Utilizing Salivary and Urinary Hormone Testing for Comprehensive Patient Support

Dr. Kara Fitzgerald: 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 thrilled to be chatting with Dr. Laura Neville. She’s with Doctor’s Data, and of course, they’re always coming out with fabulous testing options for those of us practicing functional medicine. Let me give you a little bit of her background, and we’ll jump into our conversation today.

Dr. Neville graduated from my alma mater, National University of Natural Medicine, and she maintains a private practice in Portland, Oregon with a focus on endocrine health, including type 1 diabetes, Hashimoto’s, and hormone optimization through the female lifespan.

She sits on the advisory board for Hormone University providing evidence-based alternative medicine research and clinical expertise. Dr. Neville is also a staff physician at Doctor’s Data, where she writes, researches, and consults with physicians around the world on complex cases. She is a frequent speaker at professional conferences around the country on the topic of women’s health, testing methodologies, brain health, and type 1 diabetes. Dr. Neville, welcome to New Frontiers.

Dr. Laura Neville: Thank you so, so much for having me. It’s an honor to be here.

Dr. Kara Fitzgerald: It’s just really nice to connect with you. We’ve actually been chatting far too long, folks, Laura and I, just kind of getting to know each other and our backgrounds and talking a little bit about our experience at NUNM.

You have a great story on what brought you kind of into natural medicine and really to Doctor’s Data. You landed at a laboratory, which of course I think is cool because my story is similar. I was in the medical education department at Metametrix, now Genova Labs, many, many years ago, and it really influenced me deeply in how I practice medicine. So, tell me a little bit about kind of how you got here and how you ended up at DDI.

Dr. Laura Neville: Yeah. I was really inspired to go to naturopathic medical school because of a hormone test that my ND actually ran on me when I was about 23. This was back when I knew nothing, I was eating terribly, I was doing all of the horrible things to not support my health. But this test was instrumental in my life, really changed my health path for the better.

I was actually diagnosed with type 1 diabetes when I was seven. There’s a lot that goes into that, but certainly endocrine health in general and in keeping sex hormones balanced really supports a type 1 diabetics’ health. And mine was kind of the opposite story, at least at that point in my life.

If I look back, I mean, it was that test that opened this entirely new world to me, where I understood food as medicine and how that could change not only my type 1 diabetes, but just my health in general, acne, facial hair growth that I had, fatigue.

And so, I carried a copy of this test around for years. Years later, it was a copy of a copy of a copy. I could barely read it, but I remember what those levels were and how my life changed so much when I had just a few simple treatment plans from the naturopathic doctor based on this test.

So, here I have this barely legible test that the ink is pale. Fast forward, I graduate from medical school. I’ve been working with Doctor’s Data for about three years. And I thought, well, now’s a good time to go run my own hormone panel and see what’s going on.

I went in to find the test result. I actually found my name in the system already. And I thought, “Well, that’s odd. Why am I already in the system?” I realized that was the test, the same company, the same test. I hadn’t realized that until this moment that was the hormone test that started my entire health journey.

Not only was I able to see this amazing before and after, which is crystal clear how much things improved, but I just got major goosebumps. It was this full circle moment. And now I’m sitting on the other side of that test able to help so many other people and practitioners help their patients. I don’t know if you’ve ever had those moments where you just feel, I am doing what I’m meant to be doing. This was the journey, a full circle journey.

Dr. Kara Fitzgerald: Such a beautiful story. I love it. I just got goosebumps also when you shared. It is, it’s so beautiful and so powerful. I want to know more. I want to ask you more about it and what you did and what you learned. But to have that, I mean, clearly it was exquisitely important to you because you carried around this dog-eared Doctor’s Data test, just for so many years because it was that, it was your change point. Wow. What a great story. And thank you so much for sharing that.

All right. Let’s move into talking about your area of expertise, inside and out from your own personal journey to where you are now as a medical education expert at DDI and a naturopath physician. You’re good at hormone testing. I mean, you’ve just really devoted it.

Talk to me about the different testing mediums, what ones we want to be using or how we want to consider general. As clinicians, there are a lot of labs talking to us about what we should be doing. Doctor’s Data has been around, I think the longest actually.

Dr. Laura Neville: Their 50th anniversary, 1972.

