Mark Newman: Maximizing Hormone Health With The DUTCH Test

Hormone testing is a rapidly evolving (and frankly fascinating) field! In the latest New Frontiers podcast, I welcome back Mark Newman, founder of Precision Analytical, the company behind the revolutionary DUTCH test.

Mark and I have chatted many times over the last few years and I appreciate his passion for delivering accurate and clinically relevant data when it comes to measuring hormones.

Together, we delve into the complex web of sex hormones and the factors that influence their production and metabolism (and boy are there many!), what the organic acids indican and beta-hydroxyisovalerate can tell us about hormone health, the importance of choosing not only the appropriate specimen (saliva vs blood vs urine) but also the appropriate testing method, and much more.

It was a conversation packed with clinical insight – I’m sure you’ll not only enjoy it but find it very helpful too. Tune in, and please do leave a kind review on Apple Podcasts or wherever you listen to New Frontiers. ~DrKF

In this episode of New Frontiers, Dr. Kara Fitzgerald interviews Mark Newman, the president and founder of Precision Analytical, the company behind the DUTCH test. They dive into the latest developments in hormone testing and the expansion of the DUTCH test to include the additional biomarkers of biotin and indican. They talk about the convenience and portability of the DUTCH test, as well as the importance of biotin and its role in hormone health. They also address the controversy surrounding saliva testing for hormone analysis and the challenges of monitoring hormone creams and gels.

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 I am really excited to be back with Mark Newman. He’s a longtime friend and colleague, one of the first people I podcasted with. He’s brilliant. He always leaves me thinking and just feeling like I’m a more informed, better clinician. Let me give you his background and we will jump right in.

Mark is the president and founder of the DUTCH Test. Everybody knows Precision Analytical as DUTCH, but the company is Precision Analytical, and their famous test is DUTCH. He’s a recognized expert and international speaker in the field of hormone testing. He spent nearly 25 years developing, directing 24-hour urine, organic acid and salivary hormone testing labs. His unique experience led him to pursue a revolutionary way to test hormones. Mark began his own lab precision analytical, to create the most comprehensive functional hormone test available, the DUTCH, which stands for Dried Urine Test for Comprehensive Hormones. Mark is committed to making it easier for patients and their health care providers to answer complex clinical questions through extensive education on validated hormone research.

Dr. Kara Fitzgerald (00:01:19) – Every day, he and his team of experts work through their mission to profoundly change one life and then a million more through industry leading functional hormone testing and education. Mark, once again, welcome to New Frontiers.

Mark Newman (00:01:32) – Thrilled to be here. Good to chat with you.

Dr. Kara Fitzgerald (00:01:34) – And I just want to let everybody know that, you know, I’ve got some of my most favorite blogs come from DUTCH. I mostly call you DUTCH. I think everybody calls you guys DUTCH. And we’re going to put those, we’ll put the blogs that you’ve authored for us, my favorite testosterone blog. It’s so, so useful for clinicians as well as for patients. It’s so well referenced. There’s a great blog in there on hormone replacement therapy as well. And then all of our podcasts over the years, you know, we’ll just park everything on the show notes and go there and check them out folks. You’ll certainly want to listen to some and just download some of the content. And also we will put a sample DUTCH report over on the show notes as well.

Dr. Kara Fitzgerald (00:02:18) – I often encourage people to just have that up so that when Mark refers to what they’re doing, you can take a look at it and have that. But before we dive into talking about hormones, just tell me what’s up over at over at Precision, what you guys are working on, what new analytes… you’ve been evolving the test for years. You have that foundation in hormones and then, you know, you’ve been going.

Mark Newman (00:02:44) – Yeah, we’re still just trying to tell a better story. You know, I’d say that comes kind of in three sections for us. One is just the validation of what we’ve already done, which is just trying to get publications out there that show the utility of the testing. And then also as we’ve done that, we’ve learned where there’s limited utility. And so that’s, you know, our mission is to is to put this in the hands of people at the most opportune times and scenarios and to make sure that the claims that we’re basing what we do upon are provable and then proven.

Mark Newman (00:03:19) – So there’s a lot of effort going into that in terms of statistics and writing and that sort of thing, and then just making it more palatable for people. You know, it is the C stands for comprehensive in DUTCH. And sometimes that’s so wonderful because you get so much information, but it can also be overwhelming. So we have a new interp guide that we put out that’s, you know, yay thick and just really well sectioned out. So if you want to learn about premenopausal women and cortisol or postmenopausal women and whatever or men and, you know, testosterone metabolism, whatever it is, that you’ve got a really good reference there. And then we have a new course, a mastering hormones course, so people can kind of get basically hormones 101 and DUTCH 101 and just kind of work through that so that they can just be more confident and competent at hormones generally, and then applying the DUTCH test and trying to get just trying to really get the value out of that. And then the third part of it, which is the most fun for me, is broadening the story.

Mark Newman (00:04:16) – So we’ve been adding, you know, we started with hormone metabolites, we’ve added some of those over time, but then we’ve also folded in, which is kind of been a unique thing that we’ve done is to take related, but non-hormonal tests that fold into the story. You know, we added melatonin and 8-hydroxy oxidative stress marker and, and some of those others. And then recently, fairly recently, we’ve added a biotin marker, a neuroinflammation marker and indican for a gut marker. And that’s been great to just sort of, add to the story that we’re already telling.

Dr. Kara Fitzgerald (00:04:53) – Nice, nice. I want to just again let folks know that we’ll grab the publications that Mark’s referring to and park them on the show notes. And if we can get that interp guide and have a link to that on the on the show notes as well so people can access it. You know, I remember when you launched Cortisol Awakening Response, just such an incredibly useful, essential evolution of salivary cortisol testing and really glad to have that to just kind of thinking about it historically.

Dr. Kara Fitzgerald (00:05:27) – We all use it in functional medicine. You know, it’s just such an important tool. And then after that, you brought in the organic acids to begin to look at the gut and to begin to look at nutrients and, you know, and to look and see where serotonin is and, you know, just some important markers. And so I appreciate your evolution. If anybody isn’t familiar with the Cortisol Awakening Response, I want to talk about your new organic acid markers, but just give me a little, you know, high level what it is.

Mark Newman (00:06:00) – Sure. Yeah, sure. I mean, we started with just a straight urine test, which is a nice way to look at the diurnal pattern of cortisol. You can do that in saliva. You can do it in urine. And that’s been a mainstay of functional testing. Is cortisol bouncing up high enough in the morning and then dropping off appropriately at bedtime? You know, if you’re inverted, you’ve got a problem.

Mark Newman (00:06:20) – And then the literature really compelled us to add to that story because while that’s an interesting story, the Cortisol Awakening Response (CAR), which is simply the gap between right at waking and 30 minutes later. That dynamic gap is a great way, it’s an independent marker of HPA axis function. People call it a mini stress test because what you’d want in your office is to have a bear in the closet, right? And you can test their cortisol, pull the bear out, let it chase them around, and then test them again. And you say, “Okay, when you’re like legit stressed, what happens to your cortisol?” And that biochemistry happens upon waking. Now, a urine test doesn’t work for that because when you urinate, when you wake up, that’s a while you’re sleeping measurement. But a salivary measurement right at waking gives you that baseline. And then you add one 30 minutes later. And if that’s exaggerated, then your stress response is exaggerated.

