Comparing Saliva, Urine, and Serum Hormone Testing: Choosing the Best Test for Each Patient

Dr. Kara Fitzgerald: Welcome to new Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And today is no exception. I am thrilled to be talking all things hormones, actually hormone testing with Lylen Ferris. She’s a naturopathic physician like myself actually. She graduated from National College of Natural Medicine, as I did, also Dr. Ferris is with Doctor’s Data, and we’re going to be just moving through saliva, urine and serum, hormone testing, choosing the best test for each patient.

Dr. Kara Fitzgerald: Let me give you a little bit of a background on Dr. Ferris, and we will jump in. So she went to Davidson College for undergrad, where she got a BA in cultural anthropology and a minor in art history. She did lots of traveling and witnessing different cultures and different ways of thinking, and from that, realized pursuing naturopathic medicine was her calling. She trained on her basic sciences in Australia, then came back to the United States. And as I said, she went to my alma mater, now called National University of Natural Medicine in Portland, Oregon.

And she continues to practice medicine there as well as consult with Doctor’s Data. She does a lot of teaching. She did a residency with Dr. Kimberly Windstar, who’s an ND gynecologist, kind of legendary in our field. So that was quite a great residency for her. She’s been teaching gynecology classes and continues to mentor medical students. She’s taught all over the globe. She has actually webinars and seminars. In fact, we’ll link to some of Dr. Ferris’ training in our show notes. She’s senior staff physician at Doctor’s Data. She leads a team of doctors focusing on educating practitioners globally on hormone and neurotransmitter test results and optimization. And she maintains a practice in Oregon. She focuses on women’s health, but also works with men and actually males and females of all ages. So you’re working with peds. Welcome to New Frontiers, Dr. Ferris. It’s really great to hear you here.

Dr. Lylen Ferris: Thank you. I’m so pleased to join you.

Dr. Kara Fitzgerald: So as you and I were dialoguing, our paths have fortunately crossed a few times and you were in school when I was, and we were catching up a little bit. Actually, you were a little before me only because you would have been ahead of me, but you had some kids and then you came back and finished, and you and I were talking about cycling. I was a huge committed cyclist back then, and just fondly recollecting sort of always walking around with my helmet and you remembered that, which is really funny, but we spent a lot of time watching the Tour de France, like all through med school. It was a big deal for us. And we’re just in Tour de France season now. And you were bringing up Lance Armstrong and of course, even back then, of course we all thought he was doping, but he got away with it for forever.

Dr. Kara Fitzgerald: And so you were talking about it being just a really great example about how to test for hormones, like what medium is the correct way to do it and using him as an example. So I want to know that story. I want to circle back and just have you unpack that and what the, I think it’s the, I forget the regulating body, but what they should have done to catch Lance way back in the day. So before we go back to that teaser for the cyclists out there, just talk to me about the main mediums for testing hormones.

Dr. Lylen Ferris: Well, there’s three main mediums, serum, urine, and saliva. And what I’m excited to talk to you about today is really the pros and cons and the appropriate times to test in each of them. The comparison of testing mediums, I think has somehow gotten a little bit controversial in the field of functional medicine. In my opinion, though, it’s like fighting over apples and oranges and pears, because in the question is one of those fruits better than the other? The answer is no, they’re all amazing. I love them all, but I’ll choose them for different reasons. And the same is true for hormone testing. So one of the main takeaways I hope people leave with today is that there’s no wrong way to test hormones, but there are certain pros and cons of each method, and we simply need to be aware of those so that we can choose the medium that’s most appropriate for the given situation.

Dr. Kara Fitzgerald: So talk about, I mean, do you want to give me a little background on steroid hormone physiology or actually, let’s just move through the three specimen types and talk about them. And then from that context, you can give me a little background in physiology or if we’re going, we’re going to test baseline in and so forth. So walk me through serum. When is it a good option? When isn’t it? What are its limitations?

