Welcome to Pushing The Limits, the show that helps you reach your full potential with your host Lisa Tamati, brought to you by lisatamati.com.

Lisa Tamati: Well, everyone and welcome back to Pushing The Limits this week. I have a really super duper interview coming up. I know we say that but are some of the people I have just blown me away. And this is Dr. Mansoor Mohammed who is coming on the show today, that name may ring a bell because documents or has been on the show, I think three times previous to this occasion. And he is one of my great mentors and teachers. And he's one of the world's leading geneticists, and functional genomic scientists. And it's really, really exciting to be able to work with a caliber of men, like Dr. Mansoor.

Now, today's subject that Dr. Mansoor is going to be talking about is hormones, hormones and your genetic profile in regards to your hormones. We're specifically looking at the female hormone situation today. But what I do want you to know is that the hormones cascade is exactly the same for me. So a lot—while we’re specifically focusing in on the woman today, and we'll probably focus in on the men on another episode. A lot of what we're saying here will be relevant to men too. And just understanding that you need to know about these pathways, the genetic pathways, before you go mucking around with anything hormonal. And also some of the nutriceuticals that you may or may be taking can also interfere with this pathway too. So this information that's going to be coming out to you today is absolute game changer. Really important for me.

I'm on bioidentical hormone replacement therapy, and because I'm going through the menopausal change at the moment, just being transparent. So this information for me has been absolutely crucial because I can tailor my own hormone prescription to my specific genetic needs. And then layering that on with understanding where my bloods are at as well. So it's really really key information. 

If you're a woman who is on the pill, if you're a woman who's got endometriosis, or PCOS. Or if you're a male who's got prostate problems, or if you're a male who's thinking of going on testosterone replacement, all of these things are really, really pertinent to this conversation today. So I don't want you to miss out. Now do stick around to the end of the conversation because Dr. Mansoor has a company called the DNA, a company which actually has DNA reports. So you can get your DNA tested. If after listening to this session, you are curious about what the heck your hormone pathway is, and how to optimise it, then you can—you know, stick around to the end and check out the show notes as all the links will be in there as well.

Before we head over to Dr. Mansoor, I just want to remind you, we have a new system now in Running Hot Coaching, my online run training academy. We have fully personalised, customised run training plans based specifically on your goals and where you're headed. If you want to join us in our company, we would love you to come along. You're going to get a session with me to discuss all your goals and your objectives, to answer any questions around running. And then you would also get a fully—after that consultation has been done, you'll get a video analysis so we can actually look at you running and analyse your running style and help you optimise that. And then you're going to get a fully customised training plan for your specific next goal. Whether that's a 10K or 5K, a marathon, a half marathon, it doesn't matter. We will provide the plan for you which will also include all your mobility work, your strength work, as well as your run sessions. And also guidance around nutrition and electrolytes and mindset, which are very, very important pieces of the puzzle as well. So if you want to check that out, head on over to runninghotcoaching.com. And you can find out all about it or if you've got any questions reach out to me support@lisatamati.com. 

Also wanted to remind you my latest book, Relentless is available for sale. You can grab that on my website at lisatamati.com along with my other two books Running Hot and Running to Extremes. I'd love you to check those out. If you love some of the content that's been on this podcast, then these books will definitely be up your alley.

My latest book is a bit different to the first two, which were my running adventures and all the highs and lows and disasters and successes that I had racing the world's most extreme events on the planet. The third one is really the journey I took with my mum over the last—how many—nearly five years now. After her aneurysm and bringing her back and rehabilitating her. But it's not just a book about rehabilitation. It's about mindsets about overcoming the odds. It's about the mental strength to be able to carry on when everybody's telling you there's no chance and there's no tomorrow. It's a book that will empower, inspire and have some very, very important messages that I'm really, really keen to get out in the world. So please make sure you check that out as well, Relentless. You can find all of those on lisatamati.com.

Right now over to the show with Dr. Mansoor Mohammed. 

Well, hi, everybody, and welcome back. I am super excited once again to have Dr. Mansoor Mohammed on the show today. And Dr. Mansoor is a real repeat offender on the show. I think this is the fourth podcast. You're the only person who's been on here four times, Dr Mansoor so welcome to the show again. It's fantastic to have you back.

Dr Mansoor: It's an absolute pleasure. I'm not sure does that mean I have to repeat myself to be understood?

Lisa: No, you've got so much knowledge that we have to share with everybody. That's why.

Dr Mansoor: Absolute honor.

Lisa: So Dr Mansoor, so today, we are going to be focusing everybody on genetics and hormones in particular. And we're going to be focusing in a bit on the ladies, although this is very relevant for the men out there too. So don't turn off if you're a guy and just go ‘Well, this is for one for the ladies’. This is also aimed at men. 

But Dr. Mansoor is a world leading functional genomic scientist. And we're going to be talking today about the hormone cascade and understanding our genetic pathways that we take with our hormones and why we need to understand this and how important it is for us. So Dr. Mansoor where shall we start with this journey of going through the hormones.

Dr Mansoor: I think the first thing we want our listeners to understand and it's not lost in any young woman, post menarche. And so let's just define just two quick terms menarche, the time in which a young woman begins a monthly cycle and she enters into young womanhood all the way through menopause, pre menopause, perimenopause and then postmenopausal. But in all of these wonderful stages of a young woman's life, that there's what we call sex hormones, the steroid hormones, the progesterone, the androgens, most notably testosterone, estrogens and their respective metabolites. They influence the human body at a cellular and at a holistic level, in the most fundamental of ways. Okay, so that's the first thing. Just to emphasise the importance of these sex hormones.

