The Hidden Epidemic: Testosterone Resistance Syndrome & The Lab Range Fallacy

0:10 Hey everybody. This is Hunter Williams. I hope you're doing amazing wherever you are in the world today. My video today is going to be about testosterone resistance syndrome. So basically this is the idea that all of the environmental toxins, contaminants and everything around us are actually inhibiting the function of testosterone at a cellular level. What I'm going do today, is walk through exactly what is And really more or less what is playing out at a population wide level, not only among men, but women as well.

0:42 And when we look at testosterone, most people today, if they even think to get their blood work done, a lot of times it will come back somewhat within what is the normal range. So you may have men that are 300, 400, 500, and they get told by their doctor that that's normal. And one way I want to explain that, that it's not really the range, but then also to why even those numbers are probably not exactly what they really are in practice versus the lab work, meaning that the testosterone that we even have in our body, is being inhibited at cellular level because of what is going

1:16 on in the environment. So hopefully today, I'm going to make the case that really, the only way around this, at least as it stands right now, is to use testosterone therapy for a lot of the adult population. But then also too, so you kind of have an idea of what's going on here and why the lab work isn't always exactly everything that is cracked up to be. So hopefully that makes sense, but today we're going to walk through this and I'm going explain what is going here. Now, I am not the first person to coin the term testosterone resistant syndrome. There's really good doctors, one Dr.

1:46 Keith Nichols and the other Dr Scott Howell, who have really coined this, and explained it much more in depth. than I have. So shout out to them. And obviously we stand on the shoulders of giants. Jay Campbell, obviously publishing his book about testosterone therapy eight or nine years ago now. That's what we're going to go over today. I hope this will be entertaining, exciting, and educational all at the same time. Don't forget, check out the peptide cheat sheet down in the description of the video and join Fully Optimized Health if you love being in a private community where you can talk about these things and also hop on live calls to ask either Jay or myself questions and you could also always message us inside the

2:22 group and that's where we prioritize the responses to questions. Unfortunately, because of all of outpouring of support I get from people, I cannot respond to every Instagram message or anything that people send me. So, without further ado, let me share my screen and today we're going to learn about testosterone resistance syndrome. All right. I'm Hunter Williams and today's video is all about testosterone resistance syndrome. So let's get into it.

2:55 basically is the concept that all of these chemicals in our environment, so we've got plastics, pesticides, forever chemicals, heavy metals, they basically hinder testosterone production, block its action at the receptor or disrupt the metabolism or do all the above. So even if your body produces enough testosterone on its own, and again, think man or woman, this is not just exclusive to men, these contaminants might make you functionally resistant to it. And I'm going to explain a little bit about that more. But we're looking at something that is kind of more or less type three hypogonadism, which is distinct from classic primary or secondary hypognathism.

3:30 Which is typically what has been diagnosed in the medical realm. It's not an official medical diagnosis, obviously, but really this is what we are seeing play out today. I don't think it's any secret, there's many studies to show that the average testosterone levels in men and women have steadily decreased over the past few decades, even accounting for age. There was a longitudinal analysis found that, the averaged 65-year-old man in 2002 had about 15% lower testosterone than a 65 year old man, in 1987. So in a matter of 15 years, 15%. So we're probably looking at somewhere around 1% per year decline in average testosterone levels,

4:07 and it doesn't show any sign of slowing down. So lifestyle factors can obviously explain part of the drop, but not all even when you control for it in studies. And researchers suspect that there's environmental exposure responsible for the testosterone decline. I think that is pretty obvious at this point. At the same time, rates of infertility and sexual development disorders have increased, pointing toward environmental endocrine disruptors as contributors. And there's a lot more of where that came from, as they say. So just to kind of preface and lay out a little bit of the groundwork.

