Note: This is a rebroadcast.

When men think about optimizing their hormones, they tend only to think about raising their testosterone. But while increasing T can be important, an ideal health profile also means having testosterone that’s in balance with your other hormones as well.

Today on the show, Dr. Kyle Gillett joins me to discuss both of those prongs of all-around hormone optimization. We start with a quick overview of the different hormones that affect male health. We then get into what qualifies as low testosterone and how to accurately test yours. We also discuss what causes low testosterone in individual men, and how its decline in the general male population may be linked to both birth control and the world wars. In the second half of our conversation, we discuss how to both raise testosterone and get rid of excess estrogen, including the use of some effective supplements you may never have heard of. We then get into the risks and benefits of taking TRT, before ending our discussion with what young men can do to prepare for a lifetime of optimal T and hormonal health.

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Read the Transcript

Brett McKay: Brett McKay here and welcome to another edition of The Art of Manliness Podcast. When men think about optimizing their hormones, they tend only to think about raising their testosterone, but while increasing T can be important, an ideal health profile also means having testosterone that’s in balance with your other hormones as well. Today in the show, Dr. Kyle Gillette joins me to discuss both of those prongs of all around hormone optimization. We start with a quick overview of the different hormones that affect male health. We then get into what qualifies as low testosterone and how to accurately test yours. We also discuss what causes low testosterone in individual men and how it’s decline in the general male population may be linked to both birth control and the world wars. In the second half of our conversation, we discuss how to both raise testosterone and get rid of excess estrogen, including the use of some effective supplements you may never heard of. We then get into the risk and benefits of taking TRT before ending our discussion with what young men can do to prepare for a lifetime of optimal T in hormonal health. After the show is over checkout our show notes at aom.is/optimalt.

All right, Dr. Kyle Gillette, welcome to the show.

Dr. Kyle Gillette: Thank you. My pleasure.

Brett McKay: So you are a medical doctor. You do family practice, you specialize in obesity but also hormone optimization, helping people have healthy hormones so they live a flourishing life. And today I’d like to talk about hormones, particularly male hormones. I think when most people think about male hormone optimization, they think about testosterone and which is obvious why you do that. And we’re gonna dig deep into testosterone today. But are there other hormones that affect male health that people often overlook?

Dr. Kyle Gillette: There certainly are. So even testosterone in and of itself, there’s nothing unique about it compared to other androgens. There’s just one androgen receptor. Testosterone just happens to be the most well-known androgen. So there’s DHEA, which is a very weak androgen. It’s produced by the adrenal glands, which are small glands above the kidney. There’s DHT, which is dihydrotestosterone. This is a very strong androgen. You don’t have as much of it as testosterone, but it’s vitally important for what’s called secondary sexual characteristic development, like the deepening of the voice, growing facial hair, those secondary sexual characteristics which are vital.

Brett McKay: And also I think people often overlook estrogen plays a role in male health.

Dr. Kyle Gillette: Certainly, testosterone aromatizes and directly converts to estrogen. So the way to think about estrogen is the more estrogen the better for your health because it prevents things like heart attacks at a correct ratio to where you feel good.

Brett McKay: Okay, so we gotta have some estrogen in there at the right balance. And then there’s another hormone called SHBG. What does that do?

Dr. Kyle Gillette: So SHBG is also known as androgen binding globulin. It’s a protein, it’s made in many places, the liver makes most of it, but the testes also make some of it. And SHBG stands for sex hormone binding globulin, it most strongly binds DHT and then it binds testosterone, relatively strongly, DHEA weaker than that. And then estradiol, which is your main estrogen, even weaker than that. So think of this as regulating all of the hormones and keeping them more stable. The higher the SHBG, the more stable the level will be. Men produce a lot of testosterone during sleep. So the level is generally much higher in the morning. But if you have a very low SHBG you’ll crash and you can actually have deficient levels of testosterone in the evening routinely. But normal levels in the morning if you don’t have enough SHBG, the most common cause of an SHBG deficiency is insulin resistance, which is often due to too many calories or too many carbohydrates and sugar.

Brett McKay: So what’s interesting about all those hormones is they interact with each other. It’s a complex system so if you raise the level on one, one might go down or up. So I think a lot of guys they get too focused on, well I gotta increase this one thing or reduce this one thing. Well, if you do that you’re gonna have these cascading effects that might not be optimal.

Dr. Kyle Gillette: Correct. I actually heard an advertisement from a TRT clinic this morning and it said new studies shows that men with low testosterone are more prone to cardiovascular disease and early death and diseases of aging. And I thought to myself, this is odd because they are implying that you need testosterone replacement to prevent this. But of course that is a logical fallacy because just replacing the testosterone without figuring out what’s actually causing it in the first place, not that TRT is wrong, but you need to figure out what the cause of it is and then address it.