Mark Newman (00:07:19) – And if that’s flat, then even if it’s within the normal range, but that dynamic bounce is not there, then your resilience of your stress response is maybe not what it needs to be. And that’s a really useful marker. And so, the only way we could do that with was saliva. So even though we were an all-urine test, we added the salivary markers. We tried first like spit in the tube like most people do. But the thing is that cortisol changes within five minutes. So, if your tube is half full after five minutes, you’re sunk. And so we use the cotton swabs to get a really immediate measurement at waking, and then 30 minutes later, and then we mix that with all the other stuff that we measure – cortisol metabolites and all the other things that are part of DUTCH. And we call that DUTCH Plus. It’s the saliva and the dried urine in one really comprehensive test. And it just adds one more variable, but it’s a really important one. And the literature makes that clear that if that’s abnormal, it’s worth addressing.

Dr. Kara Fitzgerald (00:08:18) – Fabulous. I know one of the biggest criticisms of salivary cortisol testing is the reliability and specimen collection and I think it’s huge that you’ve figured out a way to do that where you can actually capture that very precise moment or those two precise moments.

Mark Newman (00:08:37) – Yeah, it’s almost comical where some of the people have accidentally found themselves in terms of collection because they’ll give you a tube and they’ll say, “Don’t eat, don’t drink, don’t rinse your mouth.” You just woke up, fill this thing like that full of spit and be done in five minutes. And it’s like, “Oh my gosh.” It’s just funny little practical things that can catch us up. And then they can move to the cotton swabs, except the cotton swabs absorb progesterone. So, if you’re also doing your sex hormones out of saliva, which are notoriously difficult in saliva, which is why we use urine, then sometimes it’s just the logistical things that needed a solution to be able to put easily in people’s hands a way to get more comprehensive with that HPA axis assessment.

Dr. Kara Fitzgerald (00:09:20) – Yeah, yeah. And also, reliable, I think. Listen, we’re going to jump into the organic acids in a second but I just want to say that for anybody new to DUTCH, sort of the game changer for our patients is that they’re not collecting a 24-hour urine. They’re not going through their life for that specimen collection with a big jug, either in their house or in their car collecting every drop of urine throughout the day, which, you know, I come from a lab background and that’s what we would do in the lab when we were testing new urine analytes. Everybody in the lab would be collecting their pee and there’d be, you know, you remember those days, I’m sure. But you revolutionized that. But yeah, just talk to me.

Mark Newman (00:10:06) – Well, yeah. You laugh at each other while you’re doing it in the lab. But when you work at Nordstrom or whatever, it’s really a hindrance to actually getting the testing done, you know?

Dr. Kara Fitzgerald (00:10:17) – So you just have this four-specimen dried urine collection. It’s easy, very portable. To your point, if you’re working at Nordstrom, you can just pop them in your purse, you can put it in your pocket. They’re pretty small and they dry rapidly. And it’s consistent with a 24-hour urine.

Mark Newman (00:10:41) – Yeah. And the idea is for most of the time you can just collect at home. You get home, you collect your dinnertime, bedtime, at waking, two hours later and go about your business and then send them in the next day. Yeah, we’re trying to make it really simple for people because that’s a practical… I mean, I get some people who will say, “I’ve had this for six months and I’m literally like trying to work it into my schedule.” And so, every little bit you can do to make it easier helps.

Dr. Kara Fitzgerald (00:11:04) – Yeah, Yeah. So it’s doable. It is. I love it. It was a stroke of brilliance on your part actually, to create that testing. All right. Analytes. Let’s talk about indican. It’s one of my favorites. You know, as I was preparing for this podcast, I was curious, you know, so indican is an old school marker. The name indican is old school. The chemical name is indoxyl sulfate. But, I don’t know if you know this, Mark, and I can send it to you. It was first characterized in like 1850. And, you know, they just saw these color changes in urine and they named it indican. I mean old school naturopathic medicine. So, in my background, you know, or nature cure not necessarily NDs, but people in into nature cure were doing indican tests in their office and we knew then, like I don’t know, the 50s, the 40s maybe, that it did have to do with dysbiosis and it was something that you could just do in office. But it’s evolved and we now know that, well we knew then that it was made from tryptophan and that it is bacterial action on the tryptophan. And when there’s a high accumulation, it’s dysbiosis, you know, that was my training back in the day. But now we know it’s associated with MS. It’s potentially associated with Parkinson’s disease. It’s associated with these neurodegenerative conditions. Like it’s gotten a renewed spotlight and there’s some more sophisticated research going on. So, I think it’s a really smart addition.

Mark Newman (00:12:43) – Yeah, I appreciate that. And that’s just kind of the fun part of what we do is that peeling of the onion of the layers of relevance of these things. Because for us, really, the focus wasn’t quite so esoteric. It was just simply that if you have a gut issue, then we know you’re going to have problem getting rid of your estrogen. Right. And we’ve actually correlated that data now that people who have higher indican have higher estradiol, so both male and female patients, because if you’ve got gut issues, then you’ve got beta–glucuronidase issues.

Mark Newman (00:13:16) – So as your estrogen turns into the estrogen conjugate and it’s ready to go out, the conjugate gets broken off by that enzyme and it gets recirculated. And so, for us we know it’s not the end all be all of gut health. It’s really just an indication that it’s worth pursuing interrogation in that area. And we know gut health is so important to people. And if you’re doing an extensive gut test, it’s not that useful. But if you’re just doing your DUTCH test and that’s flared up high, then it’s definitely worth pursuing. Just trying to figure out the level of dysfunction that you have there. And the reason that we chose that marker is because practically, it works in our mass spec assay where we’re already looking for these other OATs. So that’s helpful. So we didn’t have to, in terms of pricing and things like that, it was a reasonable to do. But more importantly, there’s literature support for it. And to me that is… and I haven’t dug into the specifics for a while, but when I was doing a lot of organic acid testing way back when, that was part of my frustrations.

Mark Newman (00:14:20) – I have this whole list of gut markers. And then as I took each one and I’m like, okay, where are the papers for this one? And this one and this one? It was it was really disappointing that a lot of it was just a lot of conjecture and a lot of them were related to, Gee, if you eat this one, you know, if you eat something with a lot of benzoate in it, then it creates a lot of uric acid, whether you have gut issues or not. And like, gee, that’s a pretty cloudy picture. And so, with indican, it’s pretty clear that when it’s elevated, something’s going on in the gut. It’s not hyper-specific for conditions other than just that sort of umbrella term of dysbiosis, which has which has moved out of your voodoo naturopathic world into traditional allopathic medicine, where they’re actually going to buy into the concept that has been proven out over time. And so, it’s a nice marker to add into the hormone story, again, when you’re dealing with estrogen dominance and things that are related to the gut. It’s a nice piece of the puzzle.

