This week we welcome Dr. Mansoor Mohammed. Mansoor is the president and chief scientific officer of The DNA Company, and is considered to be a pioneer in medical genomics. He’s a classically trained molecular immunologist who has received academic and industry awards, published numerous papers, and holds patents in the general fields of molecular diagnostics and genomics research.  In this episode, we discuss the relationship of Functional Genomics and Epigenetics, both informing and transforming information on hormones from genetic testing, and Androgen Dominance and Estrogen Dominance. We also dive into the impact of oral contraceptives and its impact on genetic variances as well as, an in depth breakdown of the three Estrogens and Estrogen Metabolism.

 

Episode Overview: 

• 2:20 Introduction 
• 7:50 Dr. Mohammed’s Origin Story
• 13:00 Relationship of Functional of Genomics and Epigenetics 
• 25:40 Life Informing and Transforming Information On Hormones 
• 47:44 Androgen Dominance and Estrogen Dominance
• 54:04 Genetic Variances and The Pill 
• 56:57 The Three Estrogens and Estrogen Metabolism 
• 1:28:35 Methylation 
• 1:31:08 Morphology
• 1:33:07 Conclusion

 

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Transcription

Speaker 1 (00:08:22):
Welcome. It's a pleasure. Thank you, Stephanie, for having me, Dr. Steven,

Dr. Stephanie (00:08:27):
Uh, we, and you and I have a, you know, we've spent, we were saying in the pre-chat, you know, we've spent some many long days together filming, um, you know, uh, DNA and, uh, genetic, um, pathways for your clients. So I'm, I'm really excited to have you on the podcast today, because I think that there is, you know, we're going to talk about functional genomics today, but I think it may be worth starting first telling us a little bit for anybody who is not familiar with you, your work with the DNA company and what functional genomics are. Maybe let's start, let's start with what functional genomics are and how you found yourself in this line of work.

Speaker 1 (00:09:09):
Well, thank you. So I'm a classically trained geneticist, which means, you know, typical PhD program. I focused on bio genetics immunology, and then as with most geneticists, you don't go down a path where you start hyper focusing on a particular gene, a particular gene as it's really relevant to maybe disease States. And I was blessed at UCLA to mentor when I was doing my post-doc. So this is after my PhD. I did my clinical internship focusing on cancer diagnostics. So I spent a lot of time looking at, I think we can, all our viewers can all appreciate that a person's innate genetics can impinge upon can influence their risk factors for different cancers. And so, without getting into the details, I focused at several years of my life on the genetics of cancers, and then a very unique opportunity was posed to me because of some of the IP and some of the publications that, again, I was blessed to be with just the right place, the right time with the right mentors, Baylor college of medicine, which is arguably in some ways better than UCLA when it comes to developmental genetics.

Speaker 1 (00:10:09):
So you see, as a geneticist, you typically focus on either cancer, genetics, or developmental genetics, developmental genetics, of course, being the genetics of early childhood development. And we typically have to pick one or the other, but when I was offered the opportunity to come to Baylor and, you know, start to specialize in developmental genetics, I rushed at it. I thought, you know, why be just cancer geneticists? So at that point, I was exposed to not just the genes that when broken cause cancer speaking plainly, but so the whole genome that I was exposed to the concept of the operating manual, that a person's genetic makeup defines the newest, all of the nuances, the minutiae of how that little baby's body was developing our early childhood development and then going on to adult cellular behavior. And at about that time, shortly after I finished my work at Baylor college of medicine, a new field of genetics was starting to emerge and it was called functional genetics based exactly on what I just said that we were beginning to understand, because of course, right, at that time, we had the completion of the human genome project.

Speaker 1 (00:11:15):
So now we had the whole manual of the human genetic material decoded. And so we could actually start with vigor studying this manual and really appreciating that Stephanie, for you, me, for all of our audience members, our genetic makeup is our operating manual. And so a few years after that, it's been, gosh, I'm going to date myself now. It's been about 16 going. Yeah, but 16 years now, I focus my entire career path on this concept of functional genomics. And what is that functional genomics to conclude and to clarify which forms the basis of everything that we do at the DNA company, functional genomics as is descriptive in its term is the understanding that a person's genetic makeup is well beyond, you know, the color of our eyes and the color for our hair and what sex we are. It defines every cellular detail, the functions, how good our cells are absorbing various nutrients, utilizing those nutrients, how good our ourselves are creating energy, how good our ourselves are getting rid of toxins, metabolizing things, transporting things inside and outside of the cell, all these minutia functions that are obviously radically necessary for us to be healthy.

Speaker 1 (00:12:39):
And by the way, to the degree that we're doing these functions, either optimally or suboptimally is the degree to which we have a baseline of health, this study of the genetic manual to determine these nuances. This is the study of functional genomics. This is the focus of the DNA company. We are focused on decoding and intelligently interpreting the human genetic operating manual so that we can empower individuals to use this knowledge just as they would use an operating manual for anything else to ensure that they're using that manual codes and codes as optimally as possible.

Dr. Stephanie (00:13:19):
And I love that because I think that there is potentially a misunderstanding around genes and genomics in general, right? So we often hear, I've had clients say to me, well, it's not really that my genes, it's my epigenetics that matter. It's how those genes marinade, it's how those genes live. And of course, that's true to an extent, but I would love for you to clarify the relationship between functional genomics is operating manual, as you've, as you've just described so eloquently and the intersection of epigenetics and how those two operator, how those two influence each other

Speaker 1 (00:13:55):
Indeed. So very quickly as a quick, but accurate definition at P genetics refers to anything at P that which was above genetics refers to anything that influences your genetic makeup. And here, what we're speaking of influences your genetic makeup at the level of expression. And this is the key. You see many people and many, you know, even we might say experts, try to make it seem that your epigenetics, because that's the thing that will influence your expression of your genetic makeup. That really all of the emphasis is on epigenetics and many consumers. And ill-informed individuals walk away from this, with the, with the belief that, well, ultimately my particular genetic variation or type doesn't matter because all that matters is how I'm influencing it. And actually this is an incorrect perspective. So what is epigenetics is how we express our genes. So for example, if you, Stephanie, Dr.

Speaker 1 (00:15:00):
Sima, we've got 22,000 genes give or take 22,000 genes, which means 22,000 individual instructions that are used to orchestrate the wonder and the miracle of human cells, human organs, and then in totality, the human individual, 22,000 genes. But what you'd be surprised to know is that any given point in time, right now, any given point in time in any given cell type in the body, my skin cells versus my retinal cells versus my cardiac cells versus my lung, my liver, my brain cells, and so on and so forth, they all have the same 22,000 genes by the way. But they're using, they're expressing, they're using the instructions of these 22,000 genes at different times. And in different numbers, heart cells might use a subset of those 20 2020 2000 genes. And my skin cells might use a different subset. This is the first thing we need to understand that ourselves use potentially different parts of our operating manual.

Speaker 1 (00:16:06):
Number one, number two, that our cells, any given cell clearly, therefore is not expressing or using all 22,000 genes all at once at any given point in time, we ourselves are very efficient. We turn on and off genes and we'll talk about this stuff no later, as we get into female hormone control and metabolism, but our cells and our organs and our body turns on certain genes at the right time. So that that job conduct done. Then we turn off those genes when we don't want that job getting done. This is key to energy conservation and the cicadas rhythm. We are circadian creatures. Our body does certain things at certain times for optimal function and does not do other things at other times, and where they to do certain jobs that have to get done, but were they to do those jobs at the wrong time, in the wrong place?

Speaker 1 (00:17:07):
That's what is actually the foundation of many illnesses, pea, genetics, therefore describes when and how a certain gene will be expressed. In other words, when and how that instruction in coded in that gene will be used. And that is radically important. However, it's still returns to the fact Stephanie, that for a gene. So let's take a gene that we'll talk about later in the hormonal discussion, let's take this all important gene, 1981, CYP 1981, our audience, some sort of audience members might otherwise know this gene by its more common name, aromatase specific 1981. The name of this gene is a rural motive. It's a gene, all human beings, all women and all human beings, men as well. We have two copies of this gene. Now, this gene is the instruction for how we convert to start strong into estrogen. And yet our audience just heard me correct and heard is correct. Estrogen is produced from testosterone, other bodies, male, or female, female, or male. We must first make testosterone before we aromatase to start strolling to estrogen. So simply stated to conclude estrogen

Speaker 4 (00:18:29):
Is nothing other than aromatase

Speaker 1 (00:18:32):
Testosterone. And this gene encodes the instruction to do that radically important job. Certain things, certainly

Speaker 4 (00:18:41):
Environmental exposures, certain foods that we eat and intentionally unintentionally will either turn on the stream or turn off

Speaker 1 (00:18:51):
Gene that is RPG and ethics. So for example, there are epigenetic factors that will induce

Speaker 4 (00:18:58):
This gene to turn on. And of course, if we turn this gene on,

Speaker 1 (00:19:01):
We're converting our testosterone into estrogen or the food groups, other things will turn off this gene. And if we do that, we are slowing the process within which we convert testosterone gestures. This is our genetics. However, that very gene aromatase

Speaker 4 (00:19:20):
Basic 1981 of which we have two copies that gene comes in different versions. There is a version of that gene that you will innately