4:37 Again, what does testosterone do for us? So we have this idea of testosterone resistance. The body is becoming resistant to the testosterone that it even produces assuming it produces any which makes us not able to get all the benefits and there's in my opinion a lot of concern around the decline in testosterone levels and fertility because of what it means to The function of our society so When we look at chemicals, they can interfere with testosterone in various ways. They can block it at the androgen receptor level, inhibiting the synthesis of testosterone, altering hormone metabolism or reducing bioavailability,

5:10 which we're going to go into. There's several animal and human studies that link higher exposure to chemicals to lower testosterone levels. I don't think that's a secret. And obviously we see rampant male reproductive issues and female too, but in the case of testosterone, more so male and declining sperm counts over recent decades. And so in order to do anything about this, we at least have to recognize it. So hopefully this is kind of an alarm bell. Let me just go into a little bit more detail about testosterone resistance, what it is. Basically all these contaminants make our tissue less responsive to testosterone effects, much like how cells become insulin resistant and type two diabetes.

5:48 So I talk about that loss of all right. I talked a lot about GOP one peptides. Basically people that are diabetic become resistant to insulin. They are insulin-resistant. Their body can no longer respond to the insulin that it makes. And in a lotta cases not make insulin anymore. That's why they have to use it exogenously. So like I said, Dr. Scott Howe and Keith Nichols hypothesized that EDCs are food, water, and environment are creating a significant but under recognized form of a low testosterone state in the population.

6:18 And in this state, a man or woman might have moderate testosterone levels on paper. Like I've said that 500 to 800 lab reference range, but they still experience symptoms of deficiency due to the pollutants blocking the hormones action or metabolism. We also have this idea of androgen insensitivity, so in extreme cases, it can lead to more subtle issues like chronically low normal testosterone and symptoms of hypogonadism despite normal testosterone levels. We can even look at things like lead exposure. So welders that are exposed to lead in their lifetime were found to have lower testosterone in a higher LH and FSH, suggesting the testes were being told

6:55 to produce more testosterone but couldn't keep up. So what that means is that the lead inhibited the function of testosterone in the body, to which the brain was like, okay, I've got to make more testosterone, but the testes could not actually produce and synthesize the testosterone the bodies needs. And you will see this a lot. I have seen this in a lots of people's blood work, is someone will have low testosterone but their LH and FSH will be super high. Basically what's going on there is their brain is telling the person, hey, make testosterone. Make testosterone and they can't do it.

7:27 No matter how much HCG you take, you can keep bumping LH and FSH up. You can't really do anything about it. And then also too, we look at our environment. The environment continues to flood us with chemicals that reduce testosterone output and impede the ability to do its job contributed to this general low testosterone epidemic, which is really sad because you go to a gym today and see that people are working really hard. In a lot of cases, it doesn't do them any good. Again, don't think of this as a man or woman issue, or excuse me, just a male issue. It is a men and women issue So let's look at how environmental toxins disrupt testosterone.

8:01 So the first way is through this androgen receptor blockade. Many pollutants can bind to the andogen receptor without activating it, effectively blocking testosterone from binding. They act as androgens receptor antagonists of the body. So there are certain pesticides like DDT and DDTs metabolite DDE and fungicides like Vinclozolin that are classic antiandrogens that attach to the androgen receptor and prevent normal testosterone signaling. There's also plastics like phthalates and pthalates metabolites and industrial chemicals have the same anti-androgenic binding activity at the receptor.

8:40 So if we could think about this with analogy, because remember I love analogies, right? The result is like putting the wrong key in a lock. The receptor is occupied by the pollutant, so the testosterone key can't turn the lock and initiate the gene transcription that is needed to carry out all the functions of testosterone. So basically you introduce plastics, you introduced pesticides and all these things, it attaches to the receptor, but it kicks testosterone out, But it doesn't do what is So it's kind of like, get out, I'm here to play now, but I am not going to do my job to unlock the key to go into the house and

9:15 then to everything that is needed. So this leads to reduced expression of testosterone responsive genes and tissues, even if testosterone is present in the body. if these pollutants are blocking it off of the receptor and keeping it from going to the cell and doing its job, it's not going matter. So in essence, the hormones message is being jammed at the reception level. We can think of this as like a wifi jammer, right? For testosterone. That's how these are working. When we look at research in animals, including underdeveloped or malfunctioning male reproductive organs, they have Despite normal or high testosterone levels,

