing age have this and it's a really important cause of infertility. Walter Willett at Harvard had wrote a book called The Fertility Diet, which is a lot about this. It's also the most common hormonal disorder in premenopausal women, yet often the cause of it and treating it is not well understood by most doctors. So tell us a little bit how PCOS has sort of been the neglected stepchild of medicine and OB/GYN, and how we can kind of correct that. Dr. Heather Huddleston: Yeah. I think it's a great question. I think it's a somewhat complicated disorder in the sense that it brings in a lot of different systems and a lot of different kind of ramifications that cross a bunch of disciplines. And I think the way medicine sort of practiced in the United States these days is it's very siloed. And there's sort of certain doctors that take care of one little specialty. And PCOS has kind of fallen through the cracks in many ways of all of those specialties, in my view. I mean, so PCOS really brings in a hormonal component. It brings in a gynecologic and reproductive component. It brings in a metabolic component. And all of those things really bleed together, not only in the pathophysiology, but also in the outcomes. And there's not really one specialty that really adequately covers those. OB/GYNs maybe know some of the reproductive piece, but they're not as always up to speed on the metabolic. Endocrinologists might know a little bit more about the metabolic piece, but they're a little nervous about what's going on with the reproductive side. So as a result, I think a lot of patients with PCOS sort of end up getting bounced around to different doctors, never really getting great explanations about what's going on with them, and what are sort of some appropriate treatment pathways for them. Dr. Mark Hyman: It's so true. And I think often doctors aren't great at diagnosing it. And maybe you can take us through what are the key symptoms that you would look for in a patient who came to see you with PCOS. Dr. Heather Huddleston: Yeah. So first of all, just to echo what you said, there's been some studies, international studies that have shown that common average number of physicians or providers that people with PCOS see before getting a diagnosis is something like an average of four. Dr. Mark Hyman: Oh, wow. Dr. Heather Huddleston: People are definitely wandering around trying to get someone to really help them. But there is an international kind of consensus at this point around the way that we diagnose PCOS, and this has sort of been developed and sort of hammered out over the past 20 years. And it looks for three things, and you really just need two of those things. So the first is irregular cycles. We mean long cycles, going every 40 days, or fewer than eight periods a year. The second component is hyperandrogenism, so either clinical hyperandrogenism, meaning hirsutism and acne, or [inaudible 00:05:43]. Dr. Mark Hyman: And hair growth, hair growth on your face, yeah. Dr. Heather Huddleston: Hair growth or a blood test just showing elevated androgens. And then the third component is features of polycystic ovaries on an ultrasound. And so those are the three components, and you just need two. And so if I have someone come into me looking to see if the things that are going on with them sort of fit within the box of PCOS, those are the three components that I'm going to look at. Dr. Mark Hyman: Typically, when I was in medical school, I remember learning that there's typically overweight women, and that's not always the case. I've actually had many patients who are thin who have PCOS and struggle with acne and hair loss and irregular cycles. So can you kind of take us down the road of: What is it besides the weight that can cause this? What are the causes? Obviously, part of it can be insulin resistance and diet and sugar and starch, but it's not the only thing. So what are the causes of PCOS? Dr. Heather Huddleston: Well, I think it's a little bit of a million dollar question. There's a lot of research trying to answer that question. It's also very heterogeneous disorder, so I don't know if there's one thing that causes it for everybody. But I think we do know that a major underlying factor is the hyperandrogenism that there's elevated androgens starting at puberty, and that may then sort of underlie a lot of the phenomena that comes across with women. So one of the things we know is that there's an increase in visceral adiposity or sort of- Dr. Mark Hyman: Belly fat. Dr. Heather Huddleston: Belly fat that happens, that we know is more common in general with men, but this is what happened when you have elevated androgens in a woman, especially starting at puberty, they lay down fat in that area. And that in women causes a lot of inflammation that then can really be a setup for insulin resistance. So there may be sort of a pathway where you see hyperandrogenism then in many people also leading to the insulin resistance. Then you start to get into a little bit of a vicious cycle because the insulin resistance in and of itself causes some weight gain, but it also can drive androgen production from the ovaries. So starting at puberty, a lot of these people get into a little bit of a vicious cycle. It's very hard, if not impossible to get out of. Dr. Mark Hyman: So what starts the high levels