Evaluating Hormonal Dysfunction and Infertility with DUTCH Testing

If you’ve followed my show for some time, you’ve probably come across the wealth of conversations I’ve had with the team at Precision Analytical about their DUTCH hormone tests – this is an ever-evolving topic that continues to pique my interest as a clinician looking to level up my toolkit. In today’s show, I’m pleased to dive into some of my favorite topics of fertility, menopause, and HPA function with Dr. Jaclyn Smeaton, ND. She’s the chief medical officer at Precision Analytical, and a naturopathic physician who specializes in reproductive endocrinology and hormones. Today’s conversation is all about the latest research on hormone testing, some of our favorite interventions to address hormone imbalances and much more as you consider the best testing options for your patients. This is an incredibly useful conversation so make sure to tune in! ~DrKF

Measuring hormones, particularly hormone metabolites, can give clinicians a much clearer picture of what’s going on with a patient who may be struggling with infertility, HPA axis dysfunction, or other hormonal imbalances. In today’s show, we visit with Dr. Jaclyn Smeaton, ND, chief medical officer of DUTCH testing at Precision Analytical, about the advantages of dried urine versus serum hormone testing, targeted interventions to address test results, and the latest research on the efficacy of compounded medications for hormone replacement therapy.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine and, of course, today is no exception. I am really excited to be talking to Dr. Jaclyn Smeaton, who is, if you don’t know, she’s the chief medical officer at DUTCH at Precision Analytical, but she’s also an expert in fertility. So we’re going to be talking about the DUTCH assay today or the various assays that they offer.

I’m going to also be mining her for as many pearls as I can in her area of expertise because I know that we are … It’s an area of focus that I don’t think has been adequately mined, and so to have an expert in my midst is quite an excitement. So let me give you a little bit of her background. She’s CMO at Precision Analytical. She’s a naturopathic physician focused on infertility, reproductive, and genitourinary health in addition to her private practice, Hello Fertility.

She is a prolific teacher in the field of reproductive endocrinology and hormones, and has trained thousands of clinicians on her treatment methodology. Dr. Smeaton has extensive leadership experience in integrative medicine, including as past president for the American Association of Naturopathic Physicians, as an ambassador for the Academy of Integrative Health and Medicine, and as a board member of the Integrative Health Policy Consortium. Dr. Smeaton, welcome to New Frontiers.

Dr. Jaclyn Smeaton: Thanks, Dr. Fitzgerald. I’m so happy to be here.

Dr. Kara Fitzgerald: It’s always great to be able to connect with you, and I’m glad that you’re in the interview. I get to just really kind of pick your brain. You’re in the hot seat.

Dr. Jaclyn Smeaton: We’re going to have fun.

Dr. Kara Fitzgerald: We have a lot of content on DUTCH, and so for anybody who doesn’t know, we’ll definitely anchor it in our show notes. I’ve had some great, great conversations over the years with the founder of DUTCH, Mark Newman. But we’re going to talk a little bit about you with your clinician hat on, how you’re using it in practice, but also the methodology because I know Mark has worked really hard on it. So again, give us an overview for anybody who doesn’t know about the DUTCH test.

Dr. Jaclyn Smeaton: Yeah, I’d love to. DUTCH stands for Dried Urine Test for Comprehensive Hormones. Really, the intent of the DUTCH test is to really give you the whole hormonal story. It’s really easy because it’s an at-home collection with urine. We collect urine from the patient. It’s really easy because they utilize these little cards that you pee on. Could it be any easier? It’s easier than an ovulation kit or pregnancy test. You let them dry, and then you send them in.

From that, we can measure so many different kinds of hormones. It looks at reproductive hormones, also hormone metabolites. It looks at the HPA axis because you can measure cortisol and cortisol metabolites in urine. And then it also adds organic acids to that test. So you can get a lot of additional info on nutrient deficiencies, different markers for inflammation, for oxidative stress, and so much more. So it’s exciting to be with Precision. I’ve been there about six months.

The reason why it felt like such a great fit for me is it’s a test I used all the time in my own practice. So it’s great to get behind the curtain and see how the Wizard of Oz runs the show and gets all that information.

Dr. Kara Fitzgerald: I want to know, as I just said in my announcement that you heard because I didn’t actually tell you that I was going to be mining you for pearls as much as possible, but whenever you have a thought around how you’re using it in practice and why you’re using it in practice, I’d love to learn. I want to also say to folks, I think it’s four dried spots throughout the day. I mean I’ve done it many times myself. I should know that.

But it’s simple. You’re not carrying a jug around or actually spending the day home because you have to collect your urine.

Dr. Jaclyn Smeaton: Yeah, thank goodness for that.

Dr. Kara Fitzgerald: Yeah. It’s true. All right. So why do you think this method is better? Why are you using it in your practice as well?

Dr. Jaclyn Smeaton: Yeah. So I think the first thing is ease of collection. It’s really nice because you don’t have to have patients do a blood draw. We do still recommend you do it for women at a certain time in the menstrual cycle, so the middle of the luteal phase because that’s when you’ll catch progesterone at its highest, and it’s great to see what’s happening with that. But it’s a lot more flexible. You can do it on a number of days, four or five days out of the menstrual cycle.

It’s really easy. I think another big advantage is, as I’m sure you know and listeners know, hormones fluctuate throughout the day. So if you look at testosterone or estrogen levels, progesterone levels, if you measured them every hour over 24 hours, there would be massive variations, like 40 to 50% variations for some of those hormones. So when you look at just a single snapshot in serum, it’s tough to know if you’re truly high or low because you’re catching just a minute.

So what we’ve shown is that urine testing, the spot urine, the four spots, it’s been published in peer-reviewed literature. Our team published it. It actually matches 24-hour urine collection when it comes to validity, without having to carry the jug around all day. So you actually end up with a blended average of hormonal production through the day instead of just a single time point, and I think that is so much more accurate.

