Tools for Hormone Optimization in Males | Dr. Kyle Gillett

Andrew Huberman 0:00 (instrumental music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. Kyle Gillett. Dr. Kyle Gillett is a dual board-certified physician in family medicine and obesity medicine and an expert in hormone optimization. He is an MD, that is a medical doctor, and he treats patients with a variety of backgrounds, ages, and goals. Today, we discuss male hormone optimization. We discuss behavioral tools, nutrition-based tools, supplement-based tools, prescription drug-based tools, and their interactions in determining overall levels of testosterone, free testosterone, dihydrotestosterone, estrogen, growth hormone, thyroid hormone, and many other hormones that impact mood, libido, well-being, strength, cognition, and various psychological factors. We've covered hormone optimization in both men and women in previous episodes of the Huberman Lab Podcast, but today's discussion is different. Dr. Kyle Gillett offers very specific recommendations for people with different goals and of different ages, and we get deep into the weeds of, for instance, how does one know whether or not their testosterone is optimized or not, how often to test for specific hormones such as testosterone and other hormones, and really how to gauge how good one should feel. This is something that's often overlooked in discussions about hormone optimization or health optimization of any kind for that matter. For instance, people will talk about reduced libido and discuss whether or not testosterone levels are to blame, but how does one calibrate their libido in the first place? That is, how does one know whether or not their libido is normal, too low, or too high? We also discuss, for instance, whether or not hormone optimization should be pursued continually throughout the year, for instance, whether or not you should cycle on and off supplements and/or prescription drugs geared towards hormone optimization, and we discuss the behavioral foundations of optimal hormone function. These are things that every male should be doing and various things they should actively avoid if their goal is to have healthy hormones and to, quote-unquote, "optimize" their levels of every hormone from growth hormone to testosterone at any stage of life. And while today's discussion is about male hormone optimization, I want to emphasize that we discuss all the various ages for male hormone optimization. So for those of you that are parents, for those of you that are young, those of you that are middle-aged or old or teenagers, we explore adolescent, puberty, teen and late teens, early adulthood, adulthood, and into the late geriatric ages. So regardless of your age and whether or not you are male or female, today's episode ought to be of interest to you. I should also point out that we will soon also be hosting an expert guest on female hormone optimization. One thing that I'm certain people of all ages and biological sex will enjoy about today's conversation is that we also get into descriptions of how psychology and life events impact hormones and how hormones impact our psychology and the way that we show up to various life events. So today is really a broad overview that goes all the way down to fine details about male hormone optimization, and I'm certain that by the end of today's episode, you'll have an immense amount of new information about how this endocrine, that is hormone system in your body works, and how it interacts with your brain and other tissues, and many, many actionable tools that you can pursue regardless of stage of life.

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Andrew Huberman 7:43 Gillett. Dr. Gillett, great to have you back.

Dr. Kyle Gillett 7:46 Great to be back. Thank you.

Andrew Huberman 7:48 I'd like to begin with a question about one of the most mysterious and important phases of life, which is puberty. I've long wondered whether or not how quickly somebody goes into puberty, so at what age, and how long puberty takes, so how brief or protracted that puberty is for them to acquire the so-called secondary sexual characteristics. Things like hair growth on the face for males, uh, changes in bone and muscle, density and growth, et cetera. You know, when I was in middle school and high school, I noticed that some people transitioned into all that very fast and some-

Dr. Kyle Gillett 8:25 Mm-hmm.

Andrew Huberman 8:25 ... people, uh, took a long time to acquire those characteristics. Can we learn anything about ourselves, our hormones, and maybe even how long we're going to live based on the time in which we enter puberty and how long it takes us to progress through puberty? And I guess that also raises the question, does puberty ever truly end?

Dr. Kyle Gillett 8:46 There are many takeaways from puberty. Um, some of the actionable items from it is, yes, it can and does affect your adult height and also stature and also body composition. So puberty is a time, um, and, uh, if you're, if we're talking specifically about males, think of it as a, a time where if you have obesity as a child, you could potentially use that time to change your lifestyle and habits and reset things and it is a bit easier. It's almost like a, a free injection of testosterone and metabolism and drive and effort into your life. There is a wide variation in, um, how quickly puberty goes through. So there's stages called Tanner stages, which we don't necessarily need to get into, but if you enter puberty very early, then it can, uh, decrease your adult height or stature.

Andrew Huberman 9:45 So for a given male that enters puberty at 13 versus a male that enters puberty at 15, can we say that the guy that entered puberty at 13 is going to be shorter than the guy that e- entered puberty at 15? Or it's not quite that straightforward?

Dr. Kyle Gillett 10:01 If they are identical twins and the individual who entered puberty at age 13 also finished puberty, went all the way through the Tanner stages, and if you do a bone scan, which I believe is usually done on the left wrist, and it says, "Yes, your growth plates are mostly closed," you're not gonna grow more than a couple inches of height after that.

Andrew Huberman 10:20 Okay. Uh, just a related question. When I was growing up, it was thought, or at least people would say that, uh, resistance training, in particular lifting heavy weights, could stunt one's growth. Is that true or false?

Dr. Kyle Gillett 10:37 It is false when you're talking about just lifting heavy weights. Dirty bulking certainly has the potential to stunt one's growth for-

Andrew Huberman 10:44 Could- (laughs)

Dr. Kyle Gillett 10:44 ... for two main mechanisms.

Andrew Huberman 10:45 Could you define dirty bulking?

Dr. Kyle Gillett 10:47 Ugh. So (laughs) uh, dirty bulking is eating an excess of calories not just to acquire lean metabolically active body mass or get stronger, but, uh, purposely acquiring body fat.

Andrew Huberman 11:02 So purposely acquiring muscle and fat by overeating-

Dr. Kyle Gillett 11:06 Yes.

Andrew Huberman 11:07 ... and lifting weights can stunt one's growth. Do I have that correct?

Dr. Kyle Gillett 11:11 Correct. So it does two things. If you're doing it as a very young child, it can, that fat can pro- can become leptin-resistant and it can produce more leptin, and that leptin can activate the hypothalamus, which activates the pituitary, which releases gonadotropins, which basically just increase testosterone and estrogen earlier than it otherwise would have. It's the same mechanism behind why childhood obesity causes early puberty.

Andrew Huberman 11:39 Interesting. I do remember a paper published in Science Magazine, I believe it was, uh, focused mainly on females, but showing that when enough body fat accumulates, the hormone leptin is secreted and that triggers the onset of puberty.

Dr. Kyle Gillett 11:51 Correct.

Andrew Huberman 11:52 Given the, uh, increase in, uh, childhood obesity that we're observing now, are we seeing an earlier onset of puberty in males and females?

Dr. Kyle Gillett 12:01 Yes, in both males and females. Not to get too technical, but there's a G protein-coupled receptor on the hypothalamus and leptin directly binds it, so it does appear directly causatory and not just correlation.

Andrew Huberman 12:14 Okay. So, and if I understand correctly, what you're saying is for a young guy, let's say 13, 14, who wants to really bulk up and deliberately, deliberately, excuse me, overeats and is doing their squats and deadlifts and bench presses and really trying to get big, they will get big, but only in the lateral dimension. They are n- they're effectively limiting their total height and it can shut down the long bone growth of, of their limbs. Is that correct?

Dr. Kyle Gillett 12:42 Correct. The, the growth of the long bones is mostly related to the estradiol alpha receptor, so basically one of the receptors for estrogen, which can be secondary to, uh, early puberty, and also is related to body fat because you have that conversion of testosterone to estrogen.

Andrew Huberman 13:00 So can we assume that if a young male wants to get into resistance training, that bodyweight exercises are probably okay, and maybe even some weight training, kettlebells, et cetera, but that they should avoid doing so-called dirty bulking, trying to deliberately gain weight, up until what age? Until puberty is over?

Dr. Kyle Gillett 13:23 I would say an individual should limit the amount of, uh, body, abnormal body fat accumulation or dirty bulking indefinitely, (laughs) throughout their entire life.

Andrew Huberman 13:33 So again, if I understand correctly, that recommendation to avoid deliberate weight gain or rapid weight gain is not just to allow an individual to reach their maximum height, but also to avoid laying down a lot of body fat cells, correct?

Dr. Kyle Gillett 13:50 Correct. The balance between that is when you are going through puberty, you are able to add a lot of lean body mass, not just muscle mass, but bone mass and other mass as well.

Andrew Huberman 14:01 I started lifting weights when I was 16, and I confess, I trained pretty heavy at times. Uh, I don't know whether or not I would've been taller, uh, than I am now, but when I started that training, I had already reached what was at least close to my predicted height.

Dr. Kyle Gillett 14:17 Mm-hmm.

Andrew Huberman 14:17 Um, I can't say that I deliberately waited until I'd grown, it just so happened that I stumbled into the weight room and found that I liked it at age 16, at which point I was already the height that I am now. So in any case, um, what I'm hearing is that laying down a lot of excess ba- body fat is not a good idea. What if somebody grows up chubby or fat, uh, for whatever reason, uh, reasons related to the eating patterns in their family, maybe even some genetic reasons. Is it safe and/or wise for a young person, so let's say somebody who's around the age of puberty, or even younger, or in their late teens, to be dieting and actively trying to lose body fat? Is that safe?

Dr. Kyle Gillett 14:58 Under the supervision of a physician, it is certainly safe to change your body composition. In pediatric obesity medicine, you're often talking about a recomposition or a renormalization of the growth curve compared to peers.

Andrew Huberman 15:13 All right, thank you.