of androgens or the male hormones, testosterone and others? Dr. Heather Huddleston: It's a debated issue. I think that there's one component maybe that there's just ... If you look at some of the enzymes in the ovary and in the adrenal gland, there's just sort of an over-activity of those enzymes in the ovary and in the adrenal gland, so there's some thought that it's just an intrinsic overproduction of androgens. There's also, at least in some patients, we think just from the get go they have an increased LH secretion from the pituitary. This is a hormone that drives androgen production from the ovary, and so they may be set up by that even sort of in utero to have increased LH secretion. So we don't really know, but we know that at puberty, immediately these girls will often start to have much higher androgen levels than their peers. And then that sort of lays the groundwork for a sequence of events to happen. Dr. Mark Hyman: Yeah. One of the things that I've sort of read a lot about is the role of endocrine disruptors in our health. And endocrine disruptors are environmental chemicals. Years ago, I read a book called Our Stolen Future by Theo Colborn. It was sort of like The Silent Spring of its time, where she mapped out the ways in which environmental chemicals affect all kinds of reproductive functions, and whether it's sex, determining sex, or determining risk of cancers or infertility in animals and human models. How do you think environmental toxins play a role in the uptick of what seems like this increasing phenomena of endocrine disorders in women? Dr. Heather Huddleston: I think it's hard to know how much they are causative in terms of PCOS. I think it's possible. I certainly think it's definitely possible that they may exacerbate certain elements of it by interfering with hormonal function. But PCOS has been around for a long time as far as we can tell. It seems to be present at a pretty standard or set prevalence across many different countries and parts of the world, which somewhat argues against it being truly environmental. Now I do think that certain environmental endocrine disruptors or just societal patterns, especially diet, can definitely exacerbate the way PCOS gets manifest. So if you look at PCOS patients in Europe, especially 10 or 20 years ago, or in China, they tended to be much more lean than patients in the United States and have much less sort of inflammation and insulin resistance. And so there's certainly, if you have a PCOS phenotype and you put it in an environment where there is calorie excess, or limited physical activity, you are going to see potentially, at least in some patients, an exacerbation of the symptoms. But I don't know that in my view and from what I understand about this syndrome, I don't think it's necessarily caused by our lifestyle. Dr. Mark Hyman: And the nutritional part, what role does that play? Because I've had many patients with infertility who when we address the starch and sugar in their diet and treat the insulin resistance, they get better. I mean, I had a very close relative who had obesity and pretty severe PCOS and hirsutism and acne. And we dramatically changed her diet and she was able to get pregnant and have a baby. So can you talk about the nutritional aspects of PCOS and how that plays a role, and where it doesn't play a role? Dr. Heather Huddleston: Yeah. I mean, I think for sure there's evidence that in some people with PCOS, especially if there's evidence of insulin resistance, or if there's evidence of glucose intolerance, that they clearly have entered a phase where they're not processing glucose well, that if you act to correct that through diet and through exercise, and you reduce the degree of insulin resistance, you reduce the degree of adiposity, that in some of those patients, they will ovulate more regularly. They will have more successful, more healthy pregnancies. So that is certainly something that I think I always talk to my patients about when I see them, if I think that there's a window for that. There are patients, however, especially when you look at some of the lean PCOS patients, or patients who from the point of adolescence have never had regular cycles, I think it's a lot to say, "Oh, just change your diet and you're going to start ovulating." I don't think that's always the case. So I think every patient's a little different, and you need to really look at it. What I usually look at though is I want to say, "How are we going to get you as healthy as possible for pregnancy? And maybe that will help you get pregnant, maybe it won't. But I want to get you as healthy as you can for pregnancy and get your insulin resistance as much as possible under control." Dr. Mark Hyman: Yeah. How about the microbiome? Because this is sort of the era of the microbiome. And before, nobody ever thought that the gut played a role in hormones, or endocrine health, or infertility. But now it's clear that it sort of got its finger in everywhere. And we've seen studies [inaudible 00:13:15] on breast cancer, women who take antibiotics have high risk of breast cancer. We know that the microbiome plays a big role in hormone metabolism. So can you talk about what you're learning about that, and how that plays a role, and how you approach that? Dr. Heather Huddleston: Well, I think that there's definitely