Brett McKay: Okay. And I hope we can talk about TRT ’cause I know a lot of guys are thinking about doing it or maybe they are doing it and they might have questions about that. Let’s talk about testosterone. So there’s two ways to measure testosterone or two measurements of testosterone that I read about. One is total testosterone and free testosterone. So first, what’s the difference between the two and as a clinician is there a particular number you focus on?

Dr. Kyle Gillette: Yeah, so total testosterone is a total amount of testosterone, whether it’s bound or unbound, when testosterones bound it in general does not bind the androgen receptor, which is on the X chromosome. And total testosterone includes a testosterone bound to albumin, which is the main protein in the blood and also SHBG which we talked about earlier. But free testosterone or any free androgen is what is going to be what is actually binding to the receptor. And then it takes it into the nucleus of the cell and then it binds to DNA to cause what’s called gene transcription. So the androgen receptor gene that’s on the X chromosome is then mostly activated by free testosterone. Oddly enough, sometimes I make the analogy of plumbing. So you have a pipe that’s your bloodstream that takes testosterone everywhere and then you have different types of cells. For example, a muscle cell or a brain cell or a germ cell in the testicle or a somatic cell in the testicle, which we don’t have to get into. But anyway, the free testosterone level can be very different in the bloodstream, which is where we measure it on a blood test versus inside the cell. So it is possible to have symptoms of low testosterone because you don’t have enough androgen in the cell but have a normal level in the blood. It’s rare but it’s possible.

And the opposite is possible, to have a low level in the blood but still have enough inside the cell that’s free to be causing normal gene transcription.

Brett McKay: Okay. So just to recap there, total testosterone is made up of bound and unbound testosterone. Bound testosterone could be bound to albumin or SHBG. And then when it’s bound to those things it can’t attach to the antigen receptor in the cell and so it can’t be… Can’t effect have those changes on the cell. Free testosterone, unbound testosterone is free testosterone. So as a clinician, when you do a blood test on a patient, what number is more important to you? Which one are you gonna be focusing on more? Is it the free or the total?

Dr. Kyle Gillette: I think both are equally important. For athletic purposes, for muscle building purposes. Usually that’s more correlated with free testosterone level. However, symptoms and how you feel is usually correlated more with total. Insurance companies and academic societies usually put more weight into total testosterone, partly because free testosterones are often measured inaccurately so often it’s more accurate to calculate your free testosterone using your total testosterone and your SHBG and then you estimate what your free testosterone is. Some societies say low testosterone is often best treated if you one, have symptoms. And then two, also have a testosterone below about 400. That’s what the urologists say. Most other societies go by 300 and I tend to agree with the level of 400 with a caveat if you have significant symptoms and with a second caveat, if you cannot improve that naturally in any way after identifying the root cause.

Brett McKay: Okay. I wanna dig more into diagnosing low testosterone because there’s lots of commercials out there. You just mentioned one or these businesses popping up where you can just go in, get a blood test and like, hey, you got low T, here’s testosterone and maybe they don’t. So you mentioned two things you look at to diagnose low testosterone, you’re gonna do blood work and if it’s below 400, coupled with if the patient is reporting symptoms of low testosterone, we’ll talk about the symptoms of low testosterone here in a bit, but let’s talk about blood work. ‘Cause I think a lot of guys out there, they think it’s a panacea, if you just take a test, you take the test and it says, oh well, your T is at 400. They’re like, well I got low T. Why isn’t one blood test alone sufficient to diagnose low testosterone?

Dr. Kyle Gillette: Yeah, in general testosterone levels can have what’s called outliers. It’s the statistical phenomenon. But it’s especially true of testosterone where you could check it one time and your testosterone that morning could be low because the last two nights you’ve had poor sleep and poor diet and other lifestyle factors. Males that are generally seeking a TRT prescription know those very well because there’s various things that you can do to artificially make your testosterone level look low that morning. So in general, the recommendation is to recheck it two to three times after a good night of sleep and normal diet and whatever you’re doing normally not after you’ve dieted down to 7% body fat to do an ultramarathon or body building show, then your testosterone is certainly going to be low. But when you’re at a healthy body fat and there’s not an artificial something else that is going to make your testosterone look low. There’s a runner, his name is Nick Bare and he also is doing a body building show and I saw that he got his total testosterone checked and he’s a healthy guy. I’m not sure what his baseline testosterone is and his total testosterone was right at 100 before his body building show.

So that was obviously secondary to the caloric deficit. That wouldn’t necessarily count as a testosterone reading that you could put stock in assessing TRT or not. But for most people they probably won’t be in a scenario like that. But it is important to get at least two readings. If you’ve been sick before, then maybe just postpone the blood test by a week. That way you get an accurate reading.

Brett McKay: Let’s move on to the symptoms. So you do the blood test, what symptoms are you looking for to diagnose low testosterone?

