The Missing Link in Hormone Testing: Why Metabolism & Balance Matter

 Hey, it's Dr. Omatma, host of Egg MeatSperm, and this is the best podcast to get all of the vital information that you need to support your fertility journey holistically for you and your partner, because fertility takes two. Welcome, Dr. Liz. It's so great to have you here. And I'm so excited to dig into your amazing brain.

So, um, let's kick it off with something very basic. What the heck is endo axis? Great question. What have you been working on? Yeah. So it's, you know, endo as an endocrinology and then the axis that kind of combines all of the understanding of the both superficial and depth of hormones, right? Like putting all the pieces together.

So that was kind of that like endocrinology pieces together. Endo axis, became my brainchild name. Um, it's really the creation of Dr. Guy Citrin and, uh, He began this journey a few years ago and brought me on about a year ago to kind of help sort out and put together detailed hormone analysis. And so that's really what it is.

It's providing a very detailed view, um, of potentially very complex hormonal stories. Yes, I know that's so simplified, so, um, let's differentiate. I just want to give some context. So this is an analyzer for practitioners for patients. How do people use it and access it? Absolutely. Yes, this is a, this Great question.

This is a targeted program for providers, right? For those looking to really support patients through their hormonal journeys. Um, we are using, of course, patient lab analysis, but it's a tool for the provider to be able to upload the report, to be able to see in real time, kind of the classifications of the high level hormonal imbalances.

Um, and then get some recommendations on where next steps or strategies could be to really provide optimal outcomes for that individual to that patient. Okay. Awesome. So mostly a tool for practitioners. I love that. There are very few often tools for us. So it's great. Uh, and then what, Um, What type of testing can you upload?

Absolutely. So right now, we really, we started with urinary hormones and specifically with precision analytical and the Dutch test. So that's the dried urinary testing for comprehensive hormones. And my favorite. Yeah. I think it's a lovely test. Um, but we really wanted to have, we wanted to start with the metabolite story, right?

Because you can really, you can run parent hormones, parent sex hormones in any medium. You can do blood, you can do saliva, you can do urine, and you can see what those circulating estrogen, progesterone, and testosterone values are. And you can make assumptions off of those levels and help support patients with their symptoms.

And, but it's a pretty high level. It's like a, you know, it's. You're almost just skimming the surface when you just look at those markers and really to know what's going on. Hormonally, what are they doing with those hormones? How are they metabolizing those hormones? How do those metabolites influence their health?

Right? And what can those metabolites tell us about utilization, about processing, about environment areas that we can really. Further target and treat to give optimal results for those individuals. And so I think, you know, the only way you can get metabolites, the only way you can see that journey is through urine.

And so we really wanted to give that deep dive from the get go. Um, we do also include serum testosterone and sex hormone binding globulin, and then we're just going to continue to grow and add in more. blood tests that complement kind of the adrenal pictures, add more inflammatory markers, add in organic acids, you know, so it's just, and even genetics, my background, my baby is genomics and genetic medicine and environmental health.

And so bringing that into how it relates to sex hormone production and metabolism, I think would be, will be, um, quite the advanced programming here, but starting, starting slow and, and yet powerful and impactful with the urinary hormone metabolites. Absolutely. Like Dutch test in and of itself just has so much that you so much information and data that you've already gathered.

And then analyzing and kind of going through all of that information takes a skill set. Um, so let's talk a little bit about like, um, I guess I'm curious, like, Is this the type of tool that is going to be helpful for the really like specialized kind of hormone doctor? Or is this going to be a tool that's for like a newbie that's like, I'm edging my way into hormones and trying to figure it out.

Someone help me. And I've been both at different points. So we really want to give high. Level information. So when we're assessing those labs, I think a lot of providers, like they see the merit in doing urinary testing. Right. And they, there's so many studies out on, especially like our, you know, for hydroxyesterone, for example, like we want to know those levels.

You can only see them in urine. What do we do with those results though? Right. And I think there's a lot of overwhelm and almost like information stagnation where it's like, Nope, don't want to learn anymore. Um, Like I know what to do. I know what to do with these little protocols. Let's stay in our safety zone.

Um, but we really want to expand that we want to, we want to help providers feel comfortable and confident using this urinary advanced urinary testing tool, um, especially on their complex basis, but really for anyone, you know, in monitoring their hormonal journey. And I think the way we've built it out, it really is built in little digestible pieces.

So it says, you know, here's your high level. Here's like your don't miss these points, right? If you just want that 30 second bird's eye view. And then we dive in and we say, okay, if you want a little more information, here's some more assessment. And if you really want to dive deep and know, here are the genomic variants that can be involved in this pathway issue.

Here are the environmental factors. Here are the dietary factors, the medications, right? We really expand and give a lot of more depth and detail in our strategy and analysis analysis section. And so there really is kind of something for everyone. If you're an advanced and seasoned practitioner, but you have a complex case and you just want a second opinion and some different perspectives, we have that, right?