Speaker 1 (00:19:29):
A fast acting version of that gene. There's a different

Speaker 4 (00:19:33):
Version that you innately have a slow

Speaker 1 (00:19:36):
Acting version of that gene. And that is your genetic makeup that has nothing to do with your epigenetics. So a person can be innately. They have the fast version of aromatase, a different person has the slow

Speaker 4 (00:19:52):
Aromatase. And let's say that these are two 90

Speaker 1 (00:19:55):
In your old university student, young woman that are roommates with each other. There are two 19 year old roommates. They've lived with each other for so long. Their cycles are coordinated. They've got their cycles at the same time and they eat in the dorm together. They exercise together. They're exposed to the same environment together

Speaker 4 (00:20:13):
As the fast version of aromatase. The other has the slow version

Speaker 1 (00:20:17):
Now because of their lifestyle factors, choices, their environmental exposures, their dietary choices. They are both exposed to the same epi genetic factors that turn on and turn off their aromatase gene,

Speaker 4 (00:20:35):
A woman with the fast version of aromatase, regardless of her epigenetic factors, whenever her gene is turned on, she is simply going to be met

Speaker 1 (00:20:45):
Faster at converting her into estrogen versus her roommate who will be measurably slower at converting her estrogens or testosterone to estrogens despite the epigenetic phenomenon. So to conclude Dr. Steamer and for our audience, epigenetics is radically important. It defines how we use our operating manual, but at the end of the day, the version of the operating manual you have, which genes have the fast motion, the slow version to medium version, the optimal version of suboptimal version. That is something that is genetics. That is a nature. You, and it is before it precedes epigenetic considerations.

Dr. Stephanie (00:21:28):
I love that. And this is one of the reasons why I wanted you on the podcast for exactly what you just said, because there's so many things that, you know, I've done a lot of genetic test. I've done the 23 and me's, and you know, where it, I sort of call it like coffee table genetics, right? Like they, you know, they, one of the reports, uh, said to me, you know, you are more likely to have a uni brow. Um, I was like, listen, I'm, I'm Lebanese. And I'm Portuguese. Like, I, I already know that, like, I didn't need to pay for this. The other thing it said to me was, um, something with, um, you know, I have the certain polymorphism that allows me to smell, you know, if I, if I consume asparagus, I can smell the change in the urine, like how the, you know, so I was like, well, I'd like, I already knew that too.

Dr. Stephanie (00:22:15):
Like I have asparagus. Like I know when that happens. So I thought that, you know, and not to call it useless, but I was like, well, you know, tell me something. I don't know. But what I, what I thought was really so profound about the results that we had from the DNA company was that it told me, it told me about how I metabolize. We're going to talk about the fi the metabolome, the steroidogenesis and how we metabolize all of our sex hormones today. So told me that it told me how many number of copies I had of certain, like in my glutathione ization pathway, like how many GST fetas and muse, and pies and things that I had never considered before, or was never told about before. And that's where I think that your analysis or your company's analysis stands out because it's important to look at snips. I think it's important to look at polymorphisms. You need to look at that, but I also like that there's like, copy number variant analysis with you as well. And there's, I think there's other things that are important when we look at genes. Yes. You wanted to say something.

Speaker 1 (00:23:21):
No, no. It's so important because thank you for highlighting that let's link that back to the epigenetics. When we just said that epigenetics are factors, lifestyle factors, environmental factors, nutritional factors, things that we eat, things that we do intentional intentionally unintentionally, that then cause our genes depending on the version to be turned on or turned off well, as you've just highlighted, there are variations that we all Stephanie and I know our viewers should know this. There are certain genes that a healthy person out there may not have that gene at all. And let's repeat that slowly. There are variations beyond snips snips here being the variations in the spelling of genes and the lecturing of genes. But there's another type of its Smith, single nucleotide polymorphisms. But there's another type of variation that you've alluded to, that we also cover, which is where a gene, which we typically should have two copies of it's completely missing from the human operating manual.

Speaker 1 (00:24:18):
These are called CNVs copy number variations. That's actually what I spent the majority of my academic career discovering and writing and researching about, well, here's the point, Stephanie, if a person does not have a gene at all, meaning whatever that gene is like the GST for one, the GST fatal one that Uber important detox genes, super important, Uber important and hormone metabolism. When we come to the factory, we understand that sex hormones cause estrogen byproducts, they cause oxidative byproducts that can even cause toxic byproducts. This GSTT one gene and its job. It's enzyme super important to dealing with those byproducts. Well, what if you find out that you don't have this gene at all, and by the way, that happens, my point here is all of the epigenetics in the world does not impact a gene that you don't have. If you don't have the gene, nothing epigenetically will cause you to express that gene or use it either more or less because you don't have it.

Speaker 1 (00:25:20):
And so again, this is where that superficiality and I get it that, you know, we need to make things simple and understandable for our audience. But I think everything we're talking about here, any in tuned consumer audience member, who realize my goodness, why haven't I been told this before? And that's, I think really what you do so brilliantly is to take these concepts, make it suitable for your audience. But at the same time, don't give, don't cut the, you know, don't give them a short changed version of it. Let them know the importance of this while putting it in a manner. That's understandable. Yes.

Dr. Stephanie (00:25:53):
And, you know, just following on your example, you said, there's like, you know, if you have a one woman with a slow sip, 1981, she might have a tendency to run androgen dominant, uh, or you know, her aromatase station from testosterones to estrogens are not going to be optimal versus, you know, the same 19 year old, same environmental stimulus who very quickly is going to aromatase her. Testosterone's you're going to see generally you can, you know, without looking at her genes, you can sort of infer from her morphology, right? So that, you know, maybe you can comment on that because you can look at, uh, a woman or a man and say, okay, so I, you know, maybe looking at the size of your breasts or the size of your hips, or, you know, how much muscle you have, there can be an inference generally in terms of what your, um, you know, your genetic blueprint or your manual might

Speaker 1 (00:26:44):
Look like, would you agree with them 100%?

Speaker 4 (00:26:47):
It's one of the things that makes what I do. So cool. I'm just wondering

Speaker 1 (00:26:49):
The things that has attracted so many individuals, whether

Speaker 4 (00:26:53):
They be elite athletes or executives

Speaker 1 (00:26:56):
Or consumers of any variety, because unlike what you just said, cited as the experiences that you've had, which is the alter come and experts, you hear these things that are coffee talk, they are recreational in nature. And it's cool for the first week until you tell the rest of your family members and friends, but it didn't really impact how you approach life. When people

Speaker 4 (00:27:17):
Hear what we tell them. And they experienced

Speaker 1 (00:27:20):
Through the fact that before,

Speaker 4 (00:27:21):
Well, I even do a genetic consult with someone when I meet them. If I see them, I can say, you know what? You unlikely to have this, this, and this be your functional model.

Speaker 1 (00:27:30):
How do you know that about me? Because this is the nature functional genomics or conversely, I can see the genetic blueprints of a person having never met them, assuming

Speaker 4 (00:27:40):
That I know that they're male, female, and I can say this

Speaker 1 (00:27:42):
Genetic profile belongs to a female who is likely to have such such morphology before I had your meter. And the acuity of that is based in our ability to interpret these nuances that we're going to talk about Stephanie, Dr. Simmer, on this point, it's really important that we highlight something here for our audience

Speaker 4 (00:28:02):
Members, including the clinicians of our audience members. And that is

Speaker 1 (00:28:05):
We're about to embark now on a really cool journey for our females.

Speaker 4 (00:28:09):
Well, our audience members, but primarily our female audience members to learn some reasons,

Speaker 1 (00:28:14):
Not just cool things, but life informing and probably life transforming things about their bodies, their health, their, their viewpoints of longitudinal health as it relates to sex hormones. So before we go any further, Stephanie, I think it's so

Speaker 4 (00:28:31):
Important for our audience members to understand

Speaker 1 (00:28:34):
What are sex hormones and how do they influence the body? You know, we hear about testosterone and I think we could kind of all, most of us will understand that's an androgen testosterone. So that's the hormone that causes the more, if you want to call it male dominance or masculine lies features, and that's a very superficial way of looking at it. But testosterone is the thing that induces muscle mass development testosterone impacts the body in a number of ways, impact cellular metabolism. It even radically impacts neurologic function. It brings about certain mood, modality types, estrogens, a different sex hormone impacts the

Speaker 4 (00:29:16):
Body and what we would call the more feminizing manner.

Speaker 1 (00:29:19):
Right? So if impacts factor

Speaker 4 (00:29:21):
The position of the body, it also impacts saline. Metabolic rate

Speaker 1 (00:29:25):
Impacts the growth and the, the, the, the secondary sexual features characters, characters, the creatures of the female body to start from the male model. However, we have to be unclear that both hormones are present in both sexes, both hormones and optimal development is going to reflect the interplay between these two hormones, which brings back and begs the question, how do these hormones do what they do when you've got that shirtless six year old girl, you know, and she's with her shirtless six year old twin brother, and they're running around playing around. And if they both had a boy cut, you probably wouldn't know which one is the girl in which one is the boy. Okay. So what happens when puberty comes along the cells of their bodies, the twin girl, the twin boy, the sounds of the bodies of their bodies are programmed that when puberty hits and these hormones, the sex hormones, the progesterones, the androgens, testosterone, and others, and estrogens, when they begin to be produced, these hormones interact with the cells of the body and start to create noticeable secondary sexual features, mind you, there are as many other internal features that we do not see cell in the behavioral features that we don't see that are also changing, including brain development in relation to these hormones.