Dr. Kyle Gillette: Yeah, could be through any system. So it could be anything from depression, anxiety to low libido is certainly classic. Low muscle mass is not really one that we look for. Testosterone levels that are naturally produced are not as correlated as people would think with body composition and muscle mass and athletic performance. So it’s not uncommon to see a pretty high level athlete have a total testosterone of let’s say 450 and let’s say someone that has very low muscle mass and maybe even 20%, 22% body fats have a total testosterone of 1000 and there’s not as much correlation. But other things that you would look for seriously is, for example, erectile dysfunction, sexual health in general, sperm production. So if there’s a patient that is having even sub-fertility, just a little bit of trouble getting pregnant, that individual should certainly have a test of his testosterone as well.

Brett McKay: So with low libido, how does a guy know if he has low libido? Because that seems like it’d be pretty subjective.

Dr. Kyle Gillette: Yeah, libido obviously has a lot of psychosocial factors as well. It’s usually taken at a patient’s word and a lot of times when you’re testing these patients, you’ve known the patients for a while, sometimes you haven’t. But if they’re telling you that it’s low relative to what it usually is and no other factors have changed, for example, you know they’ve been married to the same person for five years, they’re not actively going through problems in the marriage, there’s not something else that would be affecting the libido. So that would usually come up in the social history. When you do a history and physical on a patient, it is important to dig into the social history to make sure there’s not something else that is affecting the libido.

Brett McKay: So besides the low libido, maybe the lack of drive, what are the consequences of suboptimal male hormone levels like chronically? Is it gonna affect your cardiovascular system? Is it gonna affect cancer? Does it affect things like that?

Dr. Kyle Gillette: It will. If someone is significantly hypogonadal for a long time, they’re at much higher risk of osteoporosis, which leads to bone fractures and even mortality as well. They’re at higher risk of neurodegenerative disease, likely largely due to low estrogen. If you don’t have a lot of testosterone, you’re probably not converting a lot of it to estrogen and if you’re not doing that then you’re also at risk of cardiovascular disease. Estrogen is very cardioprotective and helps with the production of good cholesterol to help take cholesterol out of the plaque. So they’ve done studies and you look at one group of people that have true hypogonadism, which is generally two levels under 264 or so, and then one group you give TRT and then one group you don’t give TRT, you would think that the group that you give TRT would’ve a shorter lifespan ’cause androgens do cause excess production of “bad cholesterol.” They do increase a particle called ApoB, which is the most important one to watch for cardiovascular risk. But the group that you give TRT actually has less heart attacks and strokes.

Brett McKay: Right, because what you were saying before, the testosterone creates estrogen and then the estrogen protects the heart. So let’s talk about the causes of low testosterone. What can be behind low T?

Dr. Kyle Gillette: Most commonly, metabolic syndrome. So excess calories, excess carbs, insulin resistance, high fasting insulin leads to the liver not producing SHBG. So you might be producing a decent amount of testosterone but it’s being metabolized so fast that it’s difficult to use. That’s most common. The second most common I think is sleep apnea or obstructive sleep apnea. Obviously that kind of goes hand in hand with metabolic syndrome but often it goes hand in hand with PTSD. I saw a study on young men that had just gotten out of the military and they had been diagnosed with PTSD and they tested them all for sleep apnea and something like 80% of them had sleep apnea and they were all under under a BMI of 25. So there’s certainly a lot of stress component as well. The limbic system includes places like the hypothalamus and the amygdala and downstream to that is the hippocampus and the amygdala, downstream of those is the hypothalamus and that’s some of the places of the brain that are involved in sleep regulation and breathing.

So the theory is that apneic episodes don’t just come from having a huge neck and excess body fat, but there are other factors like trauma at play. And when you have a patient with severe sleep apnea, they have a score called a AHI score and if that score is very high, like 100 or 200, you almost always see deficient testosterone levels.

Brett McKay: Okay, so having metabolic syndrome, being overweight, sleep apnea, any other causes of low testosterone?

Dr. Kyle Gillette: Yeah, so theoretically xenoestrogens could be a cause of low testosterone. These are things like phthalates. These are also things like bisphenol A, also known as BPA, you might see BPA free on water bottles from time to time. These do bind various estrogen receptors and are likely suppressive. By suppressive, I just mean they shut down the production of the hormones that lead to testosterone production to some degree. Heat damage is also kind of an honorable mention. Some people might be familiar with what varicose veins are. Varicocele is where there’s varicose veins in the scrotum and some people with varicocele can have venous cooling very well. The testes wanna be about 91 to 92 degrees where the body is 98.6 degrees. So if you can’t keep your testes at 91 or 92, then you’re going to have less testosterone production and less sperm production. And in the more severe cases you’ll have atrophy, which is shrinking because, think about them as factories. If you’re not using the factory, they start to shut down.

Brett McKay: And besides these lifestyle factors and environmental factors, you could also have just an issue with your pituitary system, right? You might have a tumor or something in pituitary gland that’s dysregulating the release of hormones.