And then if you're a newbie, you just like dip my toes in. I just want to know like the little bits, like get me used to this first before I dive deeper, then you can adjust those snapshot notes and still get a really good understanding of what's happening. Yeah. Yeah, amazing. So, um, I want to dive into the deep stuff.

So I'm curious, like for a practitioner, I'll just take myself as the case study and maybe like other providers will resonate. So I, I'm curious. Edged my way into doing Dutch testing, probably like 10 years ago, and certainly like overwhelmed and like, Oh, and you, Dr. Kerry Jones, like you guys were so instrumental in me being able to apply that to the fertility patients that we work with.

And now, like 10 years in, probably a hundred Dutch tests later, um, I am at that place where I don't even know if there's stuff that I'm missing, right? Like, what are the patterns that you, someone like you, who's like so well versed in this, um, what am I missing from a Dutch test? And maybe I thought this would, could be helpful for practitioners that specialize in fertility.

It could be helpful for patients just to hear like how. how we think about things from this like whole holism naturopathic perspective that has to do with their hormones and their fertility. So I want to serve both audiences and, um, I'm coming at it from this, like, what are we missing? What are we, like, what are these patterns that we could potentially be missing out on that are.

Recognizable to experts like yourself that we could benefit learning. Absolutely. I think, you know, when we're building out these patterns. It's really, it's a, it's a relationship, right? So we're, when I was building up the sex hormone patterns, I start with progesterone for cycling women or for women in general, but especially for our fertility cases, we want to know what's progesterone doing in the luteal phase.

And we compare that to their estrogens. And then we look at that estrogen detox. And so we're looking not just at a ratio of how much two hydroxy is favored over four or 16, like these intermediates of phase one detox. But we're also looking at, okay, not just the percentage, but how much of estrogen is moving into a phase one metabolite.

Are they actually transferring it into that initial clearance out of the body? Or is it really high in circulation and they have beautiful 2 hydroxy, but it's only a quarter of their actual estrone in circulation. Like that's a problem. They're not biotransforming it through phase one detox, right? Or there's something that's recirculating it.

And so we call that out in our patterns, like there's a, there's a poor clearance here, a poor, you know, initial line of transformation. And then we call out the methylation ratio. And the methylation is really, it's what we can capture in urine. It's only reflecting phase two for the catechol estrogens. So that's the two and the four hydroxine.

So we are seeing that ratio and then being able to gauge, is it too low? Is it too high? Right? These are all our Goldilocks hormones, or is it just right? And how does that compare then to all this other information that we're bringing in? And so it's, it's looking at 12 different relationships, right? And then testosterone is brought into the pattern as well.

In addition to DHEA and of course the metabolites. So the Androstone, 5 Alpha Androsine Diol, Etioclin, like all of our intermediates and what that tells us about that journey. So when we're looking at, like, what could be missed, I think some, some patterns that often do go missed, I, I, I do think that looking at that initial transference of estrone into phase one metabolites, I would hear a lot on consultations like, Oh, they're two hydroxy is 95 percent preference.

It looks great for hydroxy is nice and low. This looks beautiful. Methylation is looking good. It's balanced. I don't think I need to worry about detox. And yet their estrogens are looking at high end or even above that kind of ideal target Luteal range. It's like, well, actually, we need to look at, you know, kind of that idea of rules of half.

If you added up two, four and 16 hydroxy metabolites, those come to half of that estrone or more, right? And if not, what's going on there? Like, do we need help? Is it getting recirculated because of, you know, poor phase three detox, which we're not capturing that stool, right? But right. Elevated beta glucuronidase, for example.

And do we need to do some further investigation there? Um, do they just need. more improvement through phase one by reducing refined sugars in the diet and reducing alcohol is not a problem for them, right? Like, Hey, there's still, you know, maybe some, some areas or increased fiber, increased fish oils, right?

Decreasing inflammation can help that transformation. So I think that's one that I'll often see skipped because it's easy to skip. The patterns look great. The pie chart looks beautiful, right? Like the other one, I would say gets like the, the The low hanging fruit with fertility is looking at the progesterone estrogen ratio.

I would say, and, you know, when progesterone is low luteal, even below luteal range that 2nd, half the cycle, that's a bummer, right? Like, we need to optimize that progesterone and we need to really make sure estrogens in balance. And, um. But another 1 that I think, you know, even if estrogens don't look. too high, but patients are struggling maybe with estrogen dominant symptoms.

That 16 hydroxy metabolite is very estrogenic as an intermediate. It's not nearly as estrogenic as estradiol, but we do want to take that into consideration as well for both our fertility patients and just women's health in general. If you have a patient and they're like, maybe their progesterone does look pretty good.

