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Dr. Fiona McCulloch discusses An Integrative Approach to Polycystic Ovarian Syndrome (PCOS) with Dr. Ben Weitz.
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Podcast Highlights
3:20 Even though the name of the condition that we are discussing is Polycystic Ovarian Syndrome, you don’t actually have to have cysts in the ovaries to be diagnosed with it. And the cysts in question are not actually cysts, but follicles that haven’t really ovulated. But PCOS is really a condition of androgen (testosterone) excess, so the name is not really appropriate, but everyone is familiar with the same.
4:29 There are two prongs to this condition and one is is androgen excess and the other is insulin resistance. All PCOS patients have androgen excess, whether they have hair growth on their face, acne or hair loss from the scalp or they test positive for excess androgens, but not all PCOS patients have insulin resistance. There is a small subset (perhaps 30%) of PCOS patients who are lean and do not have insulin resistance.
6:49 The Adrenal PCOS subtype. This type of patient is often lean and tends to have higher levels of adrenal androgens, like DHEA, though higher DHEA levels usually results in higher testosterone levels, since DHEA is a precursor hormone. For each patient it is variable how much the DHEA will turn into testosterone. Patients with the high adrenal androgens are often more symptomatic when they’re younger and they tend to improve when they get older.
8:27 How PCOS develops. PCOS tends to start to develop either in-utero or during early development. Women with PCOS are more likely to have daughters with PCOS, so we know there are some genetic factors. There are a number of genes that play a role in the development of PCOS, including DENND1a. The SNP linked to Insulin Resistant PCOS is located on Chromosome 2 *in between* genes: FIGN and KCNH7. Here is a link to an Instagram post by Dr. McCulloch on this topic: PCOS Genetic Updates. Two other SNPs (genes) that play a role in the lean PCOS patients are: 1. BMPR1B, a gene that transcribes receptors for AMH, a hormone that often high in patients with PCOS. AMH is critical for the development of the follicles in the ovary and 2. PRDM helps activate the estrogen receptor. It is also involved in the development of the granulosa cells in the process of ovulation.
11:28 If an embryo is exposed to too much testosterone at certain windows of development, it can androgenize the ovaries and the brain and along with the genes and we think this is what causes PCOS.
What happens during childhood is that there’s a period in which women’s ovaries actually produce more testosterone and normally estrogen takes over at a certain point in time. But for women with PCOS, they get stuck in this androgen dominance state. And high androgens in women cause visceral fat storage and insulin resistance that is difficult to reverse later. And such women have higher rates of eating disorders.
14:20 Endocrine disrupting substances in the environment can play a role in the onset of PCOS. They have found that if you expose any embryo to Bisphenol A plastics, which are endocrine disruptors, that they can develop PCOS.
14:50 Insulin Resistance. It is the insulin resistance that puts PCOS patients at risk for an increase in cardiovascular disease, diabetes, and non-alcoholic fatty liver (NAFLD). Liver is really the center for insulin resistance. When the liver gets overloaded with fat because of too many calories being consumed and the fat inside the liver starts to leak out. The liver starts releasing glucose instead of storing it and this leads to metabolic disease and inflammation.
19:10 ALT is the most sensitive indicator of fatty liver and a level of ALT above 19 is associated with Fatty Liver, whereas the normal range is about 40 and for some labs like UCLA the reference range has recently been increased to 70, no doubt because of the decline in metabolic health of Americans during the pandemic.
Dr. Fiona McCulloch is a Naturopathic Doctor and founder of White Lotus Integrative Medicine in Toronto Canada, serving thousands of women with hormonal conditions since 2001. Dr. Fiona’s best selling book 8 Steps To Reverse Your PCOS, offers well-researched methods for the natural treatment of Polycystic Ovary Syndrome. Fiona is also a medical advisor to and developed the nutrition methodology for the OpenSourceHealth PCOS project which analyzes molecular, genetic, metabolic and hormonal markers in women with PCOS. As a woman with PCOS herself, Dr. Fiona feels fortunate to serve as a guide, providing trusted information that empowers women to manage their own health. Her website is DrFionaND.com.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.
Podcast Transcript
Dr. Weitz: Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates and to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast. Hello, rational Wellness podcasters.
Today our topic is polycystic ovary syndrome with Dr. Fiona McCulloch. Polycystic ovary syndrome is actually the most common hormonal disorder among women of reproductive age. Some of the most common symptoms are irregular periods, weight gain and difficulty losing weight, fatigue, facial hair, male pattern baldness in women, acne, infertility, mood swings, pelvic pain, headaches, sleep problems. The diagnosis of PCOS for most experts still appears to be based on Rotterdam consensus, which defines the presence of PCOS. If two out of the following three criteria are present, be delayed ovulation or menstrual cycles known as anovulation. Basically, if your cycle lasts 35 days or longer, that qualifies for this. Number two is high levels of androgen and hormones like testosterone and D H E A. And number three is polycystic ovaries seen on ultrasound. On the other hand, the PCOS society sees PCOS as primarily a condition of androgen excess. Insulin resistance is seen as one of the key factors in the pathophysiology of PCOS.