Dr. Kara Fitzgerald: Yeah. Yes. You have been at work in this world really longer than any of the other functional labs. And I know that your commitment to the science is very rigorous, and I appreciate that. What do you guys think on how we want to be running hormone tests?

Dr. Laura Neville: Yeah. I think I speak for all of us when I say that the practitioners in charge, you have the ability to decide what is the best medium. And I think this kind of argument of serum versus saliva versus urine, it’s been going on for a long time. And it’s really kind of a shame because it’s not versus. It’s just that we’re comparing apples to oranges to pears. They’re all amazing mediums. They give you very valuable information each in and of themselves. And so, really you just have to decide what is the lens at which you want to understand your patient’s hormones.

So, just briefly I think the main aspect to understand so that all of this makes sense is that we’re talking about steroid hormones when we’re talking about sex hormones. They’re derived from cholesterol. So they have different movement and physiology in the body, unlike things like thyroid stimulating hormone or FSH, these protein-based hormones.

So, when we consider that, it becomes pretty easy to just have a simple overview, knowing that serum, you’re looking at the bound or the inactive portion of the hormone. In order to float around in an aqueous bloodstream, it has to be attached to a protein carrier. That’s really what you’re looking at when you’re looking in serum.

When you’re looking in saliva, you’re looking at the unbound, more of a bioavailable look, what’s reaching the tissues very likely. And then with urine, you’re looking at how that hormone is breaking down, metabolizing, and exiting the body.

As long as you bring it back to that and come back to that simple overview, I think you’ll be in a good place to be able to choose which one is appropriate for the patient in front of you and what you’re trying to gain as a clinician, what information you want to look at.

Dr. Kara Fitzgerald: Any preference for when you’re actually prescribing hormones as a result of the lab findings or using the lab findings as guidance on your prescription? Is there a preferred specimen in your opinion?

Dr. Laura Neville: Yep. We’re talking about baseline versus monitoring therapy. And again, arguably all of them can be used for baseline, but really to your question, and it’s such a brilliant one, it’s when you’re monitoring this response to treatment, this is where it becomes a little bit more important to choose the correct medium.

The transdermals have, transdermal therapies, hormone replacement meaning, they have a unique transport in the body. They move differently than if they’re endogenously produced. And because of that, saliva really is arguably the best way to look at transdermals.

We have quite a bit of underestimation or overdosing that can happen when you’re looking at some of those other mediums to try to understand, is this dose correct for this patient? And are they absorbing this and all of that. So, saliva is definitely my preference when I’m looking at any type of hormone replacements, especially transdermals. That’s where you really need to be looking in saliva.

Dr. Kara Fitzgerald: All right. This begs one more question, and then we’ll keep moving. I don’t want to digress too far. But what if you’re using a non-HRT intervention? What if you’re using botanicals or lifestyle or diet interventions to modulate sex hormones or steroid hormones more broadly?

Dr. Laura Neville: Yeah. I have found through looking at thousands and thousands of tests over the years that the botanicals may modulate the hormones slightly. If somebody, say, isn’t ovulating, and you’re stimulating ovulation, that’s going to be a more great improvement if you can get that progesterone level up, and it’s showing that they’re ovulating.

But for the most part, it’s fairly small changes that you’re going to see. And so, I would track that much like baseline. Choose the medium you would like, and use that same type of testing to see before and after. And specifically with the botanicals, I’m much more interested in the subjective patient improvement rather than I’m not expecting to see massive changes in the hormone levels, maybe slight, but nothing remarkable to really need to be utilizing testing for that.

Dr. Kara Fitzgerald: Got it. Got it. But you might want to be looking at metabolites, right, to just see if you’ve-

Dr. Laura Neville: Yes.

Dr. Kara Fitzgerald: … actually shifted elimination?

Dr. Laura Neville: Yes. Right.

Dr. Kara Fitzgerald: That’s sort of a-

Dr. Laura Neville: I’m not so interested at what is the tissue level, how is that changing? It’s not going to change a whole lot. Metabolites and the direction at which they’re metabolizing, yes. That’s where really urine comes into play and is the star at that point.