Andrew Huberman 15:14 So as you may have sensed, we started chronologically with puberty, and I know that there's another puberty that even precedes the puberty that we're all familiar with.

Dr. Kyle Gillett 15:23 Mm-hmm.

Andrew Huberman 15:23 Uh, maybe if you want to just briefly mention that, 'cause I was talking with you about this before we started, um, the puberty that I'm most familiar with, and that I think most people are most familiar with, the acquisition of deepening of the voice, uh, growth of muscle and bone, um, uh, body hair, a- acquisition of libido and things like that, that's actually the second puberty that we all go through. Maybe just mention for us and educate us on the first puberty. I think most people will be, um, uh, hearing this for the very first time.

Dr. Kyle Gillett 15:50 The first puberty of everyone's life is the first three months of their life. You may notice that your baby has more acne the first three months, and that they also have, um, uh, in general, just more changes related to androgens and estrogens, perhaps oilier skin, um, even more genitourinary, like genital growth during the first three months. And this is mostly due to DHEA, which is an adrenal hormone. The second puberty, or the puberty that most people know of, actually starts that same way as well. It's called adrenarche, and w- it's when the adrenals kick in, um, I guess for the second time.

Andrew Huberman 16:29 Is there a standard age or age range in which the testicles descend in males?

Dr. Kyle Gillett 16:35 Usually before birth. Um, it is not uncommon to have one or even two undescended testes, but there is a risk of testicular cancer, especially if they are not fixed early, and also heat damage to the teste.

Andrew Huberman 16:49 Well, thank you for that coverage of the two puberties so early in life. I imagine some of our listeners, uh, probably, um, still in one or the oth- well pro- one or the other puberty. The ones that are in the first puberty obviously aren't aware that they're, uh, listening to this podcast, but maybe it'll be embedded in their subconscious. But some, uh, listeners probably are still in puberty. But I think everyone can remember back to their puberty and roughly when they first entered puberty, and how quickly they aggregated the secondary sex, uh, characteristics.

Dr. Kyle Gillett 17:15 Mm-hmm.

Andrew Huberman 17:15 I'd like to turn now to a

Andrew Huberman 17:17 general question about what all males ought to do in order to optimize their hormones. Uh, so if you could just list off the things that all males should do on a daily basis, weekly basis. I mean, should guys in their teens and 20s be getting their blood work done? Should they be taking supplements? We already talked about weight training. What should they be doing, what should they avoid doing if the goal is to have a long arc of healthy hormone optimization throughout the lifespan?

Dr. Kyle Gillett 17:45 There's many things that you should do. An analogy that I often make is when there's a brand-new car that comes off the assembly line, you do a full scope of diagnostic workup, hook it up to the computer, and I think we should do the same thing with humans as well. During puberty, you know, obviously you're a functioning human, but, uh, I would say there's still development. And I think that the, the human always develops. I don't think development ever ends, but you wanna monitor that progress across a person's lifespan. So for-

Andrew Huberman 18:17 Under, oh, sorry. So for blood work, I mean, what would be the earliest? Um, let me put it this way. If blood work didn't cost anything-

Dr. Kyle Gillett 18:27 Mm-hmm.

Andrew Huberman 18:27 ... and everyone could get it, when would you want to see everybody get their blood work done for the first time?

Dr. Kyle Gillett 18:33 Oh, obviously, uh, individuals under the age of 18 should talk with their parents about this. Um, and as long as that, uh, the parents and the child k- kind of agree, and the parents are on board with this as well, you can start getting blood work. Um, uh, often, a child will come in with complaints of either precocious puberty or delayed puberty, and this individual might be 9 or this individual might be 15. For a healthy child, when they're going through kind of their later Tanner stages, which is 4 and 5, so they've developed several secondary sexual characteristics, they might have, uh, hair growth, or, um, starting to notice, uh, more beard growth, that's a good time to do it....uh, if you're concerned with stature or height, or if you're not tracking along where most members of your family have, not just their height and stature but also the timing of their puberty, then that's time to get labs.

Andrew Huberman 19:28 Right. So if I could travel back in time, I would've gotten my blood work done for hormones and lipids and everything else-

Dr. Kyle Gillett 19:35 Yeah.

Andrew Huberman 19:35 ...at 18. I unfortunately didn't know where and how to get that and I didn't have any pressing clinical issues, and so-

Dr. Kyle Gillett 19:41 Mm-hmm.

Andrew Huberman 19:41 ...I think the first time that I got my blood work done, I was in my late 20s, maybe even my early 30s, and I'm still dying to know what my blood work was when, for instance, I was 17 and I felt a certain way. And I- and I- and I confess that, in many dimensions, I actually feel better now at, I'll be 47 soon, at 47 than I did in my teens and 20s. And I think-

Dr. Kyle Gillett 20:03 Mm-hmm.

Andrew Huberman 20:03 ...it was more on the psychological side.

Dr. Kyle Gillett 20:06 Yeah.

Andrew Huberman 20:06 I think that, uh, but in terms of just understanding why we felt, eh, great or why we felt or feel terrible or not so great, I think, uh, blood work is extremely informative. What do you think are the key things to look for in blood work? I mean, ev- testosterone is always the topic that comes up in the context-

Dr. Kyle Gillett 20:24 Mm-hmm.

Andrew Huberman 20:24 ...of male hormone optimization, but certainly, there are a lot of other hormones that are important as well.

Dr. Kyle Gillett 20:28 Mm-hmm. And with testosterone, you want to get either testosterone and a SHBG or a free testosterone.

Andrew Huberman 20:34 Could you define SHBG for our listeners, please?

Dr. Kyle Gillett 20:36 It is sex hormone binding globulin. It is the protein that binds up all androgens and estrogens in the body. So the stronger the androgen, the stronger it binds. During puberty, strong androgens, especially DHT, which is the strongest bioidentical androgen, has a huge role, a prominent role in secondary sexual characteristics. And if your SHBG is very high, then your DHT can run higher because it's not metabolized, but there's not quite as much free DHT. So you want a balance between, um, a high enough free DHT and a high enough total DHT.

Andrew Huberman 21:14 And obviously, these blood tests are going to have to be read and interpreted by a qualified physician.

Dr. Kyle Gillett 21:19 Mm-hmm.

Andrew Huberman 21:19 Most people aren't going to be in a position to evaluate them properly, or at least not with the full depth that they could if they had a, an MD like yourself, um, looking at them. Okay, so everyone should get blood work as early as possible, uh, um, depending on their budget and, and availability. What should everybody do in terms of monitoring those markers? So assuming that there's no major intervention, how often do you recommend that people get their blood work done?

Dr. Kyle Gillett 21:46 Let's say, w- let's take an individual who just turned 18, they just got their first set of blood work, they'll probably find something in it that they may want to optimize using shared decision-making with their physician. Usually, a good follow-up is about six months.

Andrew Huberman 21:59 Okay, so twice a year, getting blood work done.

Dr. Kyle Gillett 22:02 Mm-hmm.

Andrew Huberman 22:02 And having a physician evaluate it. That sounds reasonable to me. And for those that didn't initiate this at 18, such as myself-

Dr. Kyle Gillett 22:09 Mm-hmm.

Andrew Huberman 22:10 ...guess the best time to start then would be as soon as possible.

Dr. Kyle Gillett 22:12 Yeah.

Andrew Huberman 22:13 Right.

Andrew Huberman 22:14 Um, in terms of the other things that all males should do, meaning all males of all ages, um, puberty and beyond, uh, should do, what, what are some of those things? So on a daily basis, um, maybe you could just k- take us through the arc of a day and, um, and push out some of the protocols that you use or the things that you like to see your male patients use in order to try and optimize their hormone status.

Dr. Kyle Gillett 22:38 I'll briefly touch on some of the lifestyle pillars to start. Diet and exercise are the first two. Um, in puberty, sleep is particularly important, of course. Um, but with diet and exercise, um, throughout a lifespan, you want to not exclude things that are helping you. For example, during puberty, if you're consuming dairy and then all of a sudden you cut out all dairy, dairy can help increase IGF-1 and free IGF-1.

Andrew Huberman 23:05 And w- and just-

Dr. Kyle Gillett 23:05 Which is-

Andrew Huberman 23:05 ...uh, again, for our audience, maybe you just mention what IG- what having enough IGF-1 can do for us that's beneficial is?

Dr. Kyle Gillett 23:12 It helps you grow. It, uh, helps with, uh, genital development, secondary sexual characteristics, and long bone growth. Um, skin growth, hair growth, a host of things.

Andrew Huberman 23:22 So getting an array of nutrients that include dairy. What other sorts of nutrients are important during development?

Dr. Kyle Gillett 23:30 You want to have adequate vitamin D. Vitamin D helps with testosterone production, it helps, again, with bone mineralization and stature. Um, after an age of about 25, and there's not a strict cutoff, but up to about an age of 25, optimizing your growth hormone and IGF-1 helps with bone density and bone growth. So, uh, from the dietary standpoint, you want to have enough free estrogen. Not too much when you're growing, but you want to help, um, basically stockpile bone to prevent a risk of osteoporosis or thin bones, fractures, when you're older.

Andrew Huberman 24:07 Well, as someone who broke his left foot five times while in high school, uh, I can say that (laughs) whatever young people can do to optimize their, uh, bone density would be great. That problem seems to have resolved itself over time, but I don't know, back then I was, um, I did a short run as a vegetarian, but I've always been an omnivore.

Dr. Kyle Gillett 24:24 Mm-hmm.