I’m thrilled to have the opportunity to speak with Dr. Fiona McCulloch for the third time after appearances on both episodes, 137 and 65, three and four years ago. Dr. Fiona McCulloch is a naturopathic doctor and founder of White Lotus Integrative Medicine in Toronto, Canada, serving thousands of women with hormonal conditions since 2001. Dr. Fiona’s best-selling book, Eight Steps to Reverse Your PCOS, offers well researched methods for the natural treatment of polycystic ovary syndrome. By the way, definitely the best book I’ve read of all the books on PCOS. Dr. Fiona is also a medical advisor and developed a nutrition methodology for the Open Source PCOS Project, which analyzes molecular, genetic, metabolic, and hormonal markers in women for PCOS. As a woman with PCOS herself, Dr. Fiona feels fortunate to serve as a guide providing trusted information that empowers women to manage their own health. Thank you so much for joining us.
Dr. McCulloch: Thanks Dr. Weitz. It’s great to be here again. I love your show and I’ve been looking forward to being on it today.
Dr. Weitz: That’s great. So let’s start with the diagnosis of polycystic ovary syndrome and what do you consider some of the best ways to diagnose it and what are some of the challenges? And I wanted to say one interesting thing about PCOS is the name is polycystic ovary syndrome, but you actually don’t have to have cysts in the ovaries to be diagnosed with this.
Dr. McCulloch: Yeah, that’s right. And there’s a lot of controversy around the diagnosis because this was what it was named many years ago, and what we know is that these cysts are not actually even cysts. They’re just follicles that haven’t really ovulated. So the name, really, it doesn’t make a lot of sense because PCOS is actually conditioned around too much testosterone or hormones like that called androgens. Some people, especially when they’re younger, they do have these cysts in their ovaries, but as patients get older, many don’t, actually. So it’s really important to think of it as a hormonal condition rather than one involving cysts.
Dr. Weitz: Well, it really seems like there’s two prongs to this condition, and one is the androgen access, and the other one seems to be insulin resistance, which seems to be the other big concept here.
Dr. McCulloch: Yes, a hundred percent. And this is sort of how the center of PCOS works. And what we know is that the way they diagnosed it or do diagnose it still, even if somebody doesn’t qualify for that diagnosis later, they still do have those same tendencies. So it really shouldn’t be undiagnosed, but the tendencies are the androgen excess. So everybody tends to have that, either some clinical signs, they can have hair growth on their face, acne or hair loss from the scalp, or the other one is insulin resistance. In around 70% of patients with PCOS have that, but not everyone. There are patients with PCOS who are quite not insulin resistant. They’re very lean, and actually they think that this might be genetically distinct as a type, even though they both have androgen access. There are definitely differences between these two types, but we still need to learn a bit more about that.
Dr. Weitz: Out of curiosity, how many lean PCOS patients are there? Is that a very small percentage?
Dr. McCulloch: It’s around 30%, but yeah, technically some of those patients, so they would be considered normal body mass index, and it’s unfortunate they use that as the marker because-
Dr. Weitz: You can still have insulin resistance even if you have normal body weight?
Dr. McCulloch: Exactly. There’s a whole category of lean patients that actually do have insulin resistance. I would’ve been in that category myself. I wasn’t actually that lean, I had a lot of abdominal fat. I would gain weight very easily. But then there are patients who are actually not at all insulin resistant, and they are very different in that they don’t have this element, which is really powerful. But there are lean patients with normal body mass index who do gain weight around their midsection, and they have all those characteristics too. So yeah, it’s definitely a spectrum.
Dr. Weitz: So I guess there’s these different subtypes of PCOS. I’ve also heard you, in one of your articles or in your book, you talk about the adrenal PCOS subtype as well.
Dr. McCulloch: Yes. The adrenal type is often lean. And an interesting thing about that, since I’ve written the book, I’ve sort of changed what I think about that a little bit, just observing it over time. Because what we see with the patients with the high adrenal androgens is that this is worse when they’re younger and it improves when they get older, but the level to which that is a problem depends on how much it turns into testosterone. So much of their case is very similar to lean PCOS, but sometimes they do need a lot of additional stress support, that’s quite common in that group. But a lot of the patients who have the adrenal androgens are more in the lean PCOS category as well.
Dr. Weitz: So the adrenal androgens, you’re talking about DHEA more so than testosterone?
Dr. McCulloch: That’s right, yes. So DHEA is a hormone that comes from the adrenal glands, DHEA-S, and it is used by the ovaries to make testosterone. The brain has to tell it to do that, to take that DHEA and turn that into testosterone. So what we’ll see is that patients who have high DHEA, they usually also have high testosterone. And for each patient, though, sometimes it’s really high and sometimes it’s not that high. So it really depends on what the brain and the ovary are doing with that because it’s really a precursor. And the DHEA-S is not very androgenic compared to testosterone. It’s not very strong. It’s more of a precursor.
Dr. Weitz: So in terms of how PCOS develops, it seems as though there’s this in-utero potential and then maybe during early development. And I’ve heard you talk about what happens is that during childhood, there’s a period in which women’s ovaries actually produce more testosterone and they kind of gets stuck in that.
Dr. McCulloch: Yeah, exactly. So it’s really interesting. We never knew what caused PCOS, but over the past several years, we’ve really accelerated what we know. And there are genes that are associated with PCOS, they’re still unraveling what those are, so [inaudible 00:09:17]
Dr. Weitz: Do we know what some of the key genes are?
Dr. McCulloch: Yeah, there’s one that’s called DENND1A. That one actually is involved in the creation of androgens in the ovaries. There’s genes that are correlated to type two diabetes, insulin resistance, the sympathetic nervous system. These ones are actually in between two gene SNPs and they have, if anyone is interested, if you go to my Instagram, I have the RSIDs on there. There’s also some genes for the FSH receptor, which is basically a receptor that takes messages from the pituitary gland to help make estrogen. And then there are some around the estrogen receptor that they found too. So there’s quite a few. There seems to be some differences between the lean and the classic. In the lean PCOS, they also have found a snip that is related to a hormone called anti-mullerian hormone. And that hormone is almost always quite high in PCOS. So they’re actually finding some of these very specific SNPs. And if you’re interested in the names of those, I have them on my Instagram, and you can look them up if you have any raw data.
