Breast Health and Beyond: A Practitioner’s Guide to Functional Testing

Over 270,000 new cases of breast cancer are diagnosed each year in the US. And while BRCA mutations often get the most press, there are other, potentially more critical factors we can address. Today, Dr. Ruth Hobson joins us to delve into the realm of breast health, shedding light on both modifiable and non-modifiable risk factors, and sharing real-life strategies for supporting our patients.

We dive into a range of essential topics, from dietary and lifestyle influences to the ongoing debate around Hormone Replacement Therapy (HRT), and venture into the world of functional tests to evaluate hormones and metabolites crucial for comprehensive breast health. We’ll uncover the intricate connection between gut health and breast health – Did you know that breast tissue has its own microbiome?!? – and examine how inflammation, peripheral fat, and methylation impact cancer risk. Bring a pen and paper, this is a deep dive into the hormones and breast health that you won’t want to miss. ~DrKF

Within the realm of breast health, practitioners often face the challenge of selecting the right testing methods, interpreting results, and addressing modifiable risk factors. Dr. Ruth Hobson, a practicing Naturopathic Physician and expert from the clinical education department at Doctor’s Data, Inc., joins us to untangle these complexities. In the course of our conversation, she guides us through the optimal testing approaches and their significance in evaluating breast cancer risk. We delve into the nuances of interpreting results, identifying metabolite imbalances, and their significance, gain clarity around the safety of Hormone Replacement Therapy (HRT), and how to prioritize the most critical modifiable risk factors.

This episode is packed from beginning to end with vital information to help you navigate the complex world of breast health. Download the HuMap in advance and follow along.

 

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald (00:00:02) – Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And of course, today is no exception. I am excited to be here with Dr. Ruth Hobson where we are going to be talking about breast cancer and a functional approach to laboratory assessment and so much more. Let me tell you a little bit about her and we will jump right in. Dr. Hobson is a practicing naturopathic physician, and she is also a doctor in the clinical education department at Doctors Data. She received her bachelor’s from Brevard College in Health Science Studies with a minor in biology and chemistry. She trained as a GP at NUNM, (National University of Natural Medicine), my alma mater, tailoring her studies to focus on women’s health and pediatrics. She currently splits her time between consulting and educating at Doctor’s Data in their clinical education department and her own private practice, where she focuses on hormone health and aesthetics. She’s utilized her expertise in both research and patient care to develop curriculums for webinars, conferences, podcasts, throughout the US, focusing on hormone metabolism and optimization.

Dr. Kara Fitzgerald (00:01:12) – She also, I should add, completed a residency at NUNM as well teaching and primary care residency. Dr. Hudson, welcome to New Frontiers.

Dr. Ruth Hobson (00:01:24) – Hi, thanks for having me.

Dr. Kara Fitzgerald (00:01:26) – Yeah, absolutely. So, this is going to be an information packed podcast and again, a topic we haven’t had here on the show in a while. So, I’m so, so glad that we’re bringing it back. Breast cancer is multifactorial and we need to cast a wide net to address as many possible risk factors as we can. Talk to me about that. What do we need to be paying attention to in all of our patients? And maybe a little focus on what we need to be paying attention to on our patients with established breast cancer?

Dr. Ruth Hobson (00:02:04) – Yeah, so perfect. First, let’s start with things that we think of as risk factors that are outside of our control. There are things that come up in patient populations, and when you’re screening, you’re going through your intake forms or you’re thinking about patients, those are going to be, maybe they don’t have breast cancer, or maybe these patients do have breast cancer. That’s going to fall into the category of just assessing some risk, right? So non-modifiable risk factors, age is going to come up. Most breast cancer is diagnosed in the postmenopausal female. Men are also diagnosed, and I would say also later in age as well. But age 50 you’ll typically see is when most cancers are diagnosed. Do we see that before? Absolutely. But this is just something that’s going to come up. Also, females more than males, are typically going to be diagnosed. Race and ethnicity, we’ll see that come up as well. I would say Caucasian females tend to have higher incidence of breast cancer and we can also see there are other populations that have higher mortality would come up. Height is an interesting one, but the taller stature is going to come into play here, and I think it’s about 5 ft. 9 in. or higher. It could be more also tied to bone density.

Dr. Ruth Hobson (00:03:29) – So the higher your bone mineral density, interestingly, you’ll see more increase in breast cancer risk.

Dr. Kara Fitzgerald (00:03:36) – Why is that?

Dr. Ruth Hobson (00:03:36) – Yeah. We’re postulating, right? We think that it has to do with more estrogens that we’re seeing from bone mineral density, so the higher bone mineral density. I will say this is going to be high impact bone mineral density. This is greater than what you would typically see as the norm. There’s also some genetic mutations, I know people are pretty familiar with BRCA1, BRCA2.

Dr. Kara Fitzgerald (00:04:05) – Actually, let me just circle back to that and then let’s go on to genetic mutations. So, very good bone density in a postmenopausal, tall woman might be a flag for somebody to suggest that they’ve just got more active estrogens?

Dr. Ruth Hobson (00:04:26) – Absolutely. So those estrogen receptors are going to be things that we will think about. They are more like the targets for breast cancer and that’s why it’s the risk. It’s more estrogen receptors when we compound those factors. Yes.

Dr. Kara Fitzgerald (00:04:42) – All right. I want to circle back and talk to you, because this is where I’m going in my brain and I know the listeners will be, is what about using hormone replacement therapy and estrogen, which, one of the perks of that is improved bone density. And of course, it’s been, I think, turned upside down that there’s a risk associated with that. So, we don’t have to go down that conversation now, but let’s return to HRT.

Dr. Ruth Hobson (00:05:07) – Oh we’ll get to that. Absolutely. I think that’s a meaningful conversation for sure.

Dr. Kara Fitzgerald (00:05:10) – So we’ve got a pin in that. Everybody, assure us that that we will definitely come back. I have a note here on my on my sheet and then- But let’s move into mutations because that’s where you were going.

Dr. Ruth Hobson (00:05:21) – Yeah. Most people are familiar with BRCA1 and BRCA2. You’ll see there is genetic increased risk for breast cancer, specifically. Let’s also remind ourselves that there is also risk for other cancers that are involved with those two mutations, and it’s really the mutation in DNA repair, right? And let’s think about that as we as we move through.

Dr. Ruth Hobson (00:05:47) – And we can also have conversations about that, because when we think about the genetic component here, it’s not the number one thing that I think of.

Dr. Kara Fitzgerald (00:05:56) – It’s a pretty minor player I think, when you really look at it, when you tease it out. I mean what, maybe 25% might have a genetic association and of that less than half are BRCA associated.

Dr. Ruth Hobson (00:06:10) – Exactly. And that opens up a whole communication we can talk about too, but does having a gene mean that we are necessarily set up for that? We can dive into that too.

Dr. Kara Fitzgerald (00:06:26) – Yeah. Well, we should. You and I were talking that I have a background in doing research on DNA methylation, and the BRCA gene can be turned off via methylation. So, there’s no genetic mutation, there’s an environmental influence that will turn off this all-important DNA repair gene. But the other thing that’s pretty interesting, too, is that we know that the incidence of BRCA associated cancers was way, way, way lower in the 1930s, 40s, 50s, et cetera. The incidence was way lower. So clearly the influence is more environmental, I think, even when you have these genetic mutations.

Dr. Ruth Hobson (00:07:10) – Absolutely. And that’s what we have to think of as health care practitioners that are thinking outside the box, right? We need to come from different angles. I think there’s a lot of fear. There’s a ton of fear around breast cancer, breast health in general. Some of it warranted. Yeah. When you get a cancer diagnosis, absolutely, that’s terrifying. But we can step back and kind of tease out things that we might be able to have some control over.

Dr. Kara Fitzgerald (00:07:38) – Talk about those.

Dr. Ruth Hobson (00:07:40) – Yeah. So, we’re going to think about not being physically active. Women who are not physically active have a higher risk of getting breast cancer in general. We know this. We know that being overweight or even having obesity in menopause, so those older women who are obese, they have a higher risk. Now, that’s likely due to some aromatase activity. We’re going to dive into that as well. But these are going to be foundational lifestyle factors. We have control over these things. Can we snap our fingers and get better right away? No. But can we make progress? Absolutely.