Dr. Kara Fitzgerald: Okay. Is there anything else you want to add to this? I mean, I know we’ve talked about each of these specimen types. Any additional points? We’re talking about sex hormones, we’re leaning more towards sex hormones in this conversation. Although more broadly, we’re talking about steroid hormones. So, let me just ask you about cortisol and the specimen. What’s best to look at cortisol?

Dr. Laura Neville: I like also saliva for looking at cortisol for a few different reasons. You can capture that at 30 minutes post waking, which should be the peak of cortisol production for the day, so you can be very specific with that and that timing. And then also you can capture something called the cortisol awakening response, which is looking at waking and then 30 and 60 minutes post waking. That can really give you a great idea about HP aixs health, how that’s functioning.

You can also on top of that, in addition to that, see a diurnal rhythm. Hopefully highest in the morning, gradually dropping off, lowest at night. Sometimes people will have inverse curves where their cortisol shoots up before bedtime. So, you can really get just a very time-sensitive look at this diurnal rhythm, circadian rhythms, and the cortisol awakening response.

Dr. Kara Fitzgerald: Oh, that’s extremely helpful. Would you use serum for cortisol?

Dr. Laura Neville: I don’t prefer it. You can test there, although the timing becomes much more difficult. It’s pretty hard to get that 30 minutes after someone wakes up, roll without brushing your hair, just go straight to the lab.

And then there are some issues too. We find ACTH actually can elevate just from a venous blood draw. And ACTH will then cause a cortisol increase. So, the timing of that based on how quickly that blood draw is done could affect the actual cortisol level itself, just from that blood draw. Maybe that depends on the patient and how much they dislike needles or not, but that is something to consider with that type of testing.

Dr. Kara Fitzgerald: Let’s talk about some of the deliveries of hormone replacement therapies. Physicians are using oral. I know that there’s more oral progesterone and even oral estrogen being used in women. But then I think many of us still lean pretty heavily on transdermal.

Talk about your thoughts on the benefits of these delivery routes. And again, I know we talked a little bit about transdermal, but just talk about evaluating response to therapies using labs.

Dr. Laura Neville: Yeah. The oral delivery, I think great because it’s easy, patients are familiar with that. But really when it comes down to it with estrogen, we do see some negative effects with that. The liver seems to be a little irritated with oral delivery, and we can increase inflammatory markers and things like that.

So, for certain reasons, transdermals are oftentimes the better choice. When we’re talking about transdermals, this is where the testing gets really tricky. Endogenously delivered sex hormones are produced, are traveling around the body and through the bloodstream attached to say sex hormone binding globulin or albumin to get around.

However, when they’re applied topically, they’re actually going skin directly to capillaries. And those capillaries are small enough. We don’t have protein carriers within that. The sex hormones are actually being delivered to the target tissue, loosely bound to the red blood cell membrane, which is different than endogenously produced hormones.

That unique delivery, we think partly bound to the red blood cell membrane, partly perhaps lymph too, but they’re going directly to the tissues. They’re cleaved off, and they’re able to move into the tissues through free diffusion. So, in order to capture that, that’s really only shown in the saliva. It’s only when that red blood cell membrane carrying capacity is maxed out, does the hormone kind of slop over into the serum and you can actually see those levels in the serum.

Basically, and at the end of the day, we’re talking about transdermal overdosing. That’s the only way you can have the serum levels rise or the urinary levels rise. And so, my argument is if we want to dose our patients with physiologic levels, then we need to be tracking that through saliva testing if we’re using transdermals.

Dr. Kara Fitzgerald: And less would be required obviously for transdermal, is that correct?

Dr. Laura Neville: Say that again.

Dr. Kara Fitzgerald: Much less of the HRTs would be required for transdermal.

Dr. Laura Neville: Absolutely. Much lower doses are needed. Yeah.

Dr. Kara Fitzgerald: What about progesterone risks? I mean, what about your ideal delivery for progesterone therapies and risks associated with using progesterone?

Dr. Laura Neville: Yeah. This is a controversial topic because I think if you look in the research, oral by far is touted for its protection of endometrium, protecting the uterus from the proliferative effects of estradiol supplementation. Oral is always going to be the recommendation if someone is using a estradiol of any type.