Dr. Weitz: What’s the best panel? Are these contained in a ancestry or 23&Me panel?
Dr. McCulloch: So I checked my own because my undergraduate degree is in genetics, so I find it really interesting, and some of them are in the chip I have, but a lot of them are not. And in fact, like the last study they did, it was a genome-wide study, and some of them were new, that they don’t really have a lot of info on, but they were strongly correlated. So they weren’t in those tests, but maybe in the future they will be.
Dr. Weitz: So you don’t know of a particular panel that would be appropriate to run for this?
Dr. McCulloch: We don’t have anything like that Includes all of those. I have both Ancestry and 23andMe, and each of them have some, but yeah, nothing, not all of it in one. Yeah.
Dr. Weitz: And then can you explain, I don’t think most people are aware of the fact that during some part of childhood, women’s ovaries actually produce more androgens than they do estrogen.
Dr. McCulloch: Yes. And I should have also answered your other question about the in-utero environment because, so you can have these genes, but then in the in-utero environment, we know that if an embryo’s exposed to too much testosterone at certain windows of development, it can andogenize the ovaries, the brain, and this is what they think actually, along with the genetics, causes PCOS. So basically when that happens, everything’s very quiet during childhood. There’s no hormones. Right before puberty, what happens is our adrenals activate, and this is called adrenarche. This happens before the first period. And in this state actually our cortisol goes up. We begin to gain some weight because that’s required for reproduction. It tends to be around the abdomen and the adrenals start to make androgens. And with PCOS, what happens generally is that that process can start insulin resistance. That weight gain that is happening, that should be happening, really, there’s more androgens than normal. It can actually accelerate the gain of weight around the abdomen called visceral fat. And then when the actual periods begin to start, what happens is, for all girls, there’s a state where the androgens are more dominant for a while, and what normally should happen is that estrogen should take over. And as ovations happen, they should start to be happening more regularly. The androgens become lower over time.
But in PCOS, what happens is the androgens that are made are more, there’s too many, and this is related to what happened in the womb, but also genetics and those androgens block ovulation. So then the person gets stuck there in the state where they have high androgens. And high androgens cause visceral fat to be gained, they cause insulin resistance. And in this age group, like adolescents, I remember at that age, I would love to eat all kinds of candy and sugar and all kinds of things and it’s just a recipe where a lot of problems can happen. They can develop eating disorders. All of this is all occurring in those adolescent years, and then the person can either really develop deep insulin resistance, which is harder to undo, or the androgen access just kind of gets stuck like that. So that’s generally how it develops, according to what we know.
Dr. Weitz: Right. Okay. And we also think that these endocrine disrupting substances in the environment, these toxins are playing a role in this too.
Dr. McCulloch: Yes, absolutely. So I’m really glad you brought that up because they’ve also found that if at those windows in development, if you expose embryos to Bisphenol A plastics endocrine disruptors, they can develop PCOS as well. So that could be, it is involved almost certainly.
Dr. Weitz: So let’s talk about insulin resistance, and let’s also talk about the association of fatty liver with PCOS.
Dr. McCulloch: Yeah, so this, in my opinion, is something that is the biggest problem because PCOS is still thought of as this fertility condition. Meanwhile, insulin resistance is one of the top health problems generally that anybody can have. And it puts you at risk for cardiovascular disease, diabetes, so many things. And 70% of patients with PCOS have this, and it’s very, very much linked to fatty liver disease. The liver is really the center of insulin resistance. It creates a little cycle where it makes insulin resistance worse. So the liver becomes overloaded with energy, basically overloaded with fat, and the fat inside the liver actually starts to leak out. That creates inflammation, and then that fat actually starts depositing randomly around the body, especially around the organs, but also in areas like the muscle and inside our tissues. And that process basically causes overall inflammation, metabolic dysfunction. We start releasing glucose at the wrong times from the liver when it’s supposed to be storing it, everything just starts going wrong. It’s like the traffic lights are not synced up, and that really is all regulated by the liver. So yeah, this is a really big problem.
Dr. Weitz: So not only is fatty liver an indication of this metabolic dysfunction that’s leading to diabetes and heart disease, but fatty liver itself is considered to be one of the growing risks to our health. And we may have a tsunami of people needing liver transplants because of non-alcoholic fatty liver. So this is fatty liver not related to alcohol.
Dr. McCulloch: Yes.
Dr. Weitz: I see some debate about, I was just listening to somebody else’s podcast and they were talking about, after you eat a high fat meal being a big factor. But my understanding is, it’s really sugar and glucose and high glycemic foods that causes fat buildup in the liver.