The second is to clarify that with this importance, it's not just about external female characteristics of breast developmental, hip flare or thigh developmental, bum developmental, factor position. It's not just “about the obvious phenotypic or physiologic manifestations” of these hormones. We have to understand that sex hormones impact every aspect of cellular behaviour. These hormones when produced—and by definition, hormones are messenger molecules that are produced in one part of the body. In this case, for example, the ovaries. They then enter into the bloodstream, circulate throughout the body, and then impact every cell in that cellular behaviour. So the second more important point is our listeners have to understand that the way in which their bodies respond to these hormones define and contribute to every aspect of cellular function, every aspect of cellular function.

Now, if we can appreciate that. The third thing we've got to appreciate and the young woman’S body, okay, is that there's a circadian rhythm or circadian, generally speaking, that there's a circadian nature to these hormones. In other words, it strikes me and I attended a remarkable conference a bit over a year ago. It was with the Red Bull team of super athletes and their clinicians. And one of the clinicians, she is from the UK. She specialises in treating female athletes. That's her series dealing with female athletes. And in her presentation, we were all presenting at this conference. She said something that was alarming, heart wrenching, but almost not surprising all at once. And what was she said, she would run a survey on these female athletes. These are like Top of the World female athletes, one of which just to begin with was one of the top—if not the top—female soccer teams in the world. And she said, not a single one of these athletes, female athletes were ever asked or made aware of the health of their monthly cycle.

Lisa: Wow. Yes. And these are the top people let alone the other... 

Dr Mansoor: Yes, and so she was beside herself as a scientist and the clinician, that for something as fundamentally impactful to the human body, as those sex hormones. So for example, as she illustrated, depending on whether a woman is in her follicular phase or her luteal phase of her menstrual cycle, proclivities to injuries change, the flexibility of the ligaments, and the body changes, the response to the body to different types of motifs of exercises, changes. When is the female body—can we speak in here, at first, in generalities of the average female going through a monthly cycle, not yet on the pill, we're going to talk about the pills as a separate factor. But just is part of the normative circadian rhythm of the female body. The female body morphs physiologically, cellular metabolically at day seven of the monthly cycle is completely different. And that's speaking a little bit extreme as to the body when it's on day 15, as to the body when it's on day 20. And so you've got individuals demanding the very best from their body optimal performance. And they have not yet even come to terms with the baseline changes to the body between these stages.

And as you pointed out, so many injuries due to training in these athletes, and again, we're speaking of athletes, but we can, we can juxtapose that. Like you said the average female trying to simply be the best version of herself, could be avoided. If the young woman only knew what stage in her monthly cycle she was at. If the young woman only knew the oxidative stresses that are different during different times of the monthly cycle. So if I told you Lisa, that at a point in your menstruating cycle, you innately, naturally have surplus, oxidative stress. It really doesn't take a lot further to grow to understand in those times and days, the last thing you want to do is go—there you go. You don't want to put even more oxidative stress at that point in the body. And so on, and so on, and so forth. 

So in this third category, as you said, to establish the baseline that we're speaking of, we've got to understand the importance of hormones, we've got to understand that it's beyond just the outward superficial physiology of the body. And in this case, speaking of young women, we've got to understand that there is a circadian rhythm to these hormones. 

Now, once we understand these three bases, these three points,then we have to appreciate that part, a significant part of what controls, that's the circadian rhythm. And then within that circadian rhythm, what controls the nuances of one young woman versus the other relies upon their genetics.

Lisa: The genetics, yes.

Dr Mansoor: And so once we understand the functionality of the circadian rhythm of the female cycle, Lipson, once we understand the gears that are going through those 28, approximate dates, once we understand that rhythm, we understand the genes that control or significantly contribute to that rhythm. We understand that each individual potentially has variations in those genes that controls that rhythm. We begin to understand the nuances. We begin to understand the individuality of Paula versus Lisa versus Joanne versus Isabel. And so we begin to understand that one aspect of every aspect of intelligent medicine. But few aspects of medicine are as boldly innately different as the nuances and the individuality of a young woman's innate genetic control of the circadian rhythm. And one week we will talk about this, we need to appreciate this. 

And the most abhorrent of complications that occur, if you do not understand this individuality, one young woman to the next, and then you take that birth control pill, I am not, of course, I have no place to be anti birth control, but I'm a man. I'm not a young woman. Now. So this is not about being controlling. No, not at all. But it's the fate. The simplest thing that we think that you can take 1000 university young woman, you know, first year university students, girls, young woman. And somehow put them on the same birth control, literally the same birth control. And somehow expect that they're getting to be the same effect, and somehow minimalise and even criticise a young woman who comes back and says, ‘I find that I'm gaining weight. I find that I'm—my mood is not the same, I find a’.. And then because five other young women don't have those issues, the doctor says ‘No, that's not because of the pill’, and they are dismissed. And they're not even appreciated as to the uniqueness of their body's response to something.

Again, sometimes the pill is a saving grace for a young woman. But what we're speaking of here is in these three pillars, the fourth pillar is the individuality of the genetics of that young woman. And all of the remarkable insights that a young woman can gain from this. Before I go any further, it's not a plug in the least I hope I'm not, you know, going against any regulation of your podcast, but there’s a brilliant book called In the FLO.

Lisa: In the FLO. We’ll put the link in the show notes.

Dr Mansoor: I have no association with the author. But it's just she did an amazing job. And I'm trying to get the name as I'm speaking about. I'll remember the name. She did an amazing job, without the genetics, of showing how radically important a young woman understanding her circadian rhythm, how different points of her month, her body responds to different foods differently, her brain response, her emotive response. She's really done a beautiful job of highlighting the awesome, holistic cellular changes that go through a young woman's body in these waves of human rhythms every 28 days. So this sets the stage Lisa, everything that we might want to talk about, is predicated on this understanding. And then the genetics that explains this. 

Lisa: That’s a beautiful entry into this whole actual looking at the mechanics, if you like, of the genetic pathways that I do want to get into. Because in other words, every single woman is individual. And this is the beauty of genetics in general, is that we can actually personalise once we understand their own genetic pathways. And you know, we do this both in our profession is to understand what our genes are doing and how they're expressing and how we can optimise these genetic pathways, if you like, in this case, with our hormonal pathways. 