Speaker 1 (00:30:53):
But again, it begs the question, how do the hormones do the strong hormones and for our listeners out there, all hormones, whether they be sex hormones, we are progesterones, androgens, and estrogens. Whether they be thyroid hormones, insulin, whether they be any other hormones that we can list all hormones impact or create what they create in the human body by binding their receptors. So for every hormone, there is a receptor, a receptor is the thing that allows that hormone to bind to it, getting to the cell and change cellular behavior. So in other words, when testosterone binds its hormone, the androgen receptor, then that cell becomes androgen. NYSED. It becomes, it takes on the characteristic that is more reflective of it being testosterone, Baden, and testosterone. How does that happen? How does the binding of the androgen receptor, how does the binding of the estrogen receptor by estrogen?

Speaker 1 (00:31:59):
How does the binding of the fibroid receptor by fire at hormones? How does the binding of the insulin receptor by incident? How do these receptors when bound by their hormone? Cause the cellular change through epigenetics, these receptors when bound by their hormones go into our genetic library and those very receptors down by their hormones cause the genes to turn on or turn off. Okay. So the very concept of hormone receptors, which by the way, are the products of genes, which the way we'll talk about you have different versions of it. When activated determined by your genetic makeup then impacts your epi genetic turning on and turning off of genes, which is what causes that flat chested six year old girl, all of her cells were there, but when she hit

Speaker 4 (00:32:57):
It's 12, 11, 13, as the case might be those things

Speaker 1 (00:33:02):
Now bathe it in estrogen, estrogen,

Speaker 4 (00:33:05):
Binding the ho the hormone receptor estrogen

Speaker 1 (00:33:07):
Receptor, that receptor going into those cells and now turning on certain genes, turning off certain genes. Those now once smaller cells

Speaker 4 (00:33:18):
To take on division, start to take on cellular

Speaker 1 (00:33:21):
This growth, actual growth of the South to give breast of our development, bum developer back of the thighs development. So for everyone in conclusion, this hormones, including sex hormones, impact our bodies bye

Speaker 4 (00:33:37):
Finding to their receptors, which are the products of teams and changing gene expression,

Speaker 1 (00:33:42):
Which is epigenetics so that our cells behave differently without start getting some on the arm here. We now, you know, those boys start getting a little smell that they didn't have when they were six or seven years old, hopefully, and so on. And so for girls start taking on a different body form and so on and so forth. So now with that baseline that we understand a person's genetic makeup is radically important. We understand that the P genetic instigators,

Speaker 4 (00:34:11):
Whether it be environmental lifestyle

Speaker 1 (00:34:14):
Food, or their very own genetics, that controls epigenetics, we are going to go on a journey. As you said that by interpreting intelligently in a functional manner, which is exactly what we're going to leverage into. How can we

Speaker 4 (00:34:32):
Describe to that young woman, even without seeing her what might be her body type? Because now that we understood everything we just said, you see, let's go back to those

Speaker 1 (00:34:40):
Two roommates a second. So one of those roommates, she has the fast ability or the fast

Speaker 4 (00:34:49):
Inherently, genetically inherently faster capacity to a rural Matteis.

Speaker 1 (00:34:55):
She produces a testosterone. She is pulling more testosterone, converting more of that testosterone into estrogen than her roommate who is doing that much slower because of their genetic difference. Just this alone. And we'll take this, we'll begin to pixelate. We'll begin to add nuances to this, but Stephanie, if we take those two things are known as you beautifully and accurately, obviously highlighted the young woman who has the slow aromatase, who is smaller, converting the estrogen

Speaker 4 (00:35:30):
Under general testosterone into estrogens, which means

Speaker 1 (00:35:34):
Preserves sorts of stuff strong. She's not as quickly converting it into estrogen. What might be the features of this young woman, this roommate versus her peer? Well, immediately she's,

Speaker 4 (00:35:47):
It's going to all things equal and we'll talk about the nuances,

Speaker 1 (00:35:50):
Other genes, but all things equal. We're going to expect it to be and shields very, very likely to be smaller breasted. She's also likely to have and carry less body fat in the places that

Speaker 4 (00:36:03):
Female bodies. So beautifully times to hold body fat. She's going to tend to be a bit narrow head. She's also going to tend to mute because both of these 19 years

Speaker 1 (00:36:11):
Girls, they go to the same gym. They go to the same head classes, the same spin classes, what will happen the 19 year old with the slow aromatase. She's the young woman, she's the roommate. She gets that straight to thigh muscle. She is the roommate that doesn't have any evidence of cellulite, which is really just a fact that position phenomenon, what's some other confounding factors. Her roommate eats as clean as she does. Who exercises every bit, as much as she does, who has the same caloric intake sleeps in the same room and so on and so forth. She just not truly why, because herself,

Speaker 4 (00:36:49):
As opposed to the first roommate

Speaker 1 (00:36:50):
Is being bathed in more estrogen with each menstrual cycle. So her cells now activate the estrogen features the estrogen genes and what do estrogens gene do? They promote fat that position.

Speaker 4 (00:37:07):
They sometimes they will lower the metabolic rate of the body. So we begin to see by just one gene interpreting it.

Speaker 1 (00:37:16):
We actually, as you so beautifully noted, Stephanie, we begin to be able to predict the body dimorphic differences between roommate one and roommate two. Now let's per where we will go with this definite let's upgrade that you see before the 1981 gene, that aromatase gene that was converting to start strolling into estrogens. There is another gene, a completely unrelated gene, different gene, but related to the pathway, this gene is the CIP 17, a one gene and notice audience CYP. The first theme was Cipla 1981. This gene different gene, 1781. What you can infer from this, this, these genes belong to the same family. And these family of genes are radically important in our hormone metabolism

Speaker 4 (00:38:11):
Equally important in pharmaceutic metabolism. Many of the drugs

Speaker 1 (00:38:14):
That you take, medications that you might take in your lifetime are metabolized by these genes. So now we go, before we get to estrogens, we just said since 1981,

Speaker 4 (00:38:26):
Aromatase calibrates testosterone

Speaker 1 (00:38:28):
And to estrogen aroma ties us to Stastrom Adestra. But how do you get to start strong? You get to start strong. And by the way, the other androgens, and one of the other androgens understand Dion and Justine DOL D H E a and testosterone. These four primary androgens are made from none other than progesterone. And that's why the word progesterone is it in the sub. It is the progenitor. It is the cursor to all of them. We are the sex hormones. So we make progesterone from cholesterol. There's another word, that thing. Oh my God. The bad cholesterol. Well, actually we need cholesterol. She's the mother, she's the mother of all the farms and frankly many other hormones, right? So we take that cholesterol. Okay. Step number one, we make progesterone with it. Once we make that progesterone 17, a one convert, that's the instruction. That's the gene that makes the enzyme self names of 1781 enzyme that will convert progesterone into testosterone.

Speaker 1 (00:39:40):
Okay? And the other androgens that gene comes in different versions. There is a factor last version of thought, Jean, I'm a slow version of that gene. Now let's go back to those two roommates and let's keep it somewhat stark because by the way, these combination topic. So let's go to the roommate who had the Bruno aromatase. She converts her to Stastrom into estrogen, slower. She preserves purchase stops. And she simultaneously has fast sip 1781, which means she converts her progesterone into testosterone with the best of them. So now this young woman, she is making testosterone every monthly cycle and the circadian rhythm of the cycle. Right? And let's pause there for a moment, Stephanie, again, something that so many of our audience members don't know or miss them, it's understanding that is perpetuated sometimes even by clinicians, that the female body, if you've got an average healthy young woman, who's not on the pill who is menstruating, what she needs to know is I, she meant, she goes through her cycle of let's say, give or take 28 days on day eight of her cycle.

Speaker 1 (00:41:01):
The level of estrogens in her body are not the same as day 15 or day 22 or, or day 28. For that matter, equivalently, her progesterone levels are not the same equivalently. Her to stop. Estrogen levels are not the same. So there is a suitcase rhythm as a young woman goes through starting the cycle day one, when she first bleeds, when she first has her menses, usually let's say seven ish days. Then by day eight, she stopped her menses. She now goes in, she's no longer quote-unquote. And now she's day eight day nine day 10. During these days, her estrogen levels start to slowly increase. Then they come back down

Speaker 4 (00:41:43):
Worsley testosterone and progesterone. So the first thing to view

Speaker 1 (00:41:47):
The listener has to understand at any

Speaker 4 (00:41:49):
Given point in your circadian

Speaker 1 (00:41:51):
Rhythm, literally the sounds

Speaker 4 (00:41:55):
In your body, when you understood what we

Speaker 1 (00:41:57):
Said earlier, that your cells respond to these hormones by cues,

Speaker 4 (00:42:03):
Gene expression, the testosterone gene expression, versus the estrogen to the gene expression versus the progesterone gene expression.

Speaker 1 (00:42:12):
Or we should say the progesterone gene expression, the precursor.