Dr. McCulloch: Yeah. It is really the energy overload primarily that causes the buildup. But the interesting thing is, if a woman doesn’t have PCOS, if she were to consume extra calories, for example, it goes into subcutaneous fat, which is around the hips and the thighs, and that’s a healthy fat. It’s actually anti-inflammatory. It releases all of these lovely chemicals called adipokines that are really healthy for us, and the estrogen is what does that. So unfortunately in PCOS, the androgens start just pushing all that fat right into the liver, expanding the size of the fat cells and making visceral fat. So it’s like it’s just directed right into that area. And so any excess energy is just stored there so easily. And so it can be any energy, but the problem I find with glucose, definitely glucose is more of a problem because, especially with insulin resistance, it puts people on a glucose roller coaster. They start having hypoglycemia, eating more sugar and carbs. Also, sugar is very inflammatory. Fructose is another big problem for fatty liver. I personally think those are worse. There is also the theory though, that it’s just a total energy overload. And I do agree with certain parts of that also. So yeah, it’s really-
Dr. Weitz: It’s kind of interesting, in a functional medicine world, it’s almost a political discussion because we have the vegan party and we have the low carb party, and we have the carnivore party and everybody’s trying to blame somebody else. If you’re in the vegan camp, then you want to blame high fat for the problem because you’re mostly carbs. But anyway.
Dr. McCulloch: It’s so true.
Dr. Weitz: I saw on Instagram where you said the ALT is the most sensitive indicator, which is interesting because there’s the ALT, there’s the AST, there’s a GGT that sometimes is run. But you say the ALT, and you mentioned that ALT above 19 in women is associated with fatty liver. And the normal range, depending upon the lab, is, say, 40. By the way, UCLA recently raised their reference ranges, and I think it’s now 70. This is a scary thing. People don’t realize that the reference range in the United States and elsewhere. So in the United States, it’s just based on the average American. In fact, the average American that is being measured by that lab, so because of several years of staying home and eating more junk food and drinking more, the average liver enzymes have gone up. And now we’re considering that the reference range, which most people consider good or normal.
Dr. McCulloch: It’s shocking. And I think there is more fatty liver disease in children. It’s astronomically rising in children, something we never saw. And I think, yeah, so many people now have fatty liver that they’re flagging everyone. And now they’re like, let’s raise the reference range so it only shows us things like hepatitis ’cause we don’t want to hear about that. But it’s horrible because there’s so many people with fatty liver disease that have no idea they have, it has no symptoms. And if they knew this, they could, because it’s reversible.
Dr. Weitz: If everybody was flagged with an ALT above 19, oh my gosh, you’re talking about huge percentage of Americans and probably similar in Canada where you’re located.
Dr. McCulloch: For men, I think it’s a little higher at 24, but for women they found it was 19.
Dr. Weitz: Wow.
Dr. McCulloch: And over that is an indicator. It’s that combined with other signs. I think you see-
Dr. Weitz: Sure.
Dr. McCulloch: … a higher waist circumference and all of that. But then, yeah, I definitely see that.
Dr. Weitz: Higher ferritin, higher triglycerides, lower HDL. Right?
Dr. McCulloch: Exactly. Exactly. All those things and the insulin.
Dr. Weitz: Yeah, ferritin’s an important marker that’s not always measured. And most people just consider it a marker for iron status, but high ferritin levels is an inflammatory marker.
Dr. McCulloch: Yes. And one thing I always like to point out is it’s very unusual in women to not to have high ferritin because women often are irons efficient because of periods, especially reproductive age women, that’s very unusual. So if the ferritin is over a hundred and you’re not eating tons and tons of red meat and iron, that might be fatty liver. Now, ferritin can also be other inflammation very much, but we definitely see it raised in fatty liver.
Dr. Weitz: Right. What makes people gain weight so easily with PCOS? I guess the answer is what we just said about insulin resistance, right?
Dr. McCulloch: Yeah. There’s so many factors like the insulin resistance, once it sets in for a really long time, you’ll definitely see people who have obesity for many, many, many years. Of course, they can change their diet and lose weight, but what they have trouble with is maintenance. And it’s because we know that the cells actually have a memory of this, of insulin resistance. So once it’s been that way for a long time, you can lose the weight, but your brain and your cells will want to put it back, so it’s very challenging. And one of the big problems I see is that they don’t intervene early enough when it really could be much simpler, and instead just dismiss patients and let them go years. And that whole time they’re just developing more and more insulin resistance. So that’s one part of it. Outside of that too, that androgens themselves just drive this weight gain around the abdomen. And these are the highest when you’re the youngest with PCOS. So it’s just a recipe for insulin resistance in younger years.
Dr. Weitz: It’s so interesting how same hormone can have different effects in men and women. Because in men, testosterone tends to make men leaner, whereas testosterone makes women tend to gain weight.
Dr. McCulloch: Yes. That’s such an interesting element because it has definitely dimorphic effects in men and women, very different. And in women-
Dr. Weitz: That’s a good word, dimorphic effects.
Dr. McCulloch: They’ve actually studied that, so I did not come up with that. But yeah, what they find is there’s a sweet spot for women, it’s good if it’s at a certain amount, but when it’s so high that it’s too high and it’s disrupting ovulation, then it starts to drive it into these areas like the liver and the visceral fat. So those androgens are, yeah. But in men, it’s actually quite beneficial to have androgens. In women, as well, low androgens is not good, but in PCOS, they’re just incredibly high. Yeah, big problem.
Dr. Weitz: So you mentioned testing for testosterone. Let’s go into lab testing and then we’ll go into treatment. Why don’t we start with the testosterone? I can relate that I’ve had patients, I knew they had PCOS, I could just tell from the presentation. And yet we looked at the testosterone and it was normal on lab testing. And I understand that a lot of times it doesn’t show up.
Dr. McCulloch: Oh my goodness. Yes, so true. So basically the reference ranges for androgens are not age adjusted, firstly. So androgens are very high when you’re young and they become very low when you get to about 40 or so, and this is normal, but the reference ranges don’t include that. So what might be high at age 35 would look really normal, but it’s higher than average. So that’s one big problem. There’s also a lot of patients who are right up at the top of that range and they’re not ovulating, and that’s enough that it’s blocking the ovulation process, that’s androgen excess or they have symptoms. So the testing, again, those reference ranges are not very good.