Andrew Huberman 24:25 Um, I realize that some of this relates to ethics and food allergies and things of that sort, but would you say that, on balance, that most people would benefit from eating a combination of, you know, quality proteins from animal sources and non-animal sources, fruits, vegetables, and starches? Um, and what do you think, for instance, about people following a pure carnivore or a very, uh, pure vegan diet in their 20s and 30s?

Dr. Kyle Gillett 24:51 In their late 20s, it might be a reasonable option. In early 20s, and certainly teens, it is a horrible idea because it is likely to significantly decrease your free androgens, so you will have less testosterone acting on receptors through the body.

Andrew Huberman 25:07 Are there any other micronutrients or macronutrients that people in their 20s and 30s should emphasize?

Dr. Kyle Gillett 25:13 We haven't really touched on fatty acids or fiber too much. Uh, fiber is going to be paramount in kind of like setting your set point of your gut microbiome the rest of your life. There is prebiotic fiber which you could think of as fish food for your good gut microbiome. Your gut microbiome is kind of like an aquarium or a fish tank.

Andrew Huberman 25:33 Now, I'm just thinking about goldfish swimming around and that, um, the goldfish eating people. Don't eat goldfish, people.

Dr. Kyle Gillett 25:39 Yep. Um-

Andrew Huberman 25:39 Like you. Live or dead.

Dr. Kyle Gillett 25:41 Yeah, um, but any fiber or food that you're putting in your gut, it's either going to, it's going to skew your gut microbiome towards something that is more beneficial or m- or more detrimental.

Andrew Huberman 25:52 And would you say that the prebiotic fiber and getting essential fatty acids, uh, that would be important to do throughout the lifespan or just for the people in their 20s and 30s?

Dr. Kyle Gillett 26:02 Throughout the lifespan. Um, particularly important in the teenage, 20s, 30s, because it helps with brain development. Um, you're certainly more of an expert than me when it comes to, um, brain development, but it does continue to de- develop throu- really throughout the lifespan, but certainly through the 20s and 30s as well.

Andrew Huberman 26:20 What about, um, taking a multivitamin while you're growing up? So many people, um, do that. Uh, is it necessary? Is it useful? And if it's not necessary, is it safe to do anyway?

Dr. Kyle Gillett 26:32 It's generally safe to do anyway. Um, I do not think everybody needs a multivitamin. The more exclusionary your diet is, for example, if you have, uh, celiac disease or if you're planning on fertility soon, then perhaps it's more reasonable to take a multivitamin.

Andrew Huberman 26:48 In a previous discussion of ours, I asked you about, um, caloric restriction and testosterone, and if I recall correctly, the idea was that if somebody is overweight, they have excess fat, adipose tissue, then getting rid of some of that adipose tissue by, through caloric restriction and exercise, provided it's done not too fast and in a healthy way, is going to be beneficial for testosterone in the long run, but that for individuals who are not carrying an excess of body fat, caloric restriction is actually going to lower testosterone. First of all, do I have that correct? And second, are there any, um, addendums to that, that you'd like to, to give us now?

Dr. Kyle Gillett 27:26 That's correct. Um, if you look at an individual in a caloric deficit, several changes will happen. One is that they'll have less building blocks for hormones. Another is that they will be in a catabolic state more often so that balance of anabolism and cat- catabolism will be different. They'll likely have less signaling from growth hormone and IGF-1, and they'll also have the high SHBG that we defined earlier as the binding protein, so their free androgens and free estrogens will go down.

Andrew Huberman 27:57 Got it. Okay, so we touched on sleep being critical I would say throughout the lifespan, trying to get enough quality sleep at least 80% of the nights of your life, and the other 20% are just what happens when there's noise outside or you're stressed at just, you have an exam or you're having a great time for whatever reason. (laughs) There are a lot of good r- good reasons to lose some sleep now and again-

Dr. Kyle Gillett 28:18 Yeah.

Andrew Huberman 28:19 ... as well. But so we have sleep, we've got, um, nutrition

Andrew Huberman 28:23 and we touched on that. Uh, we'll get back into supplementation. Now, what are some of the other pillars of creating a, a proper environment for hormone optimization?

Dr. Kyle Gillett 28:33 Uh, stress is probably the next one. Um, during, uh, both puberty, but also the 20s and 30s, individuals are figuring out how they want to cope with stress and also figuring out what they want to choose to put their effort into. So if someone is over-stressed, then they can have, uh, it can put all the other lifestyle pillars and then they stop dieting well, um, they stop exercising, and everything else can go askew. Um, there is also some degree of, uh, social component to this, so perhaps I need to add a seventh pillar of social. (laughs) Um, uh, you know, during your 20s and 30s, you may be forming a family as well, perhaps you have children, and the health of the family unit is going to be vitally important. Um, not only, not necessarily directly for hormone optimization, but it's gonna throw everything else off if it's off.

Andrew Huberman 29:29 And for people that are not, uh, ha- starting their own families in their 20s and 30s, can that social connection, um, be extended to friendships and work relationships as well?

Dr. Kyle Gillett 29:38 Absolutely. In fact, if someone's not starting a family, it, it is just as concerning but for other reasons. Each individual's gonna have their close group of family and friends, and if someone does not have one of those connections, that's when things can potentially, uh, get bad, not just for them individually but also society.

Andrew Huberman 29:57 So when you say stress, you mean learn to manage your stress. Uh, what does that look like? I mean, when, if a patient, um, you know, has high blood pressure, or even if they don't, um, you just sense that they're stressed, they have a lot of pressured speech or they're not feeling well or communicating that they're not doing well, uh, what are some of the things that you recommend in order to try and ameliorate that stress?

Dr. Kyle Gillett 30:16 There's different mindfulness or relaxation techniques. Going outside can often help with this as well. Um, d- dietary changes and exercise can help with this too. Some people like prayer or meditation, and a lot of people like, um, counseling or therapy or even just talking, uh, openly with a family member or a friend.

Andrew Huberman 30:37 What would be some of the other pillars for hormone optimization? Here, I feel like we're not just talking about people in their 20s and 30s, but again, we're, uh, wrapping our arms around basically puberty onward. I mean, I, I mean, gosh, I, looking back, I, I started meditating pretty early, I started weight training and running early. I gave some thought to my diet in high school, but really it was in college that I started thinking more about what I was ingesting and why and trying to do better there. But people are coming to the table at different stages of, um, life and trying to optimize for hormones. So you know, so what, what would the, be some of the additional things that everybody should do?

Dr. Kyle Gillett 31:12 Everyone should get outside and find, um-...a movement past time to last a lifetime. You're gonna get sunlight, you're gonna get some degree of heat and cold exposure, and you're also just gonna move more. Um, being in an artificial environment where there's artificial lights, artificial air conditioning, um, is, uh, going to have many effects on your body. Um, so that's vital. Another one is finding what your purpose is in life. So I call this spirit, but it's really just the self-actualization component of Maslow's hierarchy of needs, which is basically your physical needs, your mental needs, and then your purpose in life. What you really like to do.

Andrew Huberman 31:51 Yeah, picking some goal or target. And I always say that you don't have to stick to the same goal over time. Certainly, I haven't, although I got started early in the science game and I'm still in it. Um, the idea is not to pick the end goal. It's to pick a goal, and then once you reach that goal to assess and then pick another goal and so on. I think sometimes when people hear about picking a purpose they're like, "Oh my goodness, I have to define..." Sort of like naming oneself-

Dr. Kyle Gillett 32:15 Yeah.

Andrew Huberman 32:15 ...but you, you, you actually can change your, your, your goals and purpose

Andrew Huberman 32:19 over time. This is terrific. Would you, uh, suggest that people actively use or avoid supplementation, um, prior to doing all these other things? I'm somebody that likes to throw the kitchen sink at things, but I also like to do things pretty systematically, so I always say behaviors first, then nutrition, then supplementation, and then maybe and if and only if there's a real need, and of course working with a doctor, prescription drugs.

Dr. Kyle Gillett 32:43 Mm-hmm.

Andrew Huberman 32:43 But, you know, there are probably people in their 20s or 30s, maybe even in their 50s, that aren't feeling great and they want to do something in order to be able to train more and/or to, um, feel more confident to seek out social connection. They try and go, go about the whole, um, business from the other, from the other side as well.

Dr. Kyle Gillett 33:01 Mm-hmm.

Andrew Huberman 33:01 What are your thoughts on that?

Dr. Kyle Gillett 33:03 I see supplements and medications as very similar, ones prescribed and ones not. In general, medications have more side effects or potentially stronger therapeutic with more efficacy, but they are just tools to reach an end goal. So depending on the goal, if there's an individual that's an athlete, then certainly they should consider supplementation. Or if someone, uh, desires optimal or very, a very high level of cognitive performance, they should also consider supplementation. At the same time, food is medicine, and a lot of the benefits you can get in supplements you can get in food as well.

Andrew Huberman 33:37 I guess it depends on how much time and energy you're willing to spend and also finances. You know, I know that when I was in college, I could afford just a few supplements and they were basically whey protein and some fish oil. I was fortunate that I was pointed in the direction of those things, and some creatine. I couldn't afford much else. Uh, over time, of course, I could afford more, but um, it really does often depend on, on finances.

Dr. Kyle Gillett 33:59 Mm-hmm.