Speaker 4 (00:42:17):
This is the testosterone that which comes second versus the estrogens that

Speaker 1 (00:42:23):
A female body that is menstruating healthfully literally is a body that is actually genetically gene expression variations in her cycle, secondary to the changes of her hormones.

Speaker 4 (00:42:39):
Beautiful and so profound to understand that. So we now go back to that first roommate. She's got the fast 1781. So when she makes progesterone, she's converting her progesterone into,

Speaker 1 (00:42:52):
With the best of them. And by the way, when she makes her testosterone, she does not convert it into estrogens very quickly. Now we

Speaker 4 (00:43:00):
Get an even greater sense

Speaker 1 (00:43:03):
Of her androgen ization. Now we look at this young woman and we know

Speaker 4 (00:43:07):
She's going to start having, especially to the degree that she eats well, and she's in the gym. She's going to have that triathlon stick title,

Speaker 1 (00:43:15):
Smaller breasted, longer lean muscle groups. You know her roommate. Now she had

Speaker 4 (00:43:24):
1781. She's not converting her progesterones into androgens to start strong. As quickly as

Speaker 1 (00:43:29):
Her partner, she does

Speaker 4 (00:43:31):
Going to hurt your testosterone to estrogen is much faster. So her to stop

Speaker 1 (00:43:35):
Do not stay in the body for

Speaker 4 (00:43:38):
A long period of time. They quickly

Speaker 1 (00:43:40):
Get your cert into estrogens, which means

Speaker 4 (00:43:43):
Her cells of her body, her muscle cells, the back of her thighs, her chest cells,

Speaker 1 (00:43:49):
Themselves, all of herself. They don't get as much bathing into testosterone

Speaker 4 (00:43:55):
Infrastructure. So they do not have as much originizing that leanness that muscular must do the narrative. That is a beautiful counterbalance with the femininity.

Speaker 1 (00:44:06):
See if the body, as much as her, more or less than her roommate, just these two things,

Speaker 4 (00:44:12):
Jeans. And let's now captain we'll get into a really important parts of the matter coming next, which is aware. I know you want to go to Stephanie,

Speaker 1 (00:44:18):
But let's cap the androgen discussion. You see now, Stephanie taking again, those same two roommates after we made the testosterone, which we said one was doing faster than the other. There's another gene in this cascade, the steroid five alpha reductase gene. What does this gene do? And all women have these genes. All of you have them. Men have them too. This gene is responsible just as much

Speaker 4 (00:44:46):
Aromatase, 1981. It's taking

Speaker 1 (00:44:49):
The testosterone and converting it into estrogen. [inaudible]

Speaker 4 (00:44:54):
That's taking the testosterone

Speaker 1 (00:44:56):
And upgrading not to Stastrom DHT dihydrotestosterone. One ladies out there. One molecule of DHT is worth 10 molecules of tea. One molecule of dihydrotestosterone causes your cells to behave in an organized manner. Six to 10 times more than even the testosterone. Well that SRD five 82 gene, which you all have comes in different versions. There's a,

Speaker 4 (00:45:25):
A high potency version of that gene. There's a little activity version of that gene.

Speaker 1 (00:45:31):
And there's a medium activity version of that. Gene. Let's apply this to the two roommates and let's keep it extreme. And the extremes happen just so that you can see the clarity of this. So we go back to the female, the 19 year old, who's already trending more denies. Why is she trying to modernize? Because she makes the star store the best of them. She holds onto her testosterone, the best of it. And she's making, she's a beautiful young woman. She's a gorgeous young woman, but she's not making near as much estrogens. Her body is not being bathed. All things equally they're, neither of them are on the pill there. Her body's not being bathed at near as much estrogen as her roommate. Now in that same young woman, she's

Speaker 4 (00:46:14):
Got the more potent version

Speaker 1 (00:46:16):
Of the SRD, five 82. So now let's line this up three things. She makes testosterone with the best of them. She does not make the estrogens near as quickly. And by the way, when she made the testosterone, she's pulling more quickly. Some of that testosterone into the virulent GHG, she now upgrades. She's the young woman she'll make most men blush. When we look at her abs, she's going to be that young woman. That's got that six pack, eight pack. She's got the obliques going on. She's got thighs will make me blush striated muscles, triceps. She's going to have a musculature. And she's going to have that beautiful [inaudible] female body with less of the external female characteristics of the rounding at the hips. She's not going to have any cellulite. We can bet your bottom dollar and not because of the type of muscle fibers she has at the back of her thighs.

Speaker 1 (00:47:14):
Her counterpart, her roommate has the slow version of SRD [inaudible]. So again, everything about her genetics pushes her this at this point in time, Stephanie as well, we can say roommate, number one is Andrew dominant for all of the reasons we just described. And roommate number two is Astro dominant for all of the reasons that we've described. And I'm going to pause there, Stephanie, if there's any clarification that you want, because next, what we're going to do is we're going to talk about, okay, once we've made the seminal hormones and it's impacted our bodies in the way that we've described, what does the body then do with these hormones and their consequences based on what we do with the hormones?

Dr. Stephanie (00:47:59):
Yeah, no, you're doing a fabulous job of explaining it. I have, you know, the only thing I would say is, as you are describing the morphology, so the stride and muscles, the no cellulite clinically for, and there are a lot of clinicians that listen to this podcast, you might also see, you know, thinning of the hair around the temples, you know, the mass utilization, like the, the thicker hair, uh, through the chin and not just like hair on the chin, like thick beard, like hair, right on the chest, that kind of thing. And then as she gets older, if she tends to, if she started to put on weight, she might put weight on, in a more male way. So in, through the, you know, the central, that centralized obesity through the tummy. Yes,

Speaker 1 (00:48:38):
Yes, absolutely. Because the body now is behaving in a more underutilized fashion. The cells of her body that are capable of responding to both testosterone, androgens signals, as well as estrogen estrogen, as you see the female body has the ability to polarize to have both androgen signal development, as well as estrogen signal, the male body has the same. Now all things equal. The male body is designed to respond more to the androgen signals, less to the estrogen signals, the female body vice versa, but both body types vote sexist. And obviously we understand that there's things in between, but both general body types are going to respond accordingly. So as you've just noted what we see in the Andra dominant female back when she was in university, she was a soccer player, the triathlete, she can, you know, all of the things that we can describe about her, but when she gets a little older, she, you know, she wasn't watching her diet as much.

Speaker 1 (00:49:36):
And if she starts to put weight on, she'll put weight on, in the more meal, like feature, you know, how many meals do we see? They can still walk around with skinny legs, you know, and whatever, but a big gut, they're not putting it on. They're not packing it on in the bum or the face. That's an Andrew Andrew imprinting because of how the abdominal fat cells respond when it comes to waking. And so that female that is Andrew dominant for the genetic characteristics that we've just spoken up, we'll have that type of morphology behavior, but also Stephanie. And we'll get into a little bit more of this nuance and finesse. When we get into the metabolism of the hormones, these two young women can also experience differences to the length, clarity of unsecured and rhythm of hormone cycles.

Speaker 4 (00:50:28):
That more [inaudible]

Speaker 1 (00:50:30):
Where she's not creating and converting her androgens and estrogens because her rheumatism ration is lower to say nothing of the fact that she was also more Andrew dominant for all of the reasons we said, she may, for example, start to experience irregularity to her cycles. And that irregularity is exacerbated much more easily. If she were to become very athletic, how many female athletes now look, look, here's the, which comes first, the chicken or the egg, many things.

Speaker 4 (00:51:04):
They're female athletes. And of course, depending on the sport,

Speaker 1 (00:51:07):
Because they had a more organized genetic cascade as per what we've just described and mind you then because of the stresses and the physical exertion in their bodies, which accentuates me uninjured

Speaker 4 (00:51:25):
[inaudible] of the body, and which creates a quarter

Speaker 1 (00:51:28):
So imbalanced to the body, which therefore creates a progesterone imbalance, which therefore further androgens the body. How many female athletes, elite female athletes miss their monthly cycles altogether. Why? Because their cycle now has lost the crisp of

Speaker 4 (00:51:47):
The peaks and valleys of progesterones,

Speaker 1 (00:51:50):
Androgens, and estrogens, which you need the peak of estrogen. And then it coming down to trigger ovulation and to trigger menses when we begin to not flatten. But when we do

Speaker 4 (00:52:04):
To reduce those peaks and valleys, pushing everything more towards androgen ization, we do not get the circadian triggers that lead to ovulation

Speaker 1 (00:52:16):
And menses in those elite female athletes that are already under the knife. And they're very lifestyle under devices. Then further case in point, the flip of this, the young women that are by nature, much more estrogen because of the estrogen dominance in their body. They may see other menstrual cycle, uh, variances. They may be the young woman that particularly the first

Speaker 4 (00:52:45):
Group of young women, we tend to find missing

Speaker 1 (00:52:47):
Cycles. We tend to find, especially based on lifestyle choices, they just make mistakes cycles. They may be very light. They may not follow a seclusion rhythm that is as clearly defined. That's your Andra dominant cycle. All things equal your

Speaker 4 (00:53:02):
Dominant cycle. They may have cycles

Speaker 1 (00:53:04):
Like clockwork, but they may start noticing that if especially, if they do not do something about extreme estrogen dominance, they start spotting a cool

Speaker 4 (00:53:16):
Five, seven days before their real

Speaker 1 (00:53:18):
Cycle. Why? Because the clarity between their estrogen versus projesterone projesterone that you need enough enough

Speaker 4 (00:53:28):
For dominance is quickly going from progesterone to testosterone, to estrogen. You're therefore losing a different

Speaker 1 (00:53:35):
Type of clarity versus the Andrew dominant woman. She does not have enough progesterone to maintain the clarity of the uterus

Speaker 4 (00:53:44):
Lining to maintain the integrity of the uterine lining. So she starts spotting. She starts getting some cellulous stuffing earlier, even before her real menses kicks in. So just by looking at this level,

Speaker 1 (00:53:58):
Want to go deeper for all of the listeners out there, just at this level, as Dr. Esteem has pointed out, we can infer body morphology. We,

Speaker 4 (00:54:08):
And for things like behavioral tends to see tendencies proclivities, to anxiety, proclivities to the concepts of PMs reside, largely what we've just said. And some of what we're about

Speaker 1 (00:54:20):
To say, so we can define

Speaker 4 (00:54:22):
Mythology and we can define what is happening right

Speaker 1 (00:54:25):
In that female cycle. And one last point here is Stephanie.