Dr. Kara Fitzgerald (00:15:23) – Absolutely, 100%. It’ll flag one to say further investigation needed. And you know, let’s be mindful if we’re starting HRT in this individual- or whatever is going on, that’s prompting doing the DUTCH, it’s just a little bit of insight. You’re right. It is nonspecific, but it’s important. You know, it’s bacterial action on tryptophan and widespread imbalances can ensue and that piece of activity indicates protein malabsorption. I mean, there’s just all sorts of mischievousness happening when we see high indican.

Mark Newman (00:15:57) – And it is a level of sophistication higher where you have a urine sample and you’re just looking for color change. And now it’s a quantitative assay that’s going to be relative to creatinine. And so if you’re if you’re hydrated, dehydrated, it’s still going to give you like a solid quantitative result. And so that’s going to allow us to take that analysis higher than where it would have been in your old school test.

Dr. Kara Fitzgerald – in 1800s

Mark Newman (00:16:21) – Yeah. And then to take that data and start correlating it with other things. As you mentioned, it’s getting a lot more traction in terms of its relevance. But the value needs to be as accurate as possible. And-

Dr. Kara Fitzgerald (00:16:33) – You guys are using LC tandem mass spectrometry on it. Awesome. Yeah, that’s right. That’s a tad better than the 1800s colorimetric visual. So bravo. That’s a smart addition. And then you’ve got the biotin marker, the classic biotin marker. And again, I think it’s a good addition. So this is something that could suggest bacteria as well. But you know our ability to metabolize it out is dependent on biotin. But let me just let you talk about it and you know, just why you brought it in.

Mark Newman (00:17:14) – Yeah. I mean, again, it’s telling the full story is what we’re after. And it’s a hormone story.

Mark Newman (00:17:20) – So how does that tie into hormones? So to me, one of the best uses for DUTCH is in the PCOS crowd. And you can say I have PCOS, but you can also more broadly say just women with high androgen like issues, right? So what are their issues? One, they make too much DHEA and androstenedione, meaning adrenal androgens. That’s one potential issue. Two is too much testosterone. So that can come in PCOS from the ovaries, and so that’s independent somewhat of your adrenal androgens. And then they combine. And so you’ve got that as an issue. That’s a hormone production issue. But then in addition, as we know, if you’ve got the insulin issue going on, what does insulin upregulate? It upregulates 5-alpha reductase. Now my testosterone turns into DHT, 5-alpha dihydrotestosterone, and we know that’s about three times more potent and it can lead to acne, facial hair, and thinning scalp hair. So, okay, well, if you have someone with thinning scalp hair and you’re interrogating that and the androgen contribution, what if they have an overt biotin deficiency on top of that? We know one of the consequences of biotin deficiency is hair loss.

Mark Newman (00:18:31) – And so it ties into that story in that way. Obviously, if you’re biotin deficient, it’s likely your life is less optimal. So, it doesn’t have to be about hormones, but the reason that we pursued it is, same as before, is twofold. One, there’s literature support. It’s not just a hypothetical marker for biotin deficiency. There is literature that says when this goes up in well, guess I should reverse it. When you have a biotin deficiency, this is elevated in urine. And then secondarily, as I just explained, it folds into the hormone story. Because the thing we want to avoid is someone who’s just beating their head against the wall, trying to figure out “Have I moved away from DHT production enough to get my hair loss to get better?” Well, if you have a thyroid issue or a biotin issue and, you know, the thyroid evaluation has to come from your blood testing, but if you’re not covering all of your bases, then some of those patients are going to get really frustrated.

Mark Newman (00:19:29) – And so we want to help these doctors succeed. And that’s just another tool that we can put in there. And the other thing is it’s simple. If it’s high, you’re probably deficient. If it’s not, you can ignore it, move on. Right? So it doesn’t add really to the complexity of the story, but it’s another piece.

Dr. Kara Fitzgerald (00:19:43) – I think it’s great. I think it’s awesome. You know, it’s funny, just reading your new assays prompted me to bust out my MetaMetrics handbook of all organic acids. Actually, I was one of the authors on this. I was at the lab at the time when we published this with Dr. Lord, and all those compounds are in there. I’m just thinking if people will want to access this and it’s I don’t think it’s available anymore, but the laboratory evaluations textbook might be available on Amazon. Anyway, if anybody’s interested in kind of pursuing those, let me know and I’ll you have you email it to me. You’ve got that?

Mark Newman (00:20:19) – Yeah.

Mark Newman (00:20:19) – I have it in my office somewhere.

Dr. Kara Fitzgerald (00:20:20) – Somewhere. Yeah. Yeah. It’s a great book. But these are fun. They’re older resources. But you know, these are older analytes and if we can access them, it’s a fun place to start. But with both of these compounds, what’s nice for me to see is that newer eyes are looking at them and we’re seeing newer, newer research. So, we’re not just looking at papers from, you know, the 60s and 70s anymore. We’re seeing newer scientists get interested in these markers and their reliability. And then the other piece I wanted to say about biotin, or the beta-hydroxyisovalerate, which is the marker that elevates in response to biotin deficiency, is that biotin is a gatekeeper for appropriate protein, fatty acid, and carbohydrate metabolism. So just to your point, it’s fundamental to everything. And a biotin deficiency therefore shows up all over the place.

Dr. Kara Fitzgerald (00:21:18) – We tend to see it in the tissue turning over the quickest. I mean, you can see skin changes, you talked about hair loss, but, you know, seborrheic dermatitis for me is a shoo-in to just give biotin a shot because sometimes you’ll clear real bad seborrheic dermatitis with a round of biotin. But we see it, you know, it’s such a fundamental player in such widespread processes, metabolic processes in the body, that broad body of symptomatology and powerful benefit with correcting it. When I was in the lab we used to see beta-hydroxyisovalerate elevated in kids on the autistic spectrum, and you know again, powerful responses.

Mark Newman (00:22:02) – Yeah interesting.

Dr. Kara Fitzgerald (00:22:04) – So smart. Good. And I just want to say I know the last time we talked about organic acids, you added these without shifting the price of the DUTCH. Like this was just because you guys could do it.

Mark Newman (00:22:17) – Yeah. It was independent of that. I mean bad news…  When you’re in business ten years you do have to raise prices eventually and so we we’ve had one price increase in the history of our company.

Dr. Kara Fitzgerald (00:22:28) – Wow, that’s it.

Mark Newman (00:22:29) – It was last July or something like that. And the organic acids came out before that. Yeah. Our lab people did a really great job of retooling our LC-MS (Liquid Chromatography Mass Spectrometry) method so that it could grab the things we were already testing. We have five different assays, so there’s an estrogen assay, an androgen assay and then an OATs assay. And so, they were able to creatively fold those in without it really changing the method that fundamentally, which was awesome. And that’s what we’re always trying to do is to tell the story in an efficient way too. Because we know, people’s dollars only go so far.

