As many of you might know, I worked in a specialty clinical laboratory for some years. We measured organic acids, amino acids, fatty acids, toxins, hormone metabolites … we know these tests well in FxMed – we use them daily. But what do these labs actually mean? Do they improve outcome in the practice of medicine? And – perhaps most importantly – what kind of research has been conducted on the various analytes? In my mind, these kinds of questions are where the rubber meets the road.
In today’s podcast, I chat with my friend and fellow laboratory geek Mark Newman, founder and president of Precision Analytical (creators of DUTCH), about his recent publication [Evaluating urinary estrogen and progesterone metabolites using dried filter paper samples and gas chromatography with tandem mass spectrometry (GC–MS/MS)], smartly published in an open access – and reputable – journal, BMC Chemistry, so it’s available to all, free of charge. I am thrilled that Mark and team are committed to contributing to the science behind what they’re doing, and we can expect more publications and white papers from Mark and the Dutch team! Enjoy this educational podcast, and be sure to share, like, and comment wherever you are listening to New Frontiers! ~DrKF
In this podcast, you’ll hear:
- What sets the DUTCH Test apart from other lab tests
- How looking at lab results through multiple lens, including metabolites, is key for diagnosis and treatment
- The DUTCH test’s ability to measure melatonin, oxidative stress, cortisol, CAR, sex hormones, vitamin deficiencies, and neurotransmitters
- Why transparency is critical in the lab testing industry
- Newly published data showing equivalency between dried urine samples and serum samples
- How to interpret test results showing high estradiol but estrogen metabolites
- How hormone testing can shed light on the efficiency of the methylation pathway
- Understanding and interpreting the cortisol awakening response (CAR)
- The limitations of saliva testing for sex hormones
Mark Newman, MS, Founder and President is a recognized expert and International speaker in the field of hormone testing. Mark has spent nearly 20 years within specialty laboratories, developing and directing 24-hour urine hormone testing, organic acid testing and salivary hormone testing, gaining a fairly unique and thorough perspective on blood, urine and saliva hormone testing.
This unique experience led to a vision for a revolutionary way to test hormones; Mark began his own lab, Precision Analytical, Inc., and is the creator of DUTCH (Dried Urine Test for Comprehensive Hormones).
The question of how to best test hormones is what drove the creative process that initiated this lab. Blood (serum), urine, and salivary testing all have significant limitations. DUTCH has unique testing methods which bridge the gap between existing methods to create better tools for healthcare practitioners to address the needs of their patients.
- Evaluating Urinary Estrogen And Progesterone Metabolites Using Dried Filter Paper Samples And Gas Chromatography With Tandem Mass Spectrometry (GC-MS/MS)
- DUTCH TEST Press Release
- Precision Analytics, Inc.
Dr. Kara Fitzgerald: Hi everybody, welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine and today is no exception. We’re interviewing one of the best of the best minds. My friend and the founder and president of Precision Analytical, the developers of the famous DUTCH Test. So anyway, let me give you a little bit about Mark and we’re going to jump right in and start picking his brain on a podcast that is sure to be one of the best ones this year.
Mark Newman, MS, is a recognized expert and international speaker in the field of hormone testing. He has spent nearly 20 years within specialty labs, developing and directing 24-hour urine hormone testing, organic acid testing, salivary hormone testing, really the gamut, I don’t know that there’s anyone else in our field who’s got the kind of expertise that Mark has established over the years in hormone testing and because of that he’s got a fairly unique and thorough perspective on blood, urine, and saliva hormone testing. And this experience, this collection of experience, really kind of led to the development of his lab, Precision Analytical, and the creator of the DUTCH Test, which stands for Dried Urine Test for Comprehensive Hormones. The question of how best to test hormones is what drove the creative process that initiated his lab and honestly, it’s one of the biggest questions that I’m asked all of the time, how do we test hormones? What’s the best way to do it?
Anyway, blood, which is actually serum, but urine and saliva testing all have limitations. In fact, Mark and I have been talking about quite a few of them and I finally hit the record button so we could share this conversation with you. So DUTCH, this dried urine method that he developed, has unique testing methods, which bridge the gap between existing methods to create better tools for healthcare practitioners to address the needs of their patients.