Speaker 4 (00:54:30):
Imagine then when we take that ultra underutilized female per every genetic factor that

Speaker 1 (00:54:35):
We just said, and then we put

Speaker 4 (00:54:37):
Her on the pill. In fact, let's take both roommates. So they're now 19 years old, they're off on their own they're at university.

Speaker 1 (00:54:44):
And for the first time in their lives, they're both going to go on the pill. And so they go to the campus clinician who, after speaking to them, knowing their roommates, everything else puts them on the same plan. And this particular same pill happens to be a slightly heavy dose, higher dose estrogen pill. The young woman who was already estrogen dominant her

Speaker 4 (00:55:05):
Going on that estrogenized

Speaker 1 (00:55:07):
Protocol, it will help, and it can have certain changes in her body. But what about that? Under dominant female

Speaker 4 (00:55:15):
At the time she was 11 or 12 to the time she's 19, those seven years, her body was not at all anywhere close to being bathed in the levels of estrogens. And by the window,

Speaker 1 (00:55:26):
The pill, this particular pill she's on estrogens

Speaker 4 (00:55:30):
For about the seven days between days 12.

Speaker 1 (00:55:35):
And, you know, Dave 19, give or take she's on an estrogen exposure for 21 days of her cycle. What do you think her body that was not seeing

Speaker 4 (00:55:46):
That level of estrogens and therefore herself were not behaving cells were behaving in a more

Speaker 1 (00:55:52):
Wonder feature phenotype. What is going on?

Speaker 4 (00:55:55):
What happened to her body and how might her body respond when she's put on that pill? So the point here before we go further is as Dr. Steamers

Speaker 1 (00:56:03):
Pointed out, we can infer morphology. We can infer cycle differences

Speaker 4 (00:56:08):
In cycle, normal season, certain

Speaker 1 (00:56:10):
Dysfunctions. We can infer how the body might respond, depending on the birth control of choice. These are profound things, and they become even more profound. Stephanie, when we go to the next level, which is where we're now, and I would also say like

Dr. Stephanie (00:56:24):
Mood and behavior as well, you might be able to, like you had said, you'd mentioned anxiety, like their tendency towards depression or anxiety as well. Can we can also loosely and for that as well,

Speaker 1 (00:56:33):
Loosely. And we're, we're actually understanding more and more that the brain is radically impacted by both androgens and estrogens or neurons. The cells in our brain have those receptors that allow androgens and estrogens to get into them. And what we're going to see next is oftentimes Stephanie, it's not just the primordial sex hormone, the, the testosterone or the estrogen. It is what comes from the testosterone Astrodome in this case in young woman, particularly, what's going to come from the estrogens, which is what we're going to go now. Yeah.

Dr. Stephanie (00:57:12):
So let's, let's go there. So when we talk about estrogens, you know, often people will say, people will say, did you mean to put an S at the end of estrogen? Like, is it estrogens? It's like, yes, there are three different types of estrogens. And of course there are, you know, different metabolic pathways, different metabolites that can come from, um, estrogen metabolism. So let's, let's talk about these, not one but three hormones. And let's talk about the hydroxylation or let's talk about the, let's talk about phase one of estrogen metabolism, which is to say, um, we are high, we're adding a hydroxy group. We're talking about the two Oh eight pathway, the four Oh H pathway, the 16, uh, OAG pathway. And we can talk about each of those different genetic predispositions, which each with each of those genes as well.

Speaker 1 (00:58:00):
Absolutely. And brilliant interlude and segue into this. So let's remind our audience that we're going to be talking about estrogens. So we're going to be talking about those molecules that can bind the estrogen receptor. And it is when the estrogen receptor is bound by the estrogen. Then that cells that express the estrogen receptor will begin to change its gene expression indicative of an Astro Tonies behavior. And why am I stressing this? Because this is where ladies and men out there, molecules that are not what we would call native estrogens, could the root of things like soy derivatives, things like the relatives of plastics are IE, the water that you drink. That's been sitting in that plastic bottle, not all plastics, but particularly the softer plastics that had been sitting in the car. One of my pet peeves is when I see my kids leave a water bottle sitting on the side door of the car, sitting in the sun, and then I tell them, throw that thing away. Don't drink that water because these, you know, Oh my gosh, you know, I'm a foodie and I love food logs. Stephanie, the food log is one of my little pet things. When I do take a little break, I might look at a food blog and I am amazed Stephanie, certain parts of the world that food is served in plastic bags and hot piping food

Speaker 4 (00:59:22):
App that, that has been served in plastic bags.

Speaker 1 (00:59:25):
Oh my goodness, what are we doing? You know, those foods are being exposed. What is the point here? The point is beyond that,

Speaker 4 (00:59:34):
Well, native estrogens, there are different molecules. That's where the concept of soy estrogen comes in. Either phytoestrogen Xeno,

Speaker 1 (00:59:43):
Estrogen molecules can bind to the estrogen receptor. In fact, some of these molecules can, out-compete the native estrogen to bind to the receptor. And remember, that's the key. The key is not the hormone itself. The key is what is binding to the receptor. That's the key because when the receptor is bound to that is

Speaker 4 (01:00:07):
What initiates the epigenetic cascade

Speaker 1 (01:00:09):
That leads to the gene expression changes.

Speaker 4 (01:00:13):
It leads to the Sunday, the behavioral changes that leads to cell death,

Speaker 1 (01:00:18):
More androgens or estrogen. Once we got that concept, Claire, now we get into the estrogen. So there are three primary native estrogens Astra dial, which is oftentimes shorthanded E to a stroke dial as Strohn shorthanded E one. And as trial's shorthanded, [inaudible] now the S trial is an estrogen that you usually

Speaker 4 (01:00:47):
Predominantly it's the more primary it's the more predominant

Speaker 1 (01:00:50):
Ladies when you're pregnant for this for the nine months that you're pregnant. That's the estrogen. That will be the prevailing as to cause notice, you know, having a monthly cycle while you're pregnant. And so it's the Astra dark trial that is the predominant pregnancy estrogen in your menstruating years, the two primary predominant estrogens are extra dial and a strong [inaudible] for further clarification. As ladies, as you got a little older, you will tend to find that your Astrovan becomes a bit more predominant. And so you go from being estrogen dominant to astronomy,

Speaker 4 (01:01:29):
As you get a bit older. And remember when you're pregnant,

Speaker 1 (01:01:32):
You become transiently as trial dominant. Okay. Now, why is this

Speaker 4 (01:01:36):
Important keeping in mind that all three

Speaker 1 (01:01:39):
Hormones and mind you, the mimics

Speaker 4 (01:01:41):
Of those horrible Xeno estrogens phytoestrogen

Speaker 1 (01:01:44):
Combine the receptor and it is the

Speaker 4 (01:01:47):
Binding to the receptor. That really matters.

Speaker 1 (01:01:50):
Okay, lady.

Speaker 4 (01:01:52):
No, we said that we convert. And so as Dr. Steamer, so brilliantly queued this, so now you understand that is a strategy

Speaker 1 (01:02:00):
With an S three primary estrogens for clarity, all the estrogens

Speaker 4 (01:02:07):
Juice from androgens by that same sip, 1981 aromatase. So we aroma ties understanding

Speaker 1 (01:02:15):
Dion into a stroke. We aromatase testosterone into estradiol, same gene, same enzyme, two different, slightly different androgens going into two slightly different estrogens. And the only difference quote-unquote in these two estrogens as strong versus Astrodome, because let's focus on that. Now that's going to be the primary, other than the transient estradiol, the estrogen versus estrodiol. What are the differences? There are slight differences in the ability to bind to the receptor, which is the key. So to the degree, to which a strong versus estrodial binds to the receptor is the degree to which it causes the cellular feminization estrogen at the cell. That's the first, and then the other differences, the differences in their levels. As we age, as we, as younger menstruating, women tend to be more estrodiol dominant versus Esther. And as they get older, a switcheroo happens where we go from estradiol to astrology.