Andrew Huberman 34:00 Before we get into some specific recommendations to optimize testosterone, estrogen, thyroid growth hormone, et cetera, I want to ask

Andrew Huberman 34:08 you a question I've been wondering about for a long time. You know, so often in the discussion about male hormone optimization people will say, "Well, you know, if your libido is suffering, you know, you might want to be concerned about testosterone or even estrogen." Right? Because we know that estrogen can impact libido as well. Sometimes t- having estrogen too low is detrimental for libido. Or people will say, "You're not recovering from workouts or you're just, you're feeling kind of depressed." The problem is it's all subjective. So (laughs) how does one know whether or not their recovery from workouts, their energy, their confidence, their libido is within a healthy range? I mean, obviously for people in a relationship, they can know whether or not their libido matches the sort of cadence of, of the relationship and their partner.

Dr. Kyle Gillett 34:51 Mm-hmm.

Andrew Huberman 34:52 But how should people think about this and maybe even start to talk about it? Because one of the big differences I think between, uh, males and females is that because females have a monthly cycle, they are familiar with the changes that occur in their hormones over time, because every 28 days those hormones-

Dr. Kyle Gillett 35:08 Mm-hmm.

Andrew Huberman 35:08 ...are changing dramatically in ways that impact their physiology and psychology.

Dr. Kyle Gillett 35:12 Mm-hmm.

Andrew Huberman 35:12 But for males, I feel like there's sort of a, a, uh, a dearth of language to get into the more subtle aspects of this. It also has to do with privacy issues and people feeling like they don't want to overshare, um, too much, not knowing what's appropriate to share. But when you talk to a patient who's in their 30s or maybe even their 70s or 60s, doesn't matter, a male patient, what are you listening for and w- uh, you know, I know you're not a psychiatrist but, you know, what are your ears tuned to in order to try and figure out whether or not this person could really use some help with hormone optimization or whether or not something else, or maybe they're just doing great and they don't realize it because they're placing demands on themselves that are excessive?

Dr. Kyle Gillett 35:50 You want to u- you want to use a lot of open-ended questions. This process is called motivational interviewing, and your goal is to listen to the patient and not plant an idea in their mind that they can follow.

Andrew Huberman 36:03 Mm-hmm.

Dr. Kyle Gillett 36:04 Because everybody is going to have a different goal. Um, some people are better at reading their biofeedback or, um, telling how they feel on a daily basis. There is screening questionnaires designed, for example, an ADAM questionnaire, to look at men's, uh, men's health and hormone-related health.

Andrew Huberman 36:22 Mm-hmm. It's called an ADAM questionnaire?

Dr. Kyle Gillett 36:24 ADAM questionnaire.

Andrew Huberman 36:24 A-D-A-M?

Dr. Kyle Gillett 36:25 Correct.

Andrew Huberman 36:26 Is it available online that people could administer it to themselves? Although we don't want people making clinical diagnoses of themselves or anyone else. Is it that sort of exam?

Dr. Kyle Gillett 36:33 It is.

Andrew Huberman 36:34 Interesting.

Dr. Kyle Gillett 36:35 I don't believe it is a clinically validated tool like an ASCVD, which is like a, a risk of heart attack and stroke tool or many other tools. Um, there's one for depression, there's one for anxiety. They're called PHQ-9 and GAD-7 respectively. But anyway, there's often an in- the ADAM questionnaire and what you hear from the patient, if you are a very careful listener, is often different.

Andrew Huberman 37:01 Can you give me an example of some of the questions on this ADAM questionnaire or the sorts of motivational interviewing that you might do? So say I'm your patient, we sit down. Uh, what sorts of questions would you ask to probe these kinds of dimensions of, of hormones?

Dr. Kyle Gillett 37:13 ... questions about libido, questions about athletic performance, questions about motivation. And often, a patient will answer one thing, but what you hear from them subjectively is far different.

Andrew Huberman 37:26 Interesting. Can you give me an example of a, of a question? I'm ha-

Dr. Kyle Gillett 37:29 Uh, uh-

Andrew Huberman 37:29 I'm happy to be the, the guinea pig here.

Dr. Kyle Gillett 37:31 A, a classic one is a guy comes in, and they, a lot of times they say, "Oh, no, the wife made me go to the doctor. I go, um, once a year, that's it. I don't want anything, I don't want any medications." Their screening questionnaires might be zeros across the board, so nothing, no issues. They're apparently in perfect health. They talk to you for a while, they get some rapport, they like you, and then right as you're finishing up the visit and about to go out the room, they mention that, um, their libido isn't quite there and they're having a little bit of ED as well, and perhaps they're even having some chest pressure or tightness.

Andrew Huberman 38:07 I see. So right as you're leaving the room, a patient will tell you that they're having some sexual side effects. Or not side effects, they're having some sexual challenges, and then they'll mention chest pressure. Is the chest pressure a sort of general decoy for, "It's gotta be my heart," or is it, um, or is it related to the other things they're reporting?

Dr. Kyle Gillett 38:25 It can be related. In fact, uh, erectile dysfunction is known as the canary in the coal mine. So coal miners would take the canary down and it would, um, the canary would die before the coal miners would of, I believe, carbon monoxide poisoning. And often, uh, one of the causes of ED is plaque buildup, which can happen in the coronaries as well, but sometimes they notice the symptom in the genitals before they do in the coronaries.

Andrew Huberman 38:50 So for such a patient, um, let's say that patient was a young person where plaque buildup in the arteries and veins is not all that likely if they're, let's say, in their 20s or 30s. Uh, what would be your next step of the interview at that point, and what, what would you consider? Would you immediately order labs for that person to try and rule out any kind of, um, uh, actual hormone level deficiency?

Dr. Kyle Gillett 39:11 I certainly would order labs. There are some individuals that are very similar and they come in and they have the same symptoms, and one individual might have a very, very high testosterone and one individual might be, um, severely hypogonadal. So there is a, a big difference between the subjective and what the labs look like, so I certainly order labs. You also ask them about, um, if it's situational or no- or not. You ask them if they have ED, if they're... Um, you know, you ask them about their habits. You even ask about, uh, porn, and masturbation, and all these issues. And of course, that's between the doctor and the patient. And depending on what they tell you, you can often determine if there is a situational component. Some people call it psychogenic ED, but I don't love the term psychogenic ED because it kind of puts some, some blame on the patient's, um, mind. But a lot of the time, that is the case. There's even a test, um, and this is very rarely ordered, but it's called a nocturnal penile tumescence.

Andrew Huberman 40:09 No, bec-... Is, is it true that there are periodic erections during sleep? Correct?

Dr. Kyle Gillett 40:15 Yes.

Andrew Huberman 40:15 Yeah.

Dr. Kyle Gillett 40:16 So, um, you basically put a cuff to see if you're having, um, a, a normal-sized erection during sleep. And I believe about 90% of the time they do that test, um, they are indeed having erections.

Andrew Huberman 40:28 Which would point to this psychogenic origin of whatever challenges they're having, in terms of sexual interactions. You

Andrew Huberman 40:35 mentioned porn and masturbation. Um, this topic has come up a bunch of times on this podcast and on other podcasts I've gone on because of the relationship between dopamine-

Dr. Kyle Gillett 40:43 Yes.

Andrew Huberman 40:43 ... uh, sexual motivation, and sexual behavior. And I've been of the pretty strong stance that, while I'm not judging porn or masturbation, it can create a brain wiring situation where males in particular essentially teach their brain to be aroused by watching other people have sex as opposed to being the first person actor-

Dr. Kyle Gillett 41:06 Mm-hmm.

Andrew Huberman 41:07 ... in sexual, uh, interactions. So in that sense, um, you know, that's more about the brain wiring, and neural plasticity, and dopamine, but what are your thoughts on porn and masturbation as they relate to hormones? I mean, this is a big debate on the internet. In fact, (laughs) one of the most, uh, common debates is whether or not masturbation increases or decreases testosterone in males. Certainly, it will decrease motivation to go find sexual partners. We know this.

Dr. Kyle Gillett 41:33 Yes.

Andrew Huberman 41:33 Um, and there are more and more data on this all the time. In terms of the effects of pornography and masturbation, and here I suppose we need to be, um, somewhat specific and operationally define what we're talking about. We're talking about porn and masturbation to the point of ejaculation.

Dr. Kyle Gillett 41:48 Mm-hmm.

Andrew Huberman 41:48 Right? Um, because my understanding is that the, uh, ejaculation and, and orgasm associated with it cause an increase in prolactin, which blunts libido for some period of time. The duration of that will vary from person to person and circumstance to circumstance. But basically, all of this points to the fact that porn and masturbation can really limit libido in the real world.

Dr. Kyle Gillett 42:11 Mm-hmm.

Andrew Huberman 42:11 And, uh, to me, uh, pornography and the screen is not the real world. Though screens exist in the real world, the real world doesn't exist in the screen.

Dr. Kyle Gillett 42:20 That's an accurate statement, and prolactin does have a significant acute increase after, uh, ejaculation. It does, to some degree, after orgasm as well, but prolactin acts on the pituitary to inhibit the release of the hormones LH and FSH, of which LH can increase testosterone. So this may be one of the cases where the dose makes the poison. And if it is a very frequent habit, certainly, uh, daily or more than once a day would be very detrimental from a hormonal component, not even taking into account the, uh, the neural wiring.

Andrew Huberman 42:59 Listen, I think it's terrific that you've actually defined frequency, because this is the problem. On the internet or even in the doctor's office, you'll see, um, descriptions about pornography being dangerous for certain things, or, or detrimental to hormones. People say, "Frequent." Well, what's frequent?

Dr. Kyle Gillett 43:12 Yeah.

Andrew Huberman 43:12 So you're saying daily or multiple times per day would be...... potentially detrimental to the hormone profile of a male of essentially any age.