Dr. Ruth Hobson (00:08:21) – The other thing, and we’re going to touch on this, is higher endogenous estrogens and androgen levels. I think most people are familiar with estrogen levels, but we’ll break down why androgen levels can also play a part in that. And then, of course, taking hormones. We think about women that are taking hormone replacement therapy, estrogen therapy, again for bone health. Do we have other risk factors we should be thinking of? Absolutely. But I also think about our younger population. Think about birth control that’s estrogen and progestin. Are we setting up our younger female population for breast cancer in the future? Possibly.

Dr. Ruth Hobson (00:09:04) – Again, we have to look at the individual in front of us and kind of stratify risk for them.

Dr. Kara Fitzgerald (00:09:10) – So it’s the synthetic progestins, actually the synthetic estrogens are potentially there as well, that are the problem.

Dr. Ruth Hobson (00:09:22) – Absolutely. And it’s the combination of the two when they come together. And we saw that in the Women’s Health Initiative and that’s kind of been taken forward. We know this, but I still, I don’t know about you, but I still see people in my practice on conjugated equine estrogen therapy and it drives me crazy. But it’s out there, so understanding risk and taking those steps for your patients is going to be really important.

Dr. Kara Fitzgerald (00:09:51) – I think also, and again, we’re talking to practitioners in this audience and we’re talking to really savvy non-practitioners, and I think the Women’s Health Initiative, the interpretation of that data set, has just been roundly criticized. And they should have stratified much more carefully what they were seeing and who was actually at risk and what they were doing.

Dr. Kara Fitzgerald (00:10:24) – So I think we’ve moved past the era, and tell me if you agree or not, that HRT is a problem.

Dr. Ruth Hobson (00:10:36) – Depending. I think when we look at HRT it might be route dependent-

Dr. Kara Fitzgerald (00:10:44) – I should say bioidentical HRT and taking into consideration history.

Dr. Ruth Hobson (00:10:49) – I think bioidentical replacement, again, route of administration, I think taking in risk factors- ACOG (American College of Obstetricians and Gynecologists) is not going to agree with anyone that has breast cancer taking hormones, right. So, we really have to think about this as practitioners. But you have a peri- or postmenopausal female, somewhere in that window, with lots of vaginal dryness, are we going to withhold estriol or those types of things from her? You know? Those are conversations to have. And for me, absolutely not. I think vaginal hormones have been shown to be less systemic, we’ll say that, then other estrogens. And so, we can think about, is it a route administration issue that we have seen? Typically, we’re swallowing estrogens or that’s what was seen in the data and in literature.

Dr. Ruth Hobson (00:11:49) – There’s very few studies on bioidentical topical hormones, at least large case studies that we can follow. So, I think when it comes to HRT and women’s health in general, we’re still kind of in the dark ages. We don’t know, still, enough about what we can do as far as giving hormones and then also mitigating risk. There’s a window, we kind of think about this ten-year postmenopausal window for safety that we got from the Women’s Health Initiative, and I will tread lightly with that in my practice, but there are outliers that I will say also. As we’re thinking about estrogens alone, I would say I’m typically giving progesterone for that balance, so just cluing in and keying in on what we can do as far as helping maintain balance, not increasing risk for our patients. And it’s going to be very individualized once you start to do this kind of medicine as you know.

Dr. Kara Fitzgerald (00:12:50) – Yeah. I do. Yeah, it’s interesting. And we also see- I want to keep going because we need to talk about how we’re going to cast a wide net here, but I just want to say that we look at HRT and the benefits with brain health, with cardiovascular health, I mean we see a pro-aging effect when our estrogens- you know, when we hit menopause. Women kind of catch up with men and we can measure biological age now, which is something that I’m focused on, and we see that happen when women hit menopause. They just move forward at an accelerated aging rate, potentially. So it’s an interesting conversation. It’s a conversation that I’m thinking about and having a lot these days. So, it’s the individual sitting in front of us. What are foundational tests that you’re going to be doing? You can talk about standard labs if you want to, but we’ve pulled together, we’ve taken a great history, we’ve identified what we think are potential risk factors. We’re either doing prevention or we’re working with somebody who’s got cancer or a history of cancer. What are we going to look at with labs?

Dr. Ruth Hobson (00:14:13) – I tend to let risk factors that I’ve gathered from history taking lead me in that direction. For that I think it’s obviously hormones, right? I want to see what’s happening at the hormone level. I am a practitioner who also works in clinical education at Doctor’s Data, so I am utilizing their testing, their vast catalog. It’s great for me. But there are two options that kind of come to mind and we can talk about who’s a better fit for that and what that looks like.

Dr. Kara Fitzgerald (00:14:44) – Let’s talk about it.

Dr. Ruth Hobson (00:14:45) – When we think about hormone testing, salivary hormone testing is an option. We also have urinary metabolite testing. Now, I will say, is there one that’s better than the other? That typically comes up in my mind, and really, it’s what am I trying to address? What do I want to see? If I’m utilizing saliva testing, I think “okay, well this will give me what’s happening at the tissue level.”

Dr. Ruth Hobson (00:15:11) – I can see elevations of estrone, estradiol, where’s my estriol marker? And why that’s important is that E1 and E2, they have a lot of affinity for the estrogen receptor. And remember again, we were talking, the estrogen receptor is indicated in breast cancer risk.

I want to see how much we have there. Are they at normal levels? Are they really high? They could also be really low, and that’s again, where HRT, we do have those facts. They are in the back of our mind. And then estriol, thought of as more of a protective estrogen, it’s not really proliferative, it’s kind of weak when it’s competing for that estrogen receptor. But it also has potential protection benefits and is thought of as an anti-estrogen, and interestingly for vaginal dryness. We can use it for vaginal dryness and we don’t see it raising levels of E1 and E2. So, it seems to be more of a safer bet.

Dr. Ruth Hobson (00:16:12) – So I will utilize this when I have someone who maybe has a family history of breast cancer, or maybe is thinking, I’ve had breast cancer in the past and I am at 5-year survival, and I’m just really nervous about estrogens. They have these complaints coming up. I will think about estriol. I will. I have no hesitation in that at all.

Dr. Ruth Hobson (00:16:37) – The other things to consider when we think about saliva is I like to look at my level of estradiol to progesterone. I think of these as best friends, and on a little seesaw where estrogen is going to promote growth and we have progesterone that’s going to help with differentiation. Now, when we think about cancer in general, there’s ER/PR+ cancer, so we’ll see that estrogen and progesterone can work to grow tissues together. I like to see what’s happening endogenously to say, do we have an imbalance? Is there way more estrogen than there is progesterone? Or are we really deficient in progesterone? Are we creating these estrogen dominance symptoms? And you can see that. Think about the postmenopausal female hot flashes. Climacteric symptoms are pretty easy to think about estrogen dominance.

Dr. Ruth Hobson (00:17:30) – But you’ll also think about mood instability and those types of things. And so, I like to see if we have this dysfunctional ratio, where is it? And if I’m thinking about hormones, I tend to do topical hormones, again, I want to avoid swallowing hormones. Yes, I do patches. I’m not a huge fan of pellets, and the only reason is, if you get it wrong you’ve got to ride them out. I want to assess levels, and saliva is where I can actually look and find that.

Dr. Kara Fitzgerald (00:18:01) – What about what about oral progesterone? You don’t use oral progesterone?

Dr. Ruth Hobson (00:18:06) – Yeah, I will use oral progesterone if I get a patient who has some history, let’s say still has a uterus, I’m going to want to give oral progesterone. One, because it mitigates risk. We see that in the research as far as proliferation of the endometrium.

Dr. Ruth Hobson (00:18:24) – So I’m not only thinking about breast health, right? Multiple organ systems here. I want to protect that endometrium. So, I’ll give some. I also will give it to female patients that maybe have issues with sleep, because we see it is metabolized to allopregnanolone which has those really nice GABA like sleepy effects that we can get. And so, it can be a really beautiful treatment for a lot of women. I would say, caveat, swallowing estrogen, and testosterone, that’s just not something that I will do, but progesterone I feel okay with.