And this has a real implication when it comes to things like the birth control pill, when it comes to—In my case, bioidentical hormone replacement therapy on the other end of the scale going through the menopausal years. Because this has implications whereas, you know, if I take biological hormone replacement therapy, and we've actually talked briefly on one of their podcasts about some of my hormonal which I'm happy to share as well. 

I'm on a hormone replacement therapy. But I understand my genes, and I understand where my problems may lie. And therefore I can keep an eye by from a blood perspective, you know, keep an eye on my hormone levels, but I understand my own cascade. And I can mitigate the chances for example of developing estrogen-based cancers or, you know, like breast cancers or cervical cancers. Whereas another person, if we put them on the same regime may run into trouble.

Dr Mansoor: Indeed, even without the—shall we say, more extreme outcomes or concerns, such as hormonally-related cancers, but really just even the day to day well being of the body. You know, the risk of peripheral neuropathy is, the risk of migraines or lack before resolving them fatigue, weight gain, things that are—the way your body responds to nutrients. Again, understanding where your body innately, your your innate tendency is, as per explained by your genes. And we'll get into some profound examples of this. 

And then making sure that you act in accordance because we have choices. And some of the choices we can make. And sometimes there are, you know, I think there are many times we speak about human optimisation.There are certain voices, and they have a point that can say, ‘Look, but there are universal truisms’. They're just things that we should all know, are either healthy or unhealthy. And there are a few of these things... 

But what is remarkable here is, especially when it comes to female hormones, there are things that you might deem to be universally healthy, but actually can be either unhealthy or certainly not optimal for some young woman versus others. So we’re really in the realm here of not just talking about universal truisms that are relevant with or without genetics. We're speaking of nuances that are so radically important.  

And may I say with that, if it's okay with you. I'd like to then set the stage of some of—just set the stage for themes, themes that your audience, your listeners. And then I'm going to say a few things. And my hope, and my goal is, for many of the listeners out there, at least a few of these things should resonate. For example, how many young women out there find that their introduction and their experience to cyclical migraines kick in post puberty?

In other words, here she is, she's living in the same home, same nutrition, healthy, or whatever version of lifestyle, and the day comes where she enters into your womanhood and break there after, right there after. Not directly related to her flow as per what she could physically and visually manifest. But this concept of now dealing with migraines, a concept of dealing with a circadian rhythm to her mood, and to her what she might find trouble for those first few years until she becomes an adult woman. And she's got life experiences, but she's always found that she's having a hard time to express, that she literally feels that her emotional resilience, that ability, that barometer to what tips are over that scale of resilience changes. And she's never—and no one has even asked her by the way. ‘Do you see that it comes in patterns? Do you find that it happens? And kicks in three to five days prior to your cycle? Do you find that that's when you see some of these changes in the month? Do you find that it kicks in a day before ovulation? Do you even know when ovulation is happening’? None of these conversations are going to happen. 

So that these apparently unrelated just symptomologies of ‘Well, there's some anxiety’, or you know, ‘I get migraine’. They just brushed under the growing list of things that ‘Will you just take a pill for it’? Meaning a pharmaceutical treatment. Or they're minimised and somehow they're accepted as just a routine part of all, that's what it is to life. Okay. Or how many young women out there have dealt with some of the symptoms of migraines or pain, Fibromyalgia-like pain, debilitating fatigue. And then something miraculous happens. When they become pregnant for nine months, most of all, have their symptoms resolved. How many young women have said to me, I can't tell you, Lisa. Again, I know that being in New Zealand, I'm not sure if you have to deal with the plague of Lyme disease. It's something that we have here more in Eastern America.

Lisa: Yes, more overseas.

Dr Mansoor: But yes, but it's a bacterial tick borne disease that ruins lives. And there are, interestingly, a preponderance of women who present with Lyme disease-like symptoms. Now, we worked, I worked in a clinic and I was one of the first to describe this phenomenon. And I had to say not trivialising the horridness of disease, I said to a patient, I said, ‘You know, those ticks don't like women more than men’.

Lisa: Then why more women are presenting with these symptoms?

Dr Mansoor: Presenting with the symptoms. Unless women were more likely to go trekking and hiking and be exposed to, you know. But here's the point. It was that there was a significant—in one of the clinics that we did the study in. There were a significant number of women who presented with classically, what outwardly seemed as Lyme disease symptomologies of debilitating fatigue, almost concussion-like presentations, mental malaise, muscle aches and pains, as I mentioned, Fibromyalgia-like presentations, and they were convinced that they had Lyme disease, convinced that they had Lyme disease. And because it's such a polymorphic disease, yet many doctors were going ahead and treating them with massive antibiotics, even if they couldn't confirm the Lyme disease. 

Because many doctors, almost agreeably have had to say because so many, so many true Lyme patients are being under cared for, right that there are some really good doctors wanting to do the right thing, who were treating the symptom and the presentation, per se. But amongst individuals were a preponderance of women who were not testing positive for Lyme disease. So what was going on here? And what we did when we studied these young women was, we looked at a significant number who then went ahead and became pregnant during their proposed Lyme disease. And for the nine months of pregnancy, all of their symptoms resolved. And I had to say to both the doctors and the patients I said, ‘Your Borealis, the burgdorferi Borrelia bacteria, the bacteria that causes—that doesn't just take a hike during pregnancy’.

Lisa: It doesn't just go away.

Dr Mansoor: It doesn’t just go away. It's not that. So what else is at play here? Well, how many young women understand that during their menstruating months and years, the primary estrogen in their body is estradiol? During pregnancy, your primary estrogen is estriol. Estriol is not metabolised into the same byproducts as estradiol. Estradiol can be metabolised. Every young woman metabolises this estradiol into three byproducts, 2-hydroxy estradiol, 4-hydroxy estradiol,  16alpha-hydroxy estradiol. Now every young woman produces all three. But genetically, you are predisposed to producing more of one or the other depending on your genetics. 