And it is balanced with that estradiol. And maybe we're not too concerned on the estrogen dominance front. But yet here's a patient that's struggling with fibrocystic breast and bloat and a lot of menstrual headaches. And there's 16 hydroxies off the charts, you're right. And that's an estrogenic intermediate.

We've got to address that. We don't want to miss that. And we wouldn't see that in blood. We wouldn't see that in saliva. So that's kind of a nice, you know, one that again, you don't want to miss that could easily be overlooked. Those are good. Those are great patterns. So when And this may not be exactly the pattern that you were talking about, but I've seen lately, like a higher E3 than E1 and E2.

So sometimes they even look like they're super low, but then they're over converting to E3 and they have high 16 OH E. Curious about that? Well, absolutely. And I agree. I do see that one pop up a fair amount. Um, you know, so, um, E1. E3 is technically, chemically speaking, 16 OH E2. So these are the metabolites.

They're phase 1 intermediates. of estrogen through the CYP3A4 enzyme. So they're both partnered through that path. Um, the CYP3A4 enzyme is a powerhouse enzyme, right? It's responsible for over 60 percent of metabolism of like a lot of our environmental and medication toxins. So it's the 3A4 and 2D6. That are like our big powerhouse pathways, right?

Yeah. I just got the chills. Like I know where this is going now. So right when we're looking at why an enzyme might be upregulated, we have to look at the promoters upstream for that transcriptional response. And with 3A4, because it's such a powerhouse and it's involved in so much, there can be medications that promote more transcriptional activity.

upstream, there can be medications that suppress, you know, so if you see really low, that could be a medication as well, but there's meds med involvement. Um, there can be supplement involvement. Like St. John's wort is actually a very potent promoter of the CYP3A4 enzyme. So, and this is why a lot of, especially like antidepressant meds say do not take it right with St.

John's wort, because not, not because of the serotonergic influence of St. John's wort necessarily. It's really because St. John's wort is, um, Interfering with the ability to get the pro drug, which is the active component of that SSRI. Right. And so that's like problematic. That's a little problematic, but if you're exposed to a lot of like xeno estrogenic poly aromatic hydrocarbons, these are things that require that CYP3A4 among other enzymes to be active and they're going to be increasing transcription so we can get them out of the body and taking with it the estrogen as well.

So you can see, like, environmental, especially xenoestrogens, this upregulation of both the 1B1, the 4 hydroxy, also good, um, but also the 3A4. And I think that one can get overlooked sometimes. And I feel like one of my biggest things to, like, shout from the rooftops is do not suppress that enzyme, right?

Like, if you're seeing a higher preference for 16 OH, Yes, it is estrogenic. And yes, we want to make sure we have balance, but don't get balanced by inhibiting that enzyme because if it is regulated, it is upregulated likely for a reason. And it may need to be to pull out our toxins or other exposures. And by inhibiting that, we can actually become more toxic.

So, interesting. Have you seen it upregulate at all with like too much iodine or hidden sources of iodine that maybe we didn't like compensate for? Absolutely. I think, well, so thyroid in general, like overconversion of thyroid can definitely upregulate the transcription of several of our enzymes. Um, under active thyroid can.

Actually be a problem as well, but more for the reduced activity for the CYP3A4, um, underactive thyroid can actually increase 5 alpha reductase transcriptional, so that's an interesting, I think, kind of like feedback, right? Yeah, so that, I mean, if you want to jump to that pattern, the 5, Um, sorry, say that enzyme again, the 5 alpha reductase, that one like is often, um, like feeding like the thyroid and PCOS picture kind of feed each other.

And is it that through that enzyme? It can be partially through that enzyme. Um, there's, I mean, it's. Right. It's also, of course, so many things, progesterone actually is a big one for thyroid as well. Progesterone supports thyroid conversion and thyroid balance. And so when women with PCOS, they don't ovulate regularly, they have tons of follicles, but they don't ever mature any one of them with any regularity or success.

And so the progesterone overall tends to be pretty low. And proje. If you don't have that progesterone, you don't make thyroid. Right? That's a big one. Um, and so that can definitely, I think that's more of the trigger for that thyroid relationship with PCOS. Mm-Hmm. , I think. Well, so when we talk about like the, the genomic factors with androgen dominance and PCOS risk factors, uh, the sr.

The, it's the SRD five A one, which is the five alpha reductase. That one can be. up regulated just genomically, right? You can have polymorphisms that increase preference for that pathway, and that is often associated with PCOS. It's driven by insulin. And so I think the insulin is a factor for that pathway.

Oh my God. Okay. Yes. Oh, but I think, I think that right in PCOS goes super well. So hand in hand, but I think it's the progesterone more so that's driving the thyroid issues. I do want to circle back to the 3A4 because the other feature of the estriol and 16OH, these aren't catechol estrogens, so they don't methylate.