Dr. Weitz: So what should we look at for serum levels? Can you give us some ballpark? And we’re talking about total testosterone. Does free testosterone, is that as important as well?
Dr. McCulloch: It can be, and I’m going to use Canadian values because I don’t know the US ones. I usually convert them, but I can use what I know and then maybe in the notes it could be converted.
Dr. Weitz: You got it.
Dr. McCulloch: The total testosterone I use a lot, because this picks up lean PCOS very well. Free testosterone is much better at picking up insulin resistance. So I tend to look at that in a little different way. And the way I test it is, I’ll do total testosterone. In Canada, our reference majors are around two to 2.1, but what I’ll see is that there are some people that are above that. Then as patients get older, they’re kind of up towards the top, 1.8, 1.7. If a woman is 45 years old, for example, and she has a total testosterone of 1.4, that’s very unusual. Even though it’s not even close to the range at the top of the range, it’s not common. So that is one way I look at it. DHEAS is similar, so our range goes up to about 9.7 and around 6.7 in your forties. So anything towards the top might be a problem, it really depends. One of the tests I do a lot is LH and FSH on cycle day two or three because LH makes testosterone. So you’re seeing almost like a leading indicator. If the LH is higher than the FSH, in particular, if it’s double, that is very PCOS-like and will drive androgen excess. So that is another one we can see. Sex hormone binding globulin is another interesting one because this is a hormone that, when you’re insulin resistant, it’s low, and when that’s low, the testosterone can become more powerful and free. So basically, that I like it to be around the middle of the range, so that one wouldn’t necessarily need a unit depending on what the one is there.
Dr. Weitz: Oh, interesting. So you need enough SHBG? Yeah, I’m usually concerned, and when I’m working with men, because it gets too high and it blocks the free testosterone.
Dr. McCulloch: And it’s the opposite. So when women with the SHBG, it’s very high when there’s high estrogen, and very low when there’s high insulin. And the liver, when it’s insulin resistant, it can’t make SHBG very well. So that’s why the patients who have insulin resistance, they often don’t have enough estrogen either. Sometimes they do and sometimes they don’t. It’s another I misunderstood thing, estrogen dominance, but sometimes their SHBG is so low that even the smallest amount of testosterone is just so powerful in them.
Dr. Weitz: I would imagine women with low SHBG probably have trouble with thyroid too, because they don’t have the binding globulin for the thyroid either.
Dr. McCulloch: They have so many problems with, definitely, the thyroid, all of the hormones. I just find that those patients, because they have so much insulin resistance, everything starts going off, every hormone basically.
Dr. Weitz: And I know sometimes you measure the testosterone in dry urine as well.
Dr. McCulloch: Yeah, I don’t do that as much anymore. I’m doing more serum these days. It’s just more efficient, I find.
Dr. Weitz: Get it all done in one test.
Dr. McCulloch: Yeah, I always want to test insulin, thyroid, all the things that you can’t, and so it’s just easier to do a standard blood lab because I can get the exact panel I want.
Dr. Weitz: Right. Okay. So you mentioned FSH and LH, and you mentioned androgens. Total testosterone, free testosterone, DHEAS and androstenedione. Are there a significant number of cases where you might see androstenedione high when the testosterone’s not?
Dr. McCulloch: Yes. I actually find the androstenedione is quite sensitive sometimes, so it’s a good one to run. Sometimes it’s a little more expensive, but if it’s unclear, that one is often at the top of the range.
Dr. Weitz: Okay. And then what other tests? Do you usually measure the anti-mullerian hormone?
Dr. McCulloch: I do that a lot. In particular, if I’m unclear if they might have PCOS and they’re a bit older, I’m like, I don’t know. If I run that and they have a very high egg reserve, it adds to that diagnosis. I will do that sometimes for patients who are seeking fertility treatment as well. And what I find is the lean PCOS patients, sometimes it’s very, very high. So it’s definitely-
Dr. Weitz: Technically you can’t have PCOS after menopause, or can you?
Dr. McCulloch: You actually can, and it doesn’t go away. But it’s like these diagnostic criteria, technically would be undiagnosed. But what we know from research is the androgen access is still there. They still have it. They have all these risks for cardio, diabetes, so it’s still there, so they need to do something about that.
Dr. Weitz: Yeah. And then what other factors? You look at metabolic factors?
Dr. McCulloch: Yes. I always really look into insulin resistance. So I’ll do fasting insulin, fasting glucose or an insulin glucose challenge, which is also known as the Kraft test, that’s more detailed, A1C. The lipids are always really important to inflammatory markers.
Dr. Weitz: Mention that test for insulin resistance that you just mentioned?
Dr. McCulloch: Oh yeah. It’s called the insulin glucose challenge, and it’s also known as the Kraft test. It was created by Dr. Kraft who is quite well known for all of his work on diabetes. And he is a type one diabetic and he created a test involving taking 75 grams of glucose and measuring both glucose and insulin for four hours afterwards at certain increments. And this can show you insulin resistance and its progression towards type two diabetes. So it’s really interesting.
Dr. Weitz: I think this was known as the glucose tolerance test and I think it was a six hour test, right?
Dr. McCulloch: Yeah. The glucose tolerance test is the one that we do a lot, but this one it’s similar but also includes insulin at each measurement, which-
Dr. Weitz: That makes a lot more sense.