The other thing is you get hormone metabolites. So let’s talk about estrogen, for example. Not only do you get to see estradiol levels, but you also get to see all the downstream metabolites, and some of those are active. So we see reports all the time where the actual hormone looks low, but active metabolites are high. We see this a lot with like PCOS in women.

They’ll have DHEA and testosterone that look pretty normal or even on the low end, but then they have certain androgenic metabolites that are very active that are definitely contributing to skin changes, hair changes, et cetera. So when you can see the metabolites, too, it just gives you the whole story, really, the whole hormone story. So really, that’s why I’ve always loved using the DUTCH.

I use serum testing as my gold standard in my practice because, in the world of fertility, the literature is based on serum. But I do find that this adds a lot to the whole story.

Dr. Kara Fitzgerald: Interesting. Yeah. I think a lot of us use serum just because it is in the literature, and so it just seems like it’s something that we have to lean on in the end. Unfortunately, it’s easy to do, and it’s covered by insurance. I think if it’s not, it’s generally not too crazy pricey. But yeah, your point is well taken, the fact that you guys did publish on the method, demonstrating that it’s comparative to a 24-hour. It’s cool. That’s cool.

Dr. Jaclyn Smeaton: Yeah. The team’s pretty amazing, the research team there.

Dr. Kara Fitzgerald: Yeah, I know. Yeah. Mark is invested in that. He’s invested in putting the science behind what you guys are doing. I appreciate that. Let me see. So what are big reasons people are using the test, and how are you using it in your practice?

Dr. Jaclyn Smeaton: My practice is all men and cycling women because I’m working with couples that are trying to have a baby. So that’s really where my experience comes from, is using it in cycling women. Now, they also offer a DUTCH cycle map that looks at nine different time points across the cycle. So that was always kind of a fun test to run in those cases where you really didn’t know what was going on with the patient’s hormonal system because their symptoms were all over the place. Maybe they had signs of high and low estrogens, for example. So I’ve always used that.

But I was actually really shocked when I joined DUTCH to learn that the majority of their tests are actually for HRT (hormone replacement therapy) and HRT monitoring in postmenopausal women. So it’s been really fun to circle back to that because that hasn’t been a big part of my practice since I was in primary care. So it’s been 10 years since I really spent a lot of time there. Really, I do realize just how much the DUTCH test makes sense for postmenopausal women and for HRT monitoring in a lot of instances, not all instances.

That’s another thing that I loved about their work when I started to look into it is if you asked Mark, “What should I use DUTCH for?” He would tell you exactly the times it’s good, exactly the times it’s not good, and when it’s kind of in the middle, where it might add value. Testosterone monitoring is one example where the data really shows serum is best, and no one at DUTCH would tell you otherwise. They would say, “Use serum.”

If you want to see metabolites, you could also add DUTCH. But your main information needs to come from serum when it comes to dosing. So they’re really straightforward about that. But there’s so many instances where urine is better for HRT monitoring. Some of it is just due to pharmacokinetics.

Dr. Kara Fitzgerald: Before you go into the other instances, I just want to say, as you pointed out a minute ago, that PCOS patient that you’re going to miss with serum testosterone and DHEA, you can pick up with a metabolite. So it’s hugely helpful. Or just looking at how a man’s metabolizing his testosterone, if he’s pushing it towards a more male-pattern baldness, et cetera, if he’s pushing it towards a more aggressive metabolite pattern.

Dr. Jaclyn Smeaton: Yeah. You can see DHT levels. You can see whether men are pushing down that pathway. A lot of this is dictated by genetics. So it’s kind of fun because I say this is genetics and epigenetics in action. You can do a genetic test and determine what someone’s susceptibility is to metabolize down a pathway. But what you can’t see is the nurture impact. That’s their nature.

Dr. Kara Fitzgerald: That’s right.

Dr. Jaclyn Smeaton: But what’s their lifestyle doing? DUTCH actually is showing you the actual output. So when you see things like COMT, having a SNP on COMT that affects methylation, you can actually test whether your therapeutic approaches are working because you can see that methylation step. We see it improve all the time once you address with nutrients. You pick up on a SNP. You address it nutritionally, and the metabolites improve.

There’s no guesswork. You’re just seeing the impact of genetics plus lifestyle.

Dr. Kara Fitzgerald: A lot of the people are using it for HRT. Mark, I think, has told me that over the years. But it is interesting that everybody’s just really comfortable with this method. All right. Let’s talk a little bit about estrogen. I cut you off at testosterone. So go ahead.

Dr. Jaclyn Smeaton: You’re wanting me to circle back?

Dr. Kara Fitzgerald: Yeah, circle back to where we were.

Dr. Jaclyn Smeaton: I don’t remember what I was going to say about estrogen, to be honest. You have me all excited about androgens now. I don’t know. No, but I-

Dr. Kara Fitzgerald: So, yeah.

Dr. Jaclyn Smeaton: Just it gives you all those metabolites. If you look at estrogen levels in a woman, and let’s say they are slightly elevated, the estradiol levels, if you look at a DUTCH test, you can see why they’re elevated, not just that they’re elevated. I love Carrie Jones. She used to be the medical director with DUTCH, good friend, brilliant clinician. She always used the bathtub analogy with hormones and metabolites, where you can see the water level in the tub. That’s like measuring the estrogen.

But if it’s really high, let’s say that bathtub’s overflowing, you have one of two problems. Either your faucet’s running too fast. You’re making too much or the drain is clogged. Your production might be just fine. But if the drain is clogged, it’s going to build up and overflow and cause a symptomatic picture with that kind of estrogen dominance picture.

The interesting thing is that the approach is really different. If you’re not metabolizing properly, you don’t need to address estrogen production. You need to address the downstream metabolites and keep it flowing. So it gives you a little bit more detail that allows you to take a more targeted approach to care.

Dr. Kara Fitzgerald: 100%. Yeah. You can look at the metabolites and the quantity of the safe protective metabolites versus the one associated with cancer or an increased estrogenic activity. It’s incredibly useful to do that. I’m following the program that I developed and researched, the Younger You program where we’re reversing bio age. I don’t want to go do off in that tangent. But it’s very much focused on DNA methylation.