Um, so if methylation is beautiful, if not like really high, right, they're like kicking out all the two and the four. Um, if they, the, the 16 and the estriol, the 16OH, you want to need to. They're primarily bile conjugated and excreted out in stool, pretty direct. And so it's sulfation and glucuronidation that you really want to make sure is intact if you're seeing those build up.

And so, again, anytime you're working with metabolites of estrogen through phase 1, support by reducing things that could increase that transcriptional response. And a lot of that is decreasing alcohol, decreasing environmental xenoestrogenic exposure. And checking in on their meds because they could be on promoters, right?

And not that we would want them off of those, but that could be pulling that 16 through and then really making sure that they have good gut health, that they're pooping every day, like they've got to get that out. Um, and that they're really, you know, ensuring that their bile is conjugating in a healthy way.

So supporting bile, supporting stool. checking in on their gut health, potentially making sure that they don't have elevations and beta glucuronidase or opportunistic bacteria, um, that could be augmenting their estrogen clearance. Sorry, I wanted to work out. Yeah, that's good. I wanted to loop back around to 3A4 also.

So, um, if, if we see that pattern, E3 is high, 16OH is high, uh, 4OH is, Within range and then two OHS, maybe lower within range, then would we still try to, to have more of that estrogen clear out of the, the CYP 2A1 pathway? So with the, so kind of the idea of like adding DIMM or something to upregulate 1A1 and get more of that estrogen through the 2 Hydroxy.

Yeah. Uh, that's not my first approach. Always work backwards. Work with the gut first. Because if you're pushing phase one. I think it can be a knee jerk response to want to throw in DIMM when there's estrogen dominant symptoms or I3C, um, which becomes DIMM in the stomach, right? Uh, but I think there's that knee jerk response to say, oh, let's just give them.

The dam, and it's not wrong, but it can exacerbate estrogen symptoms for somewhat for actually, I would say, in my experience anyway, a lot of women, because if they can't, if they're not getting it out fully, then you're just pushing it through this 1 phase and it's still going to pull. It's still going to be a problem.

Um, so really, it's more avoidance of the things that could be pushing negatively through the other 2. so the 3 or 4 and the 1 or the 1 B1, right? The. B isn't bad, right? Um, but that for hydroxy, we really want to keep low. That one's upregulated by polyaromatic hydrocarbons. I will throw this out too. So this is like smoked and charbroiled meat products and cigarette smoke and even like hydrocarbons in the environment.

So I have people who live in really densely crowded cities and get like a lot of that exposure. That's also, um, upregulating CYP3. Yeah, can do both. Yeah. And so that's, yeah, we want to see kind of this, we want to remove as much as we can. Right. And if you're living in a city, it's like, well, just clean up the air that's in your immediate space.

In that case, right at an air filter. Yeah. But yeah, you really want to, like, take away the things that you can, that would be, you know, Maladaptive. Increase the things that are protective. So fish oils are great for increasing hydroxy production. Interestingly, rosemary is great for pushing 1A1, um, without augmenting estrogen and, like, creating a push into 2 hydroxy, right?

It's more of a supportive, nourishing way to go, the 2 hydroxy way. increasing fiber, right? Making sure that methylation looks good, that sulfation and glucuronidation are working, and then making sure really ultimately that they're pooping every day. Start there.

Yeah, that's awesome. Awesome. But yeah, yeah, I think those would be the big one. So often, like I would see sometimes with providers who, because grapefruit is a big, inhibitor of 3A4. This is why a lot of meds also say don't take with grapefruit because it inhibits and that can be, you know, I've actually seen providers who are like, well, because they are getting too much 16 and we want to push it more to, we're giving them a little bit of grapefruit every day.

And I'm like, okay, it's like, Yeah, I think we want to embrace that 3A4 is working well, we don't want to suppress its response because it's likely working overtime for a reason, um, and then we just complement and support the other downstream. metabolites and pathways that protect the cells from oxidative stress using our Nrf2 promoters, using free radical scavengers, antioxidants, making sure glutathione's good, all those things.

Yeah, lovely. So we talked a little bit about estrogen and progesterone disharmony. We talked about, uh, kind of these, Estrogen metabolism pathways are there I'll just ask you because I've been I have my own theory. I don't know that anyone has said yes to this, but, uh, I have found that a lot of women with endometriosis don't have classical estrogen dominance like I was taught in school.

Um, but really like. Repeatedly, I've seen like the 4 O H E, 4 O H E is the one that's off the charts. Their other estrogens are usually low, and then they're not metabolizing through the other, so it's just the 4 OH E that's elevated. And that, it's always a head scratcher when I see it, then I'm like, I'm sorry, but you need to go get, you know, worked up for Endo and like 95 percent of the time it's spot on.