Dr. McCulloch: So interesting.
Dr. Weitz: Insulin is usually often not measured by most doctors and it’s so important because if you are using a lot of insulin to keep your glucose in a normal range, that’s as problematic as having high glucose.
Dr. McCulloch: And this is one of the best tests for these lean patients with the insulin resistance because what we’ll see is they’re doing the test, their fasting looks really good, and then they take this sugar, and oh my gosh, they make five times the amount of insulin as another person of the same body mass index. And you can also see hypoglycemia and exactly how it’s happening. So it’s quite a cool test actually.
Dr. Weitz: And how do you assess adrenals? Do you do the salivary adrenal testing?
Dr. McCulloch: Yeah, I do that a lot. So this is the saliva, four point cortisol is the popular one in our practice. We do also the urinary cortisols. And then sometimes I’ll just do a serum morning cortisol, even though it’s not ideal, sometimes it’s just efficient and it saves on funds. And you can see-
Dr. Weitz: I don’t get anything out of that serum cortisol test.
Dr. McCulloch: Yeah, it’s sort of a screening, so sometimes it’ll be really high or really low, and that’s really, because not everybody always has, it’s a lot of testing. But if I’m looking, really seeing a problem, I’ll usually run a saliva.
Dr. Weitz: So let’s get into treatment. And we all know, the best treatment is to just put all women on birth control, right?
Dr. McCulloch: That’s the treatment that’s offered really for everybody. It doesn’t seem to matter. That’s just what you’re getting until you’re ready to have kids, then you can come off it and then we’ll deal with it. So that’s the treatments. And then they also have metformin, that’s the other one, and that’s about it. And metformin isn’t bad, it just doesn’t do all that much. They need to be offering nutrition and exercise. There’s so many things that could be done.
Dr. Weitz: Metformin, in and of itself, is not going to do the thing. You’ve got to be doing a diet, the exercise and everything else and then metformin can have a significant effect. But there’s plenty of other natural treatments that can work as well. I understand you will sometimes recommend the use of progesterone.
Dr. McCulloch: Yes. This is actually a really interesting treatment. There’s a big clinical trial going on right now at UBC on cyclic progesterone for PCOS. Cyclic progesterone is not the same thing as birth control. A lot of people will think it is because they’re used to that. But what’s in birth control is actually a different substance, it’s called a progestin. And there’s a whole bunch of these progestins, and they all are different in what they do. Some of them actually act like estrogen, some even act like testosterone. And there’s some that have actions that are completely different from progesterone. So it’s totally not the same thing as that. It’s also not the same thing as something called medroxy provera, which is commonly used in PCOS to stimulate a bleed. This is actually natural micronized progesterone. So it’s the same exact type your body makes after ovulation. And progesterone lowers the LH hormone, so when this is done repeatedly for 14 days out of every month, what happens is the LH comes down and it can act as training wheels to teach the ovary to lower the testosterone and let the estrogen be the dominant hormone. So it’s a really interesting treatment, it’s almost like replacing what didn’t happen in the puberty timing and doing it a bit later.
Dr. Weitz: Interesting. Are there any other hormones or medications that you use? We’ll go into diet and supplements next.
Dr. McCulloch: A lot of the patients have thyroid disease, so I do a lot of natural desiccated thyroid prescribing for PCOS. So I would say these are the top hormones that I would use, that and progesterone.
Dr. Weitz: Okay. So let’s talk about the dietary strategy for PCOS.
Dr. McCulloch: Yeah, so there’s so much, like you were saying before, all these political sides on each side of it. Every diet is [inaudible 00:37:18].
Dr. Weitz: Eat only meat. Eat only vegetables.
Dr. McCulloch: Vegetables are bad. Vegetables are everything. So it’s always personal too. Many different nutrition plans can work for PCOS as long as they’re, if the person has insulin resistance, as long as it’s managing that. But it has to be sustainable. So for most people, of course, doing a very, very low carb diet like keto will lower insulin, but most people can’t do that forever. And there’s many other ways to lower insulin. So I have a way that I generally recommend as a starting point, but it’s very flexible. And this includes four different categories of food. It’s all about balancing blood sugar and stopping spikes of sugar with very healthy anti-inflammatory food and it’s protein. So about 25 to 30 grams of protein in a meal, two or three cups of vegetables, any kind, really, non-starchy. Two servings of healthy fats, so that could be nuts or seeds or avocado, guacamole, healthy oils like olive oil or avocado oil. But a serving of those nuts and seeds is a quarter cup. So pretty significant amount of healthy fats. And the amount of carbs should be variable depending on the person, a half to three quarters of a cup per meal, more of a low glycemic index carbohydrate, something with resistant starch. I find beans and lentils are a great carbohydrate. A lot of people think of them as a protein, but actually, there’s a lot of carbs in there and they’re resistant starch. So that kind of meal is super balancing to the blood sugar. But everyone might need a little tweaking to that, because people are athletic or need certain adjustments.
Dr. Weitz: Okay, let’s go into some clinical pearls for treatment with respect to specific nutraceuticals.
Dr. McCulloch: And one of the things I’ll say first just before talking about treatment is I see so many of the lean patients doing treatments for insulin resistance and it’s not working for them. So I just want to say firstly, don’t treat insulin resistance excessively if you don’t have it because sometimes people, they’re not even eating enough food and that’s actually making the situation so much worse.
Dr. Weitz: So you mean maybe women who are eating almost no carbs and taking a bunch of supplements just for insulin resistance without addressing the androgens and the other aspects of the condition?