Dr. Kyle Gillett 43:20 And that's just for masturbation. Um, with pornography, uh, with porn use as well, it would likely be worse.

Andrew Huberman 43:29 Hmm. And why, why is that? Just this- this- the sort of dopaminergic drive of the stimulus, just the really-

Dr. Kyle Gillett 43:35 Mm-hmm.

Andrew Huberman 43:35 ... the intense visual stimulus?

Dr. Kyle Gillett 43:37 Dopamine sensitivity. Um, I think that, uh, using the analogy of a dopamine wave pool, it would deepen the pool, but not increase your supply of dopamine.

Andrew Huberman 43:47 Maybe you could describe the dopamine wave pool, 'cause I think it's such a powerful way of thinking about dopamine and what dopamine does. In fact, I've, um, always credited you in- when I've done it, but I've- I've generally r- uh, stolen your analogy of the dopamine wave pool because it- it's so astute.

Dr. Kyle Gillett 44:03 The dopamine wave pool describes the natural variation of ups and downs in your dopamine or your motivation, and, uh, in the wave pool, depending on how high the peak is, you often have a deeper trough. So you do not want too high of a peak. In addition, if your peak is very, very high, for example, uh, when you're using, uh, many substances like, uh, cocaine or like, amphetamines, your dopamine can go so high, you lose almost all the water from the wave pool, and then when you crash from that, not only is the trough low, you have less dopamine in the pool to begin with. The dopamine receptor is extremely sensitive, as is the GABA receptor, which is an inhibitory receptor, whereas dopamine is technically a stimulant more related to adrenaline or noradrenaline. The depth of the pool can change very quick, so you wanna have that happy medium where you're fairly near the top, but you're not so near the top that the depth of the pool is gonna go down.

Andrew Huberman 45:06 So if I interpret, uh, that in the context of this discussion about, um, libido, sex, porn, and masturbation, it- if somebody has a very intense sexual experience, and not- not- here, we're not necessarily talking about an intense, um, orgasm. We're talking about just an int- you know, a lot of intense visual. So very, um, a lot of intense imagery or auditory input, or both. That is going to lead to a situation where dopamine is going to be depleted afterwards.

Dr. Kyle Gillett 45:34 Correct.

Andrew Huberman 45:35 A- a guest on this podcast, uh, before, my colleague at Stanford, Dr. Anna Lembke, who's an expert in addiction, talked a bit about this, this sort of see-sawing. I- here, we're talking about a wave and a crashing out of the water from the wave pool. There was a see-sawing from pleasure and pain.

Dr. Kyle Gillett 45:47 Mm-hmm.

Andrew Huberman 45:47 There's gonna be a longer and deeper period of lack of pleasure following that, and I think a lot of people think, "Oh, well, that's great." You know, they want the intense experience. But if that intense experience is coming from pornography and masturbation, or I suppose, coming from, you know, high adrenaline activities like, you know, life, uh, life-risking parkour, hanging off the side of a building, it inevitably is going to lead to depressive episodes, low libido episodes that follow. Is that right?

Dr. Kyle Gillett 46:14 Correct, in a similar physiologic way, uh, to withdrawal from stimulants like amphetamines.

Andrew Huberman 46:21 Now, is sex with a partner different? Because there are many people who are chasing more and more intense experiences with a partner as opposed to through pornography and masturbation. Again, here, we're talking about all ages, and I should always say anytime we're talking about sex with a partner, we're talking- I- you know, the- the four conditions that I always, um, lay out on the, uh, Huberman Lab podcasts are that we're talking about consensual, age-appropriate, context-appropriate, species-appropriate interactions.

Dr. Kyle Gillett 46:49 Yeah, and, uh, this is also a case where the dose makes the poison. So if there's, um, you know, obviously meeting all those criteria, if they have one preference, um, that for both of them is a positive experience, then that is likely okay. Um, you're not gonna be able to maintain dopamine over a certain threshold for a long period of time, so there very well may be a crash from that experience as well, and the crash may be different in one partner than the other.

Andrew Huberman 47:23 Hmm. Interesting. So I'll draw an analogy to food. It'd be like, you know, you don't have to serve the banquet meal seven- seven nights of the week. Maybe just two. Is that right? And there are other delicious foods out there. Kinda-

Dr. Kyle Gillett 47:34 Yes.

Andrew Huberman 47:34 ... can we use that analogy?

Dr. Kyle Gillett 47:35 That is very reasonable.

Andrew Huberman 47:36 Okay, not trying to be PG-13. Just trying to, uh, uh, um, parsimony, Occam's razor, the ability to describe a lot of things in- in a- in a few words. I'd like to return to the key things that people should do, or I should say, the key things that men should do to optimize their hormones. So we talked about getting some movement, getting some sunlight, getting quality social connection one way or the other, avoid excessively frequent masturbation and viewing pornography, and for some people, zero might be the optimal number, and I keep coming back to this.

Dr. Kyle Gillett 48:09 For mos- for most people.

Andrew Huberman 48:09 For most people. Interesting. Uh, I feel so fortunate to have grown up prior to the availability of internet pornography. I've never been a big consumer of pornography. It's just not been my thing, uh, but I hear so often from males of all ages about their addiction to it, their affliction by it. It's really a- a serious issue, and that's one of the reasons why I'm grateful that you're willing to talk about this and your clinical experience with these patients.

Andrew Huberman 48:32 I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health, and those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met, and...It tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman, and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3 K2.

Andrew Huberman 49:46 In terms of exercise, you know, here's... Again, it's a double-edged sword. Um, on the one hand, it's great to get exercise, but I'm familiar with, you know, if I train an hour a day, you know, 10 minutes of warmup and 50 minutes to an hour of weight training, or 50 minutes to an hour of cardio, I feel great, especially if once a week, I take a complete day off. That's sort of my general schedule. I'm also familiar with, when I go out for runs that are excessively long, two-hour runs, or I spend 90 minutes in the gym too frequently, I start to feel like garbage. Everything suffers. My sleep starts to suffer. It doesn't matter how much I eat, I don't seem to recover. I don't feel well. So I realize that recovery ability varies between individuals, but what do you think is a healthy, sustainable exercise regimen that anyone can follow that will also support their hormone status?

Dr. Kyle Gillett 50:35 For really vigorous exercise, around three to four times a week is very sustainable over a long period of time. On top of that, you could add in three or four more instances of less vigorous exercise.

Andrew Huberman 50:49 Okay, so for less vigorous, what do you mean? You know, zone two cardio where you can hold a conversation, but beyond which you, you can't? And for more vigorous, you're, you're thinking weight training or HIIT, uh, high-intensity interval type training? Is that right?

Dr. Kyle Gillett 51:01 Correct. Um, you can also weight train and have some benefit even at a low to moderate intensity. If you think about, um, weight training where you have... And it's not necessarily related to the incidence of DOMS, which is delayed onset muscle soreness, but if you weight train lazy or easy from time to time, obviously you want to weight train very heavy from time to time as well because of, um, more lean body mass growth, but, um, if you weight train lighter, you're going to be able to do it more often, and it can still help with the hypertrophy of, um, collagen, for example, in tendons and ligaments.

Andrew Huberman 51:39 So here again, um, I'd like to, uh, perhaps drill into this notion of intensity and light weights, because for me, some of the most brutal workouts I've ever done were in what I would consider a high repetition range, 15 to 50. Actually, I went up to Oregon to watch the International Track and Field Championships. We went by to, um, Cameron Hanes's place.

Dr. Kyle Gillett 51:58 Mm-hmm.

Andrew Huberman 51:59 Right? The, the Cameron Hanes. And he and his trainer put us through a workout that was 25 to 50 repetitions per set, and it was done in circuit, and it was brutal. So it was light. I mean, that's, those weights were nothing. In some cases, it was body weight. But the number of repetitions was brutal. So when you say limiting intensity, are you talking about limiting the number of, uh, sets to failure? Are you talking about, um, uh, really being kind of l- a lazy bear in the gym? I like to do that every once in a while. Long, long rest. That sort of thing. Um, what are, what are your thoughts on that as it relates to hormone optimization? So I'll just mention and then I'll let you answer. I feel best overall when I'm training for 10-minute warmups and about 45 or 50 minutes of weight training where I'm pretty lazy between sets. Two to three-minute rest, training somewhere in the six to ten rep range, going to failure every once in a while, but mostly getting that sort of last rep before what I would think is failure. No forced reps. That kind of thing.

Dr. Kyle Gillett 52:54 Mm-hmm.

Andrew Huberman 52:54 And then jogging on the other days. Nice and easy. When I do that, I feel fantastic in all other dimensions of life. When I train more intensely than that, even with light weight, so faster cadence and lower rest, I feel like garbage. I get a headache. I'm kind of ornery. I... Everything suffers. So what are your thoughts on kind of defining a optimal exercise strategy for hormones? I've never measured my hormones in those two different contexts-

Dr. Kyle Gillett 53:22 Mm-hmm.

Andrew Huberman 53:22 ... but I have to imagine that it's cortisol related.

Dr. Kyle Gillett 53:24 When they study the effect of exercise, specifically vigorous exercise, um, one area that's been studied is, uh, vigorous exercise episodes lasting longer than an hour, and they usually track it by a rating of perceived exertion, which isn't perfect and it's not extremely actionable, but it's helpful for clinical science. But the takeaway from that is basically do not... I- it is not hormonally helpful to train, especially regularly train, uh, vigorously for longer than an hour.