Dr. Kara Fitzgerald (00:19:03) – Even in your breast cancer patients? Or where are you at with that?

Dr. Ruth Hobson (00:19:07) – Yeah, so I typically am seeing active breast cancer patients and I will work with oncology. I have never had an oncologist say “Yeah, go ahead with hormones!”  So, we’re typically waiting until they’ve at least completed the course (of treatment), or we see that there is no growth. But I will say, survivor, if you’ve made it to your five year, you’re at this mark, I don’t have an issue with it. Most healthcare practitioners are also following up with oncology. We are doing labs, we’re making sure things are healthy, we’re looking at tissues. I think as long as we’re being smart about it and we know there’s an increased risk, I think we can do hormone therapy in a safe way.

Dr. Kara Fitzgerald (00:19:52) – Safely. Okay. So then leapfrogging there, you talked about saliva, so, you’re using your own hormones? Let’s keep talking about the labs.

Dr. Ruth Hobson (00:20:01) – Yeah. When we think about urinary testing- So urinary hormone, and I would say gosh, we’ve seen in the past 8-10 years, really exploded, not only in the labs that are available, but also the research. That’s been incredible to watch. I love urinary testing because it allows me to see what’s happening with the hormones as they’re moving through the body. I’m not utilizing it for necessarily establishing if we need hormones or if I’m going to use hormones. I’m looking at what is your metabolism? What’s the risk? What’s happening there?

Dr. Ruth Hobson (00:20:39) – It’s also helpful if you have patients that come in, I have some 5-year survivor patients who have had already hormone replacement therapy that maybe they want me to take over or assess, I can utilize this to see is it safe? Are we at a point where we think these things are safe? It’s really cutting edge. I enjoy that this is where medicine is going. We’ll see about estrogen metabolism in general because we’re still in this era we can think about, How do we have these endogenous estrogens? Where are they coming from?

Dr. Ruth Hobson (00:21:17) – So, besides E1 and E2, I will say, let’s think about their metabolites. Because their metabolites actually have action within the body. Not all of them, but you will see action within the body. Let’s just think about the three main: the 2, the 4, and the 16. So, 2-OH, and that’s going to be hydroxylated metabolism of E1 and E2. So, we’ll talk about that. I love seeing those E2 metabolites. Those are actually as harmful, or not harmful, as the E1. So, it’s nice that you can get both of those.

Dr. Kara Fitzgerald (00:21:59) – Let me just define your abbreviations. So, E1, or estrone, and estradiol, or E2, are being converted. One of their metabolites is 2-hydroxyestrone, or estradiol.

Dr. Ruth Hobson (00:22:14) – Absolutely.

Dr. Kara Fitzgerald (00:22:15) – Yeah. So you’re talking about that. You’re looking at the 2-hydroxyestrogens.

Dr. Ruth Hobson (00:22:21) – Yeah. And those are typically considered safer. And the reason they’re considered safer is they don’t really have estrogenic activity. In fact, they might be anti-estrogen.

Dr. Kara Fitzgerald (00:22:35) – Is that their protective mechanism? That they’re a little bit anti-estrogen? Okay.

Dr. Ruth Hobson (00:22:42) – Yes. And then we have 16-OH-E1, so 16-hydroxyestrone. This one is sort of a gray area as far as its ability to infer risk.

Dr. Ruth Hobson (00:22:54) – And it might also be age dependent. For 16-OH-E1, we see in the premenopausal female, 16-OH seems to impact breast health and it can be in the negative. 16-OH is estrogenic, not as estrogenic as estradiol, but has lower bonding affinity to that estrogen receptor. But it does bind. We see premenopausal breast health becomes the concern there-

Dr. Kara Fitzgerald (00:23:29) – So if they’re dumping a lot, if they’re metabolizing aggressively towards that 16-hydroxyestrone in a premenopausal woman, that’s going to grab your attention to do something about.

Dr. Ruth Hobson (00:23:42) – Absolutely. That’s absolutely going to grab my attention.

Dr. Kara Fitzgerald (00:23:44) – And that might be the cause of their complaints if they have the estrogen dominant kind of collection of symptoms, it could be that metabolite. In fact, you might even look at the estrogens themselves and they’re not remarkable and then you do a metabolite panel and you see that and boom.

Dr. Ruth Hobson (00:24:02) – Absolutely. You know, it’s just like light bulb.

Dr. Ruth Hobson (00:24:06) –I’ll bring up why 16-OH-E1 is the gray area for me, at least is when you look at the postmenopausal female, 16-OH is really important for bone health. And again, it’s because it binds the estrogen receptor, right? So, what I don’t want to do in my postmenopausal female is try to drive it low. I’m not going to drive it low. Even if it’s low range or within range I’m happy because they need all the help that they can get as far as maturity. New fall risk and break become really devastating to women as we get older. So, anything we can do to support bones is really important.

Dr. Kara Fitzgerald (00:24:51) – Yeah. Yeah. So premenopause we want it low. Postmenopause we may want to maintain it if it’s present. Can you actually encourage- Do you ever think about, in your postmenopausal, especially your osteoporotic population, actually encouraging production of 16-hydroxyestrone?

Dr. Ruth Hobson (00:25:12) – You know, a great way to do that is giving a little bit of estradiol, estriol, Biest, something in that way, and it will increase.

Dr. Kara Fitzgerald (00:25:24) – You’ll see that increase it. So that’s how you would do it. Okay.

Dr. Ruth Hobson (00:25:27) – Yeah. And there are things like vitamin D, fatty acids, those go into play as far as helping that enzyme activity work. I’ll just give you the name – CYP3A4 is going to be the enzyme that we target for 16-OH and that’s going to be, you know, you can even use things like valerian, there’s valerian research in there. Saint John’s wort-

Dr. Kara Fitzgerald (00:25:54) – A little sleep aid that actually, very indirectly, can help with bone density in our postmenopausal, and also give them a little bit of a hit of estrogen which can help with plenty of other issues. Yeah. That’s interesting. Wow I haven’t tried that. Good. Yeah, that’s really interesting. Get some good sleep and help with bone density, among other things. That’s cool. Okay.

Dr. Ruth Hobson (00:26:18) – Also, we’re thinking about the more harmful, and a lot of attention has been given to 4-hydroxyestrone and -estradiol. And we’ll typically think of those 4-hydroxy metabolites as more proliferative. I will even use things like genotoxic carcinogenic potential. I really hate to say cancer when I’m with patients, but those things can-

Dr. Kara Fitzgerald (00:26:43) – Genotoxic. Yeah

Dr. Ruth Hobson (00:26:44) – It’s genotoxic, right?

Dr. Kara Fitzgerald (00:26:45) – And that’s beyond breast cancer, is that correct? Because of the mechanism, It’s not exerting necessarily an estrogenic effect. It’s genotoxic. It’s damaging DNA.

Dr. Ruth Hobson (00:26:58) – Yeah. And it does have to do with how much we have and is it metabolizing appropriately through. So as 4-OH by itself, it has potential. And then the next step, we can talk about methylation and COMT, and we’ll kind of move into that, the next step if it’s missing, 4-OH has the potential to then move forward and create what we’ll call quinones and semiquinones. But I often think about those as just DNA damagers, right? We’re just leading to more redox reactions and things that are going to take place in that way.

Dr. Kara Fitzgerald (00:27:41) – So if you have a bunch of 4-hydroxy and you’re not appropriately methylating it, then you’re vulnerable to damaging DNA.

Dr. Ruth Hobson (00:27:50) – Yeah, absolutely. And again, we’re specifically talking about breast health. I think any time we talk about damaging DNA, this is going to be not just in these little breast genes, right? We’re potentially causing it in other areas as well.

Dr. Kara Fitzgerald (00:28:07) – Yeah. I think that’s an important point to underline and why it’s a reasonable idea for us to be looking at these metabolites in men. I mean, men have estrogen. In some men more than others. I mean, if you’re a man with a lot of inflammation you’re going to be moving your testosterone to estrogens, and I know we’re going to talk about that. But yeah, I think having some of this data on men could really be important. What do you do about that when you see somebody with a lot of 4-hydroxyestrone?