Dr. Kara Fitzgerald (00:23:09) – So yeah well nice. I’m appreciative and I’ll look forward to seeing what else you guys are adding. Okay. So let’s talk. You and I spent a long time off air and you talk about this, I think every time we chat. What’s new in precision hormone testing or how we want to test our hormones? There’s some longtime controversy in our field.  Solet’s talk about new research. Let’s talk about, you know, let’s touch on the controversy. I mean we might as well put it out there.

Mark Newman (00:23:43) – Yeah. I think the biggest controversy in our industry is just where it’s appropriate to use saliva. We have a saliva assay for cortisol. As we talked about, it’s fantastic. It’s got unique information that’s valuable. And so we put it out there. We also have salivary assays for testosterone and estradiol. And as of now, we haven’t seen that the value is there and that the quality can be at a level where it’s good enough for baseline testing. There are two different issues. There’s baseline testing, does it do an adequate job? And that depends on the hormone. And then there’s the question of now that we’re on therapy, now what? And that’s the one that tends to be the most controversial. The one that gets ignored a lot I think is just the baseline testing.

Mark Newman (00:24:31) – There’s actually a 2023 paper that came out, which was a European group. They looked at like 10,000 measurements. So, this is a big study. Well, it was a combination of five studies and they were looking at commercially available salivary estradiol assays. So that’s like right up our alley, right? Like how well does this work for a baseline test to just ask the question, are you estrogen sufficient or deficient or do you have an excess? And so, what they did is they took 10,000 measurements and they compared it to serum. And what they said is basically, hey, look, we got a thousand women collecting throughout their cycle through all these studies. So, we also have their LH (luteinizing hormone). So what you can do is if you just plot the cycle, it gets messy because some people are short, some people are long. But if you’ve got LH measurements, like those ovulation predictor kits, then they can find ovulation. And if you take all of the data and you calibrate it around ovulation, then you know what biology is.

Mark Newman (00:25:32) – A thousand women. Sure, a handful of them are all messed up as far as they’re not ovulating or whatever. But on the whole, you get the biology story, right? If you’re doing this well, you get the story of female biology. And so, what you get is a great big estradiol peak right on that LH peak, it’s shifted by like a day or whatever, but it’s a nice big peak and then it comes back down and then it surges modestly in the luteal phase. So, what they did in this study is they said, we’re going to take all this data and just see what it looks like. So they first took a subset of serum data, and what they did is, they said this is the biological pattern we should see. This was actually just for your reference, Arslan.

Dr. Kara Fitzgerald (00:26:15) -Okay, we’ll pop it in the show notes.

Mark Newman (00:26:17) – To give you a hint of where they ended up on it, the title is “Not Within Spitting Distance: Salivary Assays Of Estradiol Have Subpar Validity For Predicting Cycle Phases.”

Mark Newman (00:26:29) – And what they did is they said, We know what biology looks like. So, let’s take serum and compare actual serum measurements to the pattern we’re supposed to see. And so you know, it’s not perfect, right? And so what they found is for progesterone, the match was at like 80% in terms of theoretical versus actual. And now keep in mind, the progesterone pattern is big and lbold, right? So it’s easier to match up. The match was like 70, 80%. And then for estradiol, it’s a more subtle pattern. So you don’t expect it to match perfectly. And the serum, which becomes your gold standard was like 60% or something like that. Then they took all of the saliva data and they said, Well, how well does that work? And what they found was really interesting. With progesterone, you got this really nice analytical lesson, because when they took the data from the studies where they were using mass spec research methods, then it matched up at like, let’s say two-thirds. It was close. Like, hey, this works well enough.

Mark Newman (00:27:26) – And then when you shift over one more to, not the research methods, but the commercially available methods. These are FDA approved and they’re the ones you can automate. That’s why this is what pretty much everyone uses is you can automate it, you can do it more cost effectively, and the correlation to the real pattern there, instead of being modest as it was for the research methods, was low. When you look at the actual data, it’s like, man, you can kind of see the pattern there, but it’s lost a little bit because it’s just not sensitive enough. Now you could spend some time-

Dr. Kara Fitzgerald (00:28:00) – But what is this FDA approved kit? It’s EIA?  (aka ELISA)

Mark Newman (00:28:04) – Yeah, well, there were multiples. They compared all of the research. They looked at all of the studies where they’ve looked at hundreds and hundreds of women and their cycles and published the data and yeah, the ELISA testing it was just okay. It wasn’t up to par really with what a serum assay would look like.

Mark Newman (00:28:25) – But the problem was, when they shifted to estradiol, the saliva assay was just basically noise. Like the whole thing when they plotted the pattern-

Dr. Kara Fitzgerald (00:28:34) – All kits, all methodologies-

Mark Newman (00:28:36) – They look at the three most popular FDA approved kits and in this data there’s no ovulatory peak. It’s just kind of bleh. And so, what the data actually said in the abstract, it basically said, if we know where you are in your cycle and we guess, that gave us better data than looking at this saliva data, because it just doesn’t have the sensitivity. I mean, keep in mind, when we’re doing a urine assay and we’re using mass spec, there’s a thousand times more estrogen there than in those saliva samples. Like it’s not the fault of oral fluid. It’s the fact that the techniques that you use just aren’t sensitive enough. And it gets so complicated because there’s older data that actually look pretty decent. But those methods are like 20 times more sensitive. They’re not automatable. That’s the thing is -.

Dr. Kara Fitzgerald – Oh, so they’re not used.

Mark Newman (00:29:28) – Nobody wants to sign up to use those. But the data can be used to support it conceptually. So, what was really cool about that study is when it got published, we had just finished, like days before, doing basically, exactly that study with this Austrian group that’s looking at BRCA (breast cancer gene) patients. So they have a group of healthy controls, a group of BRCA patients, they did enough testing in serum to kind of know what they’re doing, but they wanted mass data. So they said, Well, serum sucks for that. What should we do? So they used saliva. But when they did it, they contacted us and we said, Listen, look at the data, but just while you’re collecting, have them collect a dried urine sample every day and then we’ll talk. And so they did all this saliva data and they found basically nothing. There was no pattern that matches biology. And so, then they came back in behind that and they sent us, I don’t know what it was, it was hundreds and hundreds of urine samples from these women.

Mark Newman (00:30:24) – And we did the same thing. We calibrated it to LH and there’s this great big estrogen peak there. And then you’re sort of mound in the luteal phase. And it was the same exact thing where the saliva progesterone data wasn’t as good as ours, because it’s still kind of difficult, but you could see the biology there. You could see that peak, right? And then when they shifted to the estrogen, it was just gone. It’s basically just noise. And on the same exact day, they have these dried urine samples. And the thing that was kind of fun about this study for us is getting researchers to listen as hard. They left the samples out at room temperature for two years. So, these samples were just sitting in a box and they sent them, and we said, okay, so you froze them. They were like, Wait, what? Froze? What? Like, yeah, there’s still a biological sample. You can’t just leave them out for like two years.

Mark Newman (00:31:15) – So they sat two years. They’re totally compromised. But the data, like, they’re really stable when they’re dried. And the data was beautiful. And then they were able to go in after that and find patterns for both progesterone and estrogen that were different in the BRCA patients. And so they’re teasing that out.