some really interesting research going on around microbiome and PCOS. And there's this idea that there may be a more sort of inflammatory microbiome that leads to more inflammation in the body. And we know that many patients with PCOS just have high rates of inflammation that is detectable if you look at sort of blood markers, or just even with the insulin resistance. So this is in many ways an inflammatory disorder. And so there is research going into how much of that might be driven by the microbiome, and that's a little outside my scope. It may be more your scope, exactly how that may be the case. But I think it's definitely a really interesting area for us to try to understand more how much that may be sort of setting people up to have PCOS sort of evolve at adolescence and really to exacerbate the metabolic genotype. Dr. Mark Hyman: Yeah. What you said is super interesting about the inflammation because inflammation independent of its source seems to be a trigger for all kinds of things, obviously chronic disease in many ways, but for these hormonal disorders. So can you talk and maybe unpack about a little bit more about the link between inflammation and endocrine disorders, and in particular, PCOS? Dr. Heather Huddleston: Well, I think for sure we know the inflammation may have some direct effect on ovarian dysfunction, so there are some studies showing that if you treat inflammation, you can improve sort of ovulation to some degree in the ovary. So there may be a direct effect of inflammation on the ovary. There's also a path where inflammation does drive up insulin resistance, and that's through sort of TNF alpha and other cytokines that are thought to interfere with insulin action. And we know that insulin resistance really drives androgen production from the ovary, at least in patients with PCOS, so there's definitely a metabolic sort of driver of the hyperandrogenism and hormonal dysfunction and anovulatory sort of status that we do see. And then we also know that the inflammation in and of itself has really important downstream consequences, not only in terms of cardiovascular disease, but there's more and more of a thought around depression and cognition that may be impacted by inflammation. So I do think it's really an important piece of this disorder that we want to try to get a handle on and try to treat. Dr. Mark Hyman: It's so important and there's so many causes of inflammation. It can be environmental toxins. It can be the microbiome. It can be inflammatory foods. I mean, there's so many factors that we know that are driving inflammation in our society that are just getting worse and worse. And so it might be not one thing, it may be so many different things. So can you talk about the difference between the patients you see with PCOS who would be the typical ones we learned about in medical school, who are overweight, they have acne, hair loss on their head, facial hair, irregular periods, infertility, versus the ones who are thin and exercise and don't seem to have any weight issues? Is there a different subtype? Are these the same kind of condition? How are they different? Dr. Heather Huddleston: I mean, I think that they're probably subtypes. PCOS is I think a very heterogeneous disorder. It's really just a syndrome. Right? It's a collection of things that kind of go together and sort of have somewhat of a shared pathophysiology. But it's not like if you think about something like hypothyroidism, which is very much your thyroid gland isn't functioning, you're going to have this. You fix this, it translates. PCOS is messier. And so yeah, the patient, there is a lean phenotype, we call it lean PCOS. And it's often quite different than the obese PCOS. Some of the things that may be similar is the lack of ovulation, the need for help with fertility care, so that may be a constant. The other thing that may be a constant is trouble with elevated androgens, so hair growth on the face, acne, that can still manifest in lean PCOS. But lean PCOS patients are lucky in that they're often not quite as much struggling with some of the metabolic features, although in studies where they measure insulin resistance very closely and very carefully in research settings, in even lean PCOS, they are more insulin resistant than lean non PCOS. So there is still an insulin resistance piece there, but it's sort of either genetically not as sort of exacerbated, or it may be that person has a just a very healthy lifestyle and they're able to keep a lot of it at bay. Dr. Mark Hyman: What are the consequences for people if they have PCOS? What should they be aware of? What should they know about in terms of their own health and long-term risks? Dr. Heather Huddleston: I mean, it's I think a very multifaceted disorder. There's generally sort of five or six things that I go through with patients with PCOS. So the first is menstrual cycle control, so it's important for people to have somewhat regular menstrual cycles or to have at least some sort of progesterone in their system to prevent overgrowth of the lining. There's the management of their skin or cutaneous findings with PCOS. So how can they manage their hair growth? There's fertility concerns, there's metabolic concerns, especially things like future diabetes, future cardiovascular disease. And then there's a lot of mental