Dr. Kara Fitzgerald: Mark, welcome to New Frontiers, welcome again to New Frontiers.
Mark Newman: Thanks Kara, it’s good to be here.
Dr. Kara Fitzgerald: It’s really nice, it’s always nice to have you here. So, our first podcast together and we just really, I think we’re both are just kind of lab geeks. You’re the … You dwarf me in lab geekiness actually, quite frankly, but I appreciate it and I’ve got a background in lab science and I remember when I first met you, you came to my attention through Bethany Hayes who is a friend and a colleague and a teacher of mine. Of course, Bethany is a physician who’s been teaching in hormone testing forever and Sara Gottfried, another really brilliant woman OBGYN, scientist, and both of these women who I admire, so greatly, were using DUTCH. And I, coming from a lab background, and knowing how hard it is to do some of the urine analytes you guys were looking at, some of the estrogen metabolites, I was like, “Who is this guy? And is he really doing it?” I remember when we first starting figuring out the two hydroxy and the two methoxy and the four hydroxy and methoxy estrones that they were challenging and I, our first conversation, Mark, I don’t know if you remember, but I was like, “Are you for real?”
One of the coolest things about our conversation is that you, and it continues because that was some years ago, is that you’re really one of the most real and open guys about what you’re doing and I personally became convinced and my team here at our clinic, in the value of your testing. We use it all the time now and I absolutely love it because it’s easy and the results we get are really good and we appreciate you. And we appreciate your openness. So, just give me, again, a little bit about this journey. Creating this four spot urine collection. Yeah, go.
Mark Newman: The journey for me is, it’s all about information I think for me, you know, seeing what you can get from this test, what you can get from that test and for me it was borne out of frustration of seeing situations where, if I looked through this lens of the metabolites I get in urine, I learned something and when I looked through this other lens of salivary testing and I’m looking at the cortisol pattern or some of those things, it really adds some clarity to the picture and I’m sitting there thinking, if I only see through one of these lenses, I really … I mean we’re always guessing, right? Ultimately you never know the reality of what’s going on at the tissue level and this, that, and whatever. So there’s always some guesswork and we’d like to guess well, right? And so the more lenses you look through, for a particular family of hormones or set of symptoms or whatever it is you’re trying to resolve, the better off you are.
So for me, I kind of balanced locationally from 24-hour urine to some organic acids to saliva testing and blood testing, and started trying to piece together in my own mind, of like, “Okay, if I really want to get the most complete picture of what’s going on, how do I want to do this?” And the conversation for me started a little bit with the cortisol because we had this over-arching narrative that said, “Hey, people who are heavier, have more cortisol.” There’s this general correlation between weight-gain and cortisol. But then we had people applying that knowledge to saliva testing but then when I went and looked in the literature, and looked at the data we were collecting, which was millions of data points, there wasn’t a correlation between the free cortisol levels and BMI or weight-gain or whatever and like, “Wait a minute, where did this all come from?” And then find out, oh, it’s actually the significance for that particular variable, is found in the cortisol metabolites, which you have to go to urine to find.
So now I’m going, “Okay, I want free cortisol because it’s the most important thing I can learn about your HPA-axis, is up and down free cortisol, but if I don’t have those metabolites, like there’s a really big piece of the picture missing, and so that’s where it started, is can we come up with a testing system where we can see both pictures at once and then can we look at the estrogens with sufficient accuracy, can we look at progesterone, can we look at the estrogen metabolites and androgens and so on and so forth? And that initial picture that we built, really opened up the number of lenses that you get to see through, and we had some pretty good success with that. And so then we went about the validation process and then jointly, or simultaneously, saying, “Okay, well what other lenses can we open here?” Like, oh, we can look at melatonin and we can look at oxidative stress and we can look at vitamin deficiencies and we can look at neurotransmitters for what limited value they may have.