Dr. Kyle Gillette: Correct. I suppose that would be likely one of the more common less modifiable risk factors. There’s not a lot that you can do about that. You can take supplements like vitamin B6 or like vitamin E, but a lot of times pituitary microadenomas or even macroadenomas, basically it’s a small tumor in the brainstem. The pituitary gland is where you make a lot of different hormones like growth hormone and like LH and FSH. But LH is the main hormone that’s produced there that leads to testosterone release. So there’s two different types of hypogonadism. There’s primary and secondary. So primary is where the testes are not functioning. And then secondary, think about it, it’s two steps instead of one step. So the LH can be low in secondary hypogonadism and if your LH is very low and a hormone like prolactin or IGF-1 is very high, then that might be a sign of a pituitary micro adenoma. In which case you need MRI.

Brett McKay: And LH, that’s Luteinizing Hormone, correct?

Dr. Kyle Gillette: Correct. LH is Luteinizing Hormone. FSH is follicle stimulating hormone. They do crosstalk to some degree, but LH mostly helps with testosterone production and mostly binds to the Leydig cell in the testicle. And FSH mostly binds in the seminiferous tubules and helps with spermatogenesis.

Brett McKay: So I mean listeners have probably heard reports that T levels in men have been declining in the past few decades. Do we know what’s causing this sort of general decline? Is it just all these lifestyle, like people are getting fatter, there’s not sleeping, they’re stressed, and the stuff in the environment is that kind of what we’ve decided is the cause of the lower T levels?

Dr. Kyle Gillette: The various causes that we’ve already discussed are likely the primary causes of what is causing declining testosterone levels. But I think there is another factor, and a lot of that has to do with what I’d call epigenetic drift. Some people might call it natural selection, I might call it unnatural selection, where individuals with higher testosterone levels are no longer being selected for as early. And also a lot of individuals are having kids later on in life, for example, in their 30s or even 40s, when you might have very different maternal and paternal hormone profiles. That’s one of the reasons why I recommend if men are taking medications like Finasteride or Dutasteride, that they stop their Finasteride 90 days before attempting conception and they stop Dutasteride, depending on what dose they are, usually six months before conception. By the way, spermatogenesis takes about 60 days or two months. That way they have enough time to wash out before they start producing the sperm in the germ cells so that they wouldn’t pass down any epigenetic changes to potential offspring.

Brett McKay: Okay, so maybe this is… The idea is that… Again, this is theoretical, right? The testosterone increases aggression and risk taking behaviors and that’s not as adaptive in our safe high tech modern landscape. So men with lower testosterone might be more successful these days and women choose those men for their partners and then when they have children, the men pass down his genes and then his children have lower testosterone too. And that just perpetuates, just lower testosterone in the male population overall. Also, this idea of selection, I’ve heard that, I read this somewhere, correct me if I’m wrong on this, that women on birth control, they’re not attracted to higher testosterone men. Is that true?

Dr. Kyle Gillette: Yeah, that is one of the major players of what I would call unnatural selection. Another interesting unnatural selection, I suppose, if you look at, not very recently, but the World Wars, certainly in World War I and World War II or in the Korean War or Vietnam War, but especially wars that… Even if a war has a draft, the individual that has higher testosterone and also more sensitive androgen receptors, so this is probably true throughout all of human history, you would… And this obviously cannot be proven scientifically, but theoretically that individual would be more likely to volunteer to go to the front line or to very risky positions. And if that male passes away at age 18 or age 19, then that is likely a fecundity rate of zero. So no offspring from that individual and then you start to have genetic drift.

Brett McKay: Okay, so again, this is theoretical, what you’re saying is that men with very high testosterone, they’re gonna take more risk and in doing so, that may take them out of the gene pool by taking those risks. And there’s more opportunity for that sort of risk taking during big global conflicts like the world wars, right? More high T men die, they lose the chance to reproduce and pass on their genes. And then that just contributes to the declining testosterone in men in general. And that’s gonna have echoes through the generations. And on top of that, we have selection factors going on in the mating market as well.

Dr. Kyle Gillette: Yes. And it’s not like it’s an be all end all. All or nothing. You select for high testosterone or you select for low testosterone. There’s a lot more psychosocial factors at play, but we are certainly seeing that there’s likely a decline in testosterone even a bit more than could be accounted for by just metabolic syndrome and sleep apnea. Maybe things like heat damage to the testicle, maybe things like xenoestrogens are playing some part in this, but we’ll probably never know. But it’s very fun to speculate about it.

Brett McKay: Well, the heat damage to the testicle, what would… Causes like keeping your laptop on your lap, sitting down a lot, would that cause heat damage?

Dr. Kyle Gillette: Probably not significantly enough, but if you already had a Varicocele and you already spent an hour in the jacuzzi, keeping your really hot laptop and phone directly over your scrotum is certainly not gonna help. I suppose someone could prove this at some point. They’ve actually done a lot of studies where they look at the scrotal temperature and they’ve randomized two groups of usually, college students and one group they have wear basically like a sock around their scrotum that has something really warm in it. So they warm up the scrotum artificially to 98 degrees instead of 91 or 92 degrees. And in the individuals that don’t have varicocele, they can still overcome that heat damage because their venous pooling mechanism is so good at buffering that heat damage. So that did not affect their testosterone production and it did not affect their spermatogenesis. However, in individuals that already have impaired venous cooling, for example, with varicocele or varicose veins then it did.