Dr. Lylen Ferris: Yeah, I will. Let me just preface that though, by giving you one little sort of tidbit of steroid hormone physiology, because this really is the important point when you’re trying to choose the right place to test. So remember that steroid hormones are made with a cholesterol backbone. So like cholesterol, steroid hormones are not soluble in water. They’re hydrophobic. Also, we can say they’re lipophilic. They’re fat loving. They’re water hating. So this is an important concept because urine and serum are water-based where saliva is more favorable in lipids. So, because these hormones are hydrophobic, when they’re in watery environments, they have to either be bound to a protein carrier or conjugated. So that’s sort of just the basis of the chemistry today. We don’t have to really get into it deeply, but that’s the baseline.

Dr. Kara Fitzgerald: Doesn’t that mean that when you’re looking at urine, you’re going to be looking at metabolites because they can conjugate it?

Dr. Lylen Ferris: Right, exactly, exactly.

Dr. Kara Fitzgerald: Okay, okay. All right. That is a good tidbit. Yeah, go ahead.

Dr. Lylen Ferris: So when it comes to serum, to answer your question, that’s a watery medium. So if we think about some of the advantages to testing in serum, it’s very widely available. Everyone accepts it as a mainstream marker. It’s super convenient. So if a patient is at a hospital or a clinic setting, typically there are people there who can draw their blood, and it will provide a quick snapshot of total levels at the time of the draw. It’s the best place to look for polar molecules. So these are things like thyroid hormone, prolactin, LH, FSH, but the steroid hormones that we’re really talking about today are non-polar. They’re hydrophobic. The polar molecules like thyroid hormone are water-soluble. And so they are best tested in serum because their polarity allows them to float freely in the bloodstream. That’s not true with the steroid hormone.

Dr. Lylen Ferris: So then if we think about some of the disadvantages to testing in serum, that snapshot that I mentioned, you just get a quick blood draw, you get a snapshot of the hormones at that point in time, that single point testing can be potentially a disadvantage in serum when testing hormones, because hormones are secreted in a pulsatile manner over the course of the day. So it’s difficult to know whether the level that you see reported is representing a peak or a valley or something in between, and that might change your treatment approach depending on the value you see. It’s potentially stressful for people who don’t love needles. And you’re also limited to getting to a place where someone can actually do that blood draw. So that could be potentially inconvenient to a patient if he needs to report, potentially four times over the course of the day or on a certain day of the month, depending on what you’re looking for with serum, excuse me, with hormone testing.

Dr. Lylen Ferris: One of the most important reasons though that I think serum has some limitations is because of that molecular structure of the steroid hormones. When hormones are in serum, they have to be bound to a protein carrier because they are hydrophobic. And so it’s very difficult to get an idea of what the free or bioavailable fraction of the hormone is in serum because those binding proteins can actually obscure hormone levels. And this is especially true if a woman is taking an oral estrogen, which will increase sex hormone binding globulin (SHBG). And so testosterone might be more bound up, potentially cortisol as well. Oral estrogen can increase cortisol binding globulin, and bind up some of the cortisol that you would expect to see which again, might sort of obscure the expected values.

Dr. Kara Fitzgerald: Well, what do you think about free testosterone in serum? I mean, we get it all the time. Is that a reliable biomarker?

Dr. Lylen Ferris: It can be, especially if, so typically, the free androgen index is a good calculation of trying to determine the amount of testosterone that’s free, looking at the sex hormone binding globulin and the total testosterone and doing that calculation, but it’s a calculation. It’s not a direct measurement. It’s better if they’re measuring the patient’s sex hormone binding globulin levels directly, although some labs will just sort of take an average value for SHBG and throw that into the ratio. So just make sure if you’re using something like a free androgen index that you’re getting your actual patient’s SHBG levels to put into that ratio. So you can do some calculations to try to estimate free values in serum, but again, these are calculations, not direct measurements, so there’s a potential for error.