So that’s been the quest, is how much meaningful information can we get out of one thing that’s cost-effective and relatively easy for the patient to do? So that’s been the search that we’ve been on, is how to do that and then at the same time, to really run it through a critical eye so that we can also tell people, “Here’s where it’s good, here’s where it’s great, and here’s where it’s not, and here’s, in a scenario where it’s not, we want to make sure that we’re A. being transparent about that but then also giving people the direction of where do you go for that particular question because that’s one of the things I think that really limits the lab testing world, is we want to be a solution for everything and it’s just, I think that’s just one thing that you have to admit early on, is you can’t have a tool that works on every scenario, because it’s just … Otherwise you just end up with frustrated people on both ends.
Dr. Kara Fitzgerald: That’s awesome. Alright, so now that you’ve answered every question that I had for you today, let’s talk about Theranos.
Mark Newman: Oh geez.
Dr. Kara Fitzgerald: I’m just kidding. So I want to just tease out … Well actually we could talk about Theranos. You and I are, again, have both become a little bit addicted to following that Silicon Valley laboratory disaster. It’s heartbreaking to see but one of their, of course, the big problem was, they don’t, they’re not open and you’re just … They didn’t publish anything and their data had to be proprietary because they really weren’t doing anything. They were failing and making all of these claims and it was really pretty horrible and disheartening when, in fact, you’re doing the exact opposite and you’re trying to just really keep the conversation going and out there and doing the best job that you guys can do and you just published a paper, which I’m thrilled about. We’re going to talk about it in a minute. So again, Mark, one of the reasons that I have been so drawn to Precision Analytical, is because I just have really good conversations with you and I feel like I’m heard as a clinician and my questions are answered.
You’ve got Dr. Carrie Jones in there as your chief medical officer now and I think she’s just doing a fabulous job, again, answering clinician’s questions. Being open about what we might see that we … You know when I … Having been in a lab. I know sometimes results look a little bit wonky and I want somebody to speak to me about them and not just put me on hold or send me to some distant voicemail or otherwise get me out of their range so I appreciate how consistently you guys just are there for us, for us clinicians. But anyway, so you unpacked a lot. What you’re talking about is, just multiple specimen type and methods need to be obtained if we’re going to get the most accurate picture. And you learned this with the fact that there’s more cortisol in obese individuals, but, you can’t … You’re going to actually mistreat them if you only look at that variable, as you pointed out.
You need to have the inactive cortisone, and you want to have all of the metabolites at your finger tips to be able to accurately treat. Otherwise you’re going to be attempting to just blunt that cortisol overdrive and not really nuance what’s going on in the HPA Axis in general. Would you say that that’s true?
Mark Newman: I would say it can be true. That’s the thing, if you only look through one lens, you’re going to be right a decent amount of time, but you’re going to run in the wrong direction at a sprint for too many people. When you look at … If you’re looking at a three dimensional picture, two dimensionally, you’re just not seeing everything, right? So that’s what we’re trying to do, is open it up so that in some of these cases, you’re getting more clarity on what the totality of the picture is as it relates to, in this example, cortisol, so that you can just head in the right direction more often.
So sometimes, that extra information, all it does is just confirm what you already think. And then off you go with increased confidence but in the cases where it tells a different story, or it adds a new wrinkle, those are the cases where I think we can really help people to better unpack what’s going on with that particular person, given their scenario. And then hopefully respond appropriately and just have better success with those, especially with those tricky cases.
Dr. Kara Fitzgerald: Well, you know, we actually covered some of this as a side note, Dr. Jones and I did a really fun webinar where we moved through cases. Most of the cases were from my clinical practice and I think she presented a couple from hers, but we talked about some of those conundrums, a PCOS patient who doesn’t present with a typical PCOS pattern and some more unusual cortisol patterns, and so forth. So for people interested in that pattern analysis, looking at steroid hormones, you can access this webinar and we’ll link to it in our show notes.
Okay, so let’s talk about now, you’ve been looking at urine, 24-hour urine, you’ve been looking at serum, and you’ve been looking at saliva, sex hormones, let’s move over to sex hormones. The gold standard, in the greater medical community, is serum for sex hormones. But you’re suggesting that this four-point urinary hormone collection, that you’re doing, is sufficient in most cases to supplant serum. Do you want to talk about that a little bit?