health disorders that we see in PCOS. Dr. Mark Hyman: Really? Dr. Heather Huddleston: So there's a high rate of depression, yep. Dr. Mark Hyman: Do you think it's a cause or a consequence of it? Dr. Heather Huddleston: It's something I've been really interested in researching. One of the things we've shown in some of our work has been a very strong correlation between insulin resistance, actually, and depression. And even when you control for body weight, and when you control for androgens, even when you control for hirsutism, so I do think at least in some of these patients that insulin resistance in and of itself may be contributing to depression. That's something we see in the diabetes literature as well. Dr. Mark Hyman: That's a frightening idea because when you look at the metabolic health of America, I think a new data came out from Tufts that 93.2% of Americans are metabolically unhealthy, meaning they have some degree of insulin resistance. And we also see this sort of epidemic of mental health disorders and depression. And I don't think people realize that sugar and starch and processed foods is driving not only weight issues, but also mental health issues. Dr. Heather Huddleston: Yeah. I think it's to me one of the more profound connections and profound concerns. And I think it's unfortunate because in some ways, that depression can often make it harder to address the diet and the exercise. If you're feeling depressed, you're not in the most ideal state to sort of make those important lifestyle changes. So I think it's important that we take into consideration what's happening in terms of a mental health milieu for patients with PCOS and take that into account when we kind of talk to them about treatment because that's an important component I think that needs to be addressed if we want them to make those important lifestyle changes. Dr. Mark Hyman: Yeah. For sure. So when you see someone with this problem, what's your general therapeutic approach? How do you treat these patients? What are the ways that we can help them have regular cycles, their acne, their hair growth, their hair loss? And I think you mentioned something really important, which is that you want them to have progesterone, which is sort of the antidote to this over build up of estrogens that happens in these patients. And they don't ovulate every cycle, so they don't make progesterone, which is what you do when you ovulate. So can you talk about what are kind of the therapeutic approaches? And how do we potentially use progesterone or other therapies like that? Dr. Heather Huddleston: So I think in terms of therapeutic approaches with PCOS, it's always hard because I think to some degree it depends on what is their goal. What are they trying to achieve? Are they trying to get pregnant at this moment or they're not? But in terms of the menstrual ... Let's say it's someone who's 22 and she's coming to me because she's only having three periods a year, and when she does it's very heavy bleeding, I want to address that because we know that when people go many, many, many cycles without ovulating, it means they don't get progesterone. And that means that estrogen is going to cause overtime buildup of the uterine lining, which can lead to very heavy menstrual cycles. But it also is a risk factor for endometrial cancer over time. So it is important that patients with PCOS get some sort of progesterone exposure. And that can be in the form of oral contraceptives. It can be in the form of bioidentical progesterone being taken cyclically. It can be in the form of an IUD that releases progesterone, so there's a lot of ways to do it. But if I have a patient who's having three cycles a year or something like that, that's an important conversation that I'm going to have. Look, we need to figure out some way for you to have progesterone because it's not healthy for your uterus to not have that progesterone over time. Dr. Mark Hyman: So that's helpful. What else do you do to help with their ... So besides bioidentical progesterone, what other kind of therapies support these patients? Dr. Heather Huddleston: In terms of their other concerns? Dr. Mark Hyman: Symptoms. Yeah. How do you deal with hair loss? Or how do you deal with the acne? Or how do you deal with the irregular cycles? What hormonal therapies are you using besides progesterone? Dr. Heather Huddleston: Yeah. So I think the irregular cycles would be addressed through some form of progesterone. But the hair loss, or hair growth, or acne, those skin findings are best addressed quite honestly by being on something like a birth control pill because you're going to suppress the sort of stimulation of the ovary that's driving up the androgens. And you're also going to increase sex hormone binding globulin, which is a protein from the liver that really soaks up that extra androgen. So that's honestly the best way to get benefit in terms of the especially hirsutism and acne. And then sometimes we'll even use medications that will block androgen action like spironolactone. Now I do have patients who don't want to go on those medications and feel like that's not fixing the underling problem and it's just patching it, or they don't want to be on the pill for a variety of reasons. So that tool is not always the ideal tool for our patients, but is certainly one that