Dr. Ruth Hobson (00:28:40) – Yeah. So, I will say it’s always the conversation, right? Like, do we attack diet? Do we think first about giving some supplementation? I tend to do a little combination of both.

Dr. Ruth Hobson (00:28:55) – But one thing, I do have lifestyle risk factors in my mind. So, things like polycyclic aromatic hydrocarbons, PCBs, you mentioned inflammation for sure, UV exposure. And I don’t mean just a little bit, I mean like farm workers. Think about, I’ve been out a lot or I’m an avid gardener and I’ve been doing it for 20 plus years and I wear a hat but not sunscreen. There are things to be thinking about there. All of that is going to upregulate CYP1B1, and that enzyme is what is going to increase our 4 (-hydroxyestrone). And so right there, if we can just take a little lifestyle review and think, are there things that we can take out? Are there things we could switch or replace, or habits we can change? I think that’s generally where I like to start. I’ll say most practitioners currently, we think about utilizing things like DIM (Diindolylmethane), because DIM can help raise the 2 (-hydroxyestrone), which is considered safer and move metabolism more in that way.

Dr. Ruth Hobson (00:29:59) – But I also think we should look at resveratrol. There’s a lot of interesting research in resveratrol, and what I loved about finding this research was it really changed the way looked at my practice. There was a study that came out in 2019 in the publication Nutrients, and it was looking at just metabolic health and obesity, not even breast cancer. But when we think about some of those risk factors, it sounds very similar, doesn’t it? It’s not moving our body, high insulin, inflammation. And what they found was specifically looking at urinary metabolites, is that resveratrol has the ability to upregulate 1A1. So that’s our 2(-hydroxyestrone) pathway. It also can help downregulate our CYP1B1. So that’s our 4 (-hydroxyestrone), so we can downregulate how much is going through, you want to use it in that way. And then we also mentioned semiquinones, quinones, and we’re going to get there in the next step, but it can also increase semiquinone reductase.

Dr. Ruth Hobson (00:31:09) – So that mechanism, you think about that enzyme happening, it’s going to decrease the amount of semiquinones we’re making and also be protective against genotoxic potential down the road. I love resveratrol. When we’re thinking about metabolism, I think most people’s go to is DIM, and that would be more just straight focused on – or I3C, (indole-3-carbinol), and that’s great because it can help increase 2 (-hydroxyestrone). But what if 2- is high or within range, upper range? And then what? Well, just hydroxylating, I should say – just that act of taking estrone and estradiol into that 2OH pathway, just hydroxylating, that creates a little bit of these non-paired electrons. So, even though safer, do I want the 2(-hydroxyestrone) to be really high or do I want to shove everything over because I’m worried about the 4-OH? And I would say, I don’t think that in medicine, or just in life in general, that makes a lot of sense to just keep piling on one.

Dr. Ruth Hobson (00:32:18) – So I think we need to also think about other areas where we might dive in and can we use them together? Absolutely. Absolutely.

Dr. Kara Fitzgerald (00:32:27) – So a combination to manipulate the production of 4-hydroxyestrone as well as the 2-hydroxy estrogens is going to be an intervention for you. And resveratrol is a go to, but you’re probably using DIM, I’m assuming, or I3C as well.

Dr. Ruth Hobson (00:32:44) – Yes

Dr. Kara Fitzgerald (00:32:45) I want to go back and ask you- We talked about promoting 16-hydroxyestrone, but what about inhibiting it? So, you’ve got a premenopausal woman, you don’t want to have a bunch of 16-, what are you going to do for that person, for the CYP3A4?

Dr. Ruth Hobson (00:33:05) – So this is complicated because of the enzyme it utilizes for metabolism. It also affects estriol, so our more protective. So, I tend to go lifestyle modifications first, and that would be, we could we think about adjusting if someone’s smoking, or do they have aflatoxin exposure, are they insulin resistant? Those are the things I’ll look at in that way.

Dr. Ruth Hobson (00:33:35) – Are we doing HRT? Because that could add to estrogens that are metabolizing and maybe we’re favoring this enzyme. Endogenously, let’s think about xenobiotics. So, there’s all those things that I will touch on before I see those levels really make a big shift. So, usually I’m working above. I’m working the step above.

Dr. Kara Fitzgerald (00:34:03) – Okay. Because if you inhibit the 16-hydroxyestrone production, that metabolite, you might negatively impact estriol, E3. And so, you want to avoid that. So, if you work upstream and just optimize estrogen production in general, you may be able to balance out 16-. Okay. That makes sense. Yeah, that makes a lot of sense. Just thinking about inflammation, driving increased production and imbalance of estrogens, doing that piece alone could go a very long way.

Dr. Ruth Hobson (00:34:45) – Yeah, absolutely.

Dr. Kara Fitzgerald (00:34:47) – What about glutathione? Are you using glutathione in there at all? I see that it’s something that a lot of folks are thinking about. Yeah, go ahead.

Dr. Ruth Hobson (00:34:56) – Yeah, interestingly, NAC (n-acetylcysteine), so the precursor (of glutathione), it has similar effects as resveratrol, so yes, I’m using it. If it’s in certain formulas you can get it. We still have access to it. I will say the only thing it doesn’t tend to do –  so it does have the same 2 mechanism, upregulate 2-OHE1 downregulates 4-OHE1, it doesn’t seem to upregulate semiquinone reductase. So, while I still use it, it’s maybe someone who is a great methylator, someone who maybe has really high 4-OHE1, but they are the next step. And we can kind of talk about that, but to inactivate our more harmful metabolites, we’ll think about methylation, so COMT specifically here, and we’ll think about its action there. But once we can methylate these harmful metabolites, they get to leave the body and they aren’t reactive. Once they’re methylated, they’re not reactive. So 4-methyl E1 and E2, so 4-methyl estrone and -estradiol are no longer active once you can methylate them.

Dr. Ruth Hobson (00:36:13) – So that’s the power in methylation that happens here. Let’s say that I have someone who has a lot of 4-OHE1, but they’re also good methylators, they are also producing a lot of 4-methyl. I’ll still give a little NAC because we know that 100% doesn’t really happen in biology. There’s going to be some things that are leaking through. So, I’ll do a little bit of NAC as well to kind of downregulate 4-OHE1 and then also-

Dr. Kara Fitzgerald (00:36:44) – Got it. So even though they’re methylating great, because you can follow that on the HuMap, you can see their methyl metabolites and they’re doing a good job, you’re going to be a little bit protective because their overall burden of 4-OHE1 is higher. And so why not be careful because we know that intermediate is so toxic. The 4-hydroxy. Yeah. That makes a lot of sense. That makes a lot of sense.

Dr. Ruth Hobson (00:37:07) – Absolutely. And then, having conversations with individuals who maybe aren’t the best methylator.

Dr. Ruth Hobson (00:37:14) – One thing I really love about the HuMap itself, is that you’ll see methylation potential of the 4-. There are four areas we can look. So, we can look at what’s happening with the 2- and the 4- and how are they being methylated and moved out. And they don’t always line up. You’re not going to see straight – sometimes you do – straight across the board, we’re really low in those four areas, or straight across the board really high. You’re going to kind of get a mix and mixed picture there. And so, I also like to bring in diet. I’m a big proponent of diet as, this is our 24 hour a day medicine. Supplements, they have half-lives, they come in and they go out. But when we think about diet and nutrition and things that our patients can do every single day, I have a lot of talks about, can we increase our dark leafy greens or cruciferous vegetables in general. Organ meats, I know that’s controversial, but liver is so healthy. You know, small amounts, we’ve got to be careful with sourcing. We have to think about those places. Mushrooms, we have a lot of research in mushrooms is coming up, too. So, I’ll say-

Dr. Kara Fitzgerald (00:38:25) – Specifically doing what? What are you reading about mushrooms?