Brett McKay: We’re gonna take a quick break for a word from our sponsors. And now back to the show. Let’s talk about optimal levels of testosterone. So below 400, and if you’re experiencing low testosterone symptoms, that’s not good. Is there an optimal level, as like a level that guys should reach for or is it gonna differ from man to man?

Dr. Kyle Gillette: It certainly differs, but that’s kind of an easy answer. So I’ll get into it more than that. A lot of times people have told me that I say individualized, I say that word a lot because health is individualized. We are all unique, we have different genetics, we have different epigenetics and we have different growth and development past that as well. But for most men, an optimal testosterone level is between about 500 and as high as you can go naturally. So there is some individuals with a total testosterone of 1500, they almost always have really high SHBG. So a lot of times their free testosterones only 20 or 25, between about 550 and whatever you can produce top in endogenously naturally without medication.

Brett McKay: But you also said it could be lower. I mean you mentioned there are athletes who are at 450 and they’re healthy. So if you get a blood test and it’s below 500 a little bit, you probably… I mean, I guess you shouldn’t worry too much about it if you’re not experiencing any symptoms.

Dr. Kyle Gillette: Correct.

Brett McKay: Okay, that’s good to know. So let’s say a patient comes to you reporting symptoms of low T, you do a series of blood tests that show yeah, that your T levels are low, they’re below 400. What’s your first line of attack in helping this patient get his T levels up?

Dr. Kyle Gillette: First thing to look at would be LH and FSH. If those are really low, then I’m worried about the pituitary or the brain. If those are really high, then I’m worried about the health of the testicles. If they’re in between, then I look for another pathology like diabetes, metabolic syndrome, insulin resistance, sleep apnea, etcetera. I also look at prolactin and IGF-1, make sure you assess their tumor risk. And then I also look at estradiol. If it’s a very high estradiol, then estradiol is likely what is suppressing the production of LH from the pituitary. So you have estradiol, which is your main estrogen, which is causing less testosterone production. And in that case, I look at things like alcohol consumption that can up-regulate aromatase or consumption of excess calories or fat that can up-regulate aromatase, which converts testosterone to estrogen by the way. So those are the first things.

Brett McKay: Beyond that, what are you looking at?

Dr. Kyle Gillette: Beyond that, I’d like to, if pertinent, do an exam, make sure, especially if this individual is developing, if they’re an adolescent or whatnot, you need to make sure that they’re through all the tanner stages. Basically tanner stages one to five, five is done, when you’re essentially adult growth and development to make sure that they don’t have some unusual or unlikely syndrome. And then after that I’d like to look at their fasting insulin, their A1C, see if there’s something that I can correct. I look at their cortisol. If their cortisol is high, then there’s a lot of lifestyle factors and also supplements that can help control cortisol like Ashwagandha or Emodin. I look at their prolactin. So if their prolactin is just a little bit high, then maybe I do start them on some Vitamin B6 or some Vitamin E. If their estrogen is high, maybe I start them on some Calcium D-glucarate that helps with estrogen glucuronidation and metabolism. It basically helps you excrete it through your stool and then repeat labs in one, two, maybe even three months and see if we can improve those things along with, as always, diet and exercise.

Brett McKay: Okay. So it sounds like the first line of attack, if it’s not a pituitary problem, you’re gonna be primarily doing lifestyle changes, right? Quitting drinking, getting better sleep, diet, exercise to help get that insulin sensitivity back online. So yeah, lifestyle stuff would be the first line of attack and then will it take maybe one to two months before you start seeing results from that?

Dr. Kyle Gillette: Yeah, often it does. A lot of times you feel better the first week and a lot of times your testosterone production recovers very quickly. But occasionally, I use medications as well. So some people utilize a short course of HCG, which essentially binds the LH receptor, takes the place of LH and occasionally, I’ll utilize very short courses. By very short, I mean, a week or maybe two weeks of selective estrogen receptor modifiers or sometimes longer in the right patient, especially very young patients that you’re trying to stimulate endogenous production, these are often patients that desire fertility within the near to mid near future.

Brett McKay: Besides diet, exercise, sleep, managing stress, you mentioned a few supplements that you recommend men taking to optimize male hormones. Are there ones that you recommend for just any guy who… Maybe they don’t have any problems with testosterone but they just want to feel good? Are there ones that you like and that are safe?

Dr. Kyle Gillette: Creatine 5g-10g a day would be a great start. L-carnitine would be a consideration, especially if they’re interested in athletic performance optimization or body composition optimization, L-carnitine would be reasonable. Consider checking a TMAO to make sure that it doesn’t convert to that in too high of a rate. Another reasonable addition if someone has high estradiol would be Calcium D-glucarate to make sure that they’re binding up extra estrogen and excreting it.