But we’re also a little bit more cautious using high-dose B vitamin interventions. So my recent DUTCH, I was thrilled with the fact that my COMT, the quantity, I was making such a robust quantity of 2-methoxy estrogens. I was just thrilled. So this is the protective, for anybody who doesn’t know. We want a whole bunch. We want an abundant amount of this, and we don’t want a lot of the 4-hydroxy estrogens. Actually, those are associated with damage that can drive cancer.

I had a really nice balance, and I was pleasantly surprised. I trust what I’m doing, but it had been a year since I had ran my previous DUTCH. So it was just really nice to see that the program that we’re prescribing for epigenetics actually really has a nice impact on hormones.

Dr. Jaclyn Smeaton: Congratulations on that. That’s always nice to see. Did you see a difference in that before and after your protocol?

Dr. Kara Fitzgerald: You know what? Yes, I did. I should actually look that up. But I know that I did because it’s an area that I routinely have to work on. So when I noted this time this abundance of the 2-methoxy, I was really happy about it. But yeah, that’s a really good idea. I was going to pop it into a lecture slide, and I should do that.

Dr. Jaclyn Smeaton: I always love when they see us share our own life. Sometimes it’s a bit of a walk of shame and, other times, it’s inspiring. You never know.

Dr. Kara Fitzgerald: Yeah. Yeah. It’s not always a victory lap. But I was happy with that, of validating. We were talking, just the other piece on estrogen, if you want to say anything else about it, was using it for HRT.

Dr. Jaclyn Smeaton: HRT, right.

Dr. Kara Fitzgerald: Yeah. So Anything on that?

Dr. Jaclyn Smeaton: Yeah. What I was going to say is another advantage to urine. If you’re taking oral HRT, the pharmacokinetics of different hormones affect the testing and the results. So if you were looking at oral estrogen, you’re going to metabolize that actually pretty quickly in the bloodstream. So depending upon how many hours after administration you take it, you can get a very high result or a very low result.

When we survey and look at what integrative medicine practitioners are doing, oftentimes the testing window they’re utilizing with the instructions they give their patients, they’re really not catching the majority of that estrogen dump really into the system. Urine, it takes a little bit longer, so you actually can get a little bit better picture of that. We have some nice data. I think I shared with your team a couple of studies that we published on steroids at the end of last year that looked at estrogen creams and patches and looked at what happens in urine when you administer those at different doses.

You can see a really nice linear correlation there, which doesn’t exist when you look particularly in saliva, which is one of Mark’s big things is that our industry relies heavily on saliva for HRT, and it’s pretty controversial. I mean this is an area that I went into really open-minded because, like I said, HRT is not my area of expertise. I didn’t get training from the thought leaders on it. My last training on menopause was from Tori Hudson at her menopause bootcamp probably in, I don’t know, 2008 right when I was new in practice.

So I really had to go into it with fresh eyes and look at published data, which is always where I tend to turn. It actually was surprising to me the practices that are in place in our industry. So the fact that a lot of them are really not only unsupported, but refuted in published literature and we’re not adjusting our practices. So that’s a big soapbox for Mark. I’m sure he’d love to get on here and talk about that because we really want to make sure …

Mark will be the first one to say, “Don’t use DUTCH for X, Y, and Z.” There’s even certain forms of hormones that aren’t well-monitored with a DUTCH test, but there are also many that aren’t in saliva, and we’re still doing that. We’re putting dosages, usually much lower dosages that we’re giving to patients based upon salivary testing because saliva levels tend to be really, really high when people are on particularly progesterone, which is a very fat-soluble vitamin, that we might be missing the opportunity for the patient to get clinical benefit that we’re intending for them to get.

So we know that’s another humongous story for a different day. But suffice to say, I think that as someone who’s coming in on the education side at DUTCH, we’re really motivated to just expose clinicians to what’s out there because there actually is a lot of published research out there to just allow people to make the decision for themselves of what they think is best for their practice.

Dr. Kara Fitzgerald: We will, by the way, folks, link to those studies in the show notes and make sure you have access to what Jaclyn’s referenced so far. But what would you say are the solidly reliable hormones that we can just lean on DUTCH for? I think I already know the answer to that. It’s basically everything except testosterone. The other question that I have is, I mean we are obviously doing some with cortisol using saliva. Is that it as far as you think for reliability in that specimen?

Dr. Jaclyn Smeaton: Yeah. I mean in hormone-naive patients, I think it’s great if you’re not administering hormones. We really can trust those values. It’s when you start to layer on hormone replacement therapy. You’re right. Androgens are the biggest testosterone replacement, is the most unreliable. It’s not that it doesn’t add value. We actually see a lot of men use it. Actually, my husband loves it. I always share his health on every podcast. It wouldn’t be a podcast if I didn’t talk about his low testosterone.

But he’s been on testosterone replacement therapy for quite a long time, and he was finding that he wasn’t feeling that great. He was seeing a medical doctor, doing serum testing. When we were ran a DUTCH on him, we realized that he was converting so much of that to estrogen. When we actually applied things to support estrogen detoxification, he didn’t change his dose of testosterone, but his symptom improvement went sky high when we did things like broccoli sprouts and DIM and all of the things that helped to move estrogens out.

So there is still incredible value, especially if you have patients that seem to be unresponsive at doses where you feel like they should definitely be responding. It might be that they’re converting to estrogen, and high estrogen will mimic low testosterone symptomatically. But you’re right. I think DUTCH really shines also with cortisol. Cortisol, actually, we offer a salivary panel for it as well because cortisol is measured very, very well in saliva.

It’s one of the few hormones where that’s a great medium for it. So we’re not salivary averse in total. We just want to make sure that the data’s there to support it. With reproductive hormones, we think urine is the better medium.