Andrew Huberman 53:57 Good. So, um, I'm happy to hear that because it sounds like for most people that hour of work is really the threshold. I think this is important for people to hear, especially, um, males, because I think with all of the incredible examples out there of people like Cam, like David Goggins, people who are training for very long periods of time, you know, and leaving aside, um, all issues of what people are doing in order to optimize their recovery, I think an hour a day of exercise is just a great program- (laughs)

Dr. Kyle Gillett 54:26 Yeah.

Andrew Huberman 54:26 ... um, uh, that most anyone can follow. And beyond an hour, you start running into challenges. And I... You know, the occasional 90-minute or two-hour workout is no big deal, but if you start doing that more than once every m- two months, I think you're headed for trouble. Have you seen that in people's blood, blood work, and in their hormones? Do you ever see people that are just badly overtrained because they're just training too hard and too often?

Dr. Kyle Gillett 54:51 Yes. When the blood work is particularly bad, they're often in a large caloric deficit as well. There's a synergistic effect between a caloric deficit... Uh, even if you're maintaining adequate protein intake, you might not be maintaining adequate iron intake or adequate vitamin D, and you're also just literally in a caloric deficit. Perhaps low carbs as well, very low free testosterone, and they're simultaneously doing a lot of vigorous exercise.

Andrew Huberman 55:23 Interesting. I often hear, and I'm starting to wonder whether or not some of the, um...... quicker to results nutrition tactics, things like dropping all carbohydrates, or, um, the quicker to results exercise habits like starting to do six day a week really intense workouts, whether or not in the short run they work because they cause the cosmetic changes that people are seeking, but that they really undermine the overall goal, which is, at least to me, to have your hormones maybe not optimized to the, you know, 100%, but to always be aiming for 100% and be close to it at every stage of life.

Dr. Kyle Gillett 56:02 Consistency is key here. If you are not consistent, then, uh, the law of diminishing returns certainly applies. So, uh, 80 or 90% of the benefit over many, many months is far better than, uh, 100%, but, uh, only half the time.

Andrew Huberman 56:21 Yeah, one thing that I found to be tremendously useful is to l- finish the workout while I still have energy, to not take myself to exhaustion, and then I'm able to kind of talk about the dopamine wave pool, I'm able to sort of ride that into the rest of the day feeling great. I- I sort of-

Dr. Kyle Gillett 56:35 Mm-hmm.

Andrew Huberman 56:35 ... um, save or bank some of the vigor from the training to bring it into my work. But then again, I'm not an athlete.

Dr. Kyle Gillett 56:41 Yeah.

Andrew Huberman 56:41 I d- I get paid to think and to speak, not to, uh, not to lift weights or to run.

Dr. Kyle Gillett 56:46 Another component of that is the balance between your sympathetic, which is your fight or flight nervous system, and your parasympathetic, which is your rest or digest nervous system. There is an anecdote which is likely true that many elite bodybuilders are very parasympathetic besides while they're lifting weights.

Andrew Huberman 57:04 You mean they're lazy and they like to eat a lot?

Dr. Kyle Gillett 57:05 Yeah.

Andrew Huberman 57:06 The lazy bear in the gym kind of phenomenon.

Dr. Kyle Gillett 57:08 Absolutely. Um, but that being said, after a very, very vigorous workout, for example, one where you're trained to failure, which bodybuilders and powerlifters do all the time, you feel the, uh, tiredness or you feel the strain from that heavy, uh, sympathetic activity when you are lifting a heavy weight, and it can potentially affect how you feel the rest of the day. So many people who have a job where th- that is highly cognitive do not like to have an extremely vigorous workout in the morning, which is when a lot of people are able to exercise.

Andrew Huberman 57:43 Mm-hmm. When I exercise early in the morning, that is before 9:00 AM, I have more energy all day long. If I do it mid-morning, I have experienced more of an afternoon crash. There's probably some circadian biology in there. I have also noticed, and I've actually seen in my blood work, that if I don't get out for a 45-minute jog at least once a week, all of my blood profiles suffer in the direction that I don't want them to go. In particular, testosterone and estrogen move in directions that are not conducive to my goals. Um,

Andrew Huberman 58:12 I'd like to talk about some of the approaches that people can use in order to optimize hormones, and these days, for better or for worse, I think for worse, younger guys are asking about and using testosterone replacement therapy, so-called TRT. And I just want to frame this up by saying there is no strict cutoff for what is TRT. There are plenty of people whose, um, blood levels of testosterone and estrogen are in the, within the normal reference range and decide to start doing these things. Of course, they can limit fertility, there are a bunch of issues. Even at non-, quote unquote, "steroidal," uh, (laughs) uh, performance-enhancing dosages. Um, I'd love to frame this up by first defining our terms, because one of the challenges on the internet is people talk about TRT, then they'll talk about performance-enhancing drugs, they'll talk about steroids. They're all steroids, right? I mean, testosterone, estrogen are both steroid hormones. But what one considered s- replacement therapy versus what one considers performance-enhancing is going to depend, right? So here's my question. Why in the world, why in the world would any male in his teens or 20s or th- even 30s whose blood levels of testosterone and estrogen are at the appropriate levels, meaning within the normal reference range, why would they u- take exogenous testosterone given all the negative effects on fertility, um, some of the challenges that it can present if the dosages aren't quite right, et cetera, why would they do that certainly if they are not being paid for a particular endeavor? Like.

Dr. Kyle Gillett 59:47 Yeah.

Andrew Huberman 59:47 They're not making money. If they are playing a sport, chances are they're not allowed to do that anyway. It's, uh, it's, uh, on the banned substances list. So to me, it just seems like a crazy idea. Um, but then again, I'm of a generation that really hasn't thought about doing that stuff until people were in their 40s and 50s, eh, or even never. So is there ever a case for somebody in their 20s or 30s to take testosterone esp- if their blood levels are within the 300 to 900 nanograms per deciliter reference range?

Dr. Kyle Gillett 1:00:16 Not many cases. The reason for any performance-enhancing drug, whether or not it is a steroid, synthetic, bioidentical, or otherwise, um, i- it varies a lot. Some individuals do it only for cosmetic reasons, um, even if it can, uh, have deleterious effects on, uh, like, the cosmetic appearance, for example, of your skin in the long run. But, um, you know, everyone has their different reason, uh, as far as, like, when does the benefit outweigh the detriment? Not very often if you're, um, in your 20s, and certainly, uh, probably, almost hardly never. There's always, you know, rare cases like Kallman syndrome and whatnot, but, um, almost never if you are very young.

Andrew Huberman 1:01:02 Okay, so for people in their 20s, 30s, and beyond, 40s, et cetera, whose, uh, testosterone and estrogen levels are at the appropriate ratios and in th- within the normal reference range and they feel pretty good, right? We talked about-

Dr. Kyle Gillett 1:01:15 Yeah.

Andrew Huberman 1:01:15 ... the Adams exam earlier. This is sort of like feel pretty good is sort of code for, uh, libido, energy, recovery, et cetera, and are feeling, you know, at least, um, workable for, for their lifestyle. For those people, what can they do besides get great sleep-... train, but not too hard or too often, et cetera, et cetera. What are some of the things in the realm of supplementation that can help them optimize their testosterone and estrogen without suppressing their own endogenous production of testosterone and estrogen?

Dr. Kyle Gillett 1:01:46 Let's mention creatine as the first one. Creatine is interesting because it has multiple different effects. It helps with amino acid synthesis, it also helps with oxidative stress, it can also serve as the backup fuel tank for your mitochondria, so kind of holding back up ATP, and it does slightly increase total testosterone, and it also increases the conversion of testosterone to dihydrotestosterone. So potentially, it's especially useful in, um, men in their, even their teenage years and their 20s.

Andrew Huberman 1:02:17 You mentioned the conversion of testosterone to dihydrotestosterone, and there is mythology out there that creatine can increase hair loss, I'm guessing because there's at least one study showing that creatine can increase DHT, dihydrotestosterone, and DHT is one of the primary hormones that can promote male pattern baldness. Um, so the question therefore is, does crea- creatine supplementation increase the rate of hair loss?

Dr. Kyle Gillett 1:02:44 Theoretically it can, but, uh, in, in each individual, uh, preventing hair loss is a very poor reason to take creatine, because it's not going to take you to a supraphysiologic level, it's not going to, uh, you know, increase your androgens to an un-normal level of binding. So I feel like, um, this... If that was a reason to not take creatine for hair loss, then that's-

Andrew Huberman 1:03:12 You mean for... Sorry, you mean hair loss is not a reason to avoid taking creatine?

Dr. Kyle Gillett 1:03:17 Correct. Hair loss is not a reason to avoid taking creatine. Um, it... Think of it as just bringing you to what you are, um, naturally inclined to have. If your conversion of testosterone to DHT is already high, then often creatine does not affect this. It just kind of resets your balance between testosterone being aromatized to estrogen or being 5-alpha-reduced DHT. So it's not gonna speed up hair loss more than, um, just naturally being a male does. So in some individuals, it will have no effect. In some individuals, for whatever reason, they have almost no 5-alpha reductase activity, it will return them to natural or normal.

Andrew Huberman 1:03:58 I see. Well, I take five grams a day of creatine monohydrate. I do it for the, um, tissue voluminizing effects, uh, for exercise benefits, but also for the cognitive effects. I don't know if it's increasing my hair loss. I mean, I've got a little bit of, uh, sort of a widow's peak type hair loss. That's where it is for me. Um, I suppose beard growth is associated with DHT too. Most... Is that right? I... My...

Dr. Kyle Gillett 1:04:20 Yeah.