Dr. Kara Fitzgerald: Right, right, right, right. Yeah. Actually, this is a really nice description. It sounds kind of like a crapshoot. Given the pulsatile release of them as well, when are they best assessed in serum?

Dr. Lylen Ferris: I think most people agree the morning is best, but if you look at [some] labs [that] have done collections for women every five minutes, every 10 minutes throughout the course of the day. And you can see that these values are just up and down, up and down, up and down because they pulse. And so time of day, I don’t know that there really is the best time of day to do it. I think when it comes to measuring hormones, because of that pulsatile nature, mediums that allow you to get an average of the hormones over the course of the day might provide information that is a little bit more valuable when it comes to choosing whether therapy, hormone therapy might be appropriate.

Dr. Kara Fitzgerald: What about if you’re post-menopausal though, and you’re really not making a heck of a lot of them, or you’re in andropause and you might be taking exogenous hormone replacement. Is that variable less of an issue?

Dr. Lylen Ferris: Endogenously, it may be a little bit less of an issue in andropause or menopause. If you’re talking about monitoring therapy though, we’re back to sort of the previous question about bound versus bioavailable and that sort of thing. And I’ll talk a little bit more about that as we move through the mediums, because when we talk about saliva in particular, I’ll elaborate on some of the limitations of serum.

Dr. Kara Fitzgerald: Okay, all right. Let me just ask you one more question about serum and then we’ll move on to the other mediums. What about cortisol? I mean again, it’s super easy. You can just give somebody a lab slip and they go to Quest and we can get a first cortisol draw, a first morning cortisol draw or something like that. But is it useful?

Dr. Lylen Ferris: It will give you a glimpse, but I think there are some particular drawbacks when it comes to testing cortisol. One is that concept again, of the binding proteins, especially if oral estrogen is being used, and this could be Premarin, or this could be a birth control pill, this can be any type of oral estrogen. It will increase cortisol binding globulin, which can obscure free levels. Also, if you want to test diurnal cortisol, that requires four collections over the course of the day. So four blood draws over the course of the day is not ideal for anyone, not only because it’s a time management issue, to think about the needles involved. A lot of them have hypertension, or they just don’t love needles. And if that is causing stress in your patient, that can potentially affect cortisol secretion.

Dr. Kara Fitzgerald: Sure. Yeah, I don’t know anyone who does that. I am sure there are some clinicians out there sending people off for a day, a horrible day at the lab, but yeah, not too much, it just doesn’t make sense at all. Do you recommend serum for monitoring hormone replacement?

Dr. Lylen Ferris: It really depends on the route of administration. So I find that if your patients are using pellets or injections or patches serum is probably an okay place to look, but if you’re using transdermal or transmucosal therapies, it’s not ideal. So that’s my short answer.

Dr. Kara Fitzgerald: Okay. And I want to know, are you using them? Are you using serum in practice?

Dr. Lylen Ferris: Very little these days. Sometimes if insurance, if cash payments are problematic, we’ll rely on serum, but in general, I don’t rely on serum for hormone testing these days.

Dr. Kara Fitzgerald: Okay. And what about urine? Talk to me about just the same kind of body of questions that we went through with serum, advantages, disadvantages, et cetera.

Dr. Lylen Ferris: Sure. Well, one of the advantages, we talked about people who don’t love needles, and I know a lot of my patients really don’t love them. So when you’re testing urine, there’s no needles. It’s a non-invasive way of testing. What I love about urinary testing is it’s the only way to see how the body is metabolizing hormones. It allows us to take that deeper dive into how the hormones, via their metabolites, can affect physiology. A lot of people like to keep an eye on cortisol metabolites. The free cortisol that we see in saliva is really a small percentage of the total that we make over the course of the day. And so monitoring cortisol metabolites can provide a deeper dive into what’s going on. Is it the production of cortisol or the metabolism of it that’s influencing cortisol levels? Some people like to keep an eye on the androgen metabolites to monitor that 5-alpha reductase pathway, maybe keep an eye on dihydrotestosterone and things like that. Some people really value it for the estrogen metabolites. They like to monitor the conversion of the hydroxy forms to the less carcinogenic methoxy forms. And I like to use urine in conjunction with saliva testing, because it allows me to determine if an elevation or a deficit of a hormone found there is actually an issue related to the secretion of an analyte or to the metabolism of that analyte.