9:50 the hormones can't exert their effects. So notably, this is the mechanism by which certain pharmaceuticals work. For instance, there's a drug called bicalutamide. It's an androgen receptor blocker used in prostate cancer therapy. Now, I don't think that you should do that, but that's what is common medical practice now. And unfortunately, some pollutants have similar anti-androgenic actions unintentionally as drugs like that do. That's where we're seeing We can also look at the impaired testosterone production, which is basically called steroidogenesis inhibition,

10:22 but some chemicals directly impair the synthesis of testosterone like I was talking about. So when we look at this, the latex cells in the testes undergo a complex process to produce testosterone from cholesterol involving enzymes like 17-beta-hydroxysteroid dehydrogenase and the steroidogenic acute regulatory protein, otherwise known as STAR, star producer of testosterone, right? So toxins impact this. So various toxins can disrupt these enzymes or damage the hormone producing cells.

10:52 So when we look at phthalates, which are found in plastics, vinyl, and other personal care products, shampoos, body wash, deodorant, you name it, they can block normal testosterone production in the testes, leading to male developmental disorders in rodents and lower testosterone levels in adults. Like I said, we can also look a heavy metals. So we have lead and cadmium. They can poison testosterone producing machinery, resulting in decreased testosterone level and impaired fertility in multiple species, not just humans. And then we also can look at lead exposure. So research indicates that exposures to lead or cadmium is associated with lower testosterone levels and paired fertility.

11:24 And like I said, lead exposed workers show a correlation between blood lead levels, and testosterone reduction due to the toxic effect on the testicular cells. I think one of the biggest issues here too is the conversion process. So testosterone is great, but what the real benefits really come in is when we convert testosterone into DHT and into estradiol. And again, this is for both men or women. It'll be at different ratios for each sex. But when we look at testosterone, it's really more about conversion to THT and conversion estradiol that real world give us the benefits that we want.

12:00 So even after testosterone is made by the body, It must be properly converted and metabolized to maintain balance. So environmental chemicals can interfere with the enzymes that convert testosterone into its other forms which skew hormonal balance. So not only are we impairing the production of testosterone upstream, but downstream as the body is working to turn that testosterone in to what it needs, which is DHT and estrogen, in order to function, this also becomes impaired. So let's look at atrazine. So the research by Tyrone Hayes and colleagues showed atrazzine exposure in frogs drastically lowers testosterone and increases conversion of antigens

12:38 to estrogens, essentially chemically castrating and feminizing male frogs. You probably have heard of this. If you're in the conspiracy world of Alex Jones, there's old clips of him saying that they're making the freaking frogs gay. And it's kind of a joke, but at the same time, it is real because the atazine in water or in chemicals that they spray on our food supply has this effect. It changes the conversion of testosterone. So you take a frog or a human and you introduce them to atrazine, they're going to not make testosterone as well.

13:08 And the testosterone that I do make is not going get converted into the androgen metabolite, which is DHT, and it's going over-converted into estrogen, I don't want you to think that estrogen is bad because It's not in a lot of cases, and it's very misunderstood, but we don't get the required metabolites or the right ratio of the metabolite. So chemicals like atrazine may impact the conversion of testosterone into estrogen, potentially leading to functional low testosterone and higher estrogen dominance in men. And again, don�t think about estrogen dominants the way that most people think of it.

13:38 Think about the body having the wrong amount of aromatase enzyme expressing estrogen. So it's not a high estrogen issue. It's a chemical inflammation issue that's going on in the body that is causing this. We also look at DHT. DH is very important. Again, very misunderstood. A lot of people want to block DH because they think it causes hair loss. But arguably, all of your manhood, your sexual function, drive, discipline, and determination comes from DH. So some chemicals might inhibit 5-alpha reductase, which affects the formation of DHT out of the testosterone, leading to muted androgen signaling and

14:13 symptoms of androgens deficiency or imbalance. And again, our total testosterone could be fine, but if we're not converting that total to testosterone into DHP, does it really matter? Because we are not getting the practical effects and benefits of it in our life. We also have reduced bioavailability and this is where we get into the idea of free testosterone versus total testosterone. So testosterone in circulation is mostly bound to carrier proteins like SHBG and albumin. Only the free or weekly bound fraction of testosterone can intercells and activate the receptors.