Dr. Ruth Hobson (00:38:28) – I have been interested in just-

Dr. Kara Fitzgerald (00:38:31) – Everything you’ve just listed I’m a huge fan of, but I’m curious of what you’re thinking about regarding mushrooms.

Dr. Ruth Hobson (00:38:37) – That mushrooms have potential for methylation. So that’s been a new interesting-

Dr. Kara Fitzgerald (00:38:43) – Choline, folate, yeah.

Dr. Ruth Hobson (00:38:45) – Yeah. And it makes a lot of sense, it’s the mechanism of action. I wasn’t really putting together with some of the foods we’re eating. And these are things you can’t- When you’re extracting and putting things into biopharmaceuticals, you’re extracting ingredients. I think we’re missing something.

Dr. Kara Fitzgerald (00:39:06) – Yeah, we’re missing a lot of information. We are for sure. We’re missing a ton. If you think about a fork full of a well-designed salad and the amount of information there versus an isolated constituent, it’s just it’s not even comparable.

Dr. Kara Fitzgerald (00:39:23) – And to your point, many exposures, many forkfuls at least a couple times a day for most of us, a few times for some, of this information is powerful medicine. I absolutely agree with you. My own story, I pay attention to my metabolites as well, and I’ve got a COMT mutation, I’m homozygous. So technically, it should appear as if my ability to make my 2-methoxys and 4-methoxys should be challenged because of this. But following exactly just what you said, basically the diet that we’ve been using in our research to look at DNA methylation, has been incredibly helpful for my estrogen metabolism. I’ve got the most exquisite estrogen metabolite panel now than I’ve, you know, in my life. And I was in a lab for my postdoc, too many years ago at this point, but we released one of the first, if not the first I think, panel of looking at these advanced metabolites, many moons ago.

Dr. Kara Fitzgerald (00:40:36) – The lab’s not around anymore. But yeah, I’ve been tracking them since then and they were always difficult for me to dial in. In fact, I leaned heavily on isolated nutrients. We prescribed folate and B12 all the time. I leaned heavily on those. But changing it to this very concentrated methyl donor, methylation adaptogen, in this nutrient dense diet that you just described, including liver. But I don’t eat that much liver, actually I take it in caps. It gave me an envious estrogen metabolite panel, I’m pretty psyched to see and say. So, yeah. It would be nice to actually research that, using our program and do something like that. It would be super interesting because-

Dr. Ruth Hobson (00:41:20) – I would love that. You should definitely do that. It’s so interesting.

Dr. Kara Fitzgerald (00:41:23) – Yeah, it is. It is.

Dr. Ruth Hobson (00:41:25) – Do you find now that you are relying less on those single constituents.

Dr. Kara Fitzgerald (00:41:30) – Oh, 100%. Absolutely.

Dr. Ruth Hobson (00:41:33) – But are you still utilizing them?

Dr. Kara Fitzgerald (00:41:34) – When they’re indicated in my patients of course. Yeah of course. If you’ve got somebody who’s got macrocytic anemia, or if you’ve got somebody with a real marked, phenotypic presentation of B12 deficiency, they’ve got neuropathy, etcetera, yeah. It’s too important not to utilize those nutrients. In pregnancy, pre-pregnancy there’s always a time. But in our study, we increased circulating folate significantly in our study population as compared to the control group, and without a folate in site, without a vitamin in site. So, it absolutely can be done. And I just read another study, the Green Med study, where they used a polyphenol dense Mediterranean diet and same, you know, they increased circulating folate. And I just measured my own. I’m sorry, it’s my lab time, everyone, you know, annually. So, it’s my lab time. I’ve got all this fresh data in my head from doing my own labs, and my circulating folate is great. It’s in the upper limits and so is my B12 without actually taking those isolated nutrients.

Dr. Ruth Hobson (00:42:42) – I love that. And honestly this is what I tell my patients all the time. is it takes diligence and just the willingness to change. It’s a daily practice. For a lot of people, it’s a big shift to eat this way, so that’s why capsules are just so easy for most people. But like you’re saying, you just get so much more-

Dr. Kara Fitzgerald (00:43:05) – You know, I’ve got years of data and capsules did not do as good a job as whole food. That’s what I’ve seen in my N of one. And now I’ll hopefully I’ll gather more. I’ve got plenty of patients following this and I’ll just have to go through my database and look and see if I can see a pattern in it. But it’s just been really cool to see and it would be a nice area for us to dive in. So, you can go back to Doctor’s Data now.

Dr. Kara Fitzgerald (00:43:35) – Yeah, that’s cool. All right, so where are we? We’re talking about the urine metabolites, working with the diet, some select interventions. I have to ask, somebody out there is thinking resveratrol, wine, can I just drink a nice, you know, a couple of big glasses of red wine and manipulate my estrogen metabolites favorably? What say ye?

Dr. Ruth Hobson (00:44:01) – You know, I wish I could give a big green light for that, but honestly, no. Actually, I didn’t even mention, but alcohol is one of those risk factors for breast cancer that I didn’t touch on. It’s kind of off the table when we think about it, and honestly, I recently read a study that came out that said no amount of alcohol is actually beneficial. Even though we have some data that says, may potentially (reduce) heart risk, or this or that, you know, no. I wish. It sounds great, but it’s a big no.

Dr. Kara Fitzgerald (00:44:34) – I know, I know. And there’s not that much resveratrol, unfortunately, and it inhibits methylation. So just going back to something we’ve been focusing on, alcohol specifically inhibits the methylation cycle itself. So, that would be perhaps one of the reasons why we see the associated increased risk.

Dr. Ruth Hobson (00:44:53) – Yeah, absolutely. Absolutely.

Dr. Kara Fitzgerald (00:44:55) – I’m sorry. Anybody who who’s out there drinking. I’m so sorry. Okay, so what else do I want to ask you here? Additionally, any other tests you want to add beyond the hormone testing that we’ve already talked about? Are there any standard labs you want to mention? We’re going to get into talking about gut health, or we can jump into that now. But talk to me about additional testing.

Dr. Ruth Hobson (00:45:26) – I think the other hormone that I want to touch on is androgens. We have all this data and all this research about estrogens and what happens, but we’re actually starting to…  pretty new studies. These are things that are kind of in their infancy but realizing that androgens actually play a big role in this.

Dr. Ruth Hobson (00:45:46) – And now when we think about back to our risk factors of obesity, we can think about metabolic syndrome, or not being physically active. What does that equal? The fatty tissues, right? Fatty tissues have their own hormones. We’ve known that for years. And we specifically will think about an enzyme called aromatase. So, aromatase in men, what we typically see, is that their testosterone will actually turn into estrogen. Yes, it’ll plummet and then move over into estrone, estradiol. Also, gynecomastia, right? We can see that male breast development happens. We know that there’s some growth and proliferation happening with aromatase. So that’s one thing to think about. You know, it’s interesting, the mechanism for women with aromatase, is the female population will have high androgens and then we’ll also have high estrogens, right? So, they don’t drop, we continue to stay high. What’s interesting here is we can think about how to modulate that. We could use aromatase inhibitors and there’s some nice natural ones that we can think of.

Dr. Ruth Hobson (00:46:57) – We can say like a chrysin for example, or my favorite, resveratrol, comes up here. But grape seed, ECGC (Epigallocatechin gallate) comes up. But really the foundational problem is that we have this peripheral fat, these peripheral fatty tissues. So that’s one way that androgens are going to impact. Another way that they’re going to impact is in metabolism, and this was interesting. There’s a study that came out in 2021, it was published in Cancer Epidemiology Biomarkers and Prevention. What was interesting about it is they used urinary hormones, and this is a nested case control study, so they had pre- and postmenopausal women and they were all participants in New York’s Breast Cancer Family Registry. We had 64 women that had breast cancer and 124 without, and I want to remind everybody, they all have family history. And what they found when they were doing this metabolite testing is that it was actually some androgens popped up that were surprising. And that was androsterone or some people say androsterone, and then the 11 oxidative process of that, or OHAN is how it’s written out there – OHAN, so it’s 11-hydroxy-androsterone.

Dr. Ruth Hobson (00:48:22) – And what they found was 70% of primary breast cancers had androsterone elevation. So that’s-

Dr. Kara Fitzgerald (00:48:29) – Interesting. Wow. That’s kind of that stops you.