Dr. Kara Fitzgerald: Right, yeah. I think we’re just in a whole new era with regard to what we can see with relatively routine testing, that we can look at these metabolites. It’s really empowering for us as clinicians and I think satisfying for patients, for us to be able to look at some of these potentially toxic ones and to be able to manipulate them and change them around and sort of get more of a drill down on the kind of root cause of imbalances with these metabolites. Again, we spent quite a bit of time dialoguing before we jumped on our recording, but Doctor’s Data is going to be offering a really nice look at the metabolites. Do you want to tell me a little bit about that?

Dr. Lylen Ferris: I would love to. So we have spent years in R&D researching the best and most accurate way to test these urine samples. We have determined that liquid urine gives us the most reliable and reproducible numbers. So the Doctor’s Data test will include several liquid collections over the course of the day. Doctor’s Data utilizes mass spectrometry, a liquid chromatography mass spec to analyze the urine. And the lab has devised some ways to optimize sample extraction and processing of these samples. So that in combination with the mass spec machines, which are highly sensitive, is allowing us to reliably measure clinically relevant analytes, some of which are present in such low concentrations that they really haven’t been previously available. Yeah.

Dr. Kara Fitzgerald: Right, like 2-methoxy, for starters. I know there’s some places that report it, but I know that’s tough and yeah, you’re looking at yeah, anyway, go ahead tell me.

Dr. Lylen Ferris: Yeah, exactly. We’re going to have two additional methoxy estrogen metabolites to help provide a more comprehensive picture of COMT (Catechol-O-methyltransferase) activity. And also, so there’ll be 4-methoxy estrone and 4-methoxy estrodiol, which we’re excited about. And one of the ones I’m particularly excited about is allopregnanalone.

Dr. Kara Fitzgerald: Yeah, you read my mind. That’s pretty cool that you’re going to do that. And that is tough to see.

Dr. Lylen Ferris: Yeah, and we’ve been able to find it and I’m excited to be able to monitor it because this is a compound that I will often try to push clinically with oral progesterone. All progesterone eventually becomes allopregnanolone, which acts as a GABA receptor agonist, but oral progesterone is especially efficient at raising allopregnanolone levels because of the liver first pass effect on progesterone. And so this test is going to allow me to see what endogenous allopregnanolone levels are or to evaluate if the supplementation I’m recommending is effectively raising it the way I am intending it to. So I’m excited about that one.

Dr. Kara Fitzgerald: That’s pretty cool. Yeah, for sure. So this is the all-important sort of anxiolytic sort of brain protective progesterone metabolites that we speak a lot about and to have some evidence on whether we’re actually successfully raising it in our patients is just extremely useful. And then also too, I just want to reiterate that you’re breaking down or dividing the metabolites into E1, E2. So the 2-methoxy estrone and 2-methoxy estradiol, and as well as four, which again is exciting for us. I think clinicians will find some value in this. And how do you use urine in your practice to evaluate your interventions? I mean, you’ve just spoken about some of them, but you’ve got a man on exogenous testosterone, for instance, how might you use the panel?

Dr. Lylen Ferris: Well, I like to see how he is metabolizing that testosterone. Where is it going? What mischief might it get into? But honestly, I think the things I find most valuable about estrogen, because I don’t tend to run them as often on my male patients, but with my female patients, I really like to keep an eye on the cortisol metabolites. I really like to keep an eye on the estrogen metabolites and see which pathways a woman might be favoring to make sure that methylation is supported, that sort of thing.

Dr. Kara Fitzgerald: Yep, absolutely. That makes sense. I think that’s kind of what we’re all doing. Okay, so let’s circle over to saliva. Same thing, advantages, disadvantages. I know you’re using this in your practice a lot. We can talk about sex hormones, maybe talk about cortisol. Let’s go for it.