14:43 And this is where we look at free testosterone. So some environmental chemicals are known to increase SHBG, sex hormone binding globulin, or otherwise trap hormones, thus reducing free-testosterone. Basically what is going on is some of these chemicals increase that SHPG in the body, which then sucks up the testosterone and then prevents us from getting testosterone exerted at the cellular level. For example, phthalate exposure in men has been associated with elevated SHBG and estradiol levels alongside lower testosterone. Higher SHPG means more testosterone is locked up and unavailable to the tissue.

15:17 We also can look at the influence of inflammation and liver stress. So chronic inflammation, which can be triggered by pollutants, among other things, diet, lifestyle, exercise, all those things if we're not doing properly. And liver-stress can alter how hormones are bound or broken down, potentially upping clearance of testosterone from the body. So when we look at guys with SHBG, they're like, hey, my total testosterone is 1200, but my free is only 10 or 15 or even 20 with a high total Testosterone level. A lot of times it's because their SHPG is high because they are chronically inflamed, their liver can't clear the toxins in their body,

15:50 They're being exposed to something in the environment that is not good for them, or it is a combination of all those things. And so although hormones like testosterone don't require membrane transporters, the overall bioavailability can be affected by the systemic changes going on here. So essentially your cells might be running low on fuel because much of the testosterone is handcuffed to SHBG. And it can't be rapidly metabolized due to the chemical exposure. So basically, it's blocking the metabolization of testosterone the way that we need it.

16:20 And the result is less hormone actually getting into target tissues to do its work. Again, this is why the blood work is not always the easiest or the most clear thing to rely on. Now let's look at some evidence in animals and humans. Animals have basically for years been the canary in the coal mine because we can see the effects play out much more rapidly than we across generations of humans, But researchers have repeatedly shown that dosing animals with certain EDCs lead to telltale signs of androgen disruption.

16:50 So, for example, exposing pregnant rats to a mix of anti-androgenic chemicals like phthalates, DDT, etc. produces male offspring with a whole host of abnormalities. One being undescended testicles. Two, which is urethral malformation. And then they also have reduced genital distance, low fertility, and outcomes very similar to human testicular dysgenesis syndrome. You can also see this being played out in the male population now. Male born in 2025 is going to have more of these issues than a male born 30 years ago.

17:24 The effects are directly tied to insufficient testosterone signaling during development. So each chemical can cause a pathogenomic profile of defects by its mechanism and combined exposures tend to add up an impact. So outside the womb, adult male rats, given EDCs, also showed lower testosterone levels and testicular atrophy. It's not just happening in utero, it's happening as the organism is exposed to it over a lifetime in its environment. So phthalates have consistently been shown to suppress testosterone in animal studies.

17:55 And then also venclosalin, which is the fungicide I mentioned earlier, causes the male rat to become subfertile and demasculinized due to androgen receptor blocking action. We can also look at the frog example I mentioned. So this is perhaps the most dramatic example. Comes from amphibians, obviously, because they're exposed to water. absorbing much more of these pesticides pound for pound than maybe a mammal would be. But atrazine can emasculate male frogs, causing 75% of the exposed males to become chemically castrated, which they were unable to reproduce at all,

18:28 and a portion to actually turn into females. So the male frog have virtually no testosterone and fail to develop normal male features. Now, if you look again, I'm not getting into the whole gender debate or anything like that. Look at what is happening to the population today. Look into what's happening with males. They are less fertile and they are more effeminate. Is that their fault? Is it culture, is it society, or are they being chemically castrated in utero and during their lifetime, walking around on the planet.