So I'm like, I don't know if there's anything to this theory, but it's a really interesting, um, association. I don't know that it's like established as a culprit of, of Endo. But yeah, I do endometriosis contrary to what I was taught to is not an estrogen dominance condition. It is worsened by estrogen dominance for sure.

Right. If you have high estrogen, it's going to make the symptoms intense because you have endometrial tissue outside the uterus. Right. So it's not so all of that tissue would get that response for estrogen. Right. And create issues. Um, but what, so I was actually going over a review article very recently, Because I'm like, just so fascinated.

We live in a horribly toxic world. I'm so fascinated by the world that xenoestrogens have on like so many hormonal concerns. One of them actually is endometriosis. So exposure to your estrogens in utero is strongly correlated with risk for endometriosis as an adult. Um, and did I see somewhere that also phthalates specifically correlate with endometriosis?

Specifically the phthalates as the xenoestrogens. So it's a hormone, hormonal. Estrogen mimicker. Right. Yeah. Yes. And phthalates are everywhere. They're in our perfumes, in our lotions, in our makeups, in our shoes. Like, oh, this smells so good. Phthalates, they're destroying your hormones. Yes. Yup. It really is one that, um, I think it's undervalued, but it's so, it is strongly correlated with endometriosis.

Endometriosis. Thank you. Those exposures and I think, um, you know, and then it's, it's really the, the retroverted endometrial tissue, right? Instead of being for, like, developed fully out into a nice external flow, it's this reverse flow, um, and that's where that endometrial tissue ends up, like, in the perineal cavity and, like, I had this one case of a, um.

Like, in school, but she wasn't my case. It was a case study, um, of a gal who had endometrial tissue in her nose. And every time she menstruated, she would get a bloody nose, right? She'd get epistasis. So, like, it can go anywhere, but it's most likely, most commonly in, like, the, the pelvic region, and it's going to be wrapping itself around the fallopian tubes, around the ovaries, and it's just external outside of that uterine tissue.

So, anytime you get an estrogenic response, it's proliferating, right? And causing problems, and scarring, and causing pain, and, and. Definitely fertility becomes a concern and but because the phthalates can increase are also associated right with higher for hydroxy production I could see that connection like that's interesting that you a lot and that's, I think, makes a lot of sense in my head.

I don't like I just kept seeing it and I was like wait you have endo. Okay, you also have endo. Oh, you too. And I was like, wait, all of them have had high 4 OHEs. And like, I don't know if there's anything to that. I've yet to find a study on it, but at least, Sally is for hydroxy. So there is that like kind of Right, like it makes a direct association.

I love it. I love it. You just like, made sense of this theory. Yeah, yeah, like, oh, I think that would be so valuable because honestly, like, so many women come with, with endometriosis type symptoms, but they've never been worked up for it. They don't, they just internally are like, maybe I have endo, right? The sphere thing and laparoscopic surgery is not something you want to take lightly.

So they're always like, well, I don't know. What can you do? Can you figure it out? And I'm like, well, we're going to do a Dutch test and then we'll see. And. Yeah. And this is my little hack to say yes, more testing or no, you're probably okay. Let's work on other stuff. And then you can still save the testing for later.

Um, if your symptoms don't get better. Well, and I will, I'm going to shout out because the other thing that endo axis does, so we are a, a tool to help evaluate complex hormonal patterns. starting with the Dutch, but expanding to serum and expanding to other tests as well to really enhance that story. But the other big thing that we're doing is customizing formulations based on these patterns, right?

So that providers don't have to like scrap and search and like, pull like, I like ingredient in this product. And it's like the right dough. So I'm gonna have to get this product, but I don't really care for these other stuff. You know, like I don't care for all this stuff. Like I don't want this other stuff in there.

We give you what they need for that pattern. And for, for hydroxy in particular, it's one of my favorite blends. We're using this beautiful nerf to promoting blend of true Brock, which is a glucoraphanin with mustard seed, which is morosinase to really help optimize sulforaphane. That's protecting from that oxidative stress of 4 hydroxy.

Remember, 4 hydroxy, the big issue is that when it doesn't methylate, it goes down the quinone pathway and becomes a 3, 4 esterone quinone. And those are what result in those DNA addicts that over time can lead to oxidative stress, cellular change, and even cancer risk, right? Um, and so, and that's another, you know, interesting feature of endometriosis.

There's that increased risk for endometrial cancer, which again would correlate with 4 hydroxy, right? But curious, curious. But with sulforaphane, right? Sulforaphane. Enhances phase 2 clearance and supports. It's a nerve to regularly. So it uncouples nerve from the key protein to really help improve the production of glutathione catalase and S.

O. D. So that we have these potent free radical scavengers to kind of suck up all of that. Quine on response and repair DNA and make sure that we're, you know, structurally sound. And so we have a blend with the true rocks, uh, glucoraphanin and morose and ACE. And then it has a little pomegranate. It has EGCG.