Dr. Lylen Ferris: Yeah. Well the main advantage to saliva I think is that you’re able to actually measure the active or bioavailable unbound portion of these sex steroid hormones. So back to that steroid hormone physiology, let’s think about the way endogenous hormones are secreted. So when these are secreted from the ovaries or the testes or the adrenals, they’re actually wrapped up in these protein envelopes. These are those carriers, sex hormone binding globulin, cortisol binding globulin, et cetera. And this allows them to float freely in serum. But these protein-bound hormones are not fully biologically active. When we think about the relevant hormone to what’s pushing symptoms in our patients, it’s the free portion that’s estimated to be between about 1% and 10%. That’s the biologically active portion. And saliva contains only that biologically active fraction. So that’s really where I think it shines. But additionally, here we’ve got no needles.

Dr. Lylen Ferris: Saliva samples are really easy to collect, especially if multiple samples are needed or the timing of the sample is important. So think about the cortisol awakening response when that first sample needs to be collected within five minutes of waking up or diurnal cortisol when you’re collecting several times over the course of the day or a luteal surge collection, when you need to make sure you’re collecting on a specific day of the month. And when we think about that pulsatile nature that hormones are secreted in, saliva can manage that by giving you an average. So when you test with Doctor’s Data, even if you’re not looking at cortisol, Doctor’s Data recommends that patients collect four saliva samples over the course of the day. The lab then takes a small aliquot from each tube to create a pooled tube. And it’s from this tube that sex hormones are tested. So this strategy avoids catching a peak or a trough and gives providers an average of the sex hormones, which we have found to be a more reliable value that you can base your therapeutic recommendations on.

Dr. Kara Fitzgerald: So it’s basically, you’re basically looking at sort of a surrogate for a 24 hour collection?

Dr. Lylen Ferris: Yeah, exactly.

Dr. Kara Fitzgerald: And it’s reliable? Saliva is sufficient for us to evaluate patient response to hormones regardless of the delivery route would you say? Or is there, yeah what are your thoughts on that?

Dr. Lylen Ferris: Yes. So it’s really the only reliable place to test transdermal or transmucosal therapies. And this is because, well, it’s actually pretty complicated. So let me go through some of the mechanisms at play. So think about transdermal hormones. We apply them to the skin. They’re absorbed very freely through the skin, and they’re largely not bound to those protein carriers like sex hormone binding globulin. So let me use progesterone as an example. We apply progesterone cream to the skin, so the capillary beds or right under the epidermis. It’s quickly absorbed. And it’s not coated with a protein carrier like SHBG, but it is picked up by red blood cell membranes. So these transdermal hormones now are quickly absorbed. Testing shows that the absorption shows up in saliva in minutes, indicating that it has been well absorbed. And then it moves through the bloodstream attached to these red blood cells, which are carriers for transdermal hormones, but the bonds are pretty weak.

Dr. Lylen Ferris: So when these red blood cells move through capillaries, the hormone pretty easily moves into the cells. These steroid hormones are lipid soluble so they freely diffuse through the cell membranes. And once they’re in the cells, they enter the nucleus and affect cell function and metabolism. That’s their function. But once these hormones have produced these reactions, they’re catabolized within the cell. So they’re never again seen in their initial form. So now we can monitor these hormones in their metabolized forms, but not in their original form. So that’s why urine is the best place to look for metabolites because these hormones are absorbed and utilized and then they’re metabolized more. Additionally, if we think about monitoring transdermal, hormone supplementation in serum and why that might not be the best place we have to think about the way that serum is handled. So we draw blood from a woman, for instance, who has applied transdermal progesterone, and that hormone was attached to the red blood cells, but to get the serum, the blood is spun down and those red blood cells are discarded along with the transdermal hormones that are attached to them. So this is why serum is not necessarily a great method to measure transdermal or sublingual hormones.