Dr. Kara Fitzgerald (00:31:33) – Yeah, that was my question. That was my question. So, you learned that your specimen are stable, at least for the sex hormone, at least for progesterone and estrogen for two years. I mean, is that what you learned? Your collection method is pretty stable.

Mark Newman (00:31:50) – We’ve studied it internally at 84 days, something like that. And like 60 days, a few of the metabolites start to go. So we can’t actually do that regularly. And whether some of those were compromised or not, we don’t know. But the data still was beautiful. It correlated to serum. It correlated to biology. And they were able to find meaningful differences in cancer groups and non-cancer groups, which they’re working on publishing, so I don’t want to say too much about that.

Dr. Kara Fitzgerald (00:32:15) – So they’re working on publishing?

Mark Newman (00:32:18) – But yeah.

Dr. Kara Fitzgerald (00:32:18) – I’m dying to know the difference, though. I mean, you know, one of the things that a functioning BRCA gene does is kind of control aromatase activity. So, I’m curious. I mean, it’s obviously, you know, tumor suppressor. It does a lot of stuff. But it’s an interesting- Where are they in the writing?

Mark Newman (00:32:41) – It’s submitted.

Dr. Kara Fitzgerald – It’s submitted.

Mark Newman – Yeah. Well, it’s submitted for progesterone which is not lower in the breast cancer group. Like it’s interesting. Yeah. I’m still trying to piece together all of the significance of progesterone and breast cancer and all of that. But then BRCA is a special subgroup, right? So, it’s complicated. So that’s out for review.

Dr. Kara Fitzgerald (00:33:01) – Well, just thinking about what it does and what the absence of it does. But, you know, this is definitely off topic, but it’s my area of interest.

Dr. Kara Fitzgerald (00:33:10) – You can have a hypermethylated and inhibited BRCA gene, but you don’t have the mutation. So, you could have the effect of the mutation without the actual mutation. So, it would be interesting if they could study that as well and kind of look at those with functioning BRCA genes, you know, functioning BRCA proteins, and those with actual mutations or hypermethylated. But that’s a geeky aside. I’ll look for this paper then.

Mark Newman (00:33:37) – It’s a geeky aside and you’ll get nothing useful out of me out of it. Because you know me, I’m an inch wide and a mile deep.

Dr. Kara Fitzgerald (00:33:42) – I know, I know… Okay, well that’s awesome.

Mark Newman (00:33:48) – Okay. So, we’re getting back to your actual question. So that publication in 2023, they really put to test the commercially available saliva panels that are…  and this is not putting labs at the test. This is putting the technology to the test that I as a lab have available to me. So, it’s complicated in terms of what they’re actually evaluating.

Mark Newman (00:34:11) – So then as a lab, if I use those, even though they’re FDA approved, they’re garbage. Now, that doesn’t mean you can’t do some other method that’s more sensitive. The challenge that I put to people who are using saliva is if you ask the labs that are doing that, do they have data for their method that correlates to serum? I don’t think anyone does. So, if they lean back on that data, it’s not successful. The successful data that you have to lean back on are those non-automatable methods from the 90’s.

Dr. Kara Fitzgerald (00:34:43) – What were those methods?

Mark Newman (00:34:45) – RIA (radioimmunoassay). There’s a long paper from 1990 where they get nice saliva data. It looks great. You know, it doesn’t it’s not postmenopausal, it’s just premenopausal. But it’s a nice ovulatory peak, a nice luteal peak. There’s serum correlation, but it’s literally like using 50 times more sample than you put on an ELISA. So, the fact that it works says that what’s in saliva matters.

Mark Newman (00:35:08) – But you have to really prove that the way that you are doing it is actually correlating to something meaningful. And I don’t think there’s any data out there that shows serum correlation for women in saliva for a commercially available test. That’s something that the bar needs to be raised for. So that’s part of why we’ve stayed away from saliva for sex hormones, is my baseline value isn’t good. And the way you can see that practically, which we’ve talked about before, is you just look at the methods that are available, and look at the reference ranges, and the pre- and postmenopausal ranges tend to overlap. Which tells you that you’re not separating out and showing me a real biology pattern because the real biology pattern tells me that a premenopausal woman makes ten times more estrogen than a postmenopausal woman. If your ranges don’t reflect that, there’s not a gap between them, then you’re not going to characterize that woman well as to her need for estrogen.

And then you get into the topic that we have gone over, you know, several times and it keeps evolving as well, which is when you’re on therapy, now what is the best way to test? And of course, there’s this weird dichotomy that when I talk about this in lectures, I usually start people with the data on testosterone injections because it shows this ideal that we wish was true: It’s that if you give a man or a woman a testosterone injection and you plot urine, serum, and saliva, they all three go up in concert, down in concert.

Mark Newman (00:36:36) – The magnitude of the increase is very similar. And so that would tell you conceptually same story, use whichever one works well, whatever. But then when you move to creams and gels, it’s orders of magnitude difference. When you put a hormone on your skin, the saliva goes up orders of magnitude more than the serum or the urine. And that’s been known since early 2000. And so, our interpretation of that has changed over time as data has come out, and our industry has ended up split, where some people say saliva is the way you should monitor hormone creams and gels. And some people, and I would definitely be in that camp, would say that that data is… it’s not less valuable, it’s completely clinically irrelevant and very misleading.

And so I’ve spent a lot of time, as we’ve talked about, really digging through the data of looking at every study that’s been done on those to say, is there anything, anything that suggests that those inflated values in saliva are actually moving and correlating with clinical change? You know, the things that change with testosterone, the change like with estrogen, it’s hot flashes, it’s vaginal atrophy and bone.

Mark Newman (00:37:50) – Right. If those three things change with blood, change with urine, or change with saliva, we want to know which one. And there aren’t any studies that explore all of that. But if you if you cobble all the studies together, you get a very consistent message.

Dr. Kara Fitzgerald (00:38:08) – Serum and urine are consistently reliable.

Mark Newman (00:38:13) – Well, so there’s a paper I think, that’s really underappreciated that’s not that new. 2012 Archer paper. What he did is he put women on different doses of EstroGel. So, it’s 0.27, 0.375, 0.75, 1.5. You’ve got this span of results. And then he looked at serum. And serum went from 5 to 12 to 21 to like 35, and then maybe something like that. It scaled up. And then if you put-

Dr. Kara Fitzgerald (00:38:43) – According to dosage. Yeah.

Mark Newman (00:38:44) – Right. And if you put women on that and you look at their urine results, which we published this last year, it’s a pretty similar pattern in that at one and a half or two milligrams you’ll be up in the luteal range, and at a low dose like 0.25, 0.27, it’ll increase but not very much.