I would discuss. Dr. Mark Hyman: And what role do you see as diet? Is it a strong lever for changing thee patients' reproductive health and their cycles and their symptoms? If you basically put people on a low starch, sugar sort of diet that treats the insulin resistance, do you see big changes in their clinical picture? Dr. Heather Huddleston: I think in some, for sure. And I think there haven't been great studies on this. There's been a few. I do think that if patients are able to maintain a very low carb diet, sort of a ketogenic diet, they will be able to really manage their insulin resistance, and that really takes away one of the sort of drivers, or triggers, or things that's really exacerbating their sort of phenotype or their symptoms. So if you are able to get the patient to sort of embrace that approach, I do think that you will see that often patients will see benefits. I think it's something that has to be monitored. I don't think all patients will suddenly start having regular cycles, and their hair growth isn't going to suddenly go away. But some patients may have more cycles. Some patients may be able to conceive that way on their own without fertility treatment, but others will not. So I think it's something that I try to discuss as an option, but I think I shy away from saying, "Here's a way to fix this," because I think in all honesty, it doesn't fix it for some patients. And that's really frustrating if they feel like they're sort of somehow failing. Dr. Mark Hyman: Well, it sort of speaks to how little we know because in some patients it works, and some patients, it doesn't. You don't know which one's which. Right? And it's really about personalizing care. Dr. Heather Huddleston: Yeah. I think it's a challenge, and I do think it's one ... I mean, PCOS is definitely a disorder that just takes a lot of personalization because it's such a diverse heterogeneous disorder. The concerns and the goals are often very diverse, so I think no patient and no treatment plan quite honestly is exactly the same. Dr. Mark Hyman: Years ago I read an article in the New England Journal of Medicine about d'chiro inositol and PCOS, which was, I don't know how much you remember, but a B vitamin. Seemed very promising. It kind of seemed to fall off the radar. What is the role of that and/or other supplements in the treatment of PCOS? Dr. Heather Huddleston: I mean, I think it's still on the radar in the sense that people are using it, people are trying to study it. I think that there's been sort of mixed results in the studies that are out there. I think we're somewhat hampered by the fact that people are taking it in different sort of formulations and different ratios and different dosages, which makes it a little hard to sort of figure out whether it's working. I will say anecdotally I do have patients who seem to become more regular in their cycling when they're taking it, and they find it easier to take than other medications that might do that, like metformin. So I think that there's potential there. And I there is a pretty good study being run right now that hopefully will give us some answers. So I definitely think it's still on the radar. Dr. Mark Hyman: Yeah. And what about other supplements? Do you ever prescribe other things to help with nutrition, or with insulin resistance, or any of the symptoms? Like for example, saw palmetto is something I often use, and it's a five alpha reductase inhibitor, which is what you'd use for inhibiting androgen production for the prostate, for men for example, like Proscar or Finasteride. Dr. Heather Huddleston: I have had patients taking that. I'm curious to share how much you see as a benefit. Do you see patients really come back and say it worked? Dr. Mark Hyman: Yeah, it really depends on the individual, so some are saying, "Oh, yeah," they noticed their acne better, or it's like spironolactone. It's a similar effect to that, but it's an herbal formula. It's used for men's prostates, so it's a little weird to give it to women. I say, "Well, don't worry about the name of the product. It says prostate on it," but [inaudible 00:28:07] the mechanism action of the herb. And I wonder about omega threes or vitamin D. Dr. Heather Huddleston: Yeah. So I feel like vitamin D is really important. I definitely ... We check vitamin D in all of our patients coming in. We definitely find many, many of our patients are deficient, so I do try to get patients to sort of really replete their levels of vitamin D. Beyond that though, I would just say we really just take a pretty common sense approach to the diet and try to work with where that patient is at that time. So some people's diet is terrible and there's a lot of room for improvement. Some people already are doing a lot of the right things and you're just tweaking it. I find one of the big things that's missing is exercise. And some of our studies have shown such significant benefits for patients who are able to sort of keep that as part of their life. We've looked at sort of our patients who exercise and our patients who don't, and it's dramatic I think how much sort of metabolic benefits patients can get if they can be active on a daily basis. Dr. Mark Hyman: Yeah. That's such a key thing. And so tell us about the mechanism action. You've done a lot of research on this. But how does this