I think that transdermal is likely probably protecting the endometrial tissue better than oral, but we have to take caution here. I respect the research, and as it stands now, oral is the go-to for that. There are some articles showing that the higher the dose of oral progesterone, the better the endometrial protection is. So, once we reach levels higher than a 100, 200, up to 300 and 400 milligrams of oral progesterone, that’s where you get the best endometrial protection.

However, we’ve also seen some studies indicating that those higher doses, higher than 200 milligrams, we’re starting to see the metabolites move and push towards pregnanes rather than pregnenes. That potentially has been associated or has in the research been associated with breast cancer.

I don’t think that there’s enough there to definitively say, but it does give me pause. And so, oral has been touted again, to be the safest form. I think only time will tell. Hopefully there’s more research that comes out with transdermals, but that’s where it stands as of now.

Dr. Kara Fitzgerald: Are those metabolites derivatives of progestins or bioidentical progesterone?

Dr. Laura Neville: They are derivatives of bioidentical progesterone. The pregnanes are more the metabolism towards allopregnanolones. So you get a lot more of those with oral dosing because of the liver detoxification or metabolism, whereas you’re not getting those so much with the transdermals. It’s not moving to that allopregnanolone.

Dr. Kara Fitzgerald: Sure. But there is some benefit with those modalities as well.

Dr. Laura Neville: Absolutely. Yeah. And oftentimes it is my preference if a woman is having a hard time falling asleep or has anxiety, that allopregnanolone, it’s stimulating GABA receptors. It’s amazing. People feel much better.

And so, I think it’s not an all or none here. We certainly want some of that, but once we get into those really high doses, I do have pause, or do we have just too much of that? Some is okay, and too much is not great.

Dr. Kara Fitzgerald: Right. Right. Well, let’s talk about urine, where we get to look at some of the metabolites. Using urine to identify, if you’re using HRT, whether or not they’re metabolizing cleanly, but you’re using urine for a lot of different reasons. Just kind of talk us through about how you use it to monitor HRT, maybe some of the metabolites you’re interested in. Are you able to actually pick up healthy progesterone metabolism looking at urine? And just any other thoughts you have.

Dr. Laura Neville: Sure. Urine is wonderful. It’s the go-to way to understand metabolites. I think that’s the key word there. Whether that’s endogenous production or exogenous supplementation, you want to know how, as you said so nicely, how cleanly is this person metabolizing? What direction are these metabolites moving through? What is the pattern?

We can glean some potential risk assessment from that. We do have research showing that some of these pathways are more estrogenic or more androgenic than others. For instance, with estrogen, the 2-hydroxyestrone and 2-hydroxyestradiol, those pathways are thought to be safer, less estrogenic than say the 4-hydroxy or the 16-hydroxy. Because those ones are more potent, they’re more estrogenic. So, we can actually see that in how that individual patient is metabolizing and which direction those metabolites are headed.

We can also see, okay, if they’re going through this more dangerous pathway, are they at least pushing that and methylating that basically into phase two detoxification? We can see phase one. We can also see phase two. We can see if anything is stagnant there. We have the potential to come in with modulators and help the body to improve that, which is really great.

So, for all of those reasons, it’s wonderful. I do not use it to track dosing because especially in a lot of my patients I’m using transdermals, because of the mechanism and the physiology by which that’s moving through the body. And arguably with transdermals, if you’re using physiologic doses, you shouldn’t be seeing a whole lot of that, at least the parent hormone, the unconjugated amount in the urine.

Especially with things like progesterone because of the polarity of that molecule, it’s closest to cholesterol on the steroid hormone cascade. And so, really very little of that actually ends up in the urine. So, it’s kind of looking at what’s exiting the body is not necessarily reflective of what’s at the tissue levels.

So, I don’t use it for that purpose, but I am looking at okay, with this hormone supplementation, how is that metabolizing? What does the pattern look like rather than, hey, should I change the dose here? What is the parent unconjugated hormone level in the urine? That isn’t what I’m using it for.

Dr. Kara Fitzgerald: I mean, we want to look at the metabolites. I think it’s exquisitely important when we’re doing HRT. And really arguably all of us probably need that evaluation, men and women, at some point and multiple time points through our lives. Whether we’re doing HRT or not, I think it’s that important to look at these urine metabolites.

I guess my question is, how frequently are you running the urine metabolite assays? I know you’re using saliva, but can you just tell us which saliva assay you’re using when you’re evaluating directly the response to transdermal therapies?