Mark Newman (00:39:00) – And you say, can you pause and say, okay, so I’ve got change over time, change with the dosing. What happens with those same products with saliva? And there’s not a lot of published data, but if you again, cobbled together what’s been put out there as just observational data, what you find is that even at 0.25, you’re above the luteal range. And that’s at 24 hours. That’s like when you’re ready for your next dose. So, you spend your entire day for the average woman outside the luteal range. And then as you give more and more hormone, of course, those numbers go up. You say, okay, that’s a very different message. So which one correlates with clinical outcome? And maybe the best way to ask that is to stop and predict it. If your estrogen exposure is higher than a luteal amount of estrogen on that low dose that Archer studied, which he studied clinical outcomes. That’s why it’s an interesting study. You would expect massive clinical response at 0.27 and then even more at higher doses.

Mark Newman (00:40:02) – And when you get to doses like 0.75, your conclusion would be, this is crazy. Stop giving these women so much estrogen. If, on the other hand, serum and urine are telling the right story, you should get some clinical failure at those lower doses. Because it’s changing, yes, but not that much. And what Archer showed is at that 0.27 dose, where the serum and the urine have gone up just a little bit, it failed for vaginal atrophy. And for hot flashes it failed until you used it for 12 weeks, which is a really good indication that, yes, there’s estrogen in there, but it’s not very much. Right. And if you look at the saliva data, obviously it tells a very different story. If you go back to the bone mineral density study, which is a different group, they found that at 0.75, yes, it helped bones, but it didn’t work as well as like a low dose patch. Like it was very, very clearly a modest dose of estrogen.

Mark Newman (00:40:59) – So you’ve got all three hot flashes, vaginal atrophy, and bone mineral density to tell this story that in that 0.25 to 0.75 range of an estrogen gel, it’s like it works, but it’s not hefty. And then that’s what urine and serum say, that’s what the clinical picture says. And then at those same doses, the saliva data is just really, really high. The thing that has always clouded that, is the most typical outcome for taking estrogens clinically would be what? What would be the top thing you’re monitoring in your patient when you’re giving them estrogen therapy?

Dr. Kara Fitzgerald (00:41:35) – Well, I mean, most commonly, obviously, is hot flashes.

Mark Newman (00:41:38) – Exactly. Right? And when you look at the studies, guess what explains 50% of the benefit of hot flashes? Placebo, like when you look at the placebo arm, it works really well. You give someone a cream and say, hey, there’s estrogen in this. And a lot of women feel a lot better. But I’ll tell you what you can’t fool with placebo, and that’s someone’s bones.

Mark Newman (00:41:59) – So what they’ve done historically is used micro doses of estrogen. The saliva goes up and they go, oh, we’re good. Not only are we good, the number is healthy. You do not want to use more. That’s the message that they get. And the patient comes back and says, well, I feel better. And the thing too, is these are typically brilliant doctors. So, they’re dealing with the gut, they’re dealing with lifestyle, they’re dealing with their stress, they’re dealing with their cortisol. The patient doesn’t feel better. They feel a lot better. And then they have a placebo effect from the estrogen. And then seven years later, it’s like, crap. They have osteoporosis. Like, what happened? You know, it’s like, well, you were treating with what you thought was a modest to aggressive dose of estrogen. And in fact, you were almost giving nothing. And so that’s the issue where people have really gotten caught up here and where people have learned lessons the hard way of having patients with bone loss and having to go back to the drawing board. And if you follow the data, the answers are there. They’re just complicated.

Dr. Kara Fitzgerald (00:43:06) – That’s really interesting. Okay, so most consistently reliable are for baseline and now follow up after initiating therapy according to your really careful read on the literature for what’s available including methodology, is urine and serum.

Mark Newman (00:43:29) – So for serum you want to use LC-MS because the serum ELISAs will fall apart in the postmenopausal. And then the caveat to that, which is very significant, is that if it’s a cream or a gel, the serum really moves too fast. If you look at the pharmacokinetics that are published, there’s one paper that looks at estrogen gels. It was Biest. They use 0.4, 0.5, 0.6, and it goes up and down in a couple hours. So, if you go out here and you test in serum and you get a low number, what people say a lot is, well, it’s not there.

Mark Newman (00:43:59) – Like there’s some magical way that it gets everywhere in your body, but it avoids the serum and then they go test in saliva and they go, Oh, it’s over here. We found it. Right? Because you get these really big numbers. And that’s driven a lot of people, rightfully so, to say, well, I guess this works better. But what’s happening there is the response isn’t as extreme as you think. The target isn’t as high as you think, right? In serum, you only have to get north of like 20 picograms per milliliter to get significant impact and into like the mid 30s you’re getting decent bone impact. You don’t need to be up at 100 where a premenopausal woman once lived. You just don’t need that much estrogen. But then you’ve got this pharmacokinetic challenge. So with a patch it’s pretty stable and the serum works well. But for pharmacokinetics, this is where I think urine is a fantastic choice and why we published…

Dr. Kara Fitzgerald (00:44:47) – Because it just levels it out. Yeah. Go ahead.

Mark Newman (00:44:49) – Yeah. Because if you average it over time- Järvinen published a paper where they looked at  Divigel and they tested the women over time and at the first collect, the first part where they tested, the results were a little higher than you’d want. And then in the middle of the day they were lower than you’d want. And then later in the day, they said they weren’t using it twice a day. The data is weird, but later in the day the result was really high. So you’re high, normal, low, high. It’s like, “Well, which one of those numbers do you want? Well, I don’t want any of them unless you’re going to give me all of them and then integrate them or whatever.” And if you do that, the data works really well. But of course nobody does that. And that’s like the magic of urine is it collects over time, right? Our four collections represent 14 hours of your day. So you take those highs and lows, you average them out, and then that data seems to correlate well with an integrated serum.

Mark Newman (00:45:45) – And it overlays nicely with the clinical picture that says when I push out of the postmenopausal range with those doses, there’s minimal clinical efficacy. And then as I push close to the luteal range, you don’t need to be in the luteal range necessarily, but as you get close, that’s where you see the type of effect that doctors typically want, right? Which is robust increase in bone mineral density and then pretty solid vaginal atrophy and hot flash improvement. But you haven’t been super aggressive. And that’s kind of where we have people, you know, shoot for. But admittedly, you have to piece together the data that’s available to make that case because nobody is doing outcome studies with comprehensive testing. And that’s something that I’m trying to push for, which we just have one piece of that puzzle. So, we need help, essentially, in terms of collaborating with people on maybe the pharmacy side.

Dr. Kara Fitzgerald (00:46:37) – Are there data banks? I mean, are there, can you access like NIH data or something?

Mark Newman (00:46:44) – Well, none of it includes urine because nobody traditionally is measuring hormones in urine. But for the serum, you can piece it together with the serum.

Dr. Kara Fitzgerald (00:46:52) – I wonder if they bank it.

Mark Newman (00:46:54) – Yeah, but the literature, like Archer study lays it out nicely. The problem is that serum number that he reports, it’s doing this and you’re shooting at a moving target. You know, it’s moving up and down. I mean the case for urine has really only been made the last two years. When we published our first HRT paper in ‘22 and then another one in ‘23 and another one in ‘23, and then we’ve got our latest one, which is creams, gels and patches in a comparison is out for review with menopause right now. I’m really excited to get that into print because people in our industry say all the time, you cannot monitor estrogen creams with urine testing. And the data is there. Again, it overlays nicely with the outcome data in gels. But that’s part of my sort of gripe with ourselves as an industry, is we need to put more into research because when you get to the creams, there literally are zero outcome studies for compounded estrogen creams, not a single one.