Dr. Kara Fitzgerald: Awesome. Any other key go-tos? We definitely see a variety of high estrogen patterns in our patients, not necessarily on testosterone. They could just simply be really inflamed and converting. Their aromatase is turned up, and so they’re converting their testosterone to estrogen pretty aggressively. I like the idea of using sprouts, sulforaphane, and DIM and I3C. What else? What else would you think about, just to pick your brain on that particular pattern?

Dr. Jaclyn Smeaton: Yeah. When we see high estrogen, the other thing, like you mentioned, inflammation, adiposity will cause high estrogen. Of course, that’s another estrogenic tissue. In men, it’s really active because they don’t have ovaries. So adipose tissue is one of the main places men make the aromatase into estrogen. So that’s another big one. And then environmental toxicity.

Unfortunately, we have so many compounds that are estrogenic that can drive that elevated estrogen level as well. So we have to think about where is it coming from and why is it high? And then, like you said, I think looking at those downstream metabolites to make sure things are flowing efficiently when it comes to detoxification. But we do see that elevation a lot, and sometimes those can have other underlying drivers, like poor sleep habits.

Sleep apnea we know can cause massive hormonal changes in men. So we really have to dive into that root cause piece to see what’s going on for each individual patient.

Dr. Kara Fitzgerald: Yeah, that’s really helpful. Yeah. Yes, I think sleep apnea is becoming more appreciated as a driver, but I do think that it’s still underappreciated. Any good aromatase-inhibiting botanicals that you think about?

Dr. Jaclyn Smeaton: There are. There’s some that are exciting and fun, like mushrooms. A lot of mushrooms, like white button mushrooms are great. Collard greens are great. I always look to food first-

Dr. Kara Fitzgerald: Interesting.

Dr. Jaclyn Smeaton: … because the more we can get people to live with their genetics is how I would describe it, the better off they are. There’s actually a cabernet sauvignon grape that’s in phase two clinical trials right now as aromatase inhibitor. So I’m really hoping that one pulls through, and we can recommend red wine for that reason as well. So I mean those are the big ones I think about using. It’s really more from a dietary perspective.

You also get some activity from a lot of antioxidants, like resveratrol and things like that. So a lot of the antioxidants that you’d recommend actually can support maintaining androgens as androgens when they’re supposed to be that way. What are your favorite?

Dr. Kara Fitzgerald: Nice, nice. Very cool. I would have to say that I think what I have seen the best results is there’s a handful. One, going after inflammation, no doubt about it, a radical dietary change. We’re generally seeing insulin resistance in this same population, so really cleaning up the diet, dropping down the carbs. Maybe do keto for a little while. If you really want to lower estrogen, drop it like a stone, you could consider moving into that, but just doing something low glycemic.

One of the coolest pathways for me, so beyond this, so thinking about diet, cleaning up inflammation, is the fact that we actually make aromatase in the arachidonic acid cascade. So we produce all of those pro-inflammatory eicosanoids and then PGE2, which is the biggest and the baddest of the arachidonic acid prostaglandins, aggressively pro-inflammatory, increases genetic production of aromatase.

Dr. Jaclyn Smeaton: I wasn’t aware of that at all.

Dr. Kara Fitzgerald: It just increases it. Isn’t that amazing?

Dr. Jaclyn Smeaton: Yeah.

Dr. Kara Fitzgerald: So if you think about changing the omega-3/6 ratio, so increasing omega-3, increasing DHA and EPA big time, getting that about 8% in our red blood cell membranes so that we’re packed there and we drop arachidonic acid. Then aromatase is going to be inhibited by that mechanism. We’re just not going to be making as many of those pro-inflammatory eicosanoids. And then the other thing that I think about is all of the amazing botanicals.

We have just a litany of beautiful botanicals that will inhibit those eicosanoids and, therefore, inhibit aromatase being produced by PGE2. So this is curcumin and ginger and boswellia and licorice, all of those beautiful botanicals that we were taught about in our training that we can lean on for this aromatase inhibitory effect. It’s top of mind because I just lectured on this at IFM. So it’s just right there. I talk about it every year, fresh off that particular lecture.

Dr. Jaclyn Smeaton: It’s so funny because don’t you find that no matter how specific the problem, it always ends up winding back to the most basic solutions? That’s why things like profound lifestyle change, dietary change, stress management, good sleep kind of fix everything, even when you get to a very, very specific level of a specific disease process. It’s exciting to think that you can make such a big impact with so little tools, really.

Dr. Kara Fitzgerald: Yeah. Diet, some movement, some sleep, get your omega-3. That is just such a fundamental workhorse intervention. Who aren’t we prescribing fish oil to? That is going to change the whole estrogen-dominant picture we see in men, but also in women as well. That’s all going to shift.

Dr. Jaclyn Smeaton: Yeah. I mean this is a bit of an aside. But with omegas, you have to think about the profound impact they have, one, as an anti-inflammatory, they’re amazing. But then when you think about them as a structural fat as part of the cell membrane, that takes a little bit more time because you need to have more omega-3 in your body as cells undergo repair and replication.

But when cell membranes are built of omega-3 fats instead of the trans fats we all had in our systems in the ’80s and ’90s, it’s transformational because cell membranes function better which means communication happens more efficiently, and the effects can just be really impactful.

Dr. Kara Fitzgerald: Yes. It is a good point. Again, being hot off this lecture, I can say that it’s about a three-month turnaround where you can really see the clinical impact of omega-3 fatty acids, that it isn’t an overnight. Like for pain, you can’t take two omega-3s and call your doctor in the morning. It’s not going to work. It’s a commitment.

Dr. Jaclyn Smeaton: Right. That’s what curcumin is for though.

Dr. Kara Fitzgerald: That’s what?

Dr. Jaclyn Smeaton: That’s what curcumin is for.

Dr. Kara Fitzgerald: Yeah, right.

Dr. Jaclyn Smeaton: Curcumin and boswellia.

Dr. Kara Fitzgerald: Absolutely. Well, that was a fun divergence. So everybody, you have good action plans for your estrogen-dominant, and I want to just underscore what you said on that topic is the role of toxins, the role of xenoestrogens, massive, just massive, massive. So yeah, that has to be considered in there as well. Cool. Nice divergence.