And if you happen to be the young woman who was predisposed to producing in the ratio, more than 4-hydroxy or even the  16alpha-hydroxy, and God forbid more of the following 16 hydroxy as compared to the 2-hydroxy, the 4-hydroxy. And to a degree, the  16alpha-hydroxy metabolites are particularly inflammatory. They're literally inflammatory metabolites that the body has been designed to get rid of. 

But if you were that young woman that genetically, was predisposed to producing more of these naughty metabolites, as opposed to the much, much less inflammatory two hydroxide. Then just innately, you the young woman that recycles the body, when it comes around to the body metabolising, those estradiol, your primary estrogen when you're menstruating. When that estradiol is metabolised for a period of two, three to five days, depending on your particulars, your body, literally, regardless of whether you were eating organic and living organic and breathing the best hair in the world, normally, you are producing an internal inflammogen. An internal thing that is causing both inflammation and oxidative stress. Now, during pregnancy, when you become estriol dominant.. 

Lisa: You're not getting it. 

Dr Mansoor: You don't get these metabolised. And so when a young woman gets pregnant, and she complains prior to pregnancy, of these malaise and the symptomologies and then comes pregnancy and the only thing that has changed, and I've had young women cry in my office saying ‘Dr. Mansoor, how did you know to ask me if I felt better during pregnancy’? Because usually it's quite the opposite. People think, ‘Oh, my gosh, I'm gonna get morning sickness. And I'm gonna’...  These young women were better off. And they would say, ‘You know Mansoor, wish I could stay ‘pregnant. Those were the months where I actually had a relief from symptoms’. So this is Lisa...

Lisa: Yes. Sorry Dr. Mansoor. So these 4-hydroxy in the  16alpha-hydroxy to a lesser degree, because it's a rarer situation. And this is in relation to the Cyp19a1 gene, the aromatase gene, turning our testosterones into estrogens. Is there any—so when we go on that—if we put on the pill, which is got estrogen in it. And you're one of those women who have—and this goes for me too. My husband has a 4-hydroxy dominance for example, which is a problem. He is—are we exasperating the problem when we take the pill without knowing it?

Dr Mansoor: So just to clarify and add a layer of clarity. So estrogen and the estrogen molecule and the estrogen hormone is actually nothing other than aromatised testosterone. So a lot of young women don't appreciate that, you know, they self identify with estrogen. You know, women tend to self-identify their estrogens, and men tend to “self identify with testosterone”. 

In fact, I had one of these absurd pop ups on—I was watching a food vlog which is my guilty pleasure, especially doing COVID. I like watching it, you know, foods being prepared and you've got these annoying YouTube ads that come up. And what if it was this buffed, you know, male trainer and he comes on the screen on the ad and he goes, ‘Well, testosterone is what makes a man, a man’. Not quite. 

But the point is, men need to understand that we too, make estrogens. And women need to understand that the very estrogens that they may or may not self identify with are really simply testosterone molecules that had been aromatised. Okay, so there is a gene, a specific gene, one gene Cyp19a1, as you have mentioned. And in fact, the parlance, the more common name for the Cyp19a1 gene is aromatase. And this gene with its enzyme chemically changes testosterone into estrogen, i.e. estradiol, estriol, as the case might be, okay.

But then once you make your estrogen, your estradiol, let's just fix it at that. Then there are other genes that make other enzymes, that make the two or the four or the 16 byproducts. So specifically, there's a gene known as the CYP1B1, CYP1—Bravo—1. This is the gene that makes the self named enzyme that takes some of your estrogen and turns it into the naughty, 4-hydroxy estrogen metabolite. Now, the point here is different women and different men—and just to clarify for the male listeners out there, if you would think that estrogen was a female issue, and if you would think that 4-hydroxy estrogen was a female issue, think again. And we now understand that 4-hydroxy estrogen metabolites in men contributes to prostate enlargement, contributes to the inflammation of the prostate for many years. In fact, for the last two to three decades, all of the research on benign prostate hyperplasia in men has focused on a testosterone metabolite, known as DHT. 

So DHT, dihydrotestosterone is the product, it is the metabolite of testosterone produced by the steroid five alpha reductase to the SRD5A2 gene with its enzyme produces that metabolite. And it is true, the DHT, one molecule of DHT has the potency to bind androgen receptors as six molecules of testosterone. It's a much more potent, super testosterone. Super, right. 

So here's the thing. DHT is to testosterone. As 4-hydroxy, estrogen is to estrogen. DHT is the testosterone metabolite that interacts with the androgen receptor, much in the same way as the 4-hydroxy metabolite of estrogen. 4-hydroxy overproduction and men, we have now discovered is a significant contributor to the etiology and the progression of prostate and benign prostate hyperplasia.

Lisa: I thought it was just a SRD, the DHT so I need to know. Yes, okay, I need to go and check that with my husband. 

Dr Mansoor: Now for the last couple of years. Some of the actual pharmaceutical clinical trials to treat benign prostate hyperplasia has switched everything, all of our propecia and finasteride, these medications that we currently... And just for the male listeners out there, it is unsurprising that the very medications that are often used for benign prostate hyperplasia, were found or would then use for balding. It has the same DHT that promotes male pattern balding is the same testosterone metabolites that over inflames the prostate. But now we understand that the males who have the 4-hydroxy estrogen preponderance genetically, why? Because they had a version of the CYP1B1 gene that made a version of the CYP1B1 enzyme that is more aggressive at converting estrogen into this metabolite. So men, this discussion is equally important to you. 