Dr. Laura Neville: Sure. If I want to know, hey, is this dose correct, I’m using the salivary direct immunoassay. So, we’re looking at, with our testing, it’s called a comprehensive hormone profile, looking at estradiol, progesterone, testosterone, DHEA, and maybe some diurnal cortisols.

I can marry that and match that add-on urinary metabolite testing. That to me is the most powerful approach. That’s like a slam dunk to get the best information on both sides. What is at the tissue level? I think of the body kind of like a garden. What do we have, the available starter material at the brain, the breast tissue, the bones? And then how is that metabolizing? How is that moving through the liver and detoxifying? What does that look like in the urine? Are there ways that we can support detoxification to make this dosing safer for them?

Dr. Kara Fitzgerald: That’s perfect. Do you always order that panel, that complete panel when you’re evaluating?

Dr. Laura Neville: Yeah. As a baseline, I like that one. When I’m retesting, it would kind of depend. If I’ve implemented hormone replacement and I just want to take a back peak and look at estrogen and progesterone, maybe those are the two things I’ve implemented, I may just pick those two to take another peak at. I usually will do that three to four months after I’ve begun hormone replacement to understand that, and then add on metabolite testing.

I may have looked at that at baseline too, though. That would be probably what I do most often. And again, the best way to marry those two, I think is a super powerful approach.

Dr. Kara Fitzgerald: Yeah, absolutely. I agree. Speaking of the various tests that you’re using, DDI just released a new panel. So, give us the low down on this new panel.

Dr. Laura Neville: Yeah. We have our brand new panel is the Hormone and Urinary Metabolites Assessment Profile. We call it HuMap for short so you don’t have to say all those words out every time. But it’s a really exciting test. It’s a four-point collection. It’s a liquid urine test using what’s called LCMS. It’s liquid chromatography tandem with mass spectrometry.

This type of test and kind of the laboratory methodology is very, very precise. It’s really exciting. This probably came about in the 2000s, but very exciting because it’s so, so specific. You can get really, really detailed looks at tiny little metabolites and get a full picture understanding. So, we’re all very excited.

Dr. Kara Fitzgerald: Well, tell me what’s on it, what we’re looking at in the new HuMap.

Dr. Laura Neville: Yeah. We have a real understanding from our perspective that physicians and practitioners, we just need a one to two page really good glance at what is clinically applicable for me. You tend to get these 20 page reports, and you’re like, okay, this is, this is great, but where do I go with this?

The report itself is extensive, but we’re really focusing on making the first two pages just at a glance for the busy practitioner. So page one, first of all, it’s gorgeous, let me say, but it’s giving you the most clinically relevant information. And then we’re diving into the estrogen specifically, so the estrogen metabolism of phase one and phase two and showing that to you, and then also showing you cortisol metabolism and some of the key relationships as far as the enzymes.

That’s all going to be on page one. And what’s really amazing about this report is that it’s dynamically reported so that the color coding, whether something’s high, upper range, low, normal, low range, that color coding changes for every single patient on the report on that first page. And so, really just brings to life those numbers and is very individualized, so you can just take a quick glance and have an idea, almost like a bird’s eye view as to what’s going on. Is there stagnation happening, what’s elevated, what’s low, so that you can see that when you are super busy in practice and just get straight to the point, bottom line.

Dr. Kara Fitzgerald: Yeah. I love it. It actually is. It is beautiful. Clearly you worked long and hard on synthesized and complex information and basically making it at a glance. I think drawing the clinician to where they might want to flip over to some of the more detailed explanations and do a little bit of a drill down, but really saving us from sort of the time consuming world of analyzing these broad evaluations that we’re conducting.

So yeah, it is. It’s a remarkable at glance first page. The second page is actually really cool, too, if you want to describe that.

Dr. Laura Neville: Yeah. The second page is really beautiful as well. That’s the entire steroid pathways. You’re going to see how all of the metabolites in every hormone neighborhood, estrogen, progesterone, the corticoids, the androgens, they’re all connected, and you can see that dynamically reported again. That color coding is going to change based on your individual patient’s profile.

Dr. Kara Fitzgerald: This is a urine test and you’re using saliva as well.