18:58 So while humans are not frogs, it does serve as a proof of concept that environmental chemicals in the water can obliterate testosterone function in animals walking the plan. Similar phenomena has been observed in fish downstream of industrial plants and some waterways contain enough EDCs to cause male fish to develop intersex gonads, which are ovo testes and reduce androgens. It's pretty crazy how that can happen. Now let's look at some human epidemiological studies. So one 2014 study of over 2,200 people found that phthalate exposure was associated with significantly reduced testosterone in boys age 6 to 12 and adults

19:33 age 40, both men and women. So that's man, woman, young or old, their testosterone is being cut in half. Now tell me why the amount of anxiety, depression, lack of purpose on this planet is so rampant today, whether it's among kids or older people. if they don't have testosterone. Why is this not discussed as something that could be an issue with people going on? Just by two cents. So if we look at phthalates, this suggests that phtalates may affect testosterone across the entire lifespan and children potentially affecting development

20:04 and adults contributing to angiopause-like declines. Another study in adult men found pthalate levels correlated with both lower testosterone and higher estradiol and SHBG. And this shows that human studies mirror the animal data and raise red flags about everyday exposures and how crucial those are to it. Let's look at some of these. So we've got BPA and Xenoestrogen. Research has linked high Bpa levels to sexual dysfunction and poor semen quality in men. Some studies on male rodents indicate BpA in utero can reduce angiogenital distance in testosterone in male puppies, similar to phthalates.

20:39 Human data on BPA and testosterone is mixed, but a precautionary stance is warranted since Bpa is widespread and basically in everything. It's in plastic cans, all that. We're exposed to it several times a day on a daily basis. And BpA may suppress testosterone via estrogenic feedback, tricking the body into thinking there's enough sex hormone, thus dampening testosterone production by direct testes toxicity. We also have PFAs, which are the forever chemicals. So a 2024 meta-analysis of 12 studies with over 7,500 participants found that higher blood levels of certain PFAS being PFOA and PFNA were significantly

21:14 associated with lower testosterone levels in men. Again, I know, makes sense, right? But it's just the data is there to make this a glaring issue. These associations align with observations in exposed communities where men from regions with PFAS contaminated water have reported reduced testosterone and semen quality. I would recommend that wherever you are, that you at least look at this. Look at your water quality, look these things. There's really good websites. You can look all this to see what... contaminants are in your water. And one review noted that PFOS and PFOA exposures were linked to lower T and M similar to clinical observations in infertile men.

21:49 So PFAS may interfere with steroidogenic enzymes in the testes and also with liver metabolism of hormones. Let's look at some pesticide information. So, agricultural workers with higher exposure to pesticides like DDT, which I know is an older one, but you could enter a glyphosate or atrazine or whatever, have been found to have lower androgen levels and smaller testicular size. That's a fact. If you work in agriculture and you're exposed to these, you will have a lower testosterone and small testes.

22:19 In the general population, lingering DDE in the body has been inversely correlated with testosterone and associated with impotence or sperm abnormalities. Certain newer pesticides have been tied to altered hormone levels and cross-sectional studies, and then overall people with high occupational and environmental exposure to pesticides show a greater incidence of hypogonadal hormonal profiles than unexposed groups, which is becoming further and further less likely that you're unexhosed. Now we can look at semen quality. So a 2017 meta-analysis by Swan found that total sperm counts in Western man had plummeted by around 50% between 1973 and 2011, and that's just up until 14

22:57 years ago. Who knows how much it's been even since the last 14 So EDCs are the prime suspects. Obviously a 2022 review and endocrine highlights that increased exposure to EDC may contribute to the decline in sperm counts, obviously. So when we look at EDCS, they again bind to hormone receptors, disrupt steroidogenesis, which is the synthesis of testosterone and cause epigenetic changes in germ cells leading to poorer semen parameters and male infertility. And what we are seeing lines up with both human and animal studies alike.

23:28 What are some of the issues when it comes to understanding this system-wide level. One, it's a standard definition. Obviously, testosterone resistance is just a hypothesis right now, so doctors focus on testosterone levels, but you could have normal levels and still have low testosterone. Again, I think this is the issue too, is you can go to the doctor and have a total testosterone of 700. No test that we know of so far, other than looking at your free testosterone, which still isn't the best way to look at it, Is giving us an idea of how much of that testosterone is being exerted and used at a cellular level, because you're gonna have total of testosterone at 700, and it's not going to matter based on what we're talking

24:02 about here. So the symptoms of testosterone resistance are nonspecific and can have many causes like fatigue, low libido, you name it, just being a human in third density now. And like I said, someone could have mid normal or even high normal testosterone yet still experience androgen deficiency. So measuring endocrine disruptors requires specialized, often uncovered tests. So again, the likelihood that we have tests to be able to do this, at least to the mass level, like we do even just total testosterone testing right now is very low. And then obviously too, we just have it blamed on these other things.