So green tea and CoQ10. And it's just this beautiful, it's like, I love this combination. Um, it's great for I endometriosis it's protecting themselves. It's great for fibroids, which are another one that can be really promoted through elevated, um, 16 hydroxy in particular, but Yeah. Yeah. Yeah. It's kind of a neat, neat formulation targeted to that path.

I love it. This is another fun feature because of kind of that understanding of what enzymes are involved in metabolism. The blends are really targeting the enzymes. So whether we know if they have a polymorphism or not, if there's a dysfunction in a, in a pathway, we know that that enzyme needs help, right?

That pathway needs help. Um, and so we target that with. Not the nutrients necessarily for the hormone, but for the enzyme that's supporting the hormone. Yeah. Yeah. Just a quick aside. Cool. Yeah. I love it. Um, okay. So can we, can we jump to cortisol? And, and I feel like that's another big fertility specific area.

Um, so I'm curious if you can just share like things, patterns that are outside of the realm of what most practitioners know, which is like. Oh, if it's within the range that Dutch test gives, it's good. You're good. But like the metabolizing of the cortisol, the metabolizing to cortisone, all that stuff that is just so, um, nuanced, I find.

And yet so important and critical that we don't miss, you know, um, I think, you know, the way when I, if I think back, you know, to school, the way I was taught to look at At the adrenals was to run an ASI right in the adrenal stress index, and that's a salivary test. It's looking at those key points throughout the diurnal curve of free cortisol.

And then we make assessments off of that, and I remember in school thinking, man, I'm just crashed. I have, like, all this super low cortisol and then I run a Dutch test and I realize, no, I'm just a rapid metabolizer. I shouldn't be taking anything right? So, and I'll get to this, but, um, right. So, like, the free cortisol, we're, we're so, like, ingrained.

To just look at that free diurnal response. And that is important because it's showing us in the moment what is their output to like our universal stressor to waking up, you know, in the morning. Um, and then what is the response to stress throughout the day are, are there stressors that are spiking them when they should be starting to decline or not?

Right? And so that's kind of that diurnal rhythm and assessing those key points. That's the free cortisol. It's only one to 5% of cortisol at any given time when you're looking at those measurements. Metabolized cortisol, this is 90% of all the free cortisol that was made on that day of testing. And we have to look at the two because it's the relationship between those that has the biggest impact on health and where we want to treat, right?

If you see someone who has beautiful free cortisol, they've got this great diurnal rise. You know, they wake up in the morning, they're getting that nice spike in cortisol. It's within range. It's coming down in the afternoon. It's nice and low at night. And yet their metabolites are like flatlined. There's a problem with clearance, right?

There's a problem with potentially total production, like. That free cortisol, that graph was only 5 percent at most of the free cortisol at any given time. Here we're seeing 90 percent is not looking good. What's the discrepancy? And more often than not, we see that pattern with hypothyroid with low, specifically low cellular free T3.

And so it goes beyond just looking at a TSH T4 T3. You want to look at the reverse T3 as well. How are they incorporating and utilizing that thyroid? And doesn't need help because thyroid and adrenals, they are inter, you know, interconnected. We need to treat both. Um, and so making sure that we're evaluating and addressing like what's going on.

And so often I'll see providers like just look at the stress pattern and not at the metabolites. So just the three. And yeah. Okay. Yeah, they'll base their treatments off of that and then like, for example, if it's like, say they have a really high stress pattern, they're overshooting their morning cortisol, or they're shooting up in the middle of the afternoon, but metabolism is low and you're not addressing thyroid.

And you're not addressing liver health and you're not addressing adrenal support and just like the, the nutrients to rebuild just adrenal function in general, just target phosphatidyl serine and magnolia and, you know, chamomile and the things that would calm them. What can happen is you can shut them down both sides, like they drop on both ends because now you didn't treat the roots.

You didn't treat the fact that the metabolites were compromised. There was something happening. Right. Right. That's a really big. thing to remember and what we catch, what we're looking at is that relationship. And again, conversely, you see this flatline, not to say flatline, but you know, you see really low free cortisol and then metabolized cortisol is like through the roof.

Well, that person's got a lot of exposure to cortisol. That's a lot of inflammation in their bodies. Their liver is exposed to all of that cortisol, right? That can increase fattiness. In the metabolized form. Yeah. Yep. To be a metabolite, that had, that was, you know, Produced and circulating cortisol that had to process through the liver.

So that's a lot. Right. And then if you were only looking at the free cortisol and we're like, Oh, but they're so depleted. We've got to get them. Hydrocortisone. You're putting kerosene on a burning fire. Right. Yeah. It's like, We want to treat. The HPA response, you want to calm down the inflammation in the body.