Dr. Laura Neville: The HuMap is the liquid urine metabolite test. My point to saliva is just as a clinician, I like to add that on a lot of times and marry that to something with the HuMap, but you can do just-

Dr. Kara Fitzgerald: Which you can do that, right? You can add it to the HuMap, a saliva?

Dr. Laura Neville: Sure. Yeah.

Dr. Kara Fitzgerald: Talk to me about the difference, because there are a number of labs producing kind of broad analyses of steroid metabolites. Why is this different? I do want to say that I appreciate that you’re doing LC tandem mass spec because I think you’re right, that’s the best technology to be using for steroid hormones. What else makes this a stand out?

Dr. Laura Neville: Yeah. It’s a little bit different than some of the other tests out there. It is liquid urine versus some of the companies do a dried sample. That makes it a little bit different. And then we do have some additional analytes as far as more specific analytes in the androgens section.

We also are showing estradiol methylation in addition to estrone methylation. Typically, estrone is the one that is shown, but we’re adding on both of those. And it’s really interesting because though the COMT enzyme is supporting both of those, we oftentimes don’t see the estrone methylation happening as readily with estradiol methylation or vice versa, so they don’t necessarily always match up. I think it’s an additional way to look at that and give some more clinical information as to methylation ability for your patient.

Those would probably be the standout things that are different. I think also important to realize if you do, say, neurotransmitter testing, if that’s something that you like to do in clinical practice, that is also through our lab as a urinary test. That’s something that you can actually also add on to this test with the same sample. So, no extra collection-

Dr. Kara Fitzgerald: Wow.

Dr. Laura Neville: … on the patient’s behalf, but they can use that same sample to run that.

Dr. Kara Fitzgerald: Wow. Okay. So, you could add on saliva, you could add on neurotransmitter metabolites.

Dr. Laura Neville: Yeah.

Dr. Kara Fitzgerald: Okay, perfect. We’ve been talking about interventions, we’ve talked about HRT, we’ve talked about sort of general overview of some of the botanical interventions and what we might see on labs. But tell me, what are some of the therapies that you’re using, other clinicians are using?

I mean, when I was in the Meta department, one of the things that was fun was not only was I able to look at, as you said, thousands and thousands of tests, but I was also able to talk to the clinicians and find out what they were using and what doses and what were the various indications. I mean, you really have your finger on the pulse of what’s happening in our world in an extraordinary way. So, it behooves me to pick your brain because you’re there in the trenches now learning every day so, so, so much. What are some of the standout interventions?

Dr. Laura Neville: Yeah. Yes. To your point, it is an amazing place to be. I get to see that in my clinical practice on my own, but I get to speak to people all over the world, physicians all over the world. It’s just so amazing, and it’s such an honor to be able to hear what they’re doing, and as you said, have a pulse on things that-

Dr. Kara Fitzgerald: And look at some of the most challenging cases and some of the most unusual labs and yes, more sort of genetic conditions that you wouldn’t see in a lifetime of practice.

Dr. Laura Neville: Right, exactly.

Dr. Kara Fitzgerald: Tell us what people are using, what kind of dosing. What are some of the standout therapies?

Dr. Laura Neville: Yeah, sure. I think the standout therapies, everyone’s probably heard of diindolylmethane. That’s strong in the research showing that it’s helping us to move towards that 2-hydroxylation of estrogen, urinary metabolites, and moving towards the less estrogenic side, what we think of as the safer side. Flaxseeds seem to do that as well.

There are nutrients and substances that will help to induce phase one detoxification, so supporting that, things like cruciferous vegetables, citrus, especially grapefruit. Green tea does that as well. And then there are nutrient reducers of phase one, so things that slow down phase one, like berries, quercetin in berries, and the Apiaceae vegetable family.

I find this so fascinating because this is showing us that these nutrients have a tonifying action. It’s not moving in one linear direction. So, you may want to slow down phase one if phase two isn’t happening as readily as, say, the body would like it to. And so, within these natural substances, the body seems to have this innate intelligence to be able to pull from these different types of support mechanisms to do that, which I think is just one of the most interesting parts of all of this to me.