Dr. Ruth Hobson (00:48:31) – Yeah. And actually, in the study, (they were) higher than the estrogens.

Dr. Kara Fitzgerald (00:48:40) – The androgen metabolites were higher than the estrogens in this 70%? Wow.

Dr. Ruth Hobson (00:48:47) – Yes. And then we were thinking about risk here- and they also determined that the 11 oxygenated form or hydroxy form of that, so 11-hydroxy-androsterone, that had a 90% increase. We saw a huge study that came out and this study is interesting because they’re also thinking, and the researchers here were postulating, that could we add into risk calculators like the Gail Model – Just kind of throw that out as something to think about for breast health in primary care. You can stratify your patients and put them into this calculator. You can find it online if you just Google that, you’ll find it. But their question was-

Dr. Kara Fitzgerald (00:49:35) – We’ll link to it, by the way, on the show notes. And folks, we’ll grab these papers and make sure all of this is on the show notes. In fact, we’ll make sure the HuMap, the test is on the show notes. I should have said that earlier so that you can actually look at it as we’re talking about it here, which is helpful. Go ahead.

Dr. Ruth Hobson (00:49:50) – So, they’re actually looking to determine if we could increase the efficacy of these. And what they saw was, yes, adding these androgens actually had a more predictive value of breast cancer looking in this population. I don’t have the stats on how much it increased, but I want to say it was by maybe even 2 to 5%, which can be helpful. And that was for those, again, moderate to normal risk women. So that’s pretty interesting when you think about androgens and just their metabolites. So, what would we do?

Dr. Kara Fitzgerald (00:50:29) – Yeah. What do we do? Well, let me ask you first, what’s on the HuMap for these metabolites? And then let’s talk about what we’re doing.

Dr. Kara Fitzgerald (00:50:36) – And I also want to make sure we talk about how often you’re using these tests. How often are you doing the HuMap?

Dr. Ruth Hobson (00:50:44) – When we think about HuMap, what’s on this test, you’re going to see several neighborhoods, I like to call them, of hormones. We look at progesterone, its major metabolites, we’re going to look at allopregnanolone, it’s going to be involved in that. We are going to look at-

Dr. Kara Fitzgerald (00:51:00) – That’s the feel-good progesterone metabolite. We want we want that.

Dr. Ruth Hobson (00:51:05) –That’s GABA. Yeah, you can get your sleepy wine effects from allopregnanolone there. And then we’re going to think about androgens. We’re talking about them now, but, DHEA, DHEAS is going to be on there. We will see testosterone, two major metabolites of testosterone, you’ll see etiocholanolone and androsterone. You’ll also see things like androstenedione, another big player as far as androgens happening. And then some other smaller metabolites like this 11-hydroxylated androsterone.

Dr. Kara Fitzgerald (00:51:42) – That’s on the HuMap?

Dr. Ruth Hobson (00:51:43) – It is on the HuMap.

Dr. Ruth Hobson (00:51:44) – Yeah. So, we can look at that. Interestingly enough, same study. You ever find that study and you’re like, this is amazing. Same study looked at cortisol metabolites.

Dr. Kara Fitzgerald (00:51:59) – Interesting.

Dr. Ruth Hobson (00:52:00) – And sure, we know stress is important, inflammation, we see cortisol spiking, not just in breast health, but just in in the body in general.

Dr. Kara Fitzgerald (00:52:14) – Yeah. Driving chronic disease for anything because we see the stress involvement. But yeah. Go ahead. What did they show?

Dr. Ruth Hobson (00:52:20) – So when they were looking at these metabolites, it showed that if they were doubling the concentrations of these metabolites, that – and I’m going to give you some names – but it’s really the metabolites of cortisol, cortisone and corticosterone. So THE, THF, 5A-THF and then THA and THB, those were associated with some increased risk, and that was, in the order that I gave them in, 161%, 116%, 75%, 83% and 52%.

Dr. Kara Fitzgerald (00:53:01) – Massive. Okay. Again, we’ll have that study is in the show notes, folks, which is on the website actually, DrKaraFitzgerald.com, you can go to the Learn tab, find podcast, and then you’ll pull this up or you can just click on the link in your email if you get this podcast via your email. That’s huge. I want to know what you’re doing about it. You have this data, it’s incredibly compelling. Was there anything else you wanted to add to the study before I-

Dr. Ruth Hobson (00:53:29) – No, no. That’s it

Dr. Kara Fitzgerald (00:53:30) -Before I move you towards like, let’s talk about intervention? Because those are some really powerful statistics. Some scary statistics, quite frankly.

Dr. Ruth Hobson (00:53:38) – Right. And what I found interesting about it is we are so focused on estrogens and gene mutations when there are a lot of other foundational things within the body that we could address. So, what am I doing for cortisol metabolites? Well, first of all, I’m looking at cortisol in general.

Dr. Ruth Hobson (00:54:01) – Is it spiking? Is it high? Is that the reason for these metabolites? Sometimes that’s the case. Yes, absolutely. You’ll see high cortisol, cortisone, and that will equal high metabolites. You would expect that, right? The other things that I’m finding, and this is pretty interesting, is that urinary metabolite testing will actually give you an idea of what’s happening with things like inflammation and thyroid health. Are they metabolizing? I would say more thyroid, but then inflammatory processes within the body, sometimes you’ll see just relatively normal cortisol in these massive metabolites, and so, you know you have a fire. It’s just getting to where is the fire that we need to put out. Those higher metabolites always make me go back in and say, what am I missing? And honestly, I would say in my practice you need to kind of ask, how often are you testing? What are you doing? I would say any woman with history of breast cancer – history- or anyone that is at that five-year survival.

Dr. Ruth Hobson (00:55:16) – I don’t really get a lot of active breast cancer. You could test in that population too, but those are women that I really want to see what’s happening, not only with the estrogen and how they’re metabolizing, but in lieu of this study, what’s happening overall. Or do we have a lot of androgen metabolites? Is cortisol metabolism out of control? And if it is, let’s work to see where we can modify that. And to be completely honest, I’ll say a big factor in that sometimes is also more testing. When I say that, I think specifically about inflammation. I don’t know about you in your practice, but I like to pair gut testing with that because I think I get a lot of information from just gut health, and a stool sample can tell me sometimes more about a person than they’re going to even give me in their office. So, I also will rely on these two tests together to give me the most information.

Dr. Kara Fitzgerald (00:56:17) – Awesome. So talk to me about why stool testing gives you more than you might get in a clinical history from the actual patient. That’s provocative.

Dr. Ruth Hobson (00:56:26) – They can’t hide anything, right? I see what they’re eating, I can see if they have digestive fibers that are there, I can see all the things. But the biggest thing I think about, most patients, again, risk factors, sedentary lifestyle, standard American diet, high fat, really low, nutrient dense. I’m going to see that pop up. And the way that we see that is we’ll think about dysbiosis in general. I would say it’s an emerging field, dysbiosis, and how it can relate to breast health, but dysbiosis in general is something that I attack as soon as I see it. And the reason for that is, honestly, our microbes are probably more in charge of us than we were realizing. And besides breast cancer, so many plethora of other diseases are linked to lack of diversity within the microbiome. So that’s something that’s really important to me.

Dr. Ruth Hobson (00:57:32) – But also, when we have dysbiosis, we have inflammation, we’re going to increase our macrophages and that’s going to increase our pro-inflammatory situation and increase IGF-1. And we know that’s increased in tumors and metastasis, even. I typically will think, okay, when I have someone who is high risk, I need to see what your gut looks like. Actually, this was kind of new to me when I got a couple patients that – It always happens, you get these patients that come to you and you don’t seek them out, but all of a sudden, somehow you were this breast health expert because they keep coming to you. So, it makes you dig in the research and it really does push you as a practitioner. I do love that about medicine. But I remember I stumbled upon a study and it was linking that the breast might have their own microbiome, and I thought, well, that’s really interesting.