All right. So let’s talk about HPA axis evaluation and how providers can get a look using the DUTCH. Talk about going beyond diurnal curve, and then, of course, talk about your own thoughts around it, using it in clinical practice and maybe if you have any cases.

Dr. Jaclyn Smeaton: Awesome. This is another area that since I’ve joined DUTCH, my knowledge base has gone through the roof. I was really trained looking at the diurnal curve of cortisol and addressing patient needs based upon that. But the DUTCH test offers not just that look, but actually two other really important pieces to the story that I think are underutilized clinically.

So if you’re a practitioner and you’re listening today and you work with a lot of patients with “adrenal dysfunction,” quote-unquote, or HPA axis dysfunction as we call it, if you’re looking at the diurnal curve, that’s the place to start learning. Are they making it in the right pattern where it should spike in the morning and then come down through the afternoon, be relatively low through the afternoon and evening?

Then you can gain a lot when you see, okay, are they too high or too low in the morning? Or do they have that flipped curve where they’re lower in the morning and then they spike in the afternoon? I had a patient actually recently that looked like that. When I was reviewing their results, I said, “Are afternoons really stressful for you at work?” They were like, “No. But actually, that day when I was collecting, I had to go in for a vitamin IV.” This is a fertility patient. It was the husband.

He said, “They couldn’t find my vein, and it took them six or seven tries. I was near tears, stressed out.” I was like, “Okay, that’s what we’re seeing on your test, situational anxiety and stress.” It’s really sensitive, and we could see his cortisol level skyrocketing. So that’s the first piece to look at. And then you might see patients who are generally high or generally low on that cortisol curve or that classic flat-lined patient where it doesn’t look like they’re producing much.

So let’s fast forward to the next thing that you can look at, which is cortisol metabolites. Do you take a look at that a lot in-depth on the DUTCH test?

Dr. Kara Fitzgerald: Well, you know what? It’s funny. As you said that, I was just writing down to talk to you about thyroid and the influence there. I mean I do. Yeah, I do look at it. So go ahead.

Dr. Jaclyn Smeaton: The DUTCH test also, because it’s urine, we can measure the metabolites of cortisol as well. When you compare that to the active metabolites that are shown on the curve, sometimes there’s a mismatch. In a perfect world, you would see, and we show them as these little dials, the arrows would point in the same direction. The amount that you’re manufacturing were also measuring in your urine, and it’s being excreted and metabolized.

But what can happen sometimes is there’s a mismatch where, for example, the flat-lined patient, it’s going to show active cortisol very low. That dial would be pointed to the left on low. But I recently saw one of my patients like that, and the metabolites were through the roof. They were super, super high. So then you’re like, “Okay. Well, what’s going on?” Because if I looked just at that diurnal curve, it would look like their adrenals aren’t producing a lot of cortisol. That would be what you would assume from that.

But if you know enough about metabolism and you see the metabolites are extremely high, you realize, no, they’re dumping so much into their urine. But look how much they’re dumping. Their adrenal glands are overproducing cortisol to try to keep up, but it’s all getting metabolized out quickly. From that, you can actually tell a lot. We see a lot of hyperthyroidism, which is what was going on with this patient, undiagnosed hyperthyroidism, or anything else that affects metabolism.

So in that particular patient, they didn’t have any hyperthyroid symptoms. But when we saw that cortisol mismatch of metabolites, they got tested and diagnosed with Graves’. So that was a really interesting case to see that the metabolites can add so much to the picture. Likewise, you might have patients that look normal, but their metabolites are super low. They feel tons of anxiety and tons of stress, and they’re really on edge.

When you look at the curve, you’re like, “Why do they feel so stressed out? This looks okay.” But then you see that the cortisol metabolites are not exiting the urine, and they’re sticking around and really causing that patient to feel like they’re in that fight or flight mode. So the metabolites can add a really interesting element to the curve.

Dr. Kara Fitzgerald: You can actually see if somebody is using exogenous steroids, in which case obviously we wouldn’t want them to collect. Or if somebody has finished and started their testing too soon, you can also see a flat line. You can see really abnormal cortisol output with the influence of steroids.

Dr. Jaclyn Smeaton: Yeah, you can. I had a patient actually last week with ulcerative colitis who’s on the budesonide and trying to conceive. When we ran the test, she was flat-lined, and it was really because of suppression due to the budesonide, which I’d always known about that for more traditional steroids. But I wasn’t sure what would be happening with that. But one of the members of the team talked me through.

She had some HPA axis dysfunction also, but then also steroidal suppression. But that’s real. I mean the steroidal suppression also means that she`s not got a lot of cortisol around to provide some of the anti-inflammatory benefits. So it’s not that the result’s not valid. In fact, budesonide, she’s going to be on that the rest of her life. She’s on it right now while she’s trying to conceive. So it was helpful to see her HPA axis picture on steroids because that’s what I’m treating. That’s who I’m working with.

But you’re right. We do see instances where it looks really odd, and people will call us. It’s like, “Well, did you use any anti-itch cream? Did you have bug bites?” Any kind of steroid can actually cause a change in those results, so you’ve got to be cautious. We instruct patients to avoid that when they’re doing the testing.

Dr. Kara Fitzgerald: Yeah, for sure. If they’re not, obviously, they need to go for a serious workup and looking at what’s going on there with their adrenal output-

Dr. Jaclyn Smeaton: Definitely.

Dr. Kara Fitzgerald: … if you pick that up and there is no history of steroids in any form, which we have. I mean I would imagine any clinician using the DUTCH has seen those patterns that require a further workup. I love the cortisol awakening response. I mean it’s just been a game-changer.

Dr. Jaclyn Smeaton: I was hoping you’d bring that up.

Dr. Kara Fitzgerald: Yeah, I love it. I mean it just was such a game-changing piece of information. So yeah, the diurnal output is valuable, thinking about it with the pieces that you’ve just brought up. But yeah, the cortisol awakening response is just … I think it’s a game-changing tool in our practice.