Speaker 1 (01:03:18):
Okay. Now, when we take extra dials, we're going to put aside as trial for the time being okay, that's your pregnancy, estrogen, all things equal. Now let's ask the question. We've got the extra dial. We've got the estrogen. There's a ratio of it in any given young woman who's menstruating. And we're going to ask, she's just made it, has she made lots of it? Is she Astra dominant? Has she made comparatively left of it? Is she under dominant? I E the examples of the two roommates that we've been discussing. So now those two roommates, the clearly under dominant one and the clearly Astro dominant one, they now go in ticket prepared for their cycle. They're getting into that seven, five to seven days prior to the onset of their medicines. The body has determined that this point in time that we're not pregnant, we did not.

Speaker 1 (01:04:11):
We did not fertilize that egg that was released at the point of our relation earlier in the cycle. So the body is determine, now pregnancy has not occurred. We've not fertilized the ag. So what has to happen? We need to get rid of the estrogens. Are you the estrogen, estradiol and estrone that had been previously made because ladies you're menstruating month that you in right now, the estrogen is in your body. In this menstruating month that are causing your body to behave in all the beautiful ways that it's behaving. And sometimes not. So beautiful ways are completely different than the estrogens that you produced in your previous menstruating months. You make them, you use them, are you, it impacts the body by binding to the receptor. And then you get rid of them. When are you getting rid of them? When are you metabolizing them?

Speaker 1 (01:05:02):
You metabolize them. Once the body has realized that the pregnancy has not occurred in those days, leading up to your actual lenses into your menses. So now at this point in time, the female body says, there's no pregnancy. I'm going to men. I'm going to metabolize my estrogen. There are three primary pathways, three genes making three enzymes that will, tabelized your estrogens into three distinct estrogen byproducts. So I want the ladies out there to think of that in a very pedestrian way, but it's, it's something you'll never forget during your marriage. Well cycle, you filled up about a little with estrogens. You filled up your estrogen reservoir during your menstrual cycle, you filled up an Australian resident as your cycle was going on. Now you've got to empty that reservoir. This reservoir, this, this barrel has three facets at the bottom of the barrel and getting into in the days, leading up to your medicine, your body will turn on these genes, epigenetic on the genes that were not turned on previously or not turned on to the level that they are because you don't metabolize yesterday.

Speaker 1 (01:06:20):
So we know the turn on these three genes. What are the three genes or three sets of genes? The first set of genes are what we call one 80 and one, a one sip, one 82 and sip one, a one there again. Part of that big, beautiful family of the cytochrome, P four 50 genes. These two genes, the one 81 and one 82 are the two genes that make the two lines that will metabolize your extra dial and a stroke into the two. An estrogen metabolite called two hydrogens, the estrogen to hydroxy estrogen. All it is is we took an estrogen molecule. These two enzymes metabolize them. And now you have a different, you have a metabolite called two hydroxy estrogen. It is what is it universally referred to as the desirable estrogen, metabolite? Why is it desirable? Well, why is the body metabolize? Do you want, you have to ask is why is the body metabolizing the estrogen in the first place?

Speaker 1 (01:07:22):
We're metabolizing the estrogen because so long since that estrogen was in the body, it's binding the estrogen receptor. And so long since the estrogen receptor is being bound, we are altering gene expression in a way that is unique to when that receptor is being bound. And the female body was not designed to have them. The estrogen receptor turned on 24, seven yeah, 30 days a month, 365 days a year. Your body was designed for the cells to have gene expression secondary to the activation of the ER, the estrogen receptor secondary to just a window within your cycle. This is a profound concept, Dr. Steam, when it comes to, when we go on the pill for prolonged periods of time, because when we go on the pill, assuming it's a 21 cycle pill. And now, by the way, as you know, there are certain

Speaker 4 (01:08:23):
Times where young women are being put without even

Speaker 1 (01:08:25):
A break, right? So they, they are on an estrogen 365 days a year, year after year, their cells,

Speaker 4 (01:08:35):
The estrogen receptors are being

Speaker 1 (01:08:37):
Activated every single day, causing the gene expression that is associated with that, which any normal cycle that cell

Speaker 4 (01:08:46):
And the behavior secondary to the gene expression, secondary to the activation of the extra and receptor was only secondary to estrogens for about seven, 10 days of the year.

Speaker 1 (01:08:58):
No. So we wanted to metabolize the estrogen to stop it. We want to

Speaker 4 (01:09:04):
Stop this estrogen from binding the estrogen receptor. So as to give the female cells,

Speaker 1 (01:09:11):
It's a break from that estrogen receptor gene expression. I'm stressing this for a really important purpose here because when we

Speaker 4 (01:09:22):
Metabolize estrogen into two hydroxy

Speaker 1 (01:09:24):
Estrogen that occurs two hydroxy. Estrogen has a very, very weak affinity for the estrogen receptor. So it basically is exactly what we want it to happen. We took the estrogen, we turned it into two hydroxy yesterday. The two hydrogens

Speaker 4 (01:09:42):
No longer binds the estrogen receptor zero out the body of the estrogen

Speaker 1 (01:09:47):
Response. Good. We've accomplished our task. However, another Jean sip one B one sip, one Bravo, one that another member of this amazing family it's

Speaker 4 (01:10:01):
Mobilizes your estrodiol. And you're strong into a different metabolite of estrogen known as full hydroxy

Speaker 1 (01:10:09):
Estrogen. Okay? And by the way, as Dr. Steamer has pointed out you,

Speaker 4 (01:10:14):
The tribalism going on, you're taking estrogen and these G and these enzymes

Speaker 1 (01:10:18):
Tagging a hydroxy group. That's why it's called two hydroxy, depending on where we stick this hydroxy group. If we stuck it out a particular place on the two, that's called two hydroxy yesterday. If we stuck the same hydroxy group, but in a different place of the estrogen, that's called full hydroxy. And just by virtue of sticking that hydroxy group, because of the SIPP, one B one gene, which we all have by sticking

Speaker 4 (01:10:44):
It to the slightly different place on the estrogen

Speaker 1 (01:10:46):
Molecule four hydroxy, estrogen retains its ability to bind the estrogen receptor. So now let's pause there. We will metabolizing the estrogen to stop

Speaker 4 (01:11:01):
It from binding to the estrogen receptor.

Speaker 1 (01:11:03):
And yet, despite doing what I just did metabolizing it, my metabolite four hydroxy, estrogen retains the ability to bind the estrogen receptor cause us to organization of the body. That's not what we wanted. We wanted to give the body a break. So herein lies the first fundamental difference between the metabolism of estrogens, the two hydroxy, estrogen, and four hydroxy, estrogen. And ladies, if you understood that all of the ladies out there now comes the genetics of it. You see [inaudible] [inaudible] gene combo. Those genes come in different versions, fast or slow and radically important. The sip one B one gene, that gene that is metabolizing your estrogens into what we call the naughtier. The more toxic, why do we call four hydroxy estrogen? The more toxic estrogen metabolite, because it continues to bind the estrogen receptor. It continues to induce estrogen ization at a time in your circadian rhythm, where you did not want that estrogen utilization stat.

Speaker 1 (01:12:15):
Number one. And so of course, ladies, if those two roommates, the roommate, now we're going to add something here, both roommates, the androgen dominant roommate and the estrogen dominant roommate, both of them have the faster I E undesirable version of sip. One B one. So that gene Cruz, whose kind of quirky job, we don't know why it's there because its job is converting estrogen into that naughty tablet on ladies. We all have them, but you don't know until you do your genetics, your intelligent genetics. You don't know if you have the slow version, which is what you want. All things equal, all the fast version, which would make you have genetically. And remember, this is beyond that the genetics at this point, it means that the version of your sip, one B one enzyme, that version is faster or slower at making four hydroxy estrogen.

Speaker 1 (01:13:17):
Now let's quickly go back to the under dominant roommate versus the estrogen Rubik, the dominant roommate for every reason that she's under dominant. For every reason that she's not producing a lot of estrogens in the first place, her fast sip, one B one does not negatively impact her very much because she's not really making a lot of estrogens. Therefore she's not making a lot of four hydroxy estrogen, therefore this phenomena of the toxic four hydroxy estrogen, and let's pause there very quickly. Four hydroxy estrogen compared to two hydroxy. Estrogen is not just toxic because of its proclivity to bind to the estrogen receptor. It's also toxic because four hydroxy, estrogen decomposes into these compounds that ultimately lead to oxidative stress in the body. So ladies out there listening to this, you're going to take your estrogens. And by the way, so that it's clear. I read young woman takes her estrogens, make some two hydroxy and some four hydroxy.