Dr. Ruth Hobson (00:58:39) – You know, of course we think about breastfeeding an infant and how you’ll pass your gut bugs onto an infant in that way. Okay, that makes a lot of sense. I didn’t actually think about breast tissue themselves having this microbiota situation happening. I just didn’t. And then I stumbled upon a research study, I want to say it’s 2016, it’s a team out of the Mayo Clinic, and what was interesting about this study is they were looking at benign breast disease tissue and breast cancer tissue, and these were sterile samples. And what the researchers actually ended up finding within this was that they had microbial DNA. They were kind of like, where did this microbial DNA come from these sterile samples? And so, postulating that we do have this microbiome that also exists within in our breast as well. And so that has often made me stop and think: How did it translate from our gut to our breast? And they don’t really know. The research here-

Dr. Kara Fitzgerald (00:59:51) – And there was a difference, obviously, between the healthy tissue and the breast cancer?

Dr. Ruth Hobson (00:59:55) – Oh yeah. There was a difference between- Well, they didn’t look at healthy tissue, they only looked at benign breast diseases such as fibrocystic breast disease, they had tissue that had infiltration, so not cancer per se, but in situ or something in that realm. And it all had some sort of pathogenic kind of DNA. No real markers between to say that you can land your hat on these specific microbes are involved, but just interesting that they were there. And that made my head think, oh, I do have a background in pediatrics and women’s health and you’ll see mastitis will often pop up after breastfeeding and really just in the flora there can be an imbalance, right? It can just be staph, just normal overgrowth of your own flora. And so, I started to use that mechanism and think about it a little bit, that just the imbalance in that breast microbiome that I wasn’t really considering actually could produce disease.

Dr. Ruth Hobson (01:01:02) – And so let’s think about, fast forward a little bit of time, we still don’t know how it happens, but there are some postulations out there that we have some communication between the gut and the breast that could be maybe dendritic cells, but also could be due to leaky barriers. And that is what allows some of these more inflammatory microbes to move throughout the body. And again, inflammation, if we can think about how to control that, look at all the hosts of things that we can potentially have a mark on. There was a study that came out looking at a primate breast microbiome, and basically the researchers were trying to postulate could we manipulate the internal environment, could we utilize things from the gut? Would that help with that change? And so, what they did was they looked at 40 primates and they fed a Mediterranean diet and then they fed a high-fat diet.

Dr. Ruth Hobson (01:02:14) – So, it’s Mediterranean versus standard American. Perfect. And what they saw was that the Mediterranean- And they took breast tissue samples. Sorry, I hate sometimes reading this research, but it’s very informative. And with baseline levels you see similar patterns. They increased fat in one and they gave a Mediterranean diet in the other. And what you see is Lactobacillus, which is huge and foundational within in the breast, actually bumps up about ten times that of the fat.

Dr. Kara Fitzgerald (01:02:52) – In the Mediterranean diet. So, you see more of the good guys increase on the Mediterranean diet. And this is in the actual breast tissue? This is not the surface.

Dr. Ruth Hobson (01:03:02) – Right. This is actual breast tissue samples.

Dr. Kara Fitzgerald (01:03:05) – That was so interesting.

Dr. Ruth Hobson (01:03:06) – It is really interesting. And so, it gives me an idea that if I can focus more on making sure that my internal environment in my patients is where it needs to be, and that is going to be making sure that I’m doing things like increasing short chain fatty acids. Right?

Dr. Kara Fitzgerald (01:03:27) – And that study demonstrates that it’s through the alimentary canal. It’s the influence of the food changing-

Dr. Ruth Hobson (01:03:35) – The gut. Yes.

Dr. Kara Fitzgerald (01:03:36) – The gut that’s having the systemic influence and radically altering the breast microbiome, which until this conversation I didn’t know existed. And so, folks, we’ll track down as many of those papers again and pop them on the show notes at again. DrKaraFitzgerald.com. My team has asked me to actually say the website. I say show notes all the time without actually telling people where they can find them. This is my first podcast where I’m saying the website.

Dr. Ruth Hobson (01:04:06) – Thinking about primate studies, they’re helpful. They give us a lot of information. What do we know in human studies?

Dr. Kara Fitzgerald (01:04:16) – Other than that 2016 study. Is there more research in the breast microbiome in humans?

Dr. Ruth Hobson (01:04:21) – There is. And in fact, I looked and I found, I would say, over 50 papers, you’re going to have to kind of go through. Some of them are looking at cancer. Some of them are looking at benign breast disease. One thing you can kind of land your hat on as far as human breast tissue in the influence of the microbiota, we’ll have to go back to the gut for a second, you know, we’ll think about β-Glucuronidase-

Dr. Kara Fitzgerald (01:04:47) – Of course, yeah, You haven’t said that and I think it’s an important point. So, recycling estrogens, recirculating, recycling, putting them back into circulation, and this is mediated through the gut.

Dr. Ruth Hobson (01:05:01) – Yeah. I think when we do research in the estrobolome, I didn’t have this in my mind. It’s been in the last, I don’t know, sixish years that we’ve kind of, Oh! realized this is where some of these circulating estrogens can come from.

Dr. Ruth Hobson (01:05:17) – So, that’s something that we can hang our hat on as far as what’s happening in actual humans. Can you postulate that that could also potentially be happening in the breast? We don’t have that information, but that would be very interesting to see. But you can measure β-Glucuronidase in stool testing. And so that’s another thing that I will find and I’m still testing, that if I have elevated β-Glucuronidase, it’s almost like I get relieved because it’s a slam dunk. Not that it’s easy to treat by any means, because it’s going to be increasing that soluble fiber and making sure digestion is well. But I have a reason. I have a reason for these estrogens and now we can have a more serious conversation. What we do also know, and looking at just all those studies, is that we can see differences between our standard breast tissue itself, which is typically some sort of a phyla of Actinobacteria, or I guess Bifido would be the one that most people are going to recognize, that Bifidobacteria.

Dr. Ruth Hobson (01:06:25) – And then we also see Firmicutes, so that’s the Lactobacillus. In healthy breast tissue those tend to be the dominant microbes.

Dr. Kara Fitzgerald (01:06:36) – Bifido and Lacto.

Dr. Ruth Hobson (01:06:37) – Yeah. And then when we think about tissues that are cancerous, even inflammatory, so like those benign breast diseases that are inflammatory, you’ll also see that’s where you get those Proteobacteria. And Proteobacteria are inflammatory, but you can also see things like Staphylococcus overgrowth as well, and Corynebacterium. So, we see that we’re having infiltration of these microbes within the breast microbiome. What we also know is that our gut bacteria, they’re just so smart. When we have inflammation, we have these toll-like receptors that are there, and that activates NF-κB (Nuclear factor kappa B) and we’ll see things like IL-6 or those inflammatory interleukins, IL-6, IL-12, IL-17, those happen. That’s present in all inflammatory tissue. So again, not just breasts, but I’ll say most.

Dr. Kara Fitzgerald (01:07:45) – Systemwide.

Dr. Ruth Hobson (01:07:46) – 100% Right, But, but those are really important markers to look at. When we think about what’s happening when we have inflammation, when we have dysbiosis, even within the breast, of course you’re going to see tumor growth. That makes a lot of sense because we have the initiation from those inflammatory interleukins that are there as well.

Dr. Kara Fitzgerald (01:08:13) – Super, super interesting stuff. It’s just such a great conversation. It underscores the importance of gut health and it just really brings it home. Gut health being essential for of course whole-body health, I mean we know this but this really connects it intimately to breast health. That it’s, as you said, as important, maybe it’s more important really. I think you alluded to- Well you may derive more information from it than the clinical history. It doesn’t supplant the clinical history, but it’s just a huge essential piece of information. So, thanks for bringing these studies to our attention. Really, really cool stuff.

Dr. Ruth Hobson (01:09:02) – Absolutely. It’s kind of fun to be a nerd, right?