There’s also something that is referred to as biphasic modulators. So again, really interesting. We see low dose turmeric appearing to promote phase one, whereas higher doses may actually inhibit it, so you see this dual relationship in a lot of the plant compounds. That diindolylmethane, those biphasic modulators, antioxidants, things like glutathione and melatonin, certainly utilize to mop up oxidative damage that as much as we would like that to not be happening at all, it is. And so, we can utilize that.

Other standout therapies, probably NAC and resveratrol come to mind. But again, as you mentioned, I’m learning more and more and speaking to physicians every day, but those are the ones that stand out in my mind.

Dr. Kara Fitzgerald: And some of them are tried and true for time immemorial, like diindolylmethane. Interesting though, about turmeric and the dose response, very, very interesting. We’re prescribing turmeric all the time at really pretty high doses for inflammatory conditions. And we might want to be a little bit mindful if we’ve got somebody who’s got, say something associated with estrogen dominant picture that we could be actually exacerbating that.

Dr. Laura Neville: Right.

Dr. Kara Fitzgerald: Would you say that’s true?

Dr. Laura Neville: It’s possibly true. I mean, I think once we get into those really therapeutic high doses, I think we always have to be mindful of how is this changing the landscape. I think that’s very true. Gives us pause at least.

Dr. Kara Fitzgerald: Yeah. Yeah. If we’re kind of doing a broad sweep with our patients, I’m about to actually, it’s funny. My annual labs are upon me. Every summer I do my broad sweep. I’ll do my urine metabolites, and I’ll do my cortisol awakening, but I’ll do all my nutrients and so on and so forth. I’m taking notes as I get ready for my own lab journey here in a couple of weeks. I’ll get my lipids and my-

Dr. Laura Neville: Yeah, absolutely.

Dr. Kara Fitzgerald: One of the things that can be hard to budge and can be really concerning for clinicians is an elevated 4-hydroxy. I wanted to ask you. Actually, why don’t you first talk about what that metabolite is and why it gives us pause. I’ll let you describe it. And then what are your interventions that seem to be budging that?

Dr. Laura Neville: Yeah. The 4-hydroxy is just as the bodies breaking down estrogen, it can go in three different directions, 2-hydroxy, 4-hydroxy, or 16. And we look at the research. The research tells us that the 4-hydroxy pathway that direction is potentially more risky because it’s more proliferative, it has a higher estrogenic potential. We’re thinking about breast cancer, things like that. That’s really what we’re concerned with.

So, how do we get it to budge from going in that direction more towards that 2-hydroxy pathway? I have found diindolylmethane to be effective in that, but I think it’s not just about the supplementation. I mean, really we have to be getting increases in dietary fiber intake. And so, fruits and vegetables, I think there was a study from 2018 that found the healthiest people were eating 30 or more plant-based things per week.

And so, I’ll oftentimes tell people that it’s not just the supplementation. We really have to get the gut microbiome on board. That is going to be helpful at changing these pathways. And it’s not just about one lovely supplement, as wonderful as they are. But I have found diindolylmethane to be very valuable in that regard, flaxseeds as well, turmeric as well. Those are usually the go-tos for me.

Dr. Kara Fitzgerald: Good. That’s great. You mentioned breast cancer, but obviously if we’re concerned about prostate cancer, same thing. We’re going to be looking at 4-hydroxy.

Dr. Laura Neville: Absolutely.

Dr. Kara Fitzgerald: So, men are not excluded from this investigation by a long shot.

Dr. Laura Neville: Exactly. Yeah.

Dr. Kara Fitzgerald: Okay. All right. I guess I have two more questions. Just kind of circling back to Doctor’s Data and the fact that you’ve been around the longest. I’ve known Darrell, your CEO, for many years. I really appreciate him. He’s been a good friend and a good supporter of our work here, and I appreciate the rigorous science that he advocates for over at DDI.

My two questions in wrapping up are anything else that we didn’t get to cover that our clinicians and savvy, regular folks who are listening to this podcast need to know? And then just talk to me a little bit about the Doctor’s Data and who you guys are and what you’re up to. And if there’s anything you can share, any new, new, new tests coming down the pipeline that you can tell us about. But just those two things, and then we’ll take it home.

Dr. Laura Neville: Sure. Well, I think when I first saw the testing facility at DDI, I was blown away. It was an incredible state-of-the-art testing facility. Again, I know we mentioned this before, but we have been in the business since 1972. It’s our 50th anniversary this year. So it’s really exciting.