work? Dr. Heather Huddleston: I think the main mechanism of action, it's probably deeper than this, but we know that just by increasing muscle mass, you're going to sort of improve insulin signaling, you're going to improve glucose uptake, and so there just seems to be a direct correlation with insulin resistance and exercise that I think is profound. Some of my patients will come back after exercising and they'll say, "I didn't really lose that much weight," and they'll be very frustrated about that. But if you look at their numbers, you'll see that their insulin levels have dropped. Their glucose levels have dropped. And so sometimes for me it's about really showing them, you are healthier. You probably gained some muscle and that's why it's not a different number on the scale, so I think that's one thing. But I also think getting back to the depression piece, there's a really often significant improvement in sort of self acceptance and in mood happens with exercise. But then I think it can translate into more energy for all sorts of lifestyle improvements. And that ultimately translates to insulin resistance improvements. Dr. Mark Hyman: Yeah, for sure. So you've done a lot of research. What are you most excited about that you're working on in terms of the research on this and endocrinology in general, and PCOS and fertility? Dr. Heather Huddleston: I mean, I think for me, my biggest interest has been around the mood. I've been interested in looking at cognition and how it's impacted in PCOS. And then another area that I've been really interested in doing more work in, and we have a small pilot study starting, is on sleep. I think sleep is often very disrupted in people with PCOS. We know there's a high rate of sleep apnea, but even beyond that, other sleep disorders. And I also think sleep is a really key thing that can help with insulin resistance. So I guess I'm really interested in a lot of these things around the edges of PCOS that we can sort of fix, to sort of improve quality of life. I don't know that I feel like I going to necessarily cure PCOS or make it not ever be a thing, but I think we can do a lot to improve the experience of having it. Dr. Mark Hyman: So would you say if you fix insulin resistance, that PCOS gets resolved? Or are there other factors that keep it going forward? If you've got someone's insulin perfect and you got their blood sugar normal, and you got their lipid profile normal through diet, lifestyle, whatever, would that kind of eliminate PCOS? Or is there still factors that are driving PCOS beyond insulin resistance? Dr. Heather Huddleston: I think there's still factors driving it, at least in most ... To the extent that it's truly a disorder of elevated androgens, you're not going to completely take that away by fixing the insulin resistance. You are going to minimize a lot of the symptoms. You're going to potentially make it a very manageable disorder by managing the insulin resistance. You're going to make it so it's not such a burden. But I don't know that you sort of can wave a wand and it's no longer there. I think that's sort of intrinsic physiology that a person was born with is still there, and you're just sort of helping them manage it better. Dr. Mark Hyman: Do you think it's partly genetic? Dr. Heather Huddleston: I mean, this is a huge kind of controversy as well in the field. So there was a lot of research that went on trying to look at these GWA studies looking at all of these genes. People had a lot of excitement about finding the PCOS genes. And ultimately, they did not find very much. They found some genes that maybe explain 10%. So there's some thought now that may have to do with sort of a basically epigenetic phenomenon, where maybe the maternal androgen levels may be driving or causing sort of changes in the fetus in utero, that then set the fetus up to sort of have a PCOS phenotype. And we know that's sort of true in animal models that you can induce PCOS by maternal androgens. So to what extent that explains it in humans, we don't know. Maybe there's this microbiome theory. So I don't know that we know. I think that there's probably multiple pieces, probably multiple genes and multiple environmental factors that maybe set it up initially, and then once it's in place, it kind of self perpetuates. Dr. Mark Hyman: Yeah. And it's such a common problem, like we talked about earlier. It's 5% to 10% of women at some level. That's a big chunk of the population, so you're probably very busy, my guess. You also created a platform, which is kind of exciting, which is ... Or an advisor to a platform, which is an all in one virtual care platform for people with PCOS called Allara Health. How did that work? And what does it provide? And how do people get supported through this process? Because a lot of this stuff that has to be done is behavior change, lifestyle change. And it's not just taking a pill. Dr. Heather Huddleston: Yeah. Exactly. A lot of times it's having a partner that you work with over time that can really sort of kind of take you step by step through the improvements you need to make. But Allara is, I think it's very much similar to what we do in our multidisciplinary clinic, but it's taking it to a virtual platform and making it available to people sort of all over the country. And so as we talked about, I think