24:34 Mild androgen deficiency signs are often dismissed as normal aging. You're getting old. It's not a big deal anymore, right? And so fertility issues may be attributed to other factors where toxins aren't obvious. Now, What can we do to fix this? Well, what I'm going to talk about is some of the baseline things that everyone can do, to help improve their testosterone levels. I have the opinion, doing these alone isn't going be enough, but hey, you can at least cover your bases. So one, improve your food and water. Drink clean water, eat whole food, right? It's the best thing you could do. Try to minimize plastic use, it's almost impossible now, Use safer personal care products and clean the home environment.

25:11 Dust regularly. Clean everything. Get an air filter. I've got a Jasper air filters. One of the best decisions and purchases I have ever made. When we look at diet, we can hydrate and eat plenty of fiber to help eliminate toxins from the body. Support the liver using injectable glutathione. B vitamins, antioxidants are all very important. Obviously sweat, it's huge. If you're not sweating, doing the sauna, exercising, sweating on a regular basis, you are going to burden yourself with a heavier toxic load. And then obviously to clean up, use things like cilantro, chlorella, all those things, right?

25:41 They're all great. You know, that's not what I talk about all the time. I have to say too, I think the biggest thing is to keep fat off your body. When we look at these contaminants, the likelihood that you are going to suffer from them increases exponentially the more fat you have on your body. So if you don't have fat on you body, you at least give yourself a shot. And so this is again why peptide GOP1s, exercise training, diet fasting is also important because it allows you to get the fat off your at the very least,

26:12 how some of those metallites are expressed through DHT and estradiol conversion, and how much SHBG we have. Because a lot of times, even if you're not thinking you are fat, higher fat leads to higher SHGBG, which leads less free testosterone. So again, it doesn't have to be fat. You can be skinny fat you can inflamed, but that's going to an issue. Then just ensure micronutrients, obviously, through supplementation, all the things there. I remember I've always got my Amazon storefront that you check out on the email list. Then manage stress and sleep.

26:42 That's one of the biggest things is make sure we're sleeping enough and de-stressing our body because we already, as we've seen today, are up against a lot of other stuff. Now, what I want to close out with is the real action step here. And you can do all those things that I just mentioned and that's great. But in my opinion, for the average adult in today's world that's really over probably 30 years old, it's not going to be enough to do all those things and be super anal retentive and make sure they're doing all these things because we're still in this toxic soup.

27:14 So in opinion the way to overcome this is with testosterone therapy. I'm going explain why really this going be in the future the only thing that we can do to over come the chemical cascade because I don't see them stopping this anytime soon. plastic being stopped, used anytime soon. I don't see pesticides not being sprayed on food anytime. So let's look at this at the receptor level. Many endocrine disrupting chemicals act as weak androgen receptor antagonists like we talked about. They occupy receptor sites and prevent endogenous testosterone from binding.

27:46 So, when we use testosterone therapy through injections or transcortable cream, I would recommend injections, but either one are really the two best mechanisms, we raise serum testosterone concentrations well above the physiological baseline, and the exogenous testosterone increases the likelihood the receptor sites are occupied by the correct ligand, which is kind of like the key, thereby overriding the partial blockade imposed by contaminants. So according to basic ligand receptor kinetics, the fraction of receptors bound by testosterone versus by an antagonist depends on their relative concentration

28:19 and affinity. So administering sufficient testosterone shifts the equilibrium toward productive receptor activation. And this is also too why a lot of times 100 milligrams of testosterone per week for a man is not going to be enough because it's not enough to actually overwhelm the receptor and kick out some of these things that are circulating in the body. A lot of times it's 200 or maybe even 250 for the man to actually get to symptom resolution. We can also look at bypassing impaired endogenous synthesis. So in testosterone resistant syndrome, toxins can impair the latic and theta cell function, reducing natural testosterone output.