But there are over 75 different profiles that you can run if you work with Doctor’s Data as a practitioner, not just the HuMap test that we’re talking about today, though, that in and of itself, I think is very exciting. The saliva hormone testing, as I talked about. You have access to neurotransmitter testing, microbiome testing, gastrointestinal health testing, toxic elements, so many tools at your fingertips.

We have a team of clinical practitioners, including myself and scientific support. We’re available for consults on all of the testing. I specifically and we specifically know what it’s like to be in clinical practice and just needing to talk out a case, having some struggles and feeling kind of alone and at a loss, and you all are on the forefront of testing and pushing the boundaries and knowing how to treat patients in such a holistic manner that sometimes you are the only one out there doing that.

And so, you want to get on the phone and just have a friendly voice that understands a lot of what you’re dealing with. And we’re happy to do that. I love, like we were talking about, just being able to talk to so many different providers and glean expertise in that way. I’m happy to share that with you all as much as I can.

But that’s I think a wonderful part of Doctor’s Data, is just having that support so that when you get that HuMap report, you don’t feel at a loss of, okay, how do I look at this? What should I do with my patient? We can help walk you through that and talk about different aspects.

Dr. Kara Fitzgerald: I just want to underline that as I also got to do it, and as I said earlier, I found it really rewarding. I spent many a lunch speaking with clinicians, who are famous. I won’t mention names. I mean, I would check in with them first, but just both of us kind of doing this work together. And I appreciate having an expert such as yourself to be able to chew a case over what.

If any clinician is listening to this and you haven’t reached out to the Doctor’s Data team, just do it. I think that you’ll appreciate that you’ve done it, and you may find yourself doing it really over and over and over again until you’ve got your sea legs on interpreting laboratory data. That’s I think how your team should be utilized. Would you agree?

Dr. Laura Neville: Absolutely. I want people to know we’re here for them. I think sometimes people are a little shy about calling in, or they feel like maybe they’re just beginning and they feel a little embarrassed about that, or they feel ashamed that they don’t know this test from back to front.

I will tell you, I’ve been with Doctor’s Data since 2016, and I arguably know a lot about hormones, yet when you call in, we’re all learning together. And so, I think it’s valuable to me, but I can’t tell you how many people, and I think what gives me so much pride at the end of the day is people calling in and just saying, “I thought I knew everything, but you’ve given me so many other things to think about that are going to be so valuable to this patient. So, I can’t thank you enough, and I just appreciate you being here for me.” It warms my heart. It gives me the goosebumps, and it makes me feel all happy inside.

Dr. Kara Fitzgerald: Anything else to add about Doctor’s Data?

Dr. Laura Neville: Well, I’m just very proud to work with them. Like I said, you guys know my story now, but they are impressive. It’s cutting edge research. We work with institutions like Johns Hopkins Hospital, the US Navy, California’s Criminal Justice System, many other universities. We were awarded Center of Excellence Laboratory by Salimetrics, only five institutions in the nation received that, for our work in salivary research and testing.

I just think, as you said, the science is there, and then that helpful voice on the other end of the line when you call us is really helpful to practitioners. So, it makes me proud to be there and makes me proud to be able to share that with you all. And hopefully it helps you all too.

Dr. Kara Fitzgerald: Well, Dr. Neville, it was just lovely to talk with you this afternoon. And I’m so glad that you’ve been a guest on our New Frontiers podcast.

I want to let all of our listeners know that this beautiful HuMap test that we discussed today, there’ll be a link on the show notes. I’m also going to pull together a package of links of some of the other podcasts and blogs that I’ve done over the years with Doctor’s Data, just so you have that right on the show notes, ready access to the educational content that exists on the Dr. Kara Fitzgerald platform. It’s just there at your fingertips.

Again, I encourage you all to reach out to Doctor’s Data with your questions. They’re very available. And know that you can schedule with Dr. Neville, as I know I will be doing actually, maybe on my own results.

Dr. Laura Neville: That would be great.

Dr. Kara Fitzgerald: In the not-so-distant future.

Dr. Laura Neville: Yeah.

Dr. Kara Fitzgerald: Thanks for joining me today.

Dr. Laura Neville: Thank you so much for having me.