Dr. Kara Fitzgerald: You can just wildly miss therapy. And that’s been your experience?

Dr. Lylen Ferris: It was.

Dr. Kara Fitzgerald: Do you want to give me an example of that?

Dr. Lylen Ferris: Yeah, I will actually, I had this really interesting case. A 61 year old woman came to see me. She was about seven years in the menopause and she had been seeing another provider who had put her on estradiol, estriol, progesterone and testosterone, all at dosages that I felt like were pretty reasonable. The testosterone dose, if I recall was about 0.25 milligrams, but her hot flashes were getting worse. They had improved for a time, but they were worse and she was experiencing some weight gain around the middle and she was pretty unhappy with that. So we tested her saliva, and the results showed that the testosterone value was over 1,000, which I would not expect with a dosage of 0.25 milligrams. That’s pretty conservative. And her estradiol, she was taking about one milligram of Beyaz in a four to one ratio, which means that was just 0.2 milligrams of estradiol.

Dr. Lylen Ferris: Her estradiol level was I think over about eight, and the range goes up to 3.2 or excuse me, the supplementation range I think is up to about six. So it was elevated. So it didn’t seem to be reflective of her hormone therapy. So it made me wonder what was going on. And when I talked to her in a little more depth, I realized her husband was actually using testosterone cream. He was using an AndroGel in a 50 milligram potency, and it seemed that she was getting exposed to him. So we had him do a saliva test and his testosterone was greater than 6,000, which is our detection limit. So nobody knows how high it actually was. His estradiol was also very elevated. And so in serum, both of those patients had normal testosterone and estradiol values, but we could see it in saliva that they were quite elevated.

Dr. Lylen Ferris: That transdermal testosterone that he was taking was being transferred to her, just in the normal course of being a married couple, skin to skin contact, even surfaces in the home. 50 milligrams of AndroGel is a lot of gel. And so if extreme care is not taken, people will touch the faucet, they’ll touch the light switch, they’ll touch the remote control. And then the spouse touches those things as well. And it’s pretty easy to have exogenous exposure. So saliva testing is actually a pretty great tool for catching exogenous exposure and helping to identify the cause for symptoms. If you have a woman come in and suddenly she’s got hirsutism, and she’s not using any hormones, but her husband is, often, if you test her, you’ll find that she’s being exposed. And serum would not necessarily show that.

Dr. Kara Fitzgerald: That’s interesting. So their provider, doing right by them, I’m sure was ordering plenty of serums and probably head-scratching as to why they weren’t responding. But in fact they were.

Dr. Lylen Ferris: That’s exactly right. And the story I got from him was that his symptoms were better for a time, but then they started to come back. And so the provider was raising the AndroGel dosage. And I think what you see here is tachyphylaxis, so essentially the receptors begin to down-regulate because there’s so much hormone present. And if you’re looking in serum and not seeing a change, you may assume, “Oh, we need to give him more and more hormone.” But in fact, less hormone is probably needed so that we can eventually have receptors begin to upregulate again, to become more responsive to the hormone that they need.

Dr. Kara Fitzgerald: Really interesting. And then of course, both of them were aromatizing the testosterone over to estrogen, hence their mutual high estrogen levels. Yeah, that’s a great case. So again, in your practice, you’re doing saliva. Are you starting with saliva and then going to urine after a period of time? But it looks, you do both specimens. Do you want to look at urine to just make sure they’re metabolizing it appropriately? So do you look after you’ve done therapy for a while? What is your testing structure?

Dr. Lylen Ferris: I always start with saliva. Saliva, and to my way of thinking is the cortisol awakening response can only be monitored in saliva. Diurnal cortisol is really the gold standard for saliva. Looking at hormone values, whether they’re endogenous or supplementation values, because I pretty much solely will use transdermal hormones, occasionally oral with things like progesterone, if I’m pushing allopregnanolone or maybe DHEA, which I think is pretty well utilized orally, but otherwise I prefer transdermal because of the avoidance of the first pass. So saliva is the best medium to monitor those. But then I think urine becomes really an effective tool because I do want to see with that supplementation, or even with endogenous levels, what happens to the hormone after it leaves that initial sort of parent state, where is it going? What might those metabolites, how might they be affecting physiology?