28:57 bypasses the need for endogenous steroidogenesis, which is the production of testosterone in our testes, ensuring that total hormone availability isn't constrained by enzyme inhibition or cell damage. So again, when we're relying on our own production, we are relying those cells in the testees to work properly. But if they can't make the testosterone, even taking a bunch of HCG or HMG, or testosterone boosters is not gonna matter because it's not actually gonna make enough testosterone in the cell, in latex cells, and the testes to be able to work at the receptor level we need.

29:29 So when we look at endogenous production, it may fluctuate and be dampened by toxin-induced luteinizing hormone receptor downregulation and a controlled dosing regimen of exogenous testosterone provides steady, predictable hormone levels, reducing the risk of troughs where resistance effects are most pronounced. Then we can look at optimizing the delivery to maintain therapeutic windows. So another thing that a lot of people mess up was they inject one or two times a week. God forbid you do once every two weeks, which I think is still the AMA recommended dosage.

30:02 So instead of large infrequent bolus doses, splitting the total weekly dose into three or four smaller injections or using a transdermal cream daily keeps serum testosterone within a narrow, highly occupied range, minimizing periods where an antagonist could dominate receptor binding. So again, when we were introducing testosterone in these frequent injections, it's keeping us in that high normal range where we don't have to worry about going down low enough to where now these EDCs can actually kick off the testosterone at the cellular level. And so, Intramuscular and transdermal routes often develop more stable plasma levels than these large injections all at one time.

30:40 So we can look at those more infrequent shallow IM injections to be better. Now let's look metabolic clearance and aromatization. EDC driven upregulation of hepatic CYP enzymes can accelerate testosterone metabolism. Basically that means it changes how fast we clear testosterone. So exogenous testosterone dosed intervals that account for faster clearance ensures that hormone levels don't dip below the therapeutic threshold. So again, we want to keep ourselves in this higher normal, higher, normal slash even super physiological range without dipping low.

31:17 Because if we dip low, even though you think it may be better to have a total testosterone 700 as opposed to 1500, you actually are going to put yourself at risk for these environmental toxins to overwhelm the antigen receptor and basically kick the testosterone out from doing what it's doing. We can also balance the testosterone to E2 conversion. So if pollutants increase aromatase activity, co-administration of metformin alongside testosterone therapy can preserve active androgen levels and prevent

31:48 estrogen overshoot because when we get rid of the inflammation and the insulin resistance in the body, it reduces the amount of aromatase enzyme that we have expressing, which helps testosterone metabolize properly. So when we do this, using metformin, living a healthy lifestyle, getting body fat off, it ensures that more of the administered testosterone remains available for the androgen receptor activation rather than being converted and used properly. You can also look at receptor sensitization. So I think this is important.

32:18 Chronic low androgen signaling can lead to down regulation of androgens receptor numbers. The longer that you have low testosterone, it will actually down regulate how the androgyn receptor works in the body. Sustained higher ligand availability may stimulate andogen receptor up regulation, restoring receptor density over time. So if you take someone, and this is happening for most men in the population now, you decrease their testosterone in a body because of all these things, right? The androgen receptor expression is actually going to down-regulate to which you will now have lower andogen receptor density.

32:51 So try as you may. You are actually in an uphill battle that you can't win. When we introduce exogenous testosterone at a high enough level, it's going to stimulate the androgen receptor to work better over time and increase the density over the time. And so with adequate receptor occupancy, downstream co-activator proteins can assemble more effectively, enhancing gene transcription and normalizing andogen-responsive tissue function. And lastly, let's look at just sex-specific considerations. And again, I know a lot of this probably sounds like it's framed towards men, but testosterone therapy typically involves intramuscular,

33:26 esters, and anthate or septinate dose to 100 to 200 milligrams weekly. So monitoring total free. testosterone, estradiol, LHFSH, hematocrit, and PSA. And in cases of pronounced testosterone resistance, slightly higher starting doses usually are often required. Then also when we look at women, so although baseline testosterone levels are much lower, low dose testosterone therapy, which I would recommend around 10 to 20 milligrams per week, depending on your stage of life, can help outcompete antagonists and target tissues such as the brain, the muscle, bone. You just want to make sure that you are careful with titration and monitoring.