Dr. Jaclyn Smeaton: It totally is. I love how much published data is coming out on the CAR. Cortisol awakening response refers to what happens to cortisol literally immediately upon awakening in the first hour. We have two main tests that we run. The DUTCH Complete is urine only. The DUTCH Plus adds the CAR to the HPA axis piece, and it requires saliva because it’s really hard to ask people to pee three times in the first hour. Also, what you see in urine is actually hours old because it has to go through metabolism and be filtered by your kidneys to get in the urine. Saliva is more instantaneous change.

So we actually changed the diurnal curve to be measured via saliva, and you still get metabolites in urine. But with that, you’re able to get the immediate morning sampling. What we found is it actually is kind of like a mini stress test on the body, similar to ACTH simulation that they would do in a hospital setting to measure someone’s adrenal output. You can actually see. There’s great data correlated to all kinds of diseases based upon that mini stress test.

I only run those DUTCH pluses now because the CAR, I think, is so valuable. We’re doing some data mining right now with our research team to take a look at what percentage of the results that we put out that have a mismatch in what the CAR shows and what the diurnal curve shows because we’d like to be able to understand if people are doing just the complete and getting the diurnal curve, are they missing HPA axis dysfunction in their patients that they might have picked up on had they also done a CAR?

So stay tuned. We’re hoping to actually work on that and get that published this year. But I think that’s an area that’s not well understood that could really change the game in how we evaluate patients for HPA axis function.

Dr. Kara Fitzgerald: Yeah, yeah, yeah. I love it. What diseases are associated with abnormal CARs? Just give me some of the top.

Dr. Jaclyn Smeaton: I think there was actually one on all-cause mortality recently that got published. I don’t have that data right on my desk. But different mood disorders. There’s been a lot. I, unfortunately, don’t have that right in front of me to go through that list with you, but there have been quite a number.

Dr. Kara Fitzgerald: Cardiovascular disease.

Dr. Jaclyn Smeaton: Yeah. Cardiovascular disease is another one. So it’s certainly an area where I think that research is really developing and expanding.

Dr. Kara Fitzgerald: Yeah, it’s very interesting. Okay. Well, what we can do, because I know that there are people listening who want that, maybe if you or somebody on your team can give us a little bibliography, we’ll put it on the show notes or we could send it out.

Dr. Kara Fitzgerald: Yeah, I love it. I think it’s incredibly useful and, I think, better studied than the four-point. What else do we have here? We’ve talked about some of your publications. Anything you want to add? We’ve got three that we’re going to put in our show notes. So we’ve got the two looking at estrogen, using dried urine, using the DUTCH. And then we’ve got just the validation that the four-point DUTCH collection is comparative to a 24-hour specimen collection, which is obvious.

We have those three studies that we’ll, again, park on our show notes. And then you’ve got this new one, the data dive that you guys are doing, which is awesome. That sounds really cool. You have some clinical information as well. Will you map the clinical information to the diurnal and CAR data dive?

Dr. Jaclyn Smeaton: Yeah. We can share some more resources with you, too. This is just the sampling of the studies. The team’s published a lot, and now we’re growing our research team. We’ve got a data scientist who’s a pharmacist. He’s brilliant. We’re about to open up a second position on that team for another person to be doing more writing because we’ve got so much data, and it just takes a long time to actually literally write the papers.

We have another one that’s intended to go for submission next week that actually compares estrogen delivered by cream, patch, and gel that we can show how that gets traced in urine and the validity of it and where we see successfully treated women on HRT fall within the DUTCH test, which this is not a diagnostic approach. But what we tend to see is women feel best when their estrogen levels fall between the postmenopausal range and the luteal range for a cycling woman.

Because that’s actually a really big deal is that if you look at a lot of labs, salivary or urine, and you look at their reference ranges, one big challenge for me as a clinician is that when I was looking for a lab, those reference ranges overlap for a lot of labs. So if a woman falls in that overlap, you’re like, “Okay. Well, are you low for …” Especially if she’s perimenopausal, you’re like, “Are you low? Are you high?” You could be either. It doesn’t make any sense.

But in DUTCH, there’s a gap. There’s a gap between the two that’s very solid. What we find is that when we look at clinically effective dosage ranges for HRT, we see women fall in that range. So kind of cool that we can share that information so practitioners can aim for that. But that’ll be covered in this study, which is actually kind of cool. The other thing about it is it’s one of the first studies to be published on compounded bi-est creams.

There’s not a lot of data on the efficacy of compounded medications for HRT. There’s a big research gap there. So we’re excited to be able to add a little bit to the literature.

Dr. Kara Fitzgerald: When is that coming? So that’s gone through peer review? It’s just awaiting publication?

Dr. Jaclyn Smeaton: Yeah, we’re about to submit it-

Dr. Kara Fitzgerald: You’re about submit it. Oh, okay.

Dr. Jaclyn Smeaton: … for peer review. Usually that takes a couple months once you submit, get feedback, make edits, and then submit the final. So probably middle of 2023. But we’ve got a lot on the plate with research and publication.

Dr. Kara Fitzgerald: Hold that for a second. I was just hoping that I happened to have a DUTCH panel on my desktop open that I could pop up. That piece of information you guys are going to be presenting in this study where the sweet spot is in your dataset of estrogen, people are going to be curious. We could put a DUTCH sample report so they can look at exactly what you’ve just said.

Dr. Jaclyn Smeaton: Absolutely.

Dr. Kara Fitzgerald: All right. We’ll put a sample report for anybody who doesn’t have a DUTCH test handy. I’m going to open mine after from my clinic here and just take a look at it. But just so you can look at the reference range that Dr. Smeaton just walked us through and get an idea of that while we wait for the paper to come out. What else do you guys …

Dr. Jaclyn Smeaton: I mean right now we also have a subset of a few hundred patients that have done specific DNA tests and a DUTCH test. So we are also doing some looks at what SNPs are associated with what types of results on the DUTCH test. So again, we just got that data. It’s a humongous file. It’s going to take us a while to go through that. But we really are very interested in providing more information that can be helpful to clinicians.