Speaker 1 (01:14:26):
Every young woman will make both, but depending on your genetics and depending on epigenetics, you are going to make either more to hydroxy, which is a good thing or more four hydroxy by ratio, which is not as desirable. And if you will making more four hydroxy estrogen your body during the spirit of estrogen metabolism, which is the period leading up to your menses, which is the period of PMs premenstrual syndrome. What is premenstrual syndrome? Premenstrual syndrome is the impact on cellular behavior. Head to toe of the female body cells, experiencing gene expression, secondary to the activation of the estrogen receptor. Second,

Speaker 5 (01:15:17):
Whether you are making more or less than that,

Speaker 1 (01:15:20):
Four hydroxy estrogen, more or less than desirable, oxidative stress on the body. And that oxidation, if you were making too much for hydroxy estrogen, and you will not clear enough, four hydroxy estrogen, which we'll come to next, your body will then be overly oxidized, which is an overly inflammatory state. And which cells of the body are, are, are affected by this over oxygen. Oxygenation, oxygen oxidation, sorry, not oxygenation oxygenation. The cells that are the most estrogen receptor, the lining of the uterine membrane, the lining the breast tissue cells, neural cells. So those are the cells that skin, the cells they lose are the cells that have the most estrogen receptors, therefore engulfing the naughty four hydroxy estrogen more and becoming more estrogen and more oxidized. Those are the tissues in PMs, the increased cramping, the increased clotting, the increased neural responsive to the, the, the anxiety edgy causing effects of the four hydroxy estrone and so on and so forth. And the

Speaker 5 (01:16:35):
10 and the 10, the breast

Speaker 1 (01:16:38):
Is sometimes a bit more fibrosis to the rest of that increased risk and increased risk of formation in the body as screw dominance and Astra toxic dominance is strongly associated with CIS developments in the bottom of breast cysts. Uh, just actually Fisk, generally speaking, period. It's more so suited, but fibroid development endometriosis because these tissues when constantly cycle after cycle month after month, year after year in those delicate days prior to menses, they're getting bathe in that higher toxicity, four hydroxy estrogen. We create an environment of circadian chronic inflammation in those tissues, which begin to manifest over time. Again, depending on other factors of lifestyle, environments and nutrition. So now we come back to the scenario of the two young women, the Andrew dominant female, she has the faster, both of them have the, let's say less desirable, fastest one B one, both of them convert their estrogens into the four hydroxy estrogen.

Speaker 1 (01:17:47):
That's a rate that we probably wouldn't want, but because the Andrew dominant female, isn't making as much estrogen as to begin with. She never really notices this slightly naughty pathway that she's predisposed to until she goes on the towel. Now, when the predominant young woman goes on the pill, remember we give a little hint earlier that these two young women, they were put on the same pill, but their bodies do not respond as equally because now what we do in the under dominant female, when we partner on that pill, we are basically uncovering. We are basically pulling away the veil we're we're, we're opening the commode. So to speak to a late term, extra toxicity, extra toxicity issue was predisposed to, but God did not was me giving birth to wasn't happening because of her underdominance. We put her on the pill and we exposed her to circadian research plus estrogens.

Speaker 1 (01:18:49):
And we now uncover that naughty phenomenon. So again, we can start to see how different young women respond differently and how many times that the esteem of you and I be bought. We have patients that go, Oh my God, I went on the pill. And after that first month, I knew it was not for me. My body might be everything just changed because of that radical shift that the body was exposed to in terms of estrogen metabolites. Now here, Dr. Steamer, we need to get into some of the nuances, really cool nuances. You see the sup one 82 toxicity that, that supporting two gene that makes the sip one 82 enzyme that metabolizes estrogens into the healthier two hydroxy estrogen. That is the same. Gene did metabolizes caffeine coffee.

Speaker 1 (01:19:39):
And guess what? When you drink a cup of coffee. So when you got up in the morning and you've slept for eight hours, hopefully we're all getting at least a very good seven hours, if not eight hours of sleep so important in our circadian rhythms, after having slept for eight hours, all things equal, depending on what you ate for dinner, depending on your rooms, environment and toxic exposures and mold, exposures, and so on and so forth. Your sip one 82 gene is dormant. Here's epigenetics. You've got the gene it's dormant and you didn't need to express it. When you go down to the kitchen and you make your first cup of Joe. Once you begin to enjoy that cup of coffee, once caffeine begins to get into your bloodstream and the body sees caffeine in the body, in the bloodstream now churn on the flip one 82 gene, which is the gene needed to metabolize caffeine.

Speaker 1 (01:20:32):
That's an epigenetic phenomenon that caffeine consumption P genetically turned on your sip. One 82 gene. Now mind you, this, according to gene comes in two versions, a fast version of slow version. You're going to turn on the fast version, just as much as you turn on the slow version, but once turned on now, epigenetics no longer is the issue. The issue here is did you turn on a fast acting, supporting too? Or did you turn on a slow acting sick wanting to, okay. That's besides the point, the point here is when you have that cup of Joe Young ladies, and you turn on your sip pony to gene and you turn pony to gene at the time that you need, or you want to be taking your estrogens and taking it down, desirable two hydroxy pathway. It's actually why drinking a cup of coffee, all things equal.

Speaker 1 (01:21:25):
And we're speaking of good quality, you know, mold free coffee. All of the other things that we can talk about the caffeine consumption at healthy levels has been associated with healthy female longitudinal, estrogen health outcomes. Caffeine consumption has been associated lower risk of breast cancer. For example, there are other factors clearly, but just to show you that the caffeine that P genetically initiated disappointing to gene, which is the gene that also initiates the healthy estrogen metabolism. This is really important. Now let's take the same phenomenon, cigarette smoke smoking, or the exposure to smoking. If you're not smoking, your roommates are when you go to a bar or certain other environmental toxins, particularly aerosol, nice toxins, benzene, and so on and so forth. Guess what? Turn on the turn on the sip. One B one gene on FP, genetically, the very gene that you want it to silence that gene, because when [inaudible], which of the estrogen pathways will your body prefer the less desirable for hydroxy pathway?

Speaker 1 (01:22:45):
Okay, let's go a step above that. You cruciferous. Do you know everyone out there mum knew best when she said, eat those broccoli, eat your cruciferous vegetables. Cruciferous vegetables are again assuming organic and not Laden with pesticides and on so on and so forth. Cruciferous vegetables contain ingredients called sulfuric veins. So fewer things make compound called indole three carbinol indole three carbinol makes a compound called them die in the little mini thing. And what is so radically important about them as a compound, as a food derivative, as a nutrient derivative, as a nutraceutical that you could buy, then suppresses the activity P genetically turns off or turns down your aromatase. Them turns down your body's conversion of testosterone into estrogen out. Of course, if you knew that you, when you make estrogens, you knew that you, because you had the fastest step one, B one, you converted estrogens into the toxic drugs yesterday.

Speaker 1 (01:23:58):
We can begin to see why in the hands of a skilled clinician in the hands of a skilled clinician, the likes of Dr. Steamer, the appropriate use of them at the appropriate times in your cycle is so invaluable. This is proven in pharmaceutical clinical trials is so radically beneficial to a subset of women, because what are we doing? We are draining the swamp of some of that estrogen toxicity, beautiful studies that show breast fibrosis and fibrotic breast tissue. Can you be reduced with the consumption of them, cystic development with the consumption of them and so on and so forth. So here without getting into further detail, it's just a highlighter audience that we can now begin to use intelligently intuitively and genetically guided nutraceutical or certain compounds to epi, genetically that cascade in places that we want it to go away from places that we don't want it to go duct testing.

Speaker 1 (01:25:04):
So to conclude at this point in time, Dr. Steamer, what we have, and that was, we have an understanding of what and how estrogen change body behavior and selling the behavior. The different estrogens do this at different rates for different estrogen metabolites, which we can predict based on your genetics will impact selling the behavior in different ways for hydroxy, estrogen, and a more deleterious, some of the behavioral way versus two hydroxy estrogen. We can begin to see now how profound this understanding is. And I'll just end with one quick thing, two quick things, you know, when you make that two hydroxy and four hydroxy estrogen, which we all make all make men and women, but of course the ratio that we make it, the four versus the two will be genetically driven. You have the facet one, be one, you have the slow supporting one, supporting two, that's a genetic phenomenon.

Speaker 1 (01:25:56):
And by the way, P genetically confounded on that because you had the fast support B one, I heard you were a smoker. You turned on that fast gene, and you didn't turn on the one-to-one one 82 carpet, or maybe you did things that turned off the one in one, one 80 public, not a good combination to be turning on the one B one pathway turning off the one-to-one one 82 pathway, very dangerous combination. Okay, well, when you make the two hydroxy and four hydroxy, those two metabolites of estrogen that are extremely polarized in the impact on your body cue comes the job of an Uber. Uber important gene called Colt and an Uber Uber important cellular process called methylation. And what is ComEd particle? Methyl transference. Let's break it down. Cathal methyltransferase. So this is a gene that makes an enzyme that transfers methyl groups on catechols and what are catechols estrogen metabolites.

Speaker 1 (01:27:06):
And by the way, neurochemicals, and that is why neurochemical metabolism, dopamine, nor adrenaline are in the same molecular category as four hydroxy in two hydroxyestrone. They actually belong to the same molecular class of compounds known as particles. And that is why there is such a strong correlation to the metabolism of estrogen, metabolites and behavioral outcomes, because they actually belong to the same category family. Now that comes to gene comes in three versions, a super fast version, a slow version, and a medium version, meaning the speed. The gene makes an enzyme that has three completely different biologic activities, slow, medium, and fast. And the person that has the fast company is doing the methylation. The thing that the calm this 70% faster than the person that has the Slocum, this is not a five, 10% difference. This is a massive difference. Now you will be correct in assuming if you had the fast coms, you are much faster

Speaker 4 (01:28:16):
Metabolizing your estrogen metabolites, including the norm

Speaker 1 (01:28:20):
T4 hydroxy yesterday, when you methalate through coms four hydroxy, estrogen, that molecule that had the ability to still bind to the estrogen receptor that decomposes into these

Speaker 4 (01:28:34):
Naughty compounds, including oxidants.