Mark Newman: Well, you mentioned that paper that we published, that was the central issue of the paper, was do you get equivalency for a dried urine sample as it relates to a serum sample? So we looked at urine versus serum and we looked at our dried urine versus just liquid urine, just to make sure that variable was covered.
Dr. Kara Fitzgerald: So a 24-hour urine, your four point dried urine and serum.
Mark Newman: Right, exactly and so what we found is between all those variables, we found equivalency. So we’re able to get the same information from a urine test as we’re getting from a serum test. So that’s all well and good. But if it’s the gold standard and what’s the point of, why should I move? And that where, for me, you start to see some advantages for a urine model, over serum. One of those being that when you, there’s a nice paper, it’s actually really old, where they looked at serum in women in their luteal phase, and they’re looking at progesterone, but they’re measuring it, like every five minutes or something. And some women, I mean serum work fine, but in some women the reality was, they moved from five to 35, throughout the course of the day, right? Because you’re getting these surges of LH and hormones and then boom, you’re getting these surges of progesterone and up and down it goes throughout the course of the day, and so our test represents about 14 hours of the day.
So you take the highs, you take the lows, you average them out. I think that’s an improvement. You can work with either but I think that’s an improvement.
The second thing, then, is just the added information. Yes, I can get progesterone, yes I can get estradiol on a serum, but particularly the estrogens, we’ve got, what, 10 estrogen metabolites. So that adds a lot of value, I think, in two things. One, confirming, right, so if I have a low estrogen, and all the metabolites are low, that’s nice for confirmation like, “Yeah, you’re not making any estrogen.” But then secondly, you get people with some funky metabolism patterns, right? So if I’ve got a woman who’s got high metabolites, high estrogen, everything’s high, like this is a real clear, “You just make too much estrogen,” okay fine. But if you look at a second woman, who has an elevated estradiol, your main estrogen, but then that downstream metabolite, or metabolites are low, now I look at that and go, “Hold on, this is different. Yes, you have too much of this hormone, but it’s because your clearance of that hormone is, I use the word, sluggish, a lot.” Like there’s sluggish clearance of that hormone, and if that’s the case, then the solution for you, you can be more precise by knowing that, in that my goal for you is not to dramatically decrease your production of that hormone, it’s to address what’s actually going on, which is a metabolism issue and there are things that you can dig into and look at, in terms of getting that in a more of a balanced situation.
But then, also, you can look at complimentary information of, if my estrogens aren’t metabolizing well, now I’m also worried about breast cancer risk.
Dr. Kara Fitzgerald: Yeah, that’s right.
Mark Newman: So now I dig into breast cancer and say, “Well if I look into the pathway there, what is going to help me sort of not get breast cancer, is proper methylation, we can look at methylation. Proper glutathione detox, we’ve got a glutathione deficiency marker. If you jump back to the methylation conversation, if you don’t have enough B6, B12, that’s going to hurt your ability to methylate well and the DUTCH test has, a glutathione marker, a B6 marker, a B12 marker. One of the consequences of having high estrogen can be that it in induces B6 deficiency. So that’s we’re going, well wouldn’t it be nice if you are hormone test, also had a marker for B6 deficiency, which we now have two of those? So that’s, I think, the biggest benefit of the urine test, is it’s a good average over time, but it just gives you so many more variables to look at, that you get to characterize each family of hormones at a higher level and then better solutions come from that.
Dr. Kara Fitzgerald: That’s just, it’s really useful. It’s clinically really useful. And so you can get the estrogens, you can get the progesterone metabolites, you’ve demonstrated that both the urinary estrogen and progesterone … Estrogen itself and the progesterone metabolites correlate with serum. So you demonstrated that and you published it in BMC Chemistry and there’ll be a link to this paper on the show notes folks, so please go and grab it. It’s just a really nice write up. So you’ve demonstrated that equivalency but then you’ve just articulated the really fabulous benefit, is that you get to look at all of these metabolites and really look under the metabolic, the sex hormone hood of what’s going on with the folks that you’re testing. And you can get in there and fine-tune it and make big differences in our patient’s lives. And again, you’re looking at 24 hour and you’re just not getting that in serum. You can’t keep sending somebody to get stuck.