Brett McKay: I’ve heard that Boron can impact testosterone. How does boron increase T levels?

Dr. Kyle Gillette: Boron works okay for people with really high SHBGs. It increases free testosterone by decreasing SHBG. The effect wears off to some degree if you take Boron for a very long period of time. If you have very low levels or you’re insufficient or deficient in Boron, it works extremely well and a lot of people consume Dates or Raisins because they tend to be relatively high in Boron.

Brett McKay: There’s another something I’ve been hearing about lately, Tongkat ali, I think that’s how you pronounce it. What’s going on with that one?

Dr. Kyle Gillette: Tongkat ali is also known as Longjack. So Tongkat’s active ingredients are Eurypeptides, one of which is Eurycomanone. And Tongkat is helpful because it upregulates a couple different enzymes in the steroidogenesis pathway. There’s been plenty of human study on it, with mixed results and it looks like the cause of the mixed results is, sometimes people have great activity of those enzymes. So that’s not the rate limiting step in testosterone production. So think of it as a signal, think of your testicles as a factory. Tongkat is a signal to that factory to ramp up production, but if your factory is already operating at maximum capacity or it’s limited by something else, then that’s not going to improve your testosterone level. Tongkat works on very similar enzymes that are also upregulated by insulin and IGF-1. So in general, if you’re in a caloric deficit or if you’re trying to lose weight or body fat, Tongkat will work better. If you have a low fasting insulin or a lower end IGF-1, Tongkat will also likely work better. And I’ve seen this anecdotally as well.

Brett McKay: A couple years ago, I remember ZMA was a big supplement that was pushed for increasing testosterone levels. Anything to that?

Dr. Kyle Gillette: ZMA is very reasonable to add if you have a low alk phos. So if you look at your CMP, which is your metabolic panel, there’ll be an enzyme called alkaline phosphatase. Alkaline phosphatase along with GGT are two intracellular enzymes. And the lower these two are the more likely you are to have insufficient levels of Zinc and magnesium. That’s why when I have input to various companies designing a supplement to optimize testosterone, I almost always put in Zinc, Magnesium and Vitamin D. You just wanna make sure these aren’t the right limiting step. Think about trying to optimize your testosterone is like trying to get into a fraternity. You’re not just making best friends with one of the people and then just hoping that nobody else will blackball you. You wanna make sure that you address each individual because if you… Let’s say you forget your Vitamin D and forget your Zinc, you’re deficient in Zinc, you’re deficient in Vitamin D, those two things will hold you back.

Brett McKay: Once you start down this path of increasing your testosterone or getting them optimized, is there any benefit to getting them higher? So let’s say you started off at 400, you had low T symptoms and then through lifestyle changes and maybe taking some supplements, you bump it up to like a 700. Are you gonna get any more benefit from testosterone by getting it up to 800 or 900?

Dr. Kyle Gillette: Past about 600, there’s little to no benefit, other than bragging rights.

Brett McKay: At what point would you have a patient go on testosterone replacement therapy?

Dr. Kyle Gillette: At any point when the risks outweigh the benefits and they understand both the risks and the benefits in their own terms.

Brett McKay: So what are the risk of TRT?

Dr. Kyle Gillette: Yeah, one of the risks is it causes more fluid retention and swelling. One of the risks is if you hyper convert to estrogen, estrogen will then bind to the liver and cause more SHBG and platelet production. And if your platelets go very high past a certain point, we know that people on oral estrogen, the blood clot risk is associated with how high their platelets and SHBG go. It’s likely the same for TRT. So if you go on TRT and you go into a huge bulk and you start consuming a bunch of alcohol and your platelets skyrocket, then it is gonna increase your blood clot risk. So TRT is not in and of itself going to improve health, it’s just going to be a tool to help you achieve a lot of your goals. Another risk of testosterone is if people have heard of medications called statins. Those work by decreasing the activity of an enzyme called HMG-CoA reductase. Any androgen including testosterone increases the activity of this enzyme. So often people’s cholesterol and it’s not actually cholesterol, they are lipoproteins, but people’s “bad cholesterol” gets worse. That’s why we watch that ApoB number very closely because we know that ApoB is the particle that is going to lead to plaque formation in areas like the coronary artery.

Brett McKay: And I guess the benefits of TRT is that you’ll mitigate those symptoms of low testosterone?

Dr. Kyle Gillette: Correct. And there’s of course other benefits as well like the benefits of estrogen, that we discussed earlier, being it’s cardioprotective benefit. And one of the main benefits of testosterone in a lot of individuals that I see start is they might have a… Let’s say they have an A1C of 5.7 or 5.8, which is technically pre-diabetes. You’re very unlikely to get diabetes on testosterone compared to if you are not on TRT. So a lot of individuals, perhaps they’re, I wouldn’t say doomed, but very likely to get diabetes and TRT can make a huge difference, especially when combined with other insulin sensitizing medications to prevent that.