Andrew Huberman 1:04:20 What I learned, but then again, I haven't been into this literature in a long time, is that because of chain- differences in receptors, that DHT causes hair growth on the face and hair loss on the head. Is that right?

Dr. Kyle Gillett 1:04:30 Yes. And the amount and the sensitivity and density of those receptors is genetically determined.

Andrew Huberman 1:04:37 And is it true that if your mother's father was bald that you will be bald in the same pattern, and if that he wasn't, you won't?

Dr. Kyle Gillett 1:04:45 That is a decent correlation. Part of the proposed mechanism of this... Well, there's several genes, and you can actually test your genes for hair loss. You do get a decent amount of them from your mother. The unique thing you get from your mother that she may have gotten from her fat- uh, she got one of the copies from her father, is your X chromosome. And the androgen receptor gene is on your X chromosome. So all men got their androgen receptor gene from their mother.

Andrew Huberman 1:05:12 It's on their X chromosome, not on the Y chromosome.

Dr. Kyle Gillett 1:05:15 Correct.

Andrew Huberman 1:05:16 Interesting. Even though all of the sort of, uh, quote-unquote male, male-promoting, uh, genes are on the Y chromosome, like Müllerian inhibiting, et cetera.

Dr. Kyle Gillett 1:05:25 Yes.

Andrew Huberman 1:05:25 Oh, interesting. Okay, so five grams a day of creatine, for most people, should be fine. Um, beneficial for tissue voluminizing, so strength, uh, bringing water into the muscles, and for cogni- the cognitive effects and the clinical support for creatine, I think, is, is quite strong at the five gram per day dosage. Uh, what other sorts of supplements, um, can people benefit from? We already talked about the omegas and making sure that people are getting enough prebiotic fiber, uh, to support the gut microbiome.

Dr. Kyle Gillett 1:05:52 Mm-hmm.

Andrew Huberman 1:05:52 Um, and vitamin D. Uh, so what other supplement-based tools, uh, can people consider?

Dr. Kyle Gillett 1:05:58 Another one we can loop in with creatine is betaine. Some people are non-responders to creatine, so you can increase that to 10 grams or you can use its cousin, betaine, to help with amino acid synthesis and shunting of energy. Uh, along with that, I would put L-carnitine, which is, uh, actually the smallest peptide hormone. It's just two amino acids that are put together. So it's a-

Andrew Huberman 1:06:21 It's a hormone.

Dr. Kyle Gillett 1:06:22 Um-

Andrew Huberman 1:06:23 Interesting. I'm not challenging it, I'm just-

Dr. Kyle Gillett 1:06:24 Peptides. Yeah.

Andrew Huberman 1:06:25 Yeah, I'm not challenging.

Dr. Kyle Gillett 1:06:26 I would call it a, a peptide more, more than a hormone.

Andrew Huberman 1:06:29 Uh-huh. Yeah.

Dr. Kyle Gillett 1:06:29 So I, I would not call L-carnitine a hormone.

Andrew Huberman 1:06:31 Okay.

Dr. Kyle Gillett 1:06:31 But I would call dopamine a, a hormone.

Andrew Huberman 1:06:33 Yeah, I could...

Dr. Kyle Gillett 1:06:34 Um-

Andrew Huberman 1:06:34 A neurohormone.

Dr. Kyle Gillett 1:06:35 Yeah.

Andrew Huberman 1:06:35 It's, it's so hard to, to define things as transmitters or hormones at some level. I agree. Um, so L-carnitine... Um, actually, I should backtrack. Betaine, uh, do you recall, uh, what dosage people typically would take if they're a creatine non-responder?

Dr. Kyle Gillett 1:06:51 One to three grams. In fact, se-

Andrew Huberman 1:06:53 Per day.

Dr. Kyle Gillett 1:06:53 Yeah. Several versions of creatine have betaine mixed in because it helps with the processing of methionine and homocysteine.

Andrew Huberman 1:07:01 So if somebody is already taking creatine and likes it and responds to it, and I'll raise my hand, such as myself, would adding betaine help or is it redundant with creatine?

Dr. Kyle Gillett 1:07:11 Only if their homocysteine is persistently elevated. And homocysteine is kind of like an inflammatory marker that can build up if you're not converting enough of it downstream.

Andrew Huberman 1:07:19 How would I know?

Dr. Kyle Gillett 1:07:21 Uh, just a blood test.

Andrew Huberman 1:07:22 Okay.

Dr. Kyle Gillett 1:07:22 Or if you knew your MTHFR polymorphism, which is basically how you, um, add methyl groups to, um, many things in the body.

Andrew Huberman 1:07:32 Great. Any side effects of betaine that people should be aware of?

Dr. Kyle Gillett 1:07:36 ...not that I know of.

Andrew Huberman 1:07:37 Okay. People can look it up on, examin.com is a great site for that, they'll surely list it. They just revamped their site by the way, and it was awesome before, and it's platinum now. Um, so L-carnitine, uh, what are the ways to take L-carnitine? I know that there's an oral form, so capsules, and there's injectables. The injectables, I think you need a prescription, is that right?

Dr. Kyle Gillett 1:07:58 Correct, you need a prescription for the injectables, or you should really get a prescription for the injectables. For when you inject it, um, of course, at the supervision of your doctor, it's usually done intramuscularly. It's an aqueous solution, so it does not have, like, an oil or a carrier oil in it like T- or like testosterone esters do. Um, however, if you inject it too superficially, it's not going to make it break anything, often it just burns if you inject it subcutaneously, and it does not, um, disseminate throughout the body as well. L-carnitine potentially has localized effects if you inject it. If you ingest it orally, then it has a very low bioavailability, maybe only 10%.

Andrew Huberman 1:08:40 Well, I think most people are going to be able to get L-carnitine only or, you know, i- in its capsule form. So, what are the dosages of L-carnitine that one needs to ingest then if they want to get a benefit? Because if only 10% is being absorbed, uh, it's probably a lot of L-carnitine.

Dr. Kyle Gillett 1:08:56 Mm-hmm.

Andrew Huberman 1:08:56 How much should people take per day?

Dr. Kyle Gillett 1:08:58 Usually, I recommend, uh, for oral L-carnitine between 1,000 milligrams and up to 4,000 or 5,000 milligrams.

Andrew Huberman 1:09:05 Okay, so one to four, maybe even five grams.

Dr. Kyle Gillett 1:09:08 Correct.

Andrew Huberman 1:09:09 Okay.

Dr. Kyle Gillett 1:09:09 Up to five grams a day. If you're on that much, especially if you have a dysregulated gut microbiome, you should be concerned with TMAO, which is a potential carcinogen that both carnitine and choline can convert into, and your gut microbiota determine how much that happens.

Andrew Huberman 1:09:27 Uh, is it true that I can offset any negative effects of alpha-GPC, uh, choline, that is, and L-carnitine, um, that I take, by ingesting garlic, is that right?

Dr. Kyle Gillett 1:09:37 There's a compound in garlic called allicin, I believe it's A-L-L-I-C-I-N, it's also part of the scientific name, the genus of, uh, types of garlic, and this can help decrease the conversion to TMAO. Berberine actually slightly decreases the conversion to TMAO as well, um, probably through alteration of the gut microbiome, and then just, um, optimizing your gut microbiome can decrease conversion. So, not everyone needs allicin, but it's something that you should certainly consider if you are on a high dose.

Andrew Huberman 1:10:06 I'm going to continue to take the 600 milligrams of garlic every time I take my L-carnitine, but I'm going to skip the berberine, because berberine gives me brutal headaches-

Dr. Kyle Gillett 1:10:15 (sighs) Yes.

Andrew Huberman 1:10:15 ...and it makes me crave carbohydrates because it drops my blood sugar.

Dr. Kyle Gillett 1:10:18 It has many other effects, including the dawn phenomenon, where it drops your blood sugar when you're sleeping and you can't even realize it.

Andrew Huberman 1:10:24 I am not a fan of berberine, and I'm sorry for those of you that are, um, I'm not trying to offend anyone. Although, frankly, if you're being offended by my stance on berberine, then maybe we should have another discussion. In any case, um, injectable L-carnitine, if one can get that through a doctor, how much is absorbed and how much should one take?

Dr. Kyle Gillett 1:10:43 Almost all of it's absorbed. In general, you're taking between 500 milligrams up to... You can take a pretty high dose, up to 2,000 milligrams.

Andrew Huberman 1:10:52 Okay, and what we did not talk about is what L-carnitine does. So, why should-

Dr. Kyle Gillett 1:10:57 (laughs)

Andrew Huberman 1:10:57 ...why should someone go through all of this? Is it to optimize testosterone? Is it, um, working on the receptor side? What- what's L-carnitine doing?

Dr. Kyle Gillett 1:11:05 It's a shuttle. So, I think it's named carnitine palmitoyl coenzyme A. Basically, it's- it just takes nutrients from outside your mitochondria and puts them in. It also has a unique effect... Well, not too unique, because tadalafil actually has this effect as well, is that it increases the density of the androgen receptor in the cytoplasm of your cells. So, even if your androgen receptor sensitivity doesn't change, and even if your does- testosterone does not change, you will have more testosterone binding to that increased number of receptors.

Andrew Huberman 1:11:38 Does one need to cycle L-carnitine, creatine, betaine?

Dr. Kyle Gillett 1:11:42 No reason to cycle any of those.