But coming back to the females very quickly, then Lisa. You see a young woman who does not know who's going about her, you know, her life and her teenage years and her 20s not even knowing ‘what is the degree—what is what is my innate tendency within which I convert my progesterone to testosterone? What is my innate tendency to convert testosterone to DHT? That more virulent testosterone? What is my innate tendency to convert testosterone into estrogen? And by the way, once I make the estrogens? What is my innate tendency and converting it into the twos and the fours and the 16 metabolites’?

Because you see, if a young woman were to understand this right off the bat looser, it defines why and how easily she develops lean muscle mass. It defines why she can eat the same foods, exercise the same as her mate, in fact, exercise more than her mate, and be fit and be beautiful and be strong, but never get that cut or that sort of musculature. As for not saying that that's what she wants to know. But so many women are going ‘I work so hard. I trained my bum off but I'm not seeing that type of’, this is going to be intimately described by the woman who is making less DHT from the testosterone, making more estrogens from making more 4-hydroxy estrogens from her estrogen from her testosterone. This is a young woman whose cellular level is estro dominant and estro toxic. And she cannot until and unless she appreciates this. 

And until and unless she takes steps to reduce. And of course, that's the million dollar question, ‘Can we take us to 37:00 reduce it easily’? And the overwhelming answer is, ‘Yes, we can’. Okay. But she's even unaware of this to take the steps in the first place. So let me come back to those super athletic young females for whom their doctor, when they did the research. Here they were, no one ever even asked them what their monthly cycle health was. ‘Are you having a monthly cycle? Is it irregular? How do you feel with the cycle? Are you on the pill’?

So now I answer your question, you see Lisa, if you didn't know where you were innately on that cascade. Remember, young woman out there, all of the ladies out there, in a ‘normal’, in your natural monthly cycle, without the pill. You know, just you're 16, you're 26, you're 36 you're menstruating. How many of you realise that that estrogen that you self identify with isn't produced 24/7, 30 days a month? 

Lisa: Exactly. It is when you put on the pill work.

Dr Mansoor: That's the difference isn't it? The very point that I'm trying to make is, in your natural monthly cycle, your body is only estrogenised, it is only under the influence of this hormone. And I'm going to stop beside and make a couple more points on this. But I'll finish my point here.

When you are naturally menstruating, there's only a window of about five to seven days, give or take in your 28 or 30 day or thereabouts, where you are in your unique monthly cycle, that your body is actively producing estrogens. Those estrogens are actively circulating in your bloodstream. And the cells of your body are actively responding to that estrogen. Compare and contrast that to being on the pill, where have for 21 days of a 28 day cycle, not five to seven days, 21 days, your body is under the influence of testosterone. Here's the thing Lisa, that I have to admit. And again, let me be clear, all of Lisa's amazing listeners, this is not about anti-pill. The pill is absolutely—it is your right. It is something that you control. It is absolutely a godsend for different times of your life and for different young women. But you've got to ask, Where are you in the spectrum of young woman? And how will your body respond to this differently? And you would at least need to understand that your body was not estrogen eyes for 21 days in your normal cycle. 

And here's the newest thing, Lisa. That I must admit, this gives me indigestion. Again, I have no say over the matter, but down the practice of actually having no bleed, how many women are now being put on constant pill without even a bleed through? So now you go from a normal physiology of every month, say seven days of estrogenisation to 365 days of estrogenisation. 

Lisa: Disaster.

Dr Mansoor: So now, Lisa I'm—and we would be remiss if I don't quickly emphasise to our listeners, what is estrogen? ‘What is this thing that you—okay, well, it's stopping me from getting pregnant. My hair is luscious, my skin might look really wonderful. So after all, shouldn't be a problem’. What you have to understand, and our listeners out there in the female body—and I can speak of the male and female body, I'm just going to focus on the female body for the time being. In the female body, Lisa, every single cell produces these receptors for estrogen. So if this is your cell, you have an estrogen receptor. And when that estrogen is produced, or it is taken as a pill, or as whatever the— even certain neutra estrogen analog or xenoestrogens and plastics, these molecules enter your body, they bind to these receptors on your cells, okay? Because by the way, estrogen doesn't do what it does in the body by just being produced and floating in the bloodstream. No. Estrogens do what they do in the body by being produced by then binding to these receptors. And what happens, this is the important point. What happens when estrogen binds to its receptor? What happens is the DNA expression, your genes in that cell, gene expression is radically altered? Literally, the genes, the instructions within your cellular operating manual changes when estrogen enters the cells. When there's no estrogen in the cell changes. So now let's come back, the female body..

Lisa: Apologies for the phone call people in the background.

Dr Mansoor: The female body in its normative circadian rhythm experiences a gene expression shift, change in gene expression for the days in which your estrogen was elevated. And yet, of course, it comes back down in the normal cycle. What happens when you force yourself to go into a gene expression shift to 365..

Lisa: Constantly.

Dr Mansoor:  ...days a year without change. 

Lisa: And we're talking like hundreds of genes, hundreds of thousands of genes that have been changed, turned on and off, turned on, and wow. 

Dr Mansoor: These genes impact the metabolic efficiency of your cells. Well, the thyroid function, which is why how many times we see a competitive joint problem between hypothyroidism, hyperinsulinemia—your body's response to insulin, and estrogen dominance. Wow. And when these three things come together, we euphemistically call it metabolic syndrome. You know, there's a read, there's a point behind, there's an impact behind it. 

And the point here that I want to make is, we often just think of the sometimes and arguably beneficial outcomes, outward outcomes of being on the pill. Okay. And I emphasise for the umpteenth time, please, this is not about not being on the pill. The pill can be what is right for you at certain points in your life. But it's about being educated, that taking this hormone is not something as trivial as stopping your ovaries from producing an egg. That's not what that hormone is doing only. This hormone is interacting with every cell in your body and it is changing the way your genes express in every cell of your body. 