Dr. McCulloch: That’s right. And they’re lean and they don’t have any insulin resistance and they’re like, oh, I need to do this really, really restrictive diet. I’m not dieting enough. That actually is worse. So firstly, it’s in figuring out what’s going on and what to treat. And so the treatments, one of my favorite supplements is Inositol. Inositol works for both lean and insulin resistant PCOS. It helps with insulin sensitivity, but also helps the ovaries to take messages from the brain, so it’s really important for ovulation. So that’s definitely one of my favorite supplements.
Dr. Weitz: And we have the two forms. We got the Myo-inositol and the D-Chiro inositol.
Dr. McCulloch: Exactly. Yeah, the myo is what does almost most of it. And then D-Chiro inositol, a small amount of that, seems to be very helpful if the patient has insulin resistance. So a lot of the formulas are in a 40 to one ratio of myo to D-Chiro inositol, but even just Myo-inositol can make a huge difference.
Dr. Weitz: So Myo-inositol for any form of PCOS and the combination with D-Chiro specifically when there’s insulin resistance?
Dr. McCulloch: Yes, exactly.
Dr. Weitz: Okay. Since we’re on insulin resistance, what other supplements do you like for insulin resistance? I use berberine a lot and chromium.
Dr. McCulloch: Yeah, I love berberine. It’s definitely one of my favorites. I find you’ll actually see really big changes in the glucose levels on berberine for certain patients. It’s just really effective. I also really like alpha lipoic acid if a patient has a fatty liver disease, especially. Super helpful.
Dr. Weitz: What dosage for lipoic acid do you like?
Dr. McCulloch: It really depends, but usually I’ll do around 600, something like that range.
Dr. Weitz: Any other supplements for insulin resistance?
Dr. McCulloch: Yeah, I also really like glucomannan fiber because it basically reduces the spike of sugar after a meal. It helps with fullness and it’s a prebiotic. And so we see a lot of microbiome changes with PCOS.
Dr. Weitz: How is that consumed?
Dr. McCulloch: They have this in soft gels and in powders, and basically you take it before a meal with a lot of water. If you use the powder, definitely drink it quickly because it becomes a gel and it’s not pleasant. So a lot of people like the soft gels, so it’s usually four soft gels with a big glass of water before the meal.
Dr. Weitz: So glucomannan before meals, especially meals where they’re going to have carbohydrates.
Dr. McCulloch: And a lot of the time too, if a patient’s like, I’m going out to a party, something like that, and they have that glucomannan, they can enjoy their meal and they don’t really have blood sugar spikes. Often they’re quite full too, but it really just stops the insulin spikes and sugar spikes.
Dr. Weitz: What are the best ways to address androgen excess?
Dr. McCulloch: So androgen excess, if the person’s insulin resistant, the best way is to deal with the insulin resistance and directly, because that is the biggest trigger for that person. And the reason for that is that low SHBG. So those androgens are just way more powerful, plus insulin makes more androgens and for that category of people.
Dr. Weitz: That’s an interesting cycle. I saw you had this one Instagram post where androgens increase insulin resistance. Insulin resistance increases androgens, and on and on.
Dr. McCulloch: Yeah, it’s like a really vicious cycle and it just keeps going. So that is really critical. And for the lean patients, we know that doesn’t work for them, so we go right after the androgens. I personally have found the cyclic progesterone to be the most effective direct way to do that. It works extremely well, but there are also the supplements, like inositol will lower LH and androgens. There’s also many herbs that can be helpful, like white peony and licorice, Saw Palmetto, even Reishi mushrooms. So there’s some different herbs that have anti-androgenic effects like this that we use also.
Dr. Weitz: Okay. You also mentioned iron as being really important.
Dr. McCulloch: So iron is very important generally for women’s health. And with the insulin resistance, we definitely can see sometimes the iron that’s high. In that case, we want to watch and not supplement iron unless we see those levels coming down. As patients start to ovulate and have periods, they start to have lower iron and so it’s sort of a moving target to watch. Sometimes patients, their iron’s really good and then they start having periods and then it starts to go down. So it is something to watch really closely because it has so many effects on health.
Dr. Weitz: In your book, you mentioned a few things that could be used topically specifically for the hair loss. Do you still find those things helpful? What do you think for women who are dealing with hair loss, are there some topicals that could be helpful?
Dr. McCulloch: Yeah, hair loss is a really interesting area because it is … Topicals can be quite effective because you can access that area very well. So the topicals that I use a lot are melatonin and rosemary. Those two I find to actually be helpful, but hair is very, very slow. And I also find that progesterone topically is actually very helpful for hair loss also.
Dr. Weitz: Interesting. So do you just mix all three of those together or how do you administer it? And what about when they do that vampire facelift and you use that thing to make the holes? Would you do that first?
Dr. McCulloch: So the progesterone cream, I know some people do apply it on their scalp, but you don’t have to. Most of the time, we just apply it on the wrist and that will deliver to it. It delivers through the capillaries, which is really interesting. But yeah, topically, things like the melatonin and rosemary usually, you can get the spray melatonin or rosemary. I usually suggest to add it to a spray bottle with a little aloe gel to emulsify it, making parts across the hair, just a little spray, massage it in and go across each part all the way, and at bedtime. That is really all you have to do with it.
Dr. Weitz: Interesting.
Dr. McCulloch: Yeah, it just takes forever because hair is the slowest thing. It’s been studied to be found around the same efficacy as Rogaine. I know there’s not enough-
Dr. Weitz: Really?