Andrew Huberman 1:11:45 Okay, what other supplements can one use to try and improve hormone profiles? And, and here, I realize we're using a very broad brush, because when we say improve hormone profiles, what are we really talking about? And for me, at least, I- I think about the subjective, um, stuff, you know? Do people feel like they are going to have more energy as a consequence of doing these things? Are they gonna have the, uh, more optimized libido, or are they going to have more optimized, uh, recovery from exercise, right? Because, I mean, it's not clear to me that taking one's testosterone from 600 to 800 is always going to be a good thing, especially if estrogen is increasing in parallel, that could cause issues. It could certainly make things better, it could certainly make things worse, right?

Dr. Kyle Gillett 1:12:25 Mm-hmm.

Andrew Huberman 1:12:26 So, uh, with that backdrop, uh, what are some of the other things people can take? And then we'll go back to this issue of what really is optimization.

Dr. Kyle Gillett 1:12:34 Let's briefly mention vitamin D, which is also a hormone. It's actually a sterol hormone, and have, if you have deficient vitamin D and you replace it, then you will optimize your testosterone. Let's also mention boron. So, if you have a very high SHBG, boron can acutely help lower it, usually in a dose of 5 to 12 milligrams per day. It's not really a sustained effect, but, uh, boron is depleted in soils in many countries. I believe it's very high in soils in Greece and Turkey, so eating dates or raisins that are from those areas potentially have more boron. Boron also me- might be one of the reasons why the reference range for testosterone is much higher in those countries than other countries.

Andrew Huberman 1:13:16 And just to remind people that SHBG, sex hormone binding globulin, is attaching to the testosterone molecule and eliminating the amount of so-called free testosterone that's available to have its impact on cells.

Dr. Kyle Gillett 1:13:26 Mm-hmm.

Andrew Huberman 1:13:26 When Dr. Peter Attia was on this podcast, in fact sitting in that very chair, he said that the ideal level of free testosterone in males should be about 2% of one's total testosterone. Do- would you agree with that number or disagree? I'm sure Peter would be fine if you-... that either. (laughs)

Dr. Kyle Gillett 1:13:43 2% is a good rule of thumb. Usually, the reference range is between about 1 and 4%. Some people do have genetic polymorphisms in SHBG, a specific gene mutation where they have very low SHBGs. Also, men that have varicose veins in their testes, also known as varicoceles, tend to have very high SHBGs, so that percentage would likely be less than 2%. So just because your, uh, percentage of free T to total T is a little bit above or below 2%, that's okay. We just need to figure out the reason why it is.

Andrew Huberman 1:14:19 How would somebody know if they have varicose veins in their testicles, um, especially if their testicles are still in- attached to their body?

Dr. Kyle Gillett 1:14:27 Mm-hmm. Sometimes it's hard to tell. Um, there is several grades. If you have a grade three or a grade four test- uh, varicocele, it has what's called a bag-of-worms appearance. So think about if you've just resistance-trained, or it's a really hot day, or you're wearing very tight-fitting clothing, then if you feel it and it almost feels like there's worms in the scrotum. The other way is to do-

Andrew Huberman 1:14:50 That's a, a scary visual.

Dr. Kyle Gillett 1:14:51 Yeah. Bag of worms. (laughs)

Andrew Huberman 1:14:53 Yeah. Well, just that, yeah, anyway, I think parasites when I hear that, but that's not what you're referring to. You're talking about just the, the, uh, the texture.

Dr. Kyle Gillett 1:15:01 The best way for most people to check is to Valsalva for a long period of time. When you Valsalva, venous return, uh, will decrease.

Andrew Huberman 1:15:11 Can you explain Valsalva for people?

Dr. Kyle Gillett 1:15:12 It's bearing down like you're lifting a weight or, uh, having a bowel movement where you, uh, swallow, and all, a-l-a lot of times you can almost see, um, buildup of, uh, blood in your, like, jugular veins as well. So you have, uh, increa- decreased blood return to the heart and i-i-increased, um, blood in the veins themself.

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Andrew Huberman 1:16:39 off. Okay, so vitamin D3. I'm guessing you're talking about vitamin D3 specifically when you say vitamin D. Um, and then boron, five to 12 milligrams per day. All right. Um, and then what are some of the other things to optimize, uh, testosterone that are in supplement form?

Dr. Kyle Gillett 1:16:55 We can talk about things that affect the steroidogenesis cascade, so we could touch on tongkat ali. I know we've talked about that a little bit before. It's also known as-

Andrew Huberman 1:17:01 Yeah, but I'm guessing a number of people probably haven't heard that conversation.

Dr. Kyle Gillett 1:17:05 Also known as Long Jack, and that upregulates several different enzymes in the steroidogenesis cascade. And by that, w- um, what you mean if... And this is another good thing to Google. I think anybody interested in hormone optimization should understand where hor- where sterol hormones come from. They come usually from cholesterol, and they can be shunted off to vitamin D very easily. They can be shunted off to testosterone, or estrogens, or progestogens quite easily as well. But tongkat helps with the conversion of multiple key steps where you synthesize testosterone. Another, um, I think of it as like a coenzyme or a cofactor, an up-regulator of these steps is insulin and IGF-1. So a good rule of thumb is if you're not expecting as much growth hormone, insulin, and IGF-1, for example, lower carb diets, caloric deficits, you're trying to cut body fat or body weight, then tongkat is going to be theoretically especially powerful.

Andrew Huberman 1:18:09 What sorts of dosages of tongkat do you recommend to your patients?

Dr. Kyle Gillett 1:18:13 Anywhere from 300 to 1,200 milligrams a day. With tongkat, you need to be careful with the standardization because... And if you're thinking about a general tongkat supplement, which is by far the most well-studied, then, um, you're looking at the eurycomanone content, which is a plant compound that is likely the main, um, active pharmacologic effect. So that's the compound that's having the effect on the body. And if you standardize the eurycomanone very, very high, then theoretically, you're having more effect at a lower dose.

Andrew Huberman 1:18:50 I take 400 milligrams of tongkat ali, um, per day. I take it early in the day because it has a bit of a stimulant effect, and if I take it after 2:00 PM it starts to inhibit my sleep. Um, I've been taking it for years, um, and, uh, I rather like the, the effects. It seems subtle but, you know, consistent. I've never cycled it. Um, do you recommend cycling it?

Dr. Kyle Gillett 1:19:11 I don't see any reason to cycle it. Um, there is, uh, there is a reason to cycle some supplements, but no reason to cycle tongkat.

Andrew Huberman 1:19:19 My blood work tells me that it causes an increase in free testosterone for me, and also a slight increase in luteinizing hormone for me. Um, what are some of the other effects on various hormones that you've as- observed in the blood work of your patients taking tongkat ali?

Dr. Kyle Gillett 1:19:34 Tongkat can also slightly increase DHEA, and if you have a very high SHBG, again, that's the protein that binds up your androgens and estrogens, an extremely important protein...... uh, the higher your SHBG, the more it helps decrease it. So they've studied Tongkat in, uh, populations with very normal SHBGs and it does nothing for SHBG.

Andrew Huberman 1:19:59 Interesting. Does that mean it does nothing for somebody overall? So if somebody has SHBG that's in the normal range, will taking Tongkat benefit them in any other way?

Dr. Kyle Gillett 1:20:08 Yes. It, it'll increase their total and free testosterone.

Andrew Huberman 1:20:12 Got it. Um, okay. Does it, is it known to have effects on anything else like thyroid hormone, growth hormone, or is it purely in these, uh, steroid synthesis pathways? Or steroid, I should say, uh, synthesis and receptor and modulation pathways?

Dr. Kyle Gillett 1:20:25 There's no direct effect on those pathways. However, any time you alter your free androgen or free estrogen, uh, particularly one without altering the other, it will alter the binding protein that binds thyroid hormones. So any change you make, whether it's natural optimization or hormone replacement, you're going to slightly skew your thyroid hormone profile. One common, like, actionable example of this that I see often clinically is, um, someone starts, let's say, estrogen replacement or testosterone replacement, maybe they're taking an AI with their testosterone replacement.

Andrew Huberman 1:21:02 Aromatase inhibitor.

Dr. Kyle Gillett 1:21:04 Correct, an aromatase inhibitor which blocks the conversion to estrogen. If they're taking testosterone and they have very little estrogen, then you're going to decrease the binding protein, also known as thyroxine-binding globulin, which binds active thyroid hormones. So if you start, uh, TRT and you either have low aromatase activity or no aromatase activity, no conversion to estrogen, then your free thyroid hormones will go up, even just acutely, uh, usually feedback inhibition, which is how the body talks to itself and says, you know, "We need to make more of this or less of this." But acutely, there's, um, n- not always enough time. You're going to have very high thyroid hormones, and you can have tachycardia, which is a fast heart rate, or you can feel kind of like overly fight or flight due to increased thyroid hormone activity in the end tissue.

Andrew Huberman 1:21:59 Interesting. Okay, so Tongkat Ali, this, uh, this is a broad range, 300 to 1,200 milligrams per day, and I realize that the source matters there. Um, what are

Andrew Huberman 1:22:09 some of the other hormones that you, uh, prescribe to your patients, uh, who do not want to go on testosterone replacement therapy or take exogenous DHEA or anything like that?

Dr. Kyle Gillett 1:22:20 We could talk about Fadogia next. Uh, Fadogia's interesting because... It's a genus of plants. Fadogia, uh, agrestis is one of them. There's many others that are very interesting. Um, that species is likely the most well-studied, and it will increase LH. So, um-

Andrew Huberman 1:22:35 Luteinizing hormone.

Dr. Kyle Gillett 1:22:36 ... I would not consider it an LH