Now, the point here is, if we were to do—I like to call it a heat map. If you took a young woman, and you colour code her body, from white to red, according to which cells in her body have had more estrogen receptors. What you will do is the whole body isn't going to be white, the whole body isn't going to be red, it's going to be shades of white and pink and red. And of course, unsurprisingly, the region of the breast tissue will be somewhat the reddest, because those cells and the breast tissue are some of the most sensitive to estrogen. So what does this mean? It means that when estrogen is present in the bloodstream, the cells of the breast tissue are some of the most able to absorb that estrogen. But what happens when it absorbs the estrogen? Gene expression happens, gene expression changes happens. And the cells were designed to account for a circadian rhythm to their gene expression change. Not 21 days, repeatedly, repeatedly, or 28 days, for that matter, repeatedly, repeatedly.

Again, I stress not for the young woman who is seeking birth control maybe for a few months, or periods in our life. We're speaking of the travesty of the young woman that had been on the pill since they were 14. And here they are 32.

Lisa: Unable to conceive and or cancers, or weight gain, or cellulitis, or all of these implications.

Dr Mansoor: The very metabolic machinery of that cell, you're very mitochondrial efficient efficiency of the cell is impacted during—and this brings me back to the brilliant comment by the brilliant female scientists that I was speaking of earlier, where a young woman should understand that in her natural, healthy 28 day rhythm, metabolic efficiency, mitochondrial efficiency, changes in response to the ratios and the waves and thrusts of progesterone versus testosterone versus estrogen.  Think what happens when you put a blanket of estrogen over everything, 24/7, 28 days, 30 days a month, 365 days a year. 

Now, the point here, Lisa is coming back to even more finesse point in your question is, well, that is what I what we've just explained happens in every young woman that goes into pill, every young woman that goes into pill. But what happens when you didn't realise that you had the proclivity of making more of the 4-hydroxy estrogens? What happens when you didn't realise that your ability to then neutralise the 4-hydroxy estrogen that inflammatory estrogen metabolic, which by the way, you know, not realising that you were making more of it. You were producing—when you introduce X amount of estrogen molecules more if it was going down the 4-hydroxy pathway than the healthier 2-hydroxy pathway? If you were not aware of this, and you were doubly unaware of the molecular mechanisms that neutralise? So what is the gene? —

Let's take a look at this. What is the gene that neutralises 4-hydroxy estrogen? What is that gene? The gene that neutralises, is COMT, catechol-O-methyltransferase. This is the gene, the gene that is—makes an enzyme. The same name, that's COMT enzyme. And the job one of the jobs of this enzyme is that it recognises the production of 4-hydroxy estrogen, which is inflammatory, which is pro-oxidative, pro-inflammatory, pro-estrogen. Indeed. Because here's what happens, that 4-hydroxy estrogen—think about it, Lisa and all of the listeners—you took estrogen, which was binding to its receptor, and causing all of those estrogenised changes that we spoke of. So of course, what the body wants to do is it wants to limit the duration by which estrogen can bind to its receptor. 

So it's good to metabolise the estrogen. But ironically, when you metabolise your estrogen into 4-hydroxy, estrogen, ironically it's still doing—in fact, not only is it still binding to the estrogen receptor. Some studies indicate it can bind to the estrogen receptor actually with greater proclivity within greater binding efficiency than its original estrogen. And it can induce that altered gene expression 2-hydroxy estrogen does not do it near as much, which is why we consider the 2-hydroxy estrogen prefer—to be the best pathway. 

Well, the point here is COMT converts that full hydroxy estrogen into 4-methoxy estrogen. Now, 4-methoxy estrogen dramatically loses its ability to bind to the estrogen receptor. So 4-methoxy estrogen is what we can now say it's no longer estrogenising. Okay? The other thing of the 4-hydroxy, going back now to the 4-hydroxy, estrogen, if you're not removing it, if you are not converting it by methylation into the methoxy, estrogen, 4-hydroxy estrogen, it decomposes into these nasty little molecules called quinolones. Horrible, not very nice things. And quinolones decomposed into oxidants. So the whole stagnation if—let's let's clarify the statement now.

Now, if as a young woman, you did not know that you have the predisposition, when ever your body sees estrogens, whether they are internally made, or externally introduced, when ever your body sees estrogen molecules, if you did not know that you A) tend to metabolise those estrogens into 4-hydroxy by products more than we would like and B) you will not as efficient at neutralising the 4-hydroxy estrogen by virtue of COMT, what you are unaware of is you are unaware of this thing called an estro dominant burden with estro toxicity. You are unaware that in your normal cycle for five to seven-ish days, your body is under the strain of an internal inflammatory production, internal oxidative stress more than your female companions. And will you to then take that normal exposure, but then by going day in day out on an estrogen source, think of what you're doing to the body.

Lisa: And by the same take of the bio identical hormone replacement on the other end of the scale with the menarche, the menopause. And we want like, just just to clarify, estrogens are not evil things we want. The body needs estrogens and like it keeps us younger. I mean being on—this is the dilemma that I've been facing. The biological hormone placement keeps me—my bone density good, keeps me—you know, being able to hold my muscle, my skin is better. I'm not aging as quickly the inability or cells of my vessels are better, etc, etc. However, I need to keep those in a balance so that I don't get too many chicks estrogens going in or I need to keep my progesterone up and I need to make sure I know where my testosterone is. Yeah, so that.

Dr Mansoor: Because it's about the balance. It's about finding—and so here's that final point. You know how we spoke about the cells, Lisa having these estrogen receptors? Well, your cells have androgen receptors as well. And they have progesterone receptors as well. So think now, we can almost visualise a healthy soul, a healthy female soul is one that is having—it's a traffic system. And it's one that is being trafficked into it at the proper ratios at the proper circadian pulses and rhythms. 