33:59 And with signs of viralization over time to which if you're at the right dose, you really don't have to worry about it. So again, it's all about therapeutic benefit and restoring us to levels that are healthy for us that allow us. To get the effects of testosterone that we desire. That is it for the slides. And that is my summary of Testosterone Resistant Syndrome. I want to close out with this. It is becoming more and more apparent to me, and again, this is just my opinion, don't take this as a judgment or a condemnation,

34:30 that men in today's society are not the men that they were 15, definitely not 30 or 40 years ago, because of the lack of testosterone. And I think people that are even aware of that, assuming that can even rationalize and understand that concept in their head. They look at their total testosterone, they'll say, oh, I got my blood work done and that was 500 or 700 or 800. And they really don't understand how low that actually is because of everything we just talked about.

35:01 So maybe go back 50 years ago, if a guy had a total of 800, that 800 is not the same 800 as it is today. You can look the genetic expression of men in their posture, in in their presence and their mental capability. And you can look at a man that's on testosterone and you could look in a manner that is not on Testosterone and if everything else in there lives are equal, they diet the same, train the the health, same practices and everything. The man on testosterones is going to have a better brain, a body, better life because the man that's not on testosterone cannot out compete these things

35:37 at the cellular level. He can do everything from a lifestyle standpoint, but he cannot compete at a cellular here with the environmental toxins. And that's why you look in the population. I can look at men now and tell men that are on, tell who's on testosterone versus who is not on a testosterone because of how they function mentally, because they look physically and because the life that they live because testosterone changes your life. So I would just hope this video serves as a call to help you understand that if you don't feel like you're supposed to in life and you do not have the

36:11 drive and determination, almost all the time that can be attributed in some shape or form back to testosterone and inflammation in the body, but also to understand there's a reason that men on testosterone typically have so much better function in their life across physical, mental, emotional, spiritual, all those disciplines because Even in the presence of doing everything right, you cannot outcompete the environmental toxins that are ravaging the population right now.

36:43 And I want to speak to women too, because it's very important that women also understand this concept because a lot of women, especially the Perry and Postmenopausal demographic, have no idea they even need testosterone, let alone how much their life could change for the better. And again, the thing with women is like men can like technically do stuff to optimize their testosterone levels naturally, even though it's not really worth it, in my opinion. But women don't really have a choice once they reach a certain age and they go through menopause. And they're just not going to have any testosterone.

37:14 And then by default, they are not gonna have the estrogen because their testosterone isn't being metabolized in estrogen, because there isn''t any of testosterone and so they don't really have a choice to not use testosterone The only choice they have is to either use Testosterone and hormone replacement therapy or to suffer to which most of them end up suffering and no amount of dieting, no Amount of changing their lifestyle can really affect how much testosterone is in their body again because of what we've seen today. So again, There's good news and bad news. The bad new is people now are decimated from a testosterone level standpoint.

37:48 Good news is there is an option. There is option to change the genetic expression yourself and not have to worry about the things, the environment. Not that we don't want to and change our environment to be the most optimal, but we have look at alternative methods because again, no one's stopping the plastic. No one stopping all of the different things that were all exposed to on a daily basis. unless you go live isolated somewhere, which would be cool, but it's just not realistic for 99% of people. So hopefully this was helpful. I would love to hear your feedback on this.

38:19 Whether it was insightful to you, whether you had a light bulb moment or whether it just educational and entertaining. Love to here in the comments of the people I've experienced with testosterone and how much it changed your life. Even, and I think too, there's a lot of guys that I talk to and women that say like, well my testosterone is in normal range. and then they get on testosterone and they really realize how it was not in all range. So if that's an experience you have, feel free to share below. But I appreciate you guys. Thank you so much. And again, from the bottom of my heart, I always close every video. Now, thank you, so, much for the support, whether it's just liking, commenting, subscribing or buying products or being on the email list or whatever it is.

38:51 Really from bottom my, heart the opportunity I have to bring these videos, a message to you is a dream come true for me. I hope that is reflected in the quality the material and that in some way shape or form it changes your life for the better so that you go can go out and make the world a better place yourself so thank you guys so much love each and every one of you and I will talk to you the next one peace