Speaker 1 (01:28:37):
Okay. When you methalate four hydroxy estrogen, you turn it into four methoxy estrogen for meth up, see estrogen no longer combine the estrogen receptor four method. The astronaut no longer decomposes into oxidants. So you want to methalate believe me. You want to methalate all of your four hydroxy, estrogen, and the efficiency with which you methalate your four hydroxy, estrogen, largely returns to the efficiency of your come to gene, fast, medium, slow. And then there are epigenetic factors that will turn on or turn off your comps. So God forbid, you don't want to have the slowest car gene inherently make the slowest comp ends up. Even when it's turned on, it's doing its job slow. I'll be the woman who has the slow comes, making too much four hydroxy estrogen, and will be the woman that is, has, that has poor antioxidation. Cause that's what the four drops the estrogen is going to do, and be the young woman who is incorporating lifestyle choices, environmental exposures, nutrient choices that are turning on the sip.

Speaker 1 (01:29:53):
One B one making more four hydroxy, estrogen shutting off antioxidative potential or not getting antioxidants in one's diet. I'm turning off the already slow comes. We are going to create an, a young woman just depending on choices that she can make an entirely different monthly cycle outcome of extra toxicity and its consequences versus much more healthy and informed individualized decisions that could radically change that outcome. I've gone on as Dr. Steamable we've covered. I think all of these little nuances to really create the picture of what, in conclusion, how important and intelligent functional genetic understanding is to understand the individuality, any clinician worth their salt understands the individuality of a patient, but sometimes it's befuddled at the individuality. And what function genomics does is it allows us to describe, it allows us to explain and predict that individuality, but sometimes you go, why is she behaving so differently to the same pill? Why is her body behaving so differently to exposures, to dietary choices? These are some of the fundamental contributors

Dr. Stephanie (01:31:14):
That, and, you know, just speaking about morphology with the, with the cob gene, you know, as you had mentioned, it also metabolizes your dopamine and I've often had this sort of theory that, you know, there's either you have the warriors, right? You, if someone, uh, you know, if you have, depending on the speed of your comp, you are gonna, you know, metabolize dopamine very quickly, or very slowly as you talked about the two methoxy, uh, estrogens in the form of Oxy estrogens, or you can metabolize it very quickly. And I often fi you know, I've, I've, I've had conversations sort of offline conversations in the past where I've said, you know, I bet there's like an entrepreneur gene. And I feel like this is sort of a piece of it because the entrepreneur, at least the women that I've worked with and men in the past as well, we are like, okay, where's the next hit? Like they, you know, we climb this mountain and we're like, wow, we did it. Okay, fine. Great. Next, next one. And I think it's because we metabolize dopamine so quickly

Speaker 1 (01:32:07):
On the mentally true, fundamentally true. And it's not just a dopamine, Stephanie, just to dopamine and no adrenaline, both of these counter balancing neurochemicals are metabolized by the same joke. I mean, and you hit it on the head. Actually, Stephanie, when the com gene was discovered, the very first article, the peer reviewed article called it the warrior, w a R R I O R versus worrier, w O R R I E R G. It's actually called the warrior warrior gene. Because if you've got the fast version of this gene, you claim your noradrenaline much faster, which of course is the anxiety irksome causing worry causing neurochemicals. You also clear your dopamine much faster. So what happens? These are individuals. They tend to have thicker skins. They tend to be more risk-taking because the fear doesn't bother them. They tend to need the next hit because their dopamine does not stay there. They don't stay in Lala land for very long, right? Classic entrepreneurial spirit of the serial entrepreneur actually holds psychology textbooks have been written about this gene and its impact in personality. But now for our viewers, I hope you can see that there's a very intimate dovetail between behavioral, emotional resilience and capacity and response compared to your homeowner sex hormonal circadian cycle. It's very intimately linked.

Dr. Stephanie (01:33:34):
This has just been a masterclass on hormone metabolism. I know that my audience is going to eat this all up. And like I said, one of the things I appreciate most about the DNA company and the results that you get are actionable items. So if, you know, for example, that you have a predisposition to favor that four hydroxy estrogen pathway, then we can bring in epigenetic. Uh, you know, you'd mentioned caffeine, like maybe we can bring in caffeine at certain times of the month to, to drive that two methoxy estrogen pathway. Maybe we can start using dim in a strategic way to help drive that phase. One of estrogen metabolism towards that two hydroxy estrogen pathway. There's so many nuances and you can look at the, as you said, like the individuality of it. So this has just been absolutely phenomenal. Um, I, uh, ha I would love for you to tell our listeners where they can find, you know, this is we're, you're a Canadian company, but I know that you do work. You do do work in the States as well. Like if there's

Speaker 1 (01:34:39):
Internationally, but we have a strong in fact, a very, very strong position and base in the U S so we service clients from all over the world, primarily Canadian and us clients as equally as seamlessly one to the next.

Dr. Stephanie (01:34:51):
Right. And it's just a, it's just a mailer, right? You may have like, there's a kit that's mailed to your home. You sort of spit in a, and then you, and then you send it back. So it's not, you know, you don't have to go to a lab. You don't have to have blood drawn. It's very, it's very, very simple. I've had it done. I've had it done on my kids. Um, my partner, you know, so we sorta, we really do, uh, endorse, uh, your company and some of the work that you're doing. Yeah.

Speaker 1 (01:35:14):
And for our us citizens and our U S U S clients out there, Stephanie, our kits is FDA approved. So, uh, and it's a saliva kit. So in other words, it's approved for the collection of saliva. And once you forgive the grossness of it, once you spit in the tube, it's a spit tube. Your sample is stable. So for it's is real. It's literally as easy as spitting in a tube, putting it in the mail that comes back to us within, you know, three to four weeks. We have, once we've received your sample, we've processed your sample. We've done the analysis that Stephanie and I have just discussed. And that's just the tip of the tip of the iceberg. Um, we do all the different pathways. So we could meet again to end where we started. Everything we do is to define this intelligent functionality.

Speaker 1 (01:36:00):
We're not here to tell you whether you're going to be a unibrow or not, but we are here to tell you, you know, do you have this predisposition? Are you that young woman without realizing it going about life, going about your choices that didn't realize that month after month after month, you have this increased predisposition of either Astro dominance. We feel without extra toxicity, the oxidative damage that you are ill-equipped to handle. And that by again, being vastly informed with the intelligent cooperation of a skilled clinician, the type of nutrition changes that you can make. Lifestyle changes, that you can make an environment, environmental things that you have control of, that you can avoid better the health outcomes in the years to come. They may seem narrow when we start, but multiply these effects 10 years, 15 years, 20 years, we get into menopause. We can have a young woman who can end up in completely different health outcomes in the years to come. This is what we're so passionate and why we're so passionate about this.

Dr. Stephanie (01:37:04):
Very much a monster. It's always a pleasure. Anytime I get to spend time with you is time well invested. And I am looking forward to when you know, things get back to real life to sharing some, uh, some Indian food with you. I remember last time we were filming, we had this great Indians, Fred. It was awesome. So always lovely to see you. And thank you so much. You have really, really brought some just genius. The explanations, I think, are something that everybody's going to be able to grasp on. So thank you very, very much.

Speaker 1 (01:37:33):
Really cool. Thank you, Stephanie, for having me.

Dr. Stephanie (01:37:38):
All right. All right. I hope that you got lots of value from my conversation with Dr. Monsoor definitely a episode that is worth listening to again, so you can save it. If you're listening to it on your phone, you can save it, download it to your, and read, listen to it, take notes maybe next time. And I often find that there are a couple of, couple of episodes we've done where I've needed to listen, really listen to the podcast myself. So I can fully appreciate what the guest is, um, trying to articulate. This is definitely one of them. So save this. And if you have friends that you think might benefit from it, make sure that you share this episode with them as well. So many of us struggle with lifestyle modifications and without a fundamental understanding of our genetic blueprint, it can be difficult to really reap all of the rewards that we might be expecting from those interventions.

Dr. Stephanie (01:38:34):
So subscribe and share and save far and wide. And if you are, uh, so inclined, if you feel like this podcast is bringing you value, please with aid cherry or organic cherry on top, uh, go over to iTunes, leave us a review, or at least a five star rating. That's the easiest one to do. Trust me, my team. And I are always looking for the reviews on iTunes far and wide across the globe. And we would love to shut you out. So if you love the podcast, if you think that this has adding value to your life in any way, I'd love to hear about how and, uh, in the, in the form of a review or if you're too busy, five-star rating would be just as wonderful and just as appreciated. So until next time, my Betty's,

Speaker 2 (01:39:25):
We will see you very soon. I hope you enjoyed today's episode for those of you who want to continue on this week's geeky magic carpet ride with me, visit better show.com forward slash show notes. You'll find research links, summary notes, musing that I prepared in preparation for the podcast. And I often throw in some of my best practices, bonuses, and links. All the juicy bits are in there for you.