Sometimes estrogens are getting in, altering gene expression in an estrogenised manner. Sometimes androgens are getting in altering the gene expression in an androgenised manner. Sometimes progesterones are getting it, altering the gene expression and the progesterone alised manner. And it is optimal health and optimal youthfulness and responsiveness to yourself is when we get that circadian rhythm allowing the cell and allowing its operating manual, its genes to go through this rhythm of when are the—the genes that are controlled, and that are going to be expressed because of the presence of estrogen. The genes that are going to be controlled and expressed because of the presence of testosterone, because of the presence of progesterone, these waves and rhythms of gene expression, optimal health is when these waves happen in the optimal full manner, okay?

And we can replace that optimality and we can extend the optimality and therein lies the brilliance of hormone replacement, of which it absolutely is something that you know, other knowledge can afford. But unfortunately, when we do this, without the appreciation of the individuality of these ebb and flow waves, and we push the system, without appreciating what was the a priori tendency of that young woman. Was this young woman a priori andro dominant? Was she a priori estro dominant? Was she estro toxic? Was she estro dominant and estro toxic? If you do not know these things, you're going to be guilty of—you're going to be at risk of using a one size fits all approach that will be beneficial for 10%, 20%, 50% of woman, but that most certainly equally can be deleterious for a group of young woman, unwittingly.

Lisa: And this is what shocks me is that we have done this human experiment, like 85% of the population of woman on the planet who are in their menstrual years have been on or are on the pill, including myself, who was on it for 25, 30 years, I don't even know and ended up with fibroids, ended up with endometriosis, even though I don't have the 4-hydroxy dominance.

Yes, and because I was constantly on these things, and so now with these genetics—and this is the point. We are able to tweak into change. For example, I'm on organic black seed oil, which upregulates my Cyp18a1 genes, which helps me create more 2-hydroxy because I'm 57:15 red-lighted if you like for that one as well. I take them so that I can slow down the aromatase of testosterone. I have a very quick Cyp17a1. So I need a bit more progesterone support, because I'm making my testosterones very quickly. But without this knowledge, we just like throwing mud against the wall and hoping it sticks in the right places and doing so many people and injustice.

Dr Mansoor: Think about this, Lisa, that COMT, that all important—that is that is methylating those metabolites including the naughty 4-hydroxy estrogen. Well, Lisa and listeners out there, there's a variation of very, very, very well studied variation of that come to genome. For those of you who are dabbling with a little bit of genetics, this is the rs4680 variation. So you can actually go look at the code of the variation. And these variations have coding qualifications. This is the rs4680 variation. And this variation is defined by two alleles, two versions of the gene. One is a G version, G as in George, the other is the A as in apple version. Okay? Now, the G version of this gene produces a version of the enzyme that is faster, it is kinetically more efficient at doing its job. But what is it one of its jobs? Neutralising 4-hydroxy estrogen.

So much so that if you were a GG, both copies of your comt with the fast versions, the genes and versus if you were AA, both versions were slow. The AA COMT individuals, the people that have to have the slow versions of the gene, their COMT is working at 70% to 75% slower than the person that is... We're not talking trivialities, we're not talking 5% to 10%. We're saying that if you're an AA, your enzyme is doing the job. It's doing its job. It's just doing it 70% slower than if you were a GG. Now, here's the point. If you were a COMT A and you had the fast version of Cyp1B1 making more 4-hydroxy estrogen from whatever estrogens your body is seeing. Now you’re not getting rid of it. 

And here's the final point. There are a number of nutraceutical nutritional intake things environmental exposures that can further epigenetically slow down COMT. So here's one of them. Several of the molecules, the phenolics, in red wine, which we could talk about whether red wine is good for you one glass, we can… But the phenolics in red wine epigenetically slows down COMT further. If you were in AA COMT, already dealing with a pump enzyme, it is doing its job. And then you will drink something like red wine that another person might have had, you know, perfectly fine having a glass of wine, or whatever the case might be helpfully. You don't even realise that you're doing something that is actually now nutraceutically—from a nutrition perspective, working against something in you that you were even unaware of.

Lisa: Wow. And then if you layer on that, that you don't have optimal B 12 levels and folate levels and your methylation process is slow.

Dr. Monsoor: Now we're really putting in—you're really putting fuel on the fire. So those listeners out there...

Lisa: Yes, this leads to things like cancer.

Dr. Monsoor: It leads to cancer, it leads to—again, I keep saying, you know, even before we get to cancers, it leads to a quality of life, that can be so radically either improved if we knew or simply a quality of life, where we're simply being told ‘Well, you know, that's just of the things… That's the way it is’.

Lisa: Wow, Dr.Mansoor, I know you've got another appointment coming up, and we have to jump off the call. And I don't really feel like we've finished this conversation. So again, I'm going to have to have you back. And we have to go over the men’s male hormone report too, because everything that we've seen today is also valid for the men in different races, same cascade. 

And what I want to get across though, Dr. Mansoor is that you have the power now to be able to understand these genetics. So you and the DNA company have a hormone report, which I'm going to link to in the show notes that people can go and order. The only reason I'm doing this is because I want people to get this report. I want them to understand the genetics and I want them to optimise the genetics and make informed decisions around their hormone replacement or their pill or their what nutraceuticals to take, whether you should take them with you should take black organic seed oil, goodness knows what—all of these things that we can do to optimise our pathway. So I'm going to be linking to that in the show notes that Dr. Mansoor's company has this report now. And you can find out exactly what you should do and how to optimise your your actual personal hormone situation. 

Dr. Mansoor, is there anything you wanted to add there? 

Dr Mansoor: Well, Lisa, shortly, the short answer, no. A little longer than the short answer is to emphasise what you've just said. This is about empowerment. It is the empowerment of being informed, being informed about your unique predisposition. What is your operating manual, making your more normative choices, if you will, of these cascades? And then how do you optimise the things that you want to do and the things you don't want to do. And it is this empowerment that we really want. It's not about negating any choices you have. It is rather simply about empowering you to either make healthier choices, or when you make certain choices, you make them informed about the limitations of those choices, and then you do your best to mitigate any consequences or implications thereof.