The other piece is, I think the thing again, as I started our conversation with, is that some of those analytes are in really micro-quantities and you have to be good and smart analytically, to be seeing them. And I appreciate the time and energy you’ve put into successfully looking at those.
Mark Newman: Yeah, I think there are two sides of that coin. One is, making sure that you have a method that works well and the second thing is making sure that you concede for an analyte for which you do not have sufficient sensitivity. I can look back over, what, 12 years or so and point to four different labs, ourselves being one of them, that added four methoxy E1, because it’s so interesting conceptually, and then have taken it off their panel. And why? Because it’s interesting, you want it, but there’s so little of it, that it’s this noisy little, if anything, signal I think. There have been methods that have been commercially available, where they are literally just measuring background noise and trying to tease out a four methoxy E1 value. For us, we see it on every patient. It’s below what we call a functional sensitivity, meaning I can’t, with confidence, give you a number that’s reproducible for that, therefore, we say, “Look, if you want to know about methylation, you’re going to have to look at the two.” So two hydroxy gets turned into two methoxy, just like the four gets turned into four methoxy and evaluating methylation based on those which are comfortably within the range that we can look at, both accurately and reproducibly, is a better approach than trying to do something that you just can’t do with enough confidence, that people should be making medical decisions based on it.
So yeah, it’s about methodology but then it’s also about making sure that your data is good enough to actually give it to people.
Dr. Kara Fitzgerald: Yeah, that’s right. And eventually we’ll be able to see, you know, there’ll be a method that comes out where we’ll be able to pick it up and other really interesting things too, I’m sure. But it’s not there yet, just admitting that you can’t do it and pulling it off your test is really, really important. So incidentally, Mark’s talking about some of the estrogen metabolites here, and on the show notes, we’ll put up their steroid hormone pathway chart, so that as you’re listening, you can grab it and I wish that I had mentioned it so that you could have grabbed it at the beginning of the talk. But go and look at it now and you’ll see the 4OH-E1 being converted to the 4ME-OE1. So the four hydroxy estrone being converted via a methyl transferase enzyme to the four methoxy. And then you can see on the pathway chart that it’s not highlighted in green, the four methoxy because they can’t measure it. But what is measured is highlighted in green. Right?
Mark Newman: You can see what’s measured there being the two hydroxy and the two methoxy. For the four hydroxy, we put the four methoxy there conceptually on the report, like, “This is where you want it to go, but there’s not actually a value because it’s not something we can measure with enough accuracy.”
Dr. Kara Fitzgerald: But what you have, what’s being actually measured, is highlighted in green, on this chart? Correct?
Mark Newman: Oh on that one? Oh, yeah. On the steroid pathway? Yeah, we put in green the things that we’re actually monitoring.
Dr. Kara Fitzgerald: Yeah. Okay. Alright, good. And then the other nice thing that you did, is that you were able to simplify the whole urine collection journey. It’s a pain in the butt to have to do a 24-hour urine collection and kind of drag the jug around with you, or do it on a day that you’re going to just stay home all day. And then you do it in the four spot and you’ve obviously demonstrated that that’s really nicely correlative to a 24-hour collection. Any comments on that?
Mark Newman: Well that was part of the publication, was to correlate those, blood, that’s primary. And then secondarily was to correlate it to a traditional 24-hour urine, and that data looked really solid as well. But that was part of the validation too, because A, there’s no reason to do that if you don’t have to, but B, when you do it that way, you lose your cortisol pattern. And so that’s, I think there’s a two-fold benefit to doing it the way that we do it, as opposed to how it had been traditionally done.
Dr. Kara Fitzgerald: So let’s talk a little bit about saliva. So you guys made a pretty big leap in your journey, with your cortisol assessment. And so just talking about urine cortisol, and then your movement over into cortisol and the metabolites and so forth, using saliva. Let’s talk about that and I also want to talk about your, just a few thoughts on saliva. We haven’t talked about saliva sex hormones at all, but that’s a method that’s obviously widely used by some of my colleagues. So, secondarily we’ll touch upon that conversation a little bit. But first, let’s just talk about using saliva for cortisol and metabolites versus urine and where you’re at in that journey and what you guys are doing.