Dr. Kara Fitzgerald (01:09:06) – Yeah, it’s very interesting. You know, I’ll tell you something, and then we probably need to start to wrap up. A study that moved me, and it’s not a new study – and now we’ll have to pop it into the Show Notes – showed the aromatase gene, so CYP19 is the gene that produces the enzyme aromatase. We can increase aromatase production if we’re arachidonic acid dominant. So, if you’ve got a lot of omega-6s and then you’re driving that arachidonic to your super exquisitely, pro-inflammatory prostaglandins, and this is any form of inflammation. These prostaglandins are the first step, regardless of what- or the leukotrienes. They’re an extra cousin. They’re both coming from arachidonic.

Dr. Kara Fitzgerald (01:10:00) – They’re turning the volume up. Prostaglandins, leukotrienes potently, potently, pro-inflammatory. And they start driving the car of inflammation in the body.

PG-1 (correction: PGE2, prostaglandin E2) actually upregulates transcription of aromatase on the aromatase chain, and it does so differently than other transcription factors that turn on aromatase. What this suggests- So there’s a proximal and distal region on the gene that can increase, and this is true in gene transcription in general, this proximal and distal region, and when you turn gene activation on at proximal, the protein that’s produced behaves differently, even though it’s the same thing than the distal. Does that make sense? So when you turn on aromatase via an inflammatory signal, the aromatase that’s produced, even though it’s structurally identical, behaves differently in the body. I mean, is that mind blowing or what? Yeah.

Dr. Ruth Hobson (01:11:07) – Is it active? Or has more affinity. Okay. I’m going to have to read this.

Dr. Kara Fitzgerald (01:11:12) – Yeah. You’ll have to track it down. And I don’t know. Yeah, what is it? What is the downstream influence. Why is it more pro-inflammatory. Yeah. Does it have- I mean, you would think that it would be slightly structurally different if it did have-I mean it must if it has more affinity. I don’t know. Maybe it’s electrons. I’m not entirely sure, but it was a study that really deeply influenced me and hit home the importance of arresting inflammation potently when we’re looking at the behavior of estrogens, the potential pro-inflammatory behavior of estrogen. And this is true in men and women. This is for men and women, this aromatase production. And so, thinking about fish oil and increasing our omega threes, just going back to that is going to influence estrogen production and likely the metabolites that we’ve been talking about. It’s just a piece of the puzzle and we have a whole arsenal of beautiful botanicals that can help turn the volume down on those pro-inflammatory prostaglandins and leukotrienes as well, like curcumin and ginger and Boswellia, etcetera.

Dr. Kara Fitzgerald (01:12:24) – There’s so much that we can do to have a really potent, powerful balancing effect. You really hit it home today very nicely, talking about those metabolites, really hitting home the importance of looking at the androgen metabolites, all of them. And I love that your panel is so comprehensive and just really bringing it home with gut health and why that’s exquisitely essential. Now that I’m understanding, and I’m sorry if everybody else out there was in the know that we have a breast microbiome, I actually didn’t read that paper. It’s not something that I was aware of. It’s incredibly interesting.

Dr. Kara Fitzgerald (01:13:13) – We are coming to the end of our time today, and I just want to ask you if there’s anything else that you wanted to add. Is there anything that we’re leaving out here that you think is important to put an exclamation point on the end of this conversation or, resources we’ll direct people to? We’ll put stuff on our Show Notes, but just really any summary thoughts, any final thoughts?

Dr. Ruth Hobson (01:13:38) – You know, I think it’s important to use testing as just markers for individual health. And whether you’re using salivary testing or the hormone testing, as far as HuMap, I think that’s going to be essential for your breast health patients, breast cancer or just maybe some history and some risk factors that you’ve discovered. And then again, we’ve talked about gut health for the GI360. It’s going to give you a great abundance and diversity. It’s going to let you see what’s in the microbiome, but it’s also going to allow you to see if there’s any pathogenic bacteria that’s there.

Dr. Kara Fitzgerald (01:14:19) – It’s one of the coolest stool tests out there, actually. Yeah. Hats off to you guys. I thought you did a good job.

Dr. Ruth Hobson (01:14:25) – Are there any natural agents that can potentially kill these parasites or whatever funky bug we have found? That’s really fun. We’re going to see all of the short chain fatty acids that you can think about.

Dr. Ruth Hobson (01:14:40) – I tend to lean my hat on butyrate. That’s the one that I’m working on as far as colonocytes. And then inflammatory markers. That’s lysozyme general, but you can also see do we have IBD going on. Again, when we’re thinking about breast health, let’s broaden the focus a little bit more and let’s think about total body health. And really, I postulate that most disease that we think of is just an imbalance. We’ve just gotten really out of balance and we can kind of move things forward with just those foundations of health. As a naturopath, I always like to go back to the tried and true, right? We need to move our bodies, we need to eat whole foods and try to reduce, or eliminate alcohol, and we need to sleep so we can recover. Is medicine that simple? Yes, it can be.

Dr. Ruth Hobson (01:15:40) – Again, it’s just diligence and focus and just making sure that you’re utilizing what you have in front of you as far as a patient, and then once you have metrics you’re able to see change. I think that also excites your patient.

Dr. Kara Fitzgerald (01:15:53) – Yeah, absolutely. Well, Dr. Ruth Hobson, it’s really nice to chat with you today. I’m so glad you joined me here on New Frontiers. I think this is going to really be a compelling conversation for our listeners.

Dr. Ruth Hobson (01:16:07) – Thanks for having me.

Ruth Hobson is a practicing Naturopathic Physician and doctor in the clinical education department at Doctor’s Data, Inc. She received her B.A from Brevard College in Health Science Studies with a minor in Biology and Chemistry. She trained as a general practitioner at NUNM, tailoring her studies to focus on women’s health and pediatrics. Dr. Hobson currently splits her time between consulting and educating at Doctor’s Data in the Clinical Education department and her own private practice focusing on hormone health and aesthetic medicine. She has utilized her expertise in both research and patient care to develop curriculum for webinars, conferences, and podcasts throughout the US, focusing on hormone metabolism and optimization.

HuMap summary page/report here

Video: How to Read the HuMap Report

HuMap Clinical and Therapeutic Considerations

HuMap Resource Guide

On Demand Webinar: An Intro to the HuMap

On Demand Webinar: Testing Hormone Metabolites and Neurotransmitters: Considerations for Comprehensive Patient Support

On Demand Webinar: How to Use the HuMap to Optimize Detoxification and Breast Health

Cortisol Awakening Response Sample Report

HuMap Sample Report

GI360 Sample Report

Comprehensive Plus Hormone Profile

Methylation Profile (plasma)

The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids

Breast Cancer Risk Assessment Tool: Online Calculator (The Gail Model)

Study: A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial

Article: Resveratrol and Its Human Metabolites—Effects on Metabolic Health and Obesity

Review: Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms

Scientific Report: The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease

Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention

Study: Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

No Amount Of Alcohol Is Good For Your Health, Global Study Says

Alcohol and Cancer: A Statement of the American Society of Clinical Oncology

The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids

 

Assessing Hormones at the Tissue Level

Review: Human saliva as a diagnostic specimen

Clinical Trial: Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.

Article: Hormones in saliva (https://www.tandfonline.com/doi/abs/10.3109/10408368609165797

Review: Current status of salivary hormone analysis.

Review:  Steroid analysis in saliva: an overview.

Study: The clinical usefulness of salivary progesterone measurement for the evaluation of the corpus luteum function.

The salivary hormone profile in the clinical evaluation of women.

 

Monitoring Hormone Levels During Therapy

Study : Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood.

Review: Potential and limitations of alternative specimens in doping control

Comparative Study: The permeability of the human red cell membrane to steroid sex hormones

Study: Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre- and postmenopausal women.

Study: Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.

Paper: Cyclic endogenous estrogen and progesterone vary by mammographic density phenotypes in premenopausal women.

Perspective: Percutaneous administration of progesterone: blood levels and endometrial protection. Menopause.

Blog: Harnessing Nutrient Responsive Genes Against Breast Cancer

Blog: Evaluating Estrogen Detoxification to Understand Breast Cancer Risk

DrKF Clinic: Patient consults with DrKF physicians including Younger You Concierge

Bio Age Lab Test

Bio Age Self Assessment Quiz

Younger You Group Program

Younger You book

Better Broths and Healing Tonics book