And then I will end with one very quick note. As you've said, you know, we've emphasised the ladies here and the woman viewing this, but it is as important to the men and I will give you a very quick example. How many men are going through that man no pause period. I'm 48. I can tell you a thing or two about that. But how many men have come to me having felt that they were declining in their muscle mass and declining in their performance in, you know, both in the bedroom and out of the bedroom and everything else? And they thought that testosterone was the magic fix. And what they did was they went and they were prescribed in good meaning testosterone, only to find that upon taking the testosterone, they were becoming more and more estrogenised. Right. Because remember, even when you take testosterone that same Cyp19a1, that same aromatase is going to convert some of that testosterone into estrogen. 

And men that Cyp19a1 gene comes in three different versions. A version that is going to convert your testosterone into estrogen, much faster, medium speed and slower. And so if you don't know which version of Cyp19a1 you have, you do not know what is your body's natural tendency to convert testosterone into estrogen, which can have so many implications on the choices you make, per going into hormone replacement.

Lisa: Yes. And that's a thing that I'm discussing with my husband and my brothers at the moment, you know, like the implications of testosterone therapy. And it's not—it's a very simplified thing, ‘I'll just take testosterone, and I'll take a heck of a lot of it because I want more muscles’. It's not. And there are a lot of men doing that. And it works for some, and it doesn't work for others because of this very intricate knowledge that we need to have before we make these decisions. 

So Dr.Mansoor, I think that is a brilliant place to leave it. Thank you, once again, so much for your knowledge, for your skill at teaching such a very complicated subject. And I hope we didn't lose you guys and girls out there listening along the way. Listen to it again, if we did. But make sure you go and get your hormone report done. I think that is the key, because then you will know what to do. And we can help you interpret that so you don't need to learn all of this. You just need to know what you need to know. 

Dr Mansoor, thank you once again.

Dr Mansoor: It's been an honor. 

Lisa: It’s been an honor to have you again. 

Dr. Mansoor: Always Lisa, thank you very much.

Lisa: Wow, wow, wow. I hope you enjoyed that conversation with Dr. Mansoor. It's a shame he had to go off. I could have talked for another few hours, at least with Dr.Mansoor. I just love the information that he gives, the passion that he brings to his project. So it was just absolutely an honor to have Dr. Mansoor on the show. And I hope you found that a real interest. 

Now if you if your interest is piqued and you want to get your hormones tested, if you want to know whether you're a male or female, if you're a male, reach out to me, lisa@lisatamati.com and I'll send you to the right place. If you're a female who wants to get your report done, there is a link in the show notes. And the reason why we've done that separately for the men and the women is because we're going to be doing another episode on the male hormone report. But if you're already wanting to jump on that, please just do reach out to me and I can help you there. 

But ladies out there, if you're wanting to know what your genetic profile is, in regards to your hormones need to get this tested, then there is a link in the show notes that you can go to, in order that test. What their DNA company will then do was we'll send out a test kit to you, wherever you are in the world. And you put some saliva into this test kit and you return it to them. Now this process does take about six weeks, depending, give or take, depending on the COVID situation, obviously.

And once that information is in, then what you can do—you'll be notified of that, I will be notified of that. You can book a session with me to have an interpretation, consultation about your genetics, and how to optimise your situation and what you need to be aware of and any other red flags that may come up. We'll be able to talk about, you know, hormone replacement or the pill or what supplements you should be taking or not taking it as the case may be. So if you're wanting to do that, the consultation is separate in the price to the test. So just so you know.

First step though is to go to that link, order the test, wait for six weeks, get the results. And once you have the results, then you can book a session with me just reach out to me lisa@lisatamati.com and I'll send you the link to make a booking for a consult with me. And we can go from there. The consult with me may cost $190. So you're all up to date on what is involved and how that whole process works. 

But this is sort of game changing information and stuff that you really need to know if you want to mitigate some of the downstream consequences of getting it wrong. Especially if you're on the pill and you want to know what your risk factors are. If you suspect that you have estrogen toxicity or estrogen dominance, if you suspect that you have the inflammatory estrogen problems that Dr. Mansoor was talking about, then you want to get this checked. Or if you're like me on wanting to go and buy medical hormone replacement therapy at the other end of the scale when you're going through menopause or you're having menopausal problems, then these are you know, this is key sort of information to know. So check that out all the results, all the information is there in the show notes. And if you've got any questions just reach out to me at lisa@lisatamati.com. 

I do appreciate you guys. I love doing this show. I have some fantastic guests. The information that we provide is next level because the guests I managed to get on and next level. And I do my utmost to keep up with some of these great minds. And it takes days and days and sometimes weeks of research prior to these interviews, for me to be up to speed on every area of science that I cover in these interviews, so is a heck of a lot of work that goes into what I do here. And I do really appreciate you guys giving us a rating and review. 

We are going to be having a Patreon page shortly. If you want to support us in our work here at the podcast. You know, we're going to have a Patreon page where you'll be able to donate a few dollars a month in order to help the show keep running because it is a labor of love. I can tell you that much. And it's been doing that now for five and a half years providing really valuable information and giving you guys real cutting edge because it's the sort of information that I wish I'd had five years ago when I was facing dramas with mum or my own situations with my health or recently with my father, this is the stuff I go and find the people to share the information after I've been through a journey, and usually after the fact unfortunately.

So this is really about preventative health. This is about optimising your performance. This is about helping you be the fittest, strongest, best version of yourself that you can be. And I really appreciate you listening to the podcast, to you sharing it and letting others know about it if you find this content valuable. So thanks once again and we'll see you again next week.

That's it this week for Pushing The Limits. Be sure to rate, review and share with your friends and head over and visit Lisa and her team at lisatamati.com