Dr. McCulloch: … to confirm that, but yeah, there’s something-
Dr. Weitz: Does that work for men too?
Dr. McCulloch: Yeah, men’s hair loss is more challenging too because they just have higher testosterone, so I don’t know how well those will work, but maybe if you catch it early, it’s really important for androgenetic. But yeah, these are antioxidants basically, and the androgens cause oxidative stress around the follicle and that’s what really kills them.
Dr. Weitz: Interesting. So you mentioned a category of supplements for inflammation in your book.
Dr. McCulloch: Yeah, inflammation is one of the biggest central problems because it actually drives insulin resistance and anyone with insulin resistance has inflammation, and it’s because of all that fat leaking out of the liver, it’s very inflammatory. So for inflammation, we’re always looking at antioxidants that quench that. So things like acetylcysteine has a lot of evidence. Alpha lipoic acid, again, really good as an antioxidant. There are also many anti-inflammatory types of treatments like anti-inflammatory enzymes, for example, like systemic enzyme therapies.
Dr. Weitz: Curcumin.
Dr. McCulloch: Yeah, curcumin. Exactly. Quercetin. There’s some evidence. There’s basically all of these antioxidants, most of them have shown to be beneficial for inflammation in PCOS.
Dr. Weitz: Okay. And what about supplements that are beneficial for women who are trying to get pregnant?
Dr. McCulloch: Yeah, that would be the top one is inositol for sure, because our eggs should have a large amount of inositol inside of them. It’s a marker of quality. So inositol actually builds-
Dr. Weitz: Now, is that where you just used the myo or do you use the combination and if so, what’s the dosage for that?
Dr. McCulloch: You can actually use the combination even in lean patients. If you go higher than that amount, it’s shown to be actually possibly negative, especially if you go really high with that hot D-Chiro. But if you do the 40 to one, it’s actually been shown to be beneficial for all types. The doses are 4,000 grams of myo and 100 of D-Chiro, but you can also skip the D-Chiro and just do the myo. There’s also, they studied some lower doses, but that dose is the most popular dose to use.
Dr. Weitz: Cool. Yeah. You also mention-
Dr. McCulloch: I should also just mention quickly for egg quality too, other really popular supplements, coenzyme Q10 and PQQ. Both of those are mitochondrial antioxidants and those are really important for egg quality.
Dr. Weitz: Somewhere I read you mentioned Vitex as well. I’d be a little nervous because that’s like a hormonal one.
Dr. McCulloch: Yeah, Vitex is a little tricky. It’s sort of gotten this reputation of raising progesterone, but it’s never really been shown to do that.
Dr. Weitz: Oh, is that right? It has not, huh? Interesting.
Dr. McCulloch: No. There’s some studies that show that it can help ovulation and because progesterone is produced by ovulation, they’ve now linked those things, but it’s never been shown to do that. What it does do is lower prolactin and it works on the brain and it has impacts on stress in the brain, the opiate system, and the prolactin system. So a lot of the time, if the patients are having stress-related problems with ovulation, it’s really helpful for that, but it’s not often enough to deal with this androgen excess problem.
Dr. Weitz: One more category of supplements I wanted to mention is supplements to help with the adrenal glands. And I guess it’s typically hypercortisolemia that we’re dealing with.
Dr. McCulloch: Usually, yes. And then we do have some patients who have low cortisol also just from years of dysregulation. So many different adaptogens, just depending on the situation. Ashwaganda is definitely a favorite. I’ll use Eleuthero, Tribulus. Actually, even though we think of it as raising testosterone, it actually does the opposite in PCOS, it’s been shown to-
Dr. Weitz: Interesting. I never heard of that.
Dr. McCulloch: Yeah.
Dr. Weitz: Oh, cool.
Dr. McCulloch: And that’s a really interesting one as well.
Dr. Weitz: You mentioned using licorice a lot. Do you use that for hyper or hypo or both?
Dr. McCulloch: I would usually use it for someone with low cortisol, but when it’s used for PCOS, it’s also used in a different way, sort of as part of a anti-androgenic formula with peony, but I would tend to only ever prescribe that in somebody that obviously doesn’t have high blood pressure. They generally are more tired. They have that depleted lower cortisol.
Dr. Weitz: Great. So I think that’s a wrap. I think we covered it. How can viewers, listeners find out more about you and your book?
Dr. McCulloch: Yeah, I practice in Toronto at White Lotus Clinic, so you can find us online there. I’m on Instagram @drfionand. And my book is Eight Steps to Reverse Your PCOS. You can buy that on Amazon or any bookstore as well.
Dr. Weitz: Okay, that’s great. And thank you so much.
Dr. McCulloch: Thanks. It was great to be here.
Dr. Weitz: And thank you for making it all the way through this episode of the Rational Wellness Podcast. And for those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcast or Spotify and give us a five star ratings and review, that way more people will be able to discover the Rational Wellness Podcast. And I wanted to say thank you to all the patients that we’ve been working with at our White Sports Chiropractic and Nutrition clinic who, most of whom we’ve been able to help with a range of various health conditions from various types of gut disorders to thyroid and hormonal issues, autoimmune diseases and various other cardiometabolic conditions. And so I very much appreciate you and I’m excited about going forwards, helping you to improve your health on your journey towards optimal health. And I wanted to let everybody know that I do have a few openings now for new clients, and you can take advantage of that by calling my Weitz Sports Chiropractic and Nutrition Santa Monica office at 310-395-3111, and we could set you up for a new consultation for functional medicine nutrition, and we can get that going as early as the new year. So give us a call and I’ll talk to you next week.