Dr. Kara Fitzgerald: And you’re doing this for hormone naive patients, as well as folks who are on some form of replacement?

Dr. Lylen Ferris: Well, so I think for any hormone naive patient, you can use any testing medium if you want to test baseline levels. So that’s pretty straightforward. Before hormone supplementation is utilized, pick your favorite depending on what you’re looking for. Because again, urine is not going to give you a great indication of bioavailable hormones, but you’ll get a good idea of what’s going on. Really I think it becomes more important to choose the correct method when you’re using supplementation. So if you’re trying to understand how hormone supplementation is influencing metabolism and excretion, you’re always going to want to look in urine. But if you’re monitoring patients who use transdermal hormones to try to see what those therapeutic bioavailable levels are, saliva is always going to be your best choice.

Dr. Kara Fitzgerald: And this could be bio-identical hormone or-

Dr. Lylen Ferris: Conventional.

Dr. Kara Fitzgerald: Conventional, but also this is going to be botanicals and maybe supplements. So anything that you’re doing to move sex hormone status, you can use this testing structure. This is a conversation about labs. We’re not talking about treatment to affect metabolism, but is the Doctor’s Data team available to clinicians? Does the report offer some guidance around how you might affect improved metabolism?

Dr. Lylen Ferris: Yeah, yeah, both of those are true. So there’ll be commentary to help guide treatment. There are resource guides created to help support people in choosing correct treatments. And then we have a team of clinicians who are available during business hours, Monday through Friday, who are always happy to talk to providers about next steps, what therapies might be appropriate, that sort of thing.

Dr. Kara Fitzgerald: Many of us continue to do serum. I mean, honestly myself included. I don’t only do serum, but I do use it relatively routinely. I think certainly in part, because it’s been so accepted among the greater medical community and also it’s relatively easy in some ways. And we do indeed see changes. So I just want to ask you about that. What are your thoughts?

Dr. Lylen Ferris: Well, it’s a very fair question, but again, let’s think about the structure of these hormones and how they behave in fatty versus watery environments. What I have observed is that it seems to be only when the absorbed hormone exceeds the carrying capacity, the fatty material in the blood, which is usually red blood cells, that it will sort of slop over, so to speak. So I’m really talking about transdermal hormones here. If you’re using oral therapies and that sort of thing, you’re more likely to see a change in serum, but with transdermal, you’re really only going to see a change in serum if you’re giving so much hormone that it exceeds the carrying capacity of those binding proteins. So essentially, it means that patient is getting more hormone than their body can utilize, AKA being overdosed. The fact that transdermal hormone supplementation is not easily seen in serum has been somewhat controversial, I think in functional medicine and what practitioners have often concluded from this is that the hormone is not going into the body, and this had often led patients to being overdosed because their practitioners are trying to see that rise in serum.

Dr. Lylen Ferris: But we understand through the testing of various tissues that these hormones are being absorbed. It just isn’t in the blood that’s returning to the heart, which is what we’re measuring in venous blood. So sometimes I’ll explain it to my patients like I do with oxygenated blood, blood going back to the heart is depleted of oxygen, because it’s already gone into the tissues. Same is true with hormones. If you’re testing in venous blood and saying that there’s nothing there, you might be missing the big picture, and this is probably why some providers say they don’t like saliva testing because I’ll hear people say, “Well, when I test saliva, the hormones are always high. And so it’s not reliable.” But I think if you’re prescribing transdermal or transmucosal hormone therapies and you’re monitoring in serum, and then you decide to check saliva, it’s very likely that you’re going to find elevated hormone levels.