Mark Newman (00:47:56) – And that I think is something we need to remedy. You know. What dose actually increases your bone mineral density. Everyone is guessing. Everyone is guessing because nobody’s ever proven it.

Dr. Kara Fitzgerald (00:48:08) – Wow. That’s so fascinating. God, I mean, somebody could probably do, you know, a large, some of these larger clinics doing bioidentical compounded HRT. You just go in and do a retrospective chart analysis, you know.

Mark Newman (00:48:22) – And what anyone is doing, DEXA or whatever for bone, they’ve done it anecdotally. But there’s not a thing in print, which would be a service to our industry, to get that better established.

Dr. Kara Fitzgerald (00:48:37) – I can hear your story has evolved over the years. I mean you used to be using serum more often than not. Now you’re really coming out on the validity in urine. Just speaking to your recent research and you’re you know-

Mark Newman (00:48:53) – Well, I started in saliva. I mean, not to be like insulting about it, but I drank the Kool-Aid.

Mark Newman (00:48:57) – I mean, I was taught that those high numbers in saliva are meaningful and you should shoot for them. And I lectured on it. I cobbled together this story of misappropriated research and then data that kind of made sense if you didn’t ask enough critical questions. And it was actually Dr. George Gilson, who owned a saliva lab at the time in Canada and said, you are wrong, keep digging. And he would send me data and eventually-

Dr. Kara Fitzgerald (00:49:26) – He owned a saliva lab?

Mark Newman (00:49:28) – Yeah. And he’s the only saliva person I’ve ever heard from that has said saliva testing works for this. It does not work for this. The data doesn’t actually support it. And the two of us have collaborated on that topic for a decade now. And for me, the statement that makes the most sense is that saliva has special access to fat stored hormones when you apply it transdermally. If you filter all of the data through that, to me, all of it makes sense.

Mark Newman (00:49:59) – You know, it’s a complicated picture. But when you put fat stored hormones on, for some reason you get gobs of it in saliva.

Dr. Kara Fitzgerald (00:50:05) – Yeah, the accumulation. And yeah, the question is why? Like, what’s the mechanism there? You know?

Mark Newman (00:50:11) – Yeah. I mean, people have theorized lymphatic transport and that sort of thing. But when you go in and say, does that number for testosterone correlate with bone, muscle, sexual function, LH suppression, DHEA production, estrogen production, that’s all in the literature. You can look at all of those things and realize, oh, it doesn’t correlate at all to those really high values. Time to go in a different direction. And with estrogen, you know, we just talked about it’s the same thing. It doesn’t correlate with the clinical outcomes. And our industry’s got to move beyond that. But we’ve struggled or at least a fraction of the market has really struggled, I think, to keep asking this question. And yeah.

Dr. Kara Fitzgerald (00:50:53) – So first of all, we need the little take home cheat sheet from your marketing team that summarizes what you’ve just said.

Dr. Kara Fitzgerald (00:51:02) – But I’m going to just say to you, I’m going to name a hormone and you’re going to tell me in, you get three words. What specimen, and maybe if you need to, method. I’ll give you specimen and method. Okay.

Mark Newman (00:51:16) – And we’re with or without hormones in this game?

Dr. Kara Fitzgerald (00:51:18) – We’ll do baseline and we’ll do post, we’ll do with therapy. Okay so let’s start with baseline. You get three words. Method and specimen. Baseline: testosterone.

Mark Newman (00:51:32) – Serum, LC-MS, especially for women. Meaning the LC-MS is especially for women.

Dr. Kara Fitzgerald (00:51:39) – Yeah. Got it. And you can find LC-MS if you’re going to your standard reference lab, Quest and LabCorp. I think they call them? Say it again.

Mark Newman (00:51:50) – You’ve just got to pay a little more.

Dr. Kara Fitzgerald (00:51:51) – Yeah. And I think you can look at the methodology and I think they’re called ultra-sensitive or high sensitivity?

Mark Newman (00:51:58) – It’s complicated because there’s an old school ultra-sensitive for estradiol. It’s an RIA (radioimmunoassay). It works fine. But today it’s just easier to say, give me LC-MS for testosterone.

Dr. Kara Fitzgerald (00:52:09) – So you can just write it on your rec, LC-MS and get it. Okay, that’s fine.

Mark Newman: I don’t.

Dr. Kara Fitzgerald: Go to your lab. All right. We have to keep going because we’re in the middle of the game. But just remember, LC-MS folks, testosterone, serum.  Estrogen.

Mark Newman (00:52:29) – DUTCH. Hey, one word, that’s good. If serum, LC-MS.

Dr. Kara Fitzgerald (00:52:36) – Okay, but you’ve just said and I will say these words, the caveat is that it can be depending on the time of day that you’re testing it can be all over the map. So it’s that 24 hour.

Mark Newman (00:52:47) – You said that we’re talking about baseline.

Dr. Kara Fitzgerald (00:52:48) – Oh, that’s right. We’re in baseline. Okay. So DUTCH. And if your serum.

Mark Newman (00:52:53) – Serum would be second and if serum, LC-MS and it works fine.

Dr. Kara Fitzgerald (00:52:57) – Okay. Okay. So that’s testosterone and estrogen. Progesterone.

Mark Newman (00:53:01) – And then and the reason I’m leaning into DUTCH more for estradiol is because I think the value is really solid, but then you get all the metabolites as well. That’s the thing to me that that pushes it over serum if we’re just talking about baseline.

Dr. Kara Fitzgerald (00:53:14) – Yes. And the metabolites are hugely, hugely useful for anybody not familiar with them. And we haven’t touched on them today, but we have in previous conversations. Okay. Progesterone. Baseline progesterone.

Mark Newman (00:53:28) – Serum’s easy. I think the urine is proven to be equivalent, and saliva is really method dependent. But serum works fine. There’s one paper that shows that during the day, it can bounce more than you would… I can’t believe it’s as much as that paper shows, but a woman bounces from, like 5 to 35 throughout the day. So there’s a big advantage for urine. So I like urine for progesterone, I like serum for progesterone. Saliva is just okay for me.

Dr. Kara Fitzgerald (00:53:59) – Okay. It depends on the method.

Dr. Kara Fitzgerald (00:54:01) – And I think that by and large, the methods being used today aren’t great. The FDA approved methods stink for saliva.

Mark Newman (00:54:08) – Yeah, for saliva. For serum, the levels are so high in serum that the methodology is not that important for progesterone. And keep in mind, as I’m answering this for DUTCH, I mean, the main advantage that DUTCH always has is the comprehensiveness, right? It’s good for progesterone, good for estrogen. I mean, the main thing that we have to offer is… and then you get the cortisol picture and then and, and, and… It’s the “and” that makes us, I think, so valuable. For isolated testing, serum is usually going to be cheaper because it’s 80 bucks or whatever.