Mark Newman: Yeah, what we’re kind of doing is, is use whatever bodily fluid you can to best leverage information, right? So if, and we can talk about the sex hormones, but the short story, is that saliva’s not, is not as accurate, for reasons we can get into, when it comes to sex hormones. I think there’s better ways to do it. Urine and serum both being probably a better way to do it. I think that’s a longer conversation but when it comes to cortisol, we just said earlier that the gold standard for sex hormones is serum, and that’s right. But it’s not the case for cortisol. So when you look at the literature for cortisol, it’s pretty well established that looking at free cortisol, is better than looking at a total cortisol.
So that may mean that the salivary free cortisol is better than a serum total. Like that’s your starting point. But then, looking at it at really specify points in time, is really important too and that’s where all of this literature has started to emerge on the cortisol awakening response, meaning what we’ve done, historically, is just look at the up and down pattern. So look at it in the morning, generally, look at it in the afternoon and at bed time and let’s see how this pattern looks. Well we can do that with a traditional saliva test and we can also do that with our regular urine DUTCH complete, right? The up and down pattern of free cortisol. But if you want to look at something that’s got a little bit more precision to it, which is the cortisol awakening response, you have to have a free cortisol measurement within the first five minutes of waking up.
So I wake up, my cortisol is relatively low, and as the light hits the back of your eyes, it triggers this whole biochemistry cascade that essentially simulates what happens when you’re stressed. When you’re stressed you get this sort of biochemistry cascade. The same thing happens when you wake up. So if you can capture a point within the first five minutes and then you can capture a point 30 minutes later, the cortisol awakening response is this lifting cortisol that happens in those first 30 minutes and when they look at specifically that change, and they look at things related to cortisol, fatigue, depression, whatever, that change in cortisol, is a really important parameter when it comes to assessing the HPA-axis.
When we looked at that in the literature, we said, “Well this is something we need to add.” So that’s where we developed the DUTCH plus, which is the same urine collections, four times throughout the day, but in addition to that we’re using these little cotton swabs to pop in your mouth. One when you wake up, one 30 minutes later, another one 30 minutes after that, one at dinner and one at bed time. So now I have this diurnal pattern, which we already had in the urine, now we’re getting it from saliva. Why? Because we can add that additional point right at waking, and now we have the diurnal pattern plus the cortisol awakening response, which if it’s … Even if all your results are normal, within the range, that change in those first 30 minutes is either flat, or exaggerated, meaning too small or too big. That says something about the likelihood that your stress response is either under or over responsive and so that’s kind of been … Gosh, when did we release that? Two years ago? Something like that. A year and a half? And that’s been a really nice addition because it’s taking a test the DUTCH complete, which is really complete, and it’s making it even broader in terms of what you can learn about the HPA-axis.
Dr. Kara Fitzgerald: Yeah, it is. We love it. I mean, we’re on board. I’m pretty excited about it and I appreciate it. And again, I don’t know. I’m really become a big fan, a fan girl over here. So sorry folks. But I just … I think just coming from a lab background, I just appreciate your willingness to go in there. I think you guys were really the first clinical laboratory to make a CAR available. Am I correct in this?
Mark Newman: Yeah, there was, when we released it there was a lab that was doing it, which, good for them. But it was really, you couldn’t actually do it because what they were saying, and with all due respect, I need you to wake up, don’t rinse your mouth and I need two milliliters of saliva, within the first five minutes. And most people just flat out can’t do that. So what happens is if it takes you too long to give sufficient sample, the cortisol is already gone up and you’ve screwed it up, right?
So what we did is we said, “Look, if this is going to work, we’re going to have to use the cotton swabs that they use in all the research.” And so what you do is you pop this thing in your mouth and literally 90 seconds later you have sufficient sample and you put it back in the little gizmo and then you do another one. Right? The reason that saliva labs can’t do that, is just a logistical, sort of unfortunate thing in that, those cotton swabs absorb progesterone. So if you’re trying to present an entire picture of sex hormones and adrenal hormones, at the same time, you can’t use the cotton swabs and you need a whole bunch of saliva.