Dr. Kara Fitzgerald: So are you, so for the other routes of delivery, I mean, are you still with oral delivery, is saliva sufficiently adequate or would you get concurrent serum?

Dr. Lylen Ferris: I find that saliva is adequate, but if serum is your preferred method, monitoring oral is going to be a little bit more successful there. I find that all mediums can be utilized for baseline testing. When it comes to oral therapies, I think you can look in serum or saliva. For things like pellets or ion therapies, you can monitor in saliva, serum or urine, but with the caveats that we’ve discussed. In urine, you’re really looking at downstream metabolites, not bioavailable what’s in the tissues, but I think because transdermal hormone therapies are so popular because they avoid first pass, it’s important to remember that serum and urine will typically grossly underestimate tissue uptake, which can lead to overdosing.

Dr. Kara Fitzgerald: Yeah, right, as your case just clearly illustrated. And I think we’ve all seen that. And I think we’ve all followed up, a lot of us anyway, who have had the same sort of head scratch. Why is there such a difference in saliva versus what I’m seeing in serum? So you’ve done just a terrific job answering that for me. I want to circle back to Lance Armstrong, if you don’t mind and just kind of get the lowdown on what was going on.

Dr. Lylen Ferris: Yeah. Well, so Lance and his teammates had a lot of ways to avoid detection, but one of them was that they were administering testosterone sublingually because they knew that this type of supplementation would not be reflected in the serum and the urine testing that was commonly administered to these athletes at the time. So he was able to exploit a weakness in the anti-doping testing system.

Dr. Kara Fitzgerald: Oh my gosh, how clever? I didn’t know that they were doing it sublingually and they were wow, and they certainly paid attention to how it would present in the various specimens.

Dr. Lylen Ferris: Yeah. But you know, the anti-doping docs have gotten wise because now studies have been done that promote saliva as a better screen for doping these athletes. So it’s going to be harder and harder for them to use those particular methods to avoid detection.

Dr. Kara Fitzgerald: They’ll find some other.

Dr. Lylen Ferris: I’m sure.

Dr. Kara Fitzgerald: I’m quite certain.

Dr. Lylen Ferris: Undoubtedly.

Dr. Kara Fitzgerald: I still like the Tour de France and I’m watching it now. So it’s exciting. Well, listen, I just want to thank you Dr. Ferris for coming and giving this really clear, very user-friendly interview with me today. I think it will be helpful for a lot of us out there in the space of testing hormones and treating different hormone imbalances. So just thank you so much for joining me on New Frontiers. I’m excited about the new test coming out. I’m thrilled to see allopregnanolone. That will be great. And any last words of wisdom or thoughts that you’d like to share?

Dr. Lylen Ferris: Well, we’re not exactly sure when our urine test will be available. In the next few months, we’re hoping, but I do just want to plug it for a second. One of the things we’re most excited about in offering this test is that Doctor’s Data gives providers the option to do so many functional tests that can inform metabolite testing. So not only can you do a urinary metabolite test, but you can add on neurotransmitter testing to those same samples to test neurotransmitter levels, because those are also influenced by the COMT enzymes, which help inform estrogen metabolism and that sort of thing. You can add on salivary hormones, you can test methylation, you can do beta glucuronidase testing on its own, or as part of a GI 360, because glucuronidase can affect circulating estrogen and whether or not they’re reabsorbed. And so, Doctor’s Data really is here to support providers in whatever way they need. We offer urine and saliva and hormone testing, as well as adjunct testing like the neurotransmitter testing, the methylation profiles, the microbiome testing, all the tools that can help practitioners provide comprehensive support for their patients.

Dr. Kara Fitzgerald: Well, thanks so much Dr. Ferris, and again, just thank you for joining me on New Frontiers. And this is very useful. Folks, turn to the show notes for information on this conversation. We’ll link to some other lectures that Dr. Ferris has given and any additional tidbits that you would like to share with us Lylen, we’ll just pop onto the show notes.

Dr. Lylen Ferris: Thanks, Kara. It was a pleasure.