Brett McKay: Do you keep people on TRT indefinitely? Is it like once you start to keep doing it or are there periods where you’re like, “Well, we’re gonna take you off and see what happens” or well how does that work?

Dr. Kyle Gillette: Most individuals are on indefinitely, but not everyone. Occasionally there’ll be a patient that is profoundly hypogonadal and the benefit of testosterone at that time is just huge. Let’s say it’s a patient who has a BMI of 40 and they weigh 400 pounds and they also don’t have a huge amount of lean body mass to lose in proportion. Everybody who weighs 400 pounds is gonna have a lot of lean body mass, but just less relative to your average person and they wanna maintain as much of that as possible. They need that tool in order to exercise, even if it’s somewhat of a placebo tool, that still helps. So if it gets them having a very healthy lifestyle, they go on that medication, perhaps they go on another medication like a GLP-1 for a short period of time and then they don’t really know what their baseline testosterone is. So maybe after two years they’ve learned those lifestyle interventions. They very slowly are ready to come off of every medication and then you can use a medication like HCG to help restore natural production. Perhaps one week of a medication like Enclomiphene or Novedex or even Raloxifene. And then you see what their natural production capability is. You give them a few weeks and perhaps they restore to a total testosterone of 600s, which is likely quite good in that situation or perhaps they go down to 100s again.

But a lot of people would want that chance to go back to producing their testosterone naturally. And in some cases it does work. I would say 90% of people that start on testosterone are going to remain on it indefinitely. But I would also say that 90% of people that go on testosterone can very likely regain at least their previous level of testosterone if they were to want to come off.

Brett McKay: Well, here’s a question. With female hormone therapy, you might start taking it during menopause to help with symptoms, but at a certain point, once menopause is over, I think you’re supposed to get off those hormones. Does something like that happen for men? I mean, you might do TRT throughout your 50s and 60s and then at a certain point you’re in your 70s and you’re like, Well I don’t need to do this anymore. Or are there 80-year-old or 90-year-old guys taking TRT?

Dr. Kyle Gillette: There are 80 or 90-year-old guys taking TRT. Occasionally, you’ll do a dose adjustment. It just kind of depends on the situation, but a lot of times when males reach that age, they are less likely to have as much benefit and they are more likely to have slightly more harm. So it’s a moving target over time where you get out the scale and you’re weighing the risks and the benefits and at that point when a patient’s already on TRT, you also weigh the risks of how difficult it would be to come off, which is not extremely difficult. But it is difficult because there’s medication regimens that you have to go with and even with those medications often there is a short period of time when you don’t feel great.

Brett McKay: So we’ve been talking about optimizing male hormones in grown men, but let’s say we got some dads and moms out there listening and they’ve got boys who are about to start or are in the middle of puberty. What can they do for their sons? What can young guys do to make sure they set themselves up for a lifetime of male hormone optimization?

Dr. Kyle Gillette: First and foremost, no huge dirty bulk in early adolescence. What I mean by that is, I mean, let’s say there’s somebody that’s trying to put on weight for football or whatever other reason, can’t think of any reasons where it would be worth it, but they’re putting on weight and also putting on fat. Adipose tissue in fat, adipose tissue is fat, that is going to increase the conversion to estrogen and estrogen is gonna close the growth plates of the bone. So that’s gonna prevent you from reaching full stature, both in height and other areas of your skeletal developments as well. So that’s a great initial recommendation. Thinking about gut health and fiber consumption is also very important. That’s gonna prevent, again from over, it’s called intrahepatic circulation of estrogen. Estrogen is not necessarily the enemy. In fact, a little bit of estrogen is neat to what’s called priming the pituitary in order to fully kickstart adolescence.

And that’s one of the reasons why boys with very high body masses have higher estrogens. The pituitary gets primed too early and something called precocious puberty is happening, which is too early of puberty. So that’s another thing to consider. In addition to that, you wanna have a reasonable balance between cardiovascular exercise and resistance training. You certainly want to do both because adolescents can be thought of as your free endogenous steroids of, I’ll say cycle, just because people understand it. But your free endogenous steroid boost where you know you are going to be one, super sensitive to all the androgens that are released, probably most people remember puberty and you’ll also be having a lot of androgen around, regardless of what you do, even if your health hasn’t been great. So when that endogenous steroid burst happens, that is the perfect time to take advantage of those lifestyle tools to build up very high bone mineral density and very high lean body mass without putting on excess body fat.

Brett McKay: I imagine young people getting plenty of sleep is important too.

Dr. Kyle Gillette: Yes, extremely important. And that might be one of the most common causes of suboptimal hormone profiles in adolescents.

Brett McKay: What about supplementation? Is supplementation something you encourage in young people to optimize their hormones or is you just focus on the diet and exercise?