We’ve done a lot of the data validation for the testing, and we feel excited to move on to new things that can be really applied clinically and answer questions that are just unanswered that we use our best educated guesses on to solve clinically. We are hoping we can put some data behind it.

Dr. Kara Fitzgerald: I’m so interested to see what you guys come up with. How relevant is COMT? I mean we certainly see COMT functioning fabulously or appearing not to be, but there could be other pieces involved. I’m really curious. It is one of the better research, I think, SNPs, as far as being clinically relevant. But yeah. I’ll be really curious to see what you guys find there.

Anything else you want to add? Any other research things? I’m really excited to hear how much is going on over there.

Dr. Jaclyn Smeaton: There’s a lot. I don’t think so. We have a research page on our website. So if you want to see some of the older stuff especially, you can check that out. We’ll link in the show notes to our newest publications for anyone listening that’s more curious about estrogen, HRT, and what it looks like in the urine.

Dr. Kara Fitzgerald: Okay, perfect. Yeah, we’ll pop a link up on to the research if you want to. But you can actually listen to some really deep dives with Mark and I over the years, and we’ll put those links up as well.

Dr. Jaclyn Smeaton: I’m going to have to dig those old podcasts up, too. That sounds fun.

Dr. Kara Fitzgerald: We were talking about creatinine. We were talking about it early. Yeah, quite a bit about creatinine. I think maybe he had published on it or something. We spent a lot of time talking about it. Creatinine is what we use to just make sure that the urine specimen are reliable and an individual is generating an adequate concentration of the hormones. We use a creatinine-

Dr. Jaclyn Smeaton: Yeah. We have a special method at DUTCH that we utilize that allows us to get … Oftentimes, what you find is more dilute urine means lower levels of hormone, and then the instruments have a tough time being precise. You can get 30 or 40% variation in your results if you retest and retest and retest. That wouldn’t meet our standards to be data we’d give to a clinician. So they actually developed a different method that … I don’t know how much I can give away. It’s kind of an insider secret.

But it helps to normalize the concentration that runs through the machine so that we can actually produce a more accurate result even at really low levels of hormones. So that’s something that you could nerd out. Like you said, you talked for six hours on creatinine. You talk to someone in the lab, they could talk to you for hours on these methods and all the testing. Thank goodness for people like that because I’m a typical clinician where I just want to make sure the data’s right. But if you tell me it’s right, I’m going to pretty much just believe you.

If you can show me a validation study, awesome. That’s even better. But I don’t want to have to read. I don’t want to have to learn about creatinine for six hours.

Dr. Kara Fitzgerald: Yeah, yeah. Amen. Although I do enjoy a good conversation on creatinine. I have a lab background. All right. But we were going to pick your clinician brain. So in our final minutes together, I just wanted to take some time to talk about cases. I really wanted to lean on some of the interesting fertility work that you’ve done and some pearls. I know we’re going to fold it into what you might be seeing on the DUTCH, but maybe just guide us. Grab your phone or your pens and your paper, people. But yeah.

Dr. Jaclyn Smeaton: Well, let me just give you the maybe one-minute fertility overview. If you’re new to treating patients with fertility, one of the reasons why I love working with couples when they’re trying to get pregnant, number one, they are so committed to your protocols. So that is wonderful because your compliance level’s going to be really high, and you can get success in really difficult cases because patients are just so dedicated to your plan.

But the second piece is that it is whole person medicine. So although it’s a specialty, it’s not a specialty because so many things have to be right in order for couples to conceive. So some of the things I think about, one is that Younger You approach. Biological aging is so real. When it comes to fertility, that’s the first area that we see the effects of biological aging. In fact, I’m working on a talk right now for AANP this summer where I’m going to be speaking on male fertility as the canary in the coal mine because there’s so much data showing that men with infertility have higher disease rates than men who are fertile.

It’s a marker for biological aging that predisposes them to metabolic syndrome, heart disease, so many other conditions. So you have to think about that Younger You approach when it comes to fertility. A lot of the same theories apply from that healthy living, antiaging world where you have to have healthy mitochondria. The cells with the most mitochondria in the body are reproductive cells, not cardiovascular. They’re really mitochondrial dependent. It’s oxidative stress. It’s omega-3 status. It is gut health and microbiome.

This is, in the last three years, literally erupting the industry. I went to school 15+ ish years ago. That’s close enough. We learned that the womb was sterile, that the microbiome was established in a baby during vaginal delivery. We were so wrong. There is a microbiome in meconium, which means that there’s a microbiome inside the baby’s gut while they’re in the womb, which means that develops from the placenta and actually mom’s oral microbiome.

We know there’s a microbiome within the uterus and certain microorganisms, ureaplasma is the worst, even at really low levels can because infertility and recurrent miscarriage. Gut microbiome impacts fertility. There’s so much to it. So all the things that you think about for whole person health apply in a really specific way for fertility patients, too. So you really have to do that whole person approach.

And then of course, hormonal health is a big piece of it, and that’s where the DUTCH comes in for me as such a useful tool because DUTCH is an overview of hormonal health. But on the OATs, which we didn’t talk about much about today, I feel like they’re kind of the gift that’s stuck under the Christmas tree that a lot of people forget is there. They don’t notice it’s there.

There are OATs in there that are different markers for nutrients. You can start to pick up on nutrient sufficiency patterns. There is a marker for inflammation on our OAT panel. 8-OHdG is on there, which is a marker for oxidative stress. So as kind of a bonus, I’m starting to get a view of some of those underlying functional patterns that might be existing for a patient as a bonus when I’m looking at their hormone levels.

Dr. Kara Fitzgerald: That’s awesome. That’s organic acids, folks, if you don’t know the OAT acronym.

Dr. Jaclyn Smeaton: Thank you.