That's like a very prone. That's a high excess T3 pathway. Right. Get it out of the body. Um, so checking it on thyroid in that case too, opposite problem, but, um, and then really addressing like, yeah, these people are going to feel exhausted because they have no like diurnal response, but they're kicking out a lot of cortisol, so they're like exhausted, but inflamed and anxious and agitated.

And so these are people where. support that inflammation and blood sugar, get them on adaptogenic herbs that are supporting that free rise a little more sufficiently. If they're not hypertensive, licorice is actually a great herb here because it slows metabolism of cortisol while also augmenting immune function and reducing inflammation.

Yeah. Yeah. Um, is that so, That, like, over metabolizing of the cortisol, is that a need that the body has? Because cortisol's anti inflammatory, so is that like too much inflammation? We need to like have more cortisol to, you know, Decrease inflammation, or is it the cortisol metabolizing over metabolizing is causing more inflammation.

No, the cortisol is produced because of inflammation, right? Yeah. So the signal from, from the body to the brain is some sort of inflammatory trigger, like usually a cytokine, um, I'll six like, so. You know, a big reason why we might see this over metabolism is actually excess adipose tissue or more metabolically active kind of fat tissue.

Um, adipose tissue releases a low grade level of IL6 all the time. So this is an inflammatory cytokine. Uh, and that's going to be in circulation. That's going to be affecting our blood vessels. It's also going to be crossing into our brain and telling our brain, Hey, We've got some stress here and the brain's kicking out CRH, right?

Kicking out ACTH, knocking on those adrenals saying we've got to make some cortisol. Well, adipose tissue is, it's a unique endocrine gland, right? It kind of, Misbehave sometimes. Um, at no fault of its own. It's trying to protect us, right? Evolutionarily, it's doing the right thing, but it will actually sequester that cortisol for its own metabolic purposes and actually pull cortisol out of circulation and over metabolize it.

It's not that they aren't making cortisol. It's just that it's getting metabolized too, too efficiently, like too quickly, right? It's there. It's affecting the body, right? And that means that there is inflammation present. So the metabolized cortisol is high because there was a response somewhere in the body could be the fat tissue could be pain, chronic pain, joint pains, muscle pains, headaches, right?

Um, it could be, uh, another one is like, um, more like environmental stressors or even so 60 percent of our immune system is kind of regulated by our gut. So like low grade. Dysbiosis can be a factor there. That's just driving up that inflammatory response in the body. But, um, yeah, I think of it kind of like the fire hose is wide open.

It's like, trying to just get it out, like, get it made, get it out, you know, um, depleting what we have in the moment for our receptors to be like, okay, let's stimulate, you know, so you're lacking a nice, you know, Right. Yeah. It's basically like the fires are so intense compared to, Oh, I need this so that I have energy.

So it's like putting out the fires is more urgent than like, I have a need to function in my life. It's like not keeping it around long enough for your brain to utilize it and get that like cortisol awakening response to get all the benefit from that rise to get, yeah. neurotransmitter upregulation, acetylcholine, dopamine response.

Yeah. So that's, that's where we get like foggy brain and achy and agitated and tired. And I will say first of all awakening response, even if you have like. Like if they agree and that's the ideal, it's like, okay, they agree. Um, they're making and utilizing cortisol efficiently, right? Making it and clearing it.

Um, if you don't get that rise in the morning. And so this is really something that you can determine in the salivary car. So this would be like the Dutch plus. So you use the urine for metabolism, but you are looking at the, in the moment production of cortisol using saliva, much more sensitive marker for that.

Um, and so watching that, what they call the car, the cortisol awakening response. Yeah. Before you even. Open your eyes, right? You take this first salivary sample. So you're up, but you haven't gotten out of bed. You put this little swab in your mouth. You're collecting all that cortisol. Should be nice and low, right?

Because you haven't had a response yet, but then you open your eyes, you're getting sunlight, hopefully. Oh, very, very importantly active. And so cortisol should be rising significantly 50 to 160 percent in that 30 minutes. Right. And we can see that. Within a few minutes, we can see that rise starting. So we want to capture that at the 30 minute mark, and then we want to capture the 60 minutes to see, well, does it keep rising or does it come down or does it come down too fast?

Are they over like over utilizing or not sustaining that cortisol? But the importance, the really important part is that. Zero to 30, right. Waking for 30 minutes. Mm-Hmm. . Mm-Hmm. . If you're not getting a rise of 50 to 160%, that can lead to all sorts of dysregulation to your immune system, to fertility, to HPO response.

Right. Your diurnal, all of our body is very diurnal and it's activity and it, yeah, we're not in a good rhythm and that can be seen by that cortisol in particular, we're not gonna have that same like fertility. Response, I guess that would be the way to describe that. But yeah, infertility can be a risk, low, low.