PCOS sort of falls through the cracks and there's not a lot of providers who really own this disorder. So I was really excited when I heard about Allara as just something that could sort of bring I think an evidence based approach to PCOS that incorporates things like nutrition and mental health support and can do it sort of virtually and can do it over time in a way that really sort of partners with a woman, and just improves access because I think that there's a lot of people with PCOS out there that don't feel like they're getting the care they need. Dr. Mark Hyman: Oh, millions. Clearly, millions of people have this. Right? Dr. Heather Huddleston: Exactly. And I mean, there's a few PCOS clinics- Dr. Mark Hyman: If not millions of you. Dr. Heather Huddleston: In a few cities, and there's always going to be a few practitioners who really own it and understand it and want to talk about it, but many practitioners don't. And so this is a way I think to give access to more people to sort of feel like they have a home for their PCOS, feel like someone who understands PCOS can sort of walk them through the ways to improve their quality of life, or achieve the goals that they want to achieve. Dr. Mark Hyman: So if you were sort of ... This is really great because I think it offers a forum for people to get connected to other people that have this issue. It offers guidance on how to do the things you need to do to kind of reset your system and move yourself down the path of health. From the perspective of an expert in this field, when you see a patient, just kind of take us through maybe a case before we close of what you see, maybe a few cases of how they presented. What were the different kind of findings? And what were the approaches that you used? And how did you sort of move them down the path to health? Dr. Heather Huddleston: Okay. I mean, I think I've always found that partnering with patients and being able to sort of see them somewhat frequently has been a really big sort of helpful way to kind of help them make the improvements they want to make. I think an example might be, let's say a 22 year old that I originally say, who came in, didn't know why she wasn't having periods, didn't know why she had excessive hair growth and acne. And we did a workup, we identified PCOS. We did a lot of education around PCOS. At that time, it made sense for this patient to go on birth control pills to sort of manage a lot of the symptoms. And so she went on birth control pills for a few year. But then several years later, came back, didn't want to be on birth control pills anymore, had gone off, had gained some weight, was thinking about starting a family soon. So at that point, I ran some metabolic tests and found that she was insulin resistant, and wanted her to work on that before starting to try to conceive. And so at that point, we had her sort of work with a nutritionist, or I worked with her and had her start exercising. That would be sort of the program I would want that patient on at that time to sort of optimize her health before getting ready to conceive. And then ideally, those things have then improved and then it would be time to sort of think about the different ways to help someone get pregnant. But as you said, some patients through the use of sort of diet, exercise, or other ways to improve insulin resistance may start ovulating on their own. And in those cases, they are very much capable of conceiving. PCOS is not a fertility diagnosis. It's just a disorder of ovulation. So many of those patients may be able to conceive on their own, but if not, if they're not ovulating regularly enough despite doing all those right things, then there are other ways that we can help people get pregnant by boosting ovulation through medication. Dr. Mark Hyman: For sure, amazing. One of the things you said, I just want to touch on because it's not really common, is measuring insulin. Now I never learned to do that in medical school. I almost never see insulin measured on any lab panels that patients come to me with from other physicians. It's something you measure, I've been measuring it for almost 30 years. And I'm curious about: How do you diagnose insulin resistance? Because if you look at the data under metabolic health, 90% of Americans are metabolic unhealthy. And that to some degree is a degree of insulin resistance. And yet it's the most common disorder in the world right now, and yet most doctors don't know how to diagnose it. So how do you approach diagnosing someone with insulin resistance? Dr. Heather Huddleston: Yeah. We take a deep dive I think into people's metabolic health in ways that a lot of doctors maybe don't. We measure. I like to measure fasting insulin and fasting glucose. And the simplest way to diagnose insulin resistance there would be to calculate a HOMA-IR, which is you plug two numbers in basically to a formula and you can get a HOMA-IR. And if it's over 2.1, there's some degree of insulin resistance. Even simpler though is just looking at the fasting insulin. I think if you're in the double digits, you already know you're probably a little insulin resistant. And many of our patients with PCOS are much higher than that. We also do a glucose tolerance test, which is another test I think a lot of doctors don't do, but I think it's also really helpful. A lot