Dr. Kyle Gillette: With the oversight of a doctor, I do encourage supplementation, if it makes sense. For example, let’s say there’s a young person and they get a stool test and the beta-glucuronidase enzyme is very high. We know that that individual is just recycling their estrogen over and over again, that makes something like a Calcium D-glucarate or with the oversight of the doctor maybe even a very low dose of an aromatase inhibitor, a very reasonable addition. And then if you get blood tests, you can actually check the hormones to make sure that they’re increasing at the correct rates, that your DHT is optimal, your testosterone’s optimal, your estradiol is optimal, your IGF-1 is optimal, and then you can tweak a supplement. Supplements are just like medications, they have pharmacologic effects so they have an effect on the body and the body metabolizes them.

So things like Creatine can be very reasonable. Creatine does not affect the development of the kidneys. I did a podcast with my good friend James O’Hara recently. We get a lot of questions from pediatricians because the AAP, which is a society of pediatricians, still recommends no Creatine supplementation whatsoever up to the age of 18. So not even, not even a 17-year-old. So I just kind of thought that was… And it’s been 15 years. So they’re gonna update their recommendation within the next couple years whenever they have a joint meeting. But that’s definitely a vestige of times past when we thought that Creatine was harmful to healthy kidneys. You just check a Cystatin C because Creatine makes your creatinine blood marker look abnormally high. Falsely high. So Creatine can make sense in a lot of kids as well. And then if there is a kid that has really low insulin IGF-1, sometimes Tongkat makes sense in that individual.

And then in some kids that do have optimal hormone profiles, let’s say there’s an athlete and he’s developing or she’s developing and they have very high testosterone, very high IGF-1, that’s great, you know that Myostatin levels are gonna be really high after you have that burst of androgen during adolescence. Myostatin is gonna stop the muscle from developing and cause you to start putting more fat into the tissue. I think that Myostatin inhibitors, week ones like Fortetropin, which comes from fertilized egg yolks or Epicatechin. CocoaVia is a good source of Epicatechin. Different cocoa powders have a lot of Epicatechin. Green tea has EGCG, which is another Epicatechin. Basically, those take down the levels of Myostatin. Those are also very reasonable to take for the right patient.

Brett McKay: What about, should parents be sweating about xenoestrogens in their kids? Like, make sure they get certain types of deodorants or cosmetic products and avoiding plastics?

Dr. Kyle Gillette: Bisphenol A and phthalates. Yes. That’s kind of where I personally draw the line, where if you are worried about every single thing, we live in an unnatural environment, more so than ever. So those are usually the ones that I say to avoid. If you live in an area that more likely has contaminants and microplastics, a lot of times I do recommend testing your water. There are a lot of services that do this. I personally used MyTapScore to test both the water, from the tap and the water through my Berkey filter. If you have young children. And that seems like a very reasonable time to use a water filter if you don’t know what the contents of your water is. And then as far as foods, of course, avoiding ultra processed foods, I think, it was ultra processed mac and cheese that got a bad name for having high phthalates. I assume they fixed that by now, but I actually don’t know. So a lot of times it’s the same recommendations as any other whole food diet. And then know your sources, try to avoid contaminants at very high levels and use the Pareto principle, try to do right most of the time and you’ll get most the benefit even if you’re just doing it some of the time.

Brett McKay: Well Kyle, this has been a great conversation. Where can people go to learn more about your work?

Dr. Kyle Gillette: My hub is on Instagram, kylegillettmd, and it’s Gillett Health on all other platforms. I do have a podcast that we fairly recently have, I guess, gotten pretty good audio and video of, but that’s on YouTube, Spotify and Apple Podcasts. We have a clinically, I guess, a clinical grade podcast. And then we have a layman’s podcast that we’re gonna call After Hours, which should provide good entertainment.

Brett McKay: Fantastic. Well, Dr. Kyle Gillett, thanks for your time. It’s been a pleasure.

Dr. Kyle Gillette: Thank you.

Brett McKay: My guest today was Dr. Kyle Gillett. You can find more information about his work at his website, gilletthealth.com. Also, check out his podcast, Gillett Health podcast and check out our show notes at aom.is/optimalt where you’ll find links to resources where we delve deeper into this topic.

Well, that wraps up another edition of The AOM podcast. Make sure to check out our website at artofmanliness.com, where you can find our podcast archives as well as thousands of articles that we’ve written over the years about pretty much anything you think of. And if you’d like to enjoy ad-free episodes of the AOM podcast, you can do so on Stitcher Premium. Head over to stitcherpremium.com, sign up, use code MANLINESS at checkout for a free month trial. Once you’re signed up, download the Stitcher app on Android or iOS and you can start enjoying ad-free episodes of the AOM podcast. And if you haven’t done so already, I’d appreciate if you take one minute to give us a review on Apple podcast or Spotify, it helps out a lot, and if you’ve done already, thank you. Please consider sharing the show with a friend or family member who you think could get something out of it. As always, thank you for the continued support. And until next time, it’s Brett McKay, reminding you to not only listen to the AOM podcast, but put what you’ve heard into action.