So then you’re stuck in this little, sort of between a rock and a hard place, where you want to give this information, it’s sort of there, but you just can’t. So that’s where we came in and said, “Look, we need to do this and we need to do it right,” which means two things. One, you have to collect using the cotton swabs so that if the timing is correct, and then two, which is a more minor distinction, you don’t have to do this, is use mass spec. So we use LCMS so that you not only get cortisol but you also get the inactive cortisone which is essentially just a secondary version of that up and down pattern and in a small fraction of people, there’s some funkiness there that needs to be teased out between the two. But in the average person, all you need is the cortisol. But the timing has to be right, or it’s not really useful data.
Dr. Kara Fitzgerald: Yeah, and it’s always nice that you’re using the same method that they used in the research which is kind of heartening. So then if you’re looking at the studies and hoping that you’re doing … You know, if you’re a clinician, like me, and we’re looking at the CAR research out there, we want to be doing as close to that as possible if we’re going to infer their findings to what we’re seeing.
Mark Newman: Right, so that’s where the, it’s the lab’s job to set this up well, right, because if you give your patient a kit and they go home and collect and they don’t tell you, “Hey, it took me 12 minutes to collect enough sample.” And then you say, “Hey, you have a flat CAR.” Well maybe they don’t, you know what I mean? So that’s where it’s on us to really dig in to these types of things and make sure they’re set up well, so that there’s not this unknown, uncertainty, embedded in the method that you’re using to evaluate all of this.
Dr. Kara Fitzgerald: Yeah, that’s right. I mean it is … Well, I’m glad that you’re doing that, and correctly actually capturing the specimen. I mean it is, it’s not simple. Our patients, we have to work with them pretty carefully to make sure they get the CAR, and having just done it myself, as you know, because we were talking about my lab results recently. It is really kind of a pain in the butt. But if you want to get that accurate specimen, it’s worth it and it’s cool that you’re using the same method.
Alright, so anything else you want to comment on, with regard to the research paper as we’re just wrapping up here? Other findings that you didn’t report on that are useful for us to know?
Mark Newman: Well I think the only other thing that was revealing from the study, which was we didn’t attempt to publish as of yet, which I think again highlights some of the utility when you’re just trying to be practical, when it comes to sex hormones, is what we kind of alluded to earlier, is the challenge of doing the same thing with saliva testing because there is this temptation to say, “Look, if I go to the literature, I really like salivary cortisol. Why? Because it’s easy to collect and it’s free cortisol and that’s a legitimate advantage.” So then you take that information and you apply it to the estrogen, and you say, “If free cortisol is better, free estrogen is better too.” But what you may not realize, is you have just dropped 10000 fold in terms of concentration levels.
Okay, so now what you have is you have something that’s very difficult to do well, analytically and what we’ve found from our study is … So we’ve got these women, right? They’re doing these blood tests, they’re doing the urine tests, and the same day, they gave us enough saliva that we can send it to, I think, seven different labs, right? So we’ve got all kind of different methods. Some of them are using mass spec, some of them are using EIA and LIAs and whatever. And what we found, is that if you want to simplify the findings, is that if you just isolate the women in the luteal phase, which means this is “normal” for a premenopausal woman, and then you isolate the post-menopausal women that we had do the test, in serum, there’s a ten-fold difference between the average of those two groups. Meaning luteal is way up here and the post-menopausal women are way down here and there’s a big difference between the two. And that’s good, because that’s what you’re trying to do in your practice is say, “Who are you? Are you sufficient, are you deficient? Do you have excess?” Whatever. You need to be able to tell the difference.
When we look at the urine, you get the same thing, there’s this ten-fold gap of the average pre-menopausal woman is at three, the average post-menopausal woman is 0.3, right? So there’s this enormous gap to ask the question, which of these groups do you fall in, but when we looked at those same people, on the same day, in saliva, there was essentially a co-mingling of all of that data, meaning the average post-menopausal woman was about the same, and inter-mixed with all of the pre-menopausal women. Now why is that? Is that a reality of saliva? Probably not. The issue there, is that those hormone levels, whether you’re pre or post-menopausal are really below the level at which that technology can give you a good number. And that’s part of the problem.