of patients with PCOS, their fasting glucose is going to be relatively normal. But if you give them that 75 grams of sugar, two hours later, their sugar is still really high, so that's another way of sort of ... I mean, it's not quite specifically insulin resistance, but essentially it is because you're basically showing this patient is not able to dispose of glucose. Dr. Mark Hyman: Do you measure insulin too on that test? Dr. Heather Huddleston: To be honest, I do. I think it's almost more of research, kind of like I don't know that we have really validated measures of what's a firm cutoff there. But I will say in many of our patients with PCOS, we see very, very high two hour numbers, sometimes 300. And to me, I like to see that because it really tells me kind of what I'm working with and how sort of entrenched that degree of insulin resistance is. Dr. Mark Hyman: Yeah, that's such an important observation. I had a patient once who was typical apple shape, very central obesity, very overweight. And I was shocked because her hemoglobin A1C, which is your average blood sugar, was normal. Her fasting blood sugar was perfect in the 90s. I said, "Well, let's just do a glucose tolerance test," and we measured insulin and we measured glucose. And it was shocking, her blood sugar never budged. It went from maybe 90 to 110. It was perfect at one and two hours. But her insulin was high fasting, probably 20 or 30. But it went up to 200 or 300. And I was like, "Holy crap." This person clearly when you look at her was insulin resistant, but her blood sugar and hemoglobin A1C was normal, which is what most doctors will check. So you miss so much if you don't look at the insulin also, so I think that's a real take home for people. Ask your doctor to check your insulin at least fasting. And you say the double digits, now if you look at the reference range on insulin on most labs, it's 15 or something, or even more. That's not optimal. That's probably less than five is good. Dr. Heather Huddleston: Right, exactly. Dr. Mark Hyman: Five to 10 is maybe okay. Over 10, no way. So I think we just have the to kind of get better at diagnosing this as a medical profession because we're really bad at it. It's such a key driver not just in fertility and hormonal disorders, but obviously diabetes and heart disease and cancer and dementia, so it's just really across the board one of our biggest problems. Dr. Heather Huddleston: Yeah. I mean, I think we know that just even those high levels of insulin, hyperinsulinemia, I mean clearly is driving some of the problems in PCOS. But there's thoughts of how much that might drive cancer growth and things like that. And if you see that patients underneath the surface, it's almost like you're seeing how things are playing out, you see that their insulin are sky high two hours after glucose, which is happening to that person every single day when they have glucose, you're getting almost this sort of underneath the hood look at what's going on in their physiology, and you can see where that's going to go. It's going to not go well. And so to me, that's often a really great way to look at those numbers with a patient and explain that to them. And often, it can be really motivating for patients when they see that to make the changes that they want to make. Dr. Mark Hyman: Yeah, that's great. I mean, there's so much new technology, the continuous glucose monitors that are emerging. I met somebody who's developing this company, which is like a Band-Aid that measures your blood sugar. It's sort of a new tech thing. I don't even know how it works, some transdermal way to measure. So I think people are going to be getting more and more able to understand their health in real time. And I think the work you're doing is so important. So I really appreciate what you're doing, and I think it's very helpful because from listening to it, it's really clear that you can make a lot of progress with both a condition and the symptoms, both in improving fertility, regular cycles, improving acne, hair loss, and the things that really are distressing for women. So I think it's a very helpful conversation and it's great that you're looking at all the intersectionality of inflammation and the microbiome and environmental toxins, and diet and all these things that often are kind of stepchildren of medicine, but actually play a big role in all these disorders, whether we like it or not. So thank you so much for what you do, and I'm looking forward to keeping track of your work. You can find more about Dr. Heather Huddleston by checking on Allara Health, or ucsf.org providers, [inaudible 00:44:16] providers, Dr. Heather Huddleston. And if you like this podcast and you know someone who'd benefit from it, please share it on social media, subscribe wherever you get your podcasts. Leave a comment how you've helped your own condition of infertility or PCOS. And maybe we can learn something from you. And we'll see you next week on The Doctor's Farmacy. Outro: Hi everyone. I hope you enjoyed this week's episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, seek out a qualified medical practitioner. If you're looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It's important that you have someone in your corner who's trained, who's a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.