Yeah, I absolutely, absolutely. Like we spend so much time trying to optimize the diurnal response because that's going to be the foundation for. fertility hormone regulation. So everyone's so focused on those. And if we get the foundation right, then we might have a really great house to build. Yes, it's working on the root, like the, the deep, like foundational work that then everything else just becomes easier, right?

Everything else just happens and it becomes not easy. Like, wow, everything's so much better. I'm like in the morning, like getting outdoors, get fresh air. Yes. Yes. Yes. Get a little elbow movement, you know, just kind of do some jumping jacks or, you know, uh, but just get that body moving. And I think movement throughout the day too, just to keep that circadian regulation going, you know, we don't want to be too sedentary.

You know, the other thing that's interesting with the cortisol rise, You know, sleep, right? Like I get patients all the time. Often we get this blunted car over time because people aren't sleeping well, right? So I always want to optimize that sleep. But it's almost a vicious cycle because If they're not sleeping, right?

So, well, okay. So if you're not getting a, so if they're not sleeping, they're not getting that nice response in the morning. They're not getting that rise, that sharp rise in cortisol. Cortisol and adenosine kind of are complimentary in the brain. Um, they bind to the same receptors. Cortisol blocks adenosine from binding and making us tired.

So we feel really energized. Coffee does the same thing, which is why we get a little perk when we drink coffee. We're blocking adenosine from binding, but we should, as cortisol goes down, we should be getting more and more adenosine binding and we should be feeling more and more groggy. Well, denticine is stimulated, is produced or, um, with norepinephrine surges.

And so the more norepinephrine we get, which happens with cortisol, right? The more active we are, the more cortisol response we get, the better our denticine production and the better our response at night. So I will have patients all the time that are like, well, no, I need to work on sleep, not my car. You know, I don't know.

You actually need that because that will help your sleep. And so I think that's what, yes. Oh, that's so good. The car. So important. So important. And a car is very interesting. It's there's some research saying that car is actually the biggest predictor of lifespan than everything else. So, yeah, it's like a pretty powerful Cool.

necessity that our body has to like make that cortisol in the morning. So very, very, very important for all of you non practitioners that are trying to get pregnant. Optimize, optimize, optimize, go get some sunshine, do some jumping jacks like Dr. Liz said, get that, get. If you're dragging and you need coffee to wake up and you don't function, your brain is still off before your coffee, like those are all the people that need that stimulation of cortisol awakening in the morning.

That programs, that programs the body for the rest of the day. If you don't get that awakening, you're tired all day long. Yeah, yeah, yeah, yeah, absolutely. Yeah, go for a little walk in the morning. Make that part of your routine. I love it. I, I love to drop my child off to the bus stop in the morning because it gets me out and it's like 15 minutes in the sunshine and he's like, mom, can you be a car rider?

Can you drop me off in the car? I'm like, no. This is my time. This is the time I get sunshine and all that. So yeah, it's so good. Yeah. So good. Um, well, thank you so much for being with us for practitioners that are listening. How can they get supported with endo access? Where do they go to get started? Our website is www.

we are coming in March, March: 2024

read some reports, see what the input is, see if you're getting, I mean, really what we want this to be as a second opinion type system. Like you just want to run it by another medical professional, you get an automated version of that. And then you get access into our catalog of all of our amazing supplements.

We have 26 supplements being launched along with the program. So, um, lots of really targeted. In my opinion, beautiful, but very targeted, uh, blends to address not just the hormones, but that enzymatic dysfunction that's leading to these hormonal imbalances. I love it. I love it. And for those of you listening in, I am sure you can already tell Dr.

Liz's brain is like, amazing, just amazing, like, uh, so the value, like, For those of you that don't know, Dr. Liz is a lot of the brains behind EndoAxis. So when you get, see that report, you could be like, whoa, this is the creator right here, you guys. And Dr. Guy is also really brilliant and really smart and has contributed so much to this.

So Um, yes. Like amazing minds behind this is what I'm getting at. Yeah. Yes. It's been a great, amazing experience and amazing team that I've been able to work with and collaborate. And yeah, we're just, we're just, and the beauty of this is it's just going to continue to advance and grow from here. We are not limited.

You know, if you're going through, this is my other just PF, not public service announcement announcement per se, but just by a little plug, um, give us feedback, give us insights. You know, we want to know, we want to know how to make this. It's really good and, uh, and good for all providers. So yeah, use us, check us out, give us feedback and just know that we're going to continue to grow in advance.

So I love it. I love it. Well, thank you for joining me today, Dr. Liz. And for those of you listening in, we'll see us again very soon. Take care and have a blessed day. If you love this episode, show us some love. And if you would love to leave me a voice memo, tell me what you love, what you hate, and what questions you have that you would like me to answer on Egg Meets Sperm.

We're doing that all season long. So send me a memo, let me know what you love, let me know what needs improvement, and most of all, send me your questions.