This gets to the point of why we published our data because if you go to, and again, I don’t mean to be overly negative on saliva, but it’s an important point that if you go to a saliva lab and say, “How can I know that this correlates with serum?” They’ll give you a publication. And it’s likely, the Wong study from 1990, which did show good serum correlation with estradiol. But if you got to go into the lab and look at their methods, most of the methods that people are using, are about 20 times less sensitive than the method that that gentlemen used to prove his point.
So you still are left with the burden of proof of knowing that using a commercially available method, that we can differentiate well, the sufficient from the deficient. Now when you move into an easier hormone, like cortisol, yeah, it’s easy. Any lab that does salivary cortisol, that is a halfway decent lab, is going to give you something really useful when it comes to salivary cortisol. But you move to, let’s just say testosterone and progesterone, that’s kind of in that middle range, some of the labs do a really good job, and some of them, the methods just aren’t that sensitive and it’s a struggle and you’re going to start to get a co-mingling of sufficient and deficient people.
But when you move to the estrogen, what I have found, and that’s not to say it’s impossible for someone to do it well, but what I have found from evaluating the commercially available methods, is none of them can well differentiate sufficient from deficient. And that’s one of the things that we found in our study, although that’s not data that we’ve published at this point, but I think it’s a, I’ll just say it’s a nice benefit for the urine test that the deficient crowd and the sufficient crowd, is really well-separated and it allows you to tease out information.
I’ll give you an example. The progesterone, if I see a post-menopausal woman, she’s going to have low levels of progesterone, right? But because my method is really sensitive, I can actually see within that group, which post-menopausal women are even low for a post-menopausal woman. Now what do I do with that information? Well I know that for a post-menopausal woman, this is no longer an ovarian hormone. It’s an adrenal hormone, right? Progesterone comes from the adrenal gland when you are post-menopausal. So if you’re lower than the rest of your post-menopausal friends, now it’s a key, it’s a clue to say, “Go look at the cortisol.” So then, what does the DUTCH Test have? It has this enormous about of information on cortisol, I was just looking at a woman’s results the other day, who had this very picture of low, really, really low, severely low progesterone and she was on an opioid. And when you look at her cortisol, it was flat as can be.
And so that’s where we want to offer a more compelling and complete picture so that you don’t go into that woman’s case and start trying to fix this low progesterone, with progesterone. Maybe she needs progesterone, but what’s her bigger issue? Is the poor woman’s got no cortisol and so we want to make sure we give you enough information to do well with those types of patients.
Dr. Kara Fitzgerald: Right, and this is influenced by the opioid, which…
Mark Newman: In that case, yes.
Dr. Kara Fitzgerald: Okay, right, right, right. So again, having the whole picture is, it’s really beneficial. Okay, Mark, as always, it’s fun to get to pick your brain for a while and I think that this was a good conversation it will be useful for clinicians. We’ll ping you on any questions we get and then we’ll circle back and continue the conversation. I know you’ve been thinking a lot about saliva and optimal specimen, or multiple specimen and we’ll talk about, we’ll continue this conversation. We’ll talk a little more about testosterone next time actually. We didn’t really touch on testosterone at all this time but we’ll just continue to tease this out for clinicians.
Mark Newman: Yeah, because there are lots of little sub-topics within this and I think each of those is worth getting to the bottom of so we’re making good decisions. And the decision is not always that DUTCH is the best option but for the situations for which it works, it works pretty well.
Dr. Kara Fitzgerald: That’s right, yeah. And I appreciate you clarifying that for everybody. Alright, well thank you for joining me today and to be continued.
Mark Newman: Thank you for having me.
Great podcast: opioids effect more than cortisol: Opioids and endocrine dysfunction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590093/
Yes, you are of course, correct. Indeed- we could’ve discussed the opioid influence on HPA for the full hour. Always nice to hear from you, Dr. L! — DrKF
Please share the webinar link with Dr. KF and Dr Carrie Jones! I could not find it!