Dr. Kara Fitzgerald (00:54:38) – But you’re going to get all those fabulous metabolites. You’re going to get the cortisol awakening response, because.. Just get the DUTCH plus you might as well. I mean, I only use the DUTCH plus these days and, you know, get it. I test mine.

Dr. Kara Fitzgerald (00:54:51) – But I guess I suppose if you’re using a follow up because you’re evaluating therapy, you may not need the CAR (Cortisol Awakening Response) if the CAR was fine. But anyway, you don’t need to go down that rabbit hole. Okay. So let’s get back to follow up testing. You’ve initiated therapy, so follow up testing, testosterone, best specimen.

Mark Newman (00:55:09) – Testosterone is nice that it’s simple: serum. Serum as a primary. DUTCH as a nice complementary product. Because it’ll show you how much estrogen am I making? How am I breaking that down? How am I breaking down my testosterone? If my man has low testosterone and symptoms to go along with that? You want to keep his cortisol managed also because if you’re stressed out of your mind, your low T symptoms are going to get worse. So DUTCH is complimentary. Serum is primary.

Dr. Kara Fitzgerald (00:55:33) – Awesome. Okay, that’s testosterone. Estrogen follow up testing. So you’re on hormone therapy. Specimen.

Mark Newman (00:55:40) – I don’t recommend oral, but if it’s oral, it’s got to be serum.

Mark Newman (00:55:45) – If it’s transdermal, vaginal, I think DUTCH is awesome. We’ve published data for all of those patches, gels, creams, vaginal. You get the metabolites, I think that’s the best way to go. Serum works if you’re on patches. Otherwise, the up and down pattern is just- I don’t like it.

Dr. Kara Fitzgerald (00:56:04) – Okay. So the easiest is DUTCH. Progesterone: specimen.

Mark Newman (00:56:10) – There is not a lab test that will tell you what’s going on in the endometrium or any way that people take progesterone. That’s an important thing for people to know. Is there feedback from labs that can be useful? Yes, but none of it speaks for the endometrium. We could talk about that if we wanted to, but there are different reasons for vaginal, different reasons for oral, different reasons for serum and urine as to why it doesn’t speak well for it. But if you’re using vaginal progesterone, I don’t think there’s really a lot of useful feedback from labs. We know what doses work, we use it, it works.

Mark Newman (00:56:45) – With oral, the serum and saliva should be avoided, I think because you can misdose someone because it goes up and down so fast. Right? If you study the behavior of bats and you only study them during the day, you never learn the critical information because the critical information happens while you’re sleeping. Same thing with oral progesterone. You take it at bedtime, it goes up and down really fast, and then you test in the morning. That’s a really bad idea. With urine, with progesterone, the urine tells you about the GABA impacting metabolites like allopregnanolone. How much do you make of that? That can be interesting, but that doesn’t tell you about the endometrium. So there’s limited value in labs for monitoring progesterone therapy. That’s the main lesson. And don’t use transdermal, not for balancing estrogen. It is not proven to work.

Dr. Kara Fitzgerald (00:57:35) – Okay. Okay. So, we just obviously need to pay attention to clinical and, you know, do imaging studies.

Mark Newman (00:57:43) – Right. We know that 100 and 200 of oral works. We know that, what is it, 45 and 90 or whatever works for vaginal. We know that works. And other than that, there’s no lab magic number that if you hit it, it works. When you’re not on therapy, we know what number means you’re ovulating. It’s enough. Whatever. But it just doesn’t-

Dr. Kara Fitzgerald (00:58:04) – That doesn’t stack up if you’re on therapy.

Mark Newman (00:58:06) – Yeah. It just doesn’t work that way.

Dr. Kara Fitzgerald (00:58:08) – Well, listen, this was a really fun conversation, Mark. I know. I’m going to just, you know, we’re going to play three second answers. People are going to find this valuable. And maybe my team can kind of collate a little bit of a table, a take home table. It’s super, super useful information. I just love talking to you. I love geeking out with you. And I know we’ll get to hang out at a conference.

Dr. Kara Fitzgerald (00:58:31) – I’ll see you certainly in December. But that’s a ways off in Vegas for A4M.

Mark Newman (00:58:38) – Yes. Geeking out will continue.

Dr. Kara Fitzgerald (00:58:40) – Yeah. All right. Anything else? Anything that I missed?  I think we covered a lot of material.

Mark Newman (00:58:47) – Yeah. I think that’s a good conversation. There’s too much more to go into anything else. But I appreciate the conversation and it’s been fun.

Dr. Kara Fitzgerald (00:59:00) – Awesome. Thanks so much for joining me.

Mark Newman, MS, is a recognized expert and international speaker in the field of hormone testing. Mark spent nearly 25 years developing and directing 24-hour urine, organic acid, and salivary hormone testing labs. His unique experience led him to pursue a revolutionary way to test hormones. Mark began his own lab, Precision Analytical Inc., to create the most comprehensive functional hormone test available, DUTCH®—Dried Urine Test for Comprehensive Hormones. Mark is committed to making it easier for patients and their healthcare providers to answer complex clinical questions through extensive education on validated hormone research. Every day, he and his team of experts work toward their mission to profoundly change one life, and then a million more through industry-leading functional hormone testing and education.

The DUTCH Interpretive Guide puts functional hormone mastery into the hands of integrative healthcare providers. This exclusive provider resource delivers fundamental hormone education so providers can create effective treatment plans for a variety of patient populations using the results in each DUTCH report.

Become a Provider

Precision Analytical

DUTCH Blog

DUTCH Sample Reports

Interpretation Videos

DUTCH Education: Mastering Functional Hormone Testing Course

Not within spitting distance: Salivary immunoassays of estradiol have subpar validity for predicting cycle phase.

Transdermal estradiol gel for the treatment of symptomatic postmenopausal women

Evaluating urinary estrogen and progesterone metabolites using dried filter paper samples and gas chromatography with tandem mass spectrometry (GC-MS/MS)

Steady-state pharmacokinetics of oestradiol gel in post-menopausal women: effects of application area and washing

Transdermal (TD) Estradiol (E2) A Critical Review of the Literature and Available Data

DrKF’s favorite DUTCH Blogs

Testosterone Therapy in Males with Testosterone Deficiency (TD): Debunking the Myths

In Pursuit of Best Practice: Menopausal Hormone Therapy (MHT)

Estrogen + Microbiome = Estrobolome

Evaluating Estrogen Detoxification to Understand Breast Cancer Risk

YES! Urine Testing Can be Used to Monitor Transdermal Estrogen Creams or Gels

Previous Podcasts With DUTCH

Testosterone Therapy: Latest Evidence and Clinical Applications with Dr. Doreen Saltiel

Sponsored: In Pursuit of Best Practice for Menopausal Hormone Therapy (MHT)

Evaluating Hormonal Dysfunction and Infertility with DUTCH Testing

What does “Evidence-based” look like in Functional Lab Testing?

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