Dr. Kara Fitzgerald: I remember when Mark was developing those, and you guys were working on them and picking them out. I think he picked out really good, really evidence-informed markers like 8-OH2dG is a fabulous, well-studied marker of oxidative stress. And then I think you have methylmalonic acid and formimidoyl glutamate as well. That’s a marker for B12 and folate-

Dr. Jaclyn Smeaton: Yeah. Kynurenate and quinolinate. We’re very picky about what organic acids we’ll put on the test because there’s very extensive panels available, but a lot of them encourage clinicians to draw conclusions that are more theoretical that we won’t include on the test until there’s some studies that actually back up the clinical utility of that as a marker. So we’re a little slower to add them on, and that’s intentional. We just want to make sure we’re really giving the best information possible.

Dr. Kara Fitzgerald: You said something about urea. I was actually just trying to look it up while you were talking.

Dr. Jaclyn Smeaton: Ureaplasma.

Dr. Kara Fitzgerald: Yeah. Is that a de rigueur investigation for you in your fertility patients?

Dr. Jaclyn Smeaton: It’s started to become something that I’m screening for. I see a lot of unexplained infertility, a lot of recurrent miscarriage or failed transfers where couples have embryos that have been genetically tested and they know they’re normal, but they’re not transferring. There’s actually a test that’s started to move in the conventional space called an EMMA ALICE, just like the women’s names. It actually is an endometrial biopsy where they look for probiotic microbiome organisms and infectious organisms in the endometrial lining.

The EMMA is the beneficial, and the ALICE is the pathogenic organisms. It’s really been transformative, I mean treating even very low level pathogens. Because if you imagine if you have a low grade infection, you’ve got inflammation in the uterus. Pregnancy requires a couple things. One is great blood flow. We didn’t talk about that before, but the whole nitric oxide world is very relevant to fertility as well. So you need really good micro circulation.

And then you also need inflammation to be really perfectly balanced in order for mom’s immune system to be able to not recognize or not attack a pregnancy, which is foreign tissue. So really, there’s so much to it. That microbiome piece is huge, and it’s an area that I’m loving learning more about because there’s more and more papers every month coming out on it.

Dr. Kara Fitzgerald: Yeah. I know this is beyond the scope of this conversation, but there’s the four types. A Brazilian group, you must be aware of their work looking at the specific microbiome types associated with infertility. Are these pro-inflammatory sub infections?

Dr. Jaclyn Smeaton: Yeah. They don’t disclose. I don’t know a lot of the details of it. That’s Microgenesis, I think, that you’re talking about. They have a system, and there’s one practitioner, Robin Rose, who’s a great doc, DUTCH customer, functional medicine doc that does a lot on that. I don’t know their methods specifically. But yeah. I think there’s about 64 or 65 types of microbiome that they’ve analyzed, and there’s customized protocols and treatment plans, I think, that involve antibiotics and antimicrobial herbs and lifestyle to address each of those.

I just watched a webinar that they gave a couple of weeks ago. They have a 75% success rate in couples that were previously infertile, and so that’s really remarkable, especially when you think about functional medicine having that kind of impact because fixing the microbiome, of course, is such a fundamental piece of what we do that I think it’s probably going to grow to be a bigger or more well-understood cause of infertility in the next five to 10 years.

Dr. Kara Fitzgerald: Oh, interesting. Wow. Okay. All right. Are they publishing on their work?

Dr. Jaclyn Smeaton: I’ve not found any publications. They might have some. But like I said, I just have started to look, and I think they’re trying to keep it kind of proprietary-

Dr. Kara Fitzgerald: They are. Yeah.

Dr. Jaclyn Smeaton: … I think just as far as their approaches go.

Dr. Kara Fitzgerald: Yeah. Yeah. It is proprietary, hence my pulling the thread here in this conversation. That’s what I’ve found. My curiosity is piqued, but I obviously have limited understanding since I thought there were four types and you’re telling me there’s 64 types. Well, I want to bring you back on for another podcast where we’ll just really dive into the infertility work if you’re interested in doing that. I would love to pick your brain.

This is just great. This is interesting. And then we can chat about how you’re using the DUTCH and that, but just going well beyond this. Maybe after you do your AANP talk, we can circle back, do a podcast version of it if you’re interested.

Dr. Jaclyn Smeaton: Yeah, that’d be great.

Dr. Kara Fitzgerald: All right. All right. So we’re closing. Anything else you want to add? This has really been a great conversation.

Dr. Jaclyn Smeaton: Yeah, it’s been a lot of fun. Thanks for having me.

Dr. Kara Fitzgerald: Thank you. All right, everybody. Stay tuned for a lot more, and we’ll make sure we pack our show notes with all of the content that we’ve talked about. Thanks so much.

Dr. Jaclyn Smeaton, ND, is the Chief Medical Officer (CMO) at Precision Analytical, creators of the DUTCH Test, and a naturopathic physician focused on infertility, reproductive, and genitourinary health. In addition to her private practice, Hello Fertility, she is a prolific teacher in the field of reproductive endocrinology and hormones and has trained thousands of clinicians on her treatment methodology. Dr. Smeaton has extensive leadership experience in integrative medicine including as President for the American Association of Naturopathic Physicians, as an Ambassador for the Academy of Integrative Health and Medicine, and a board member of the Integrative Health Policy Consortium.

Assessing estrogen exposure from transdermal estradiol patch therapy using a dried urine collection and a GC-MS/MS assay

Assessment of estrogen exposure from transdermal estradiol gel therapy with a dried urine assay

Reliability of a dried urine test for comprehensive assessment of urine hormones and metabolites

Dutch Test Research

Evaluating Estrogen Detoxification to Understand Breast Cancer Risk

Estrogen + Microbiome = Estrobolome

HPA, Organic Acids and the DUTCH Test with Dr. Carrie Jones

Prescribing Bioidentical Hormones using the DUTCH Test with Dr. Lynne Mielke

Dutch Research And Validation In Peer-reviewed Journal Article

DUTCH: A Novel (and useful!) Urinary Hormone Test with Mark Newman, MS

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