Episode 57: Unlocking Male Hormones Part 2 with Dr. Mark Holthouse, MD

Podcast Drop Date: 4/30/2025

In Part 2 of this two-part series on optimizing male hormones, host Amber Warren, PA-C, continues the conversation with Dr. Mark Holthouse, MD, exploring the role of testosterone and growth hormone in aging and mental health. They discuss natural ways to boost hormone production using growth hormone secretagogues, review lifestyle strategies for optimizing testosterone, and break down the pros and cons of various testosterone delivery methods. Dr. Holthouse also outlines how to determine candidates for testosterone therapy through detailed medical history and lab analysis, emphasizing a personalized, root-cause approach to men's health. Subscribe for more expert insights on root-cause medicine!

Transcript:

Amber Warren, PA-C: Welcome to the Functional Medicine Foundations podcast, where we explore root cause medicine, engage in conversation with functional and integrative medicine experts, and build community with like minded health seekers. I'm your host, Amber Warren. Let's dig deeper.

Dr. Mark Holthouse, MD: So part of what I enjoy so much doing with these men is to get them fully functioning again.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: So they're a team, a part of a unit, a cohesive, um, family again where they don't feel down, depressed, irritable, marginalized. Uh, and guess what? Their kids, their boys and their daughters are going to see that. And I think they're going to be better for it.

Amber Warren, PA-C: Absolutely.

Dr. Mark Holthouse, MD: Um, otherwise, you know, it just gets kind of distilled down to, you know, what are we trying to do here? Just create these, you know, oversexed, muscular guys that aren't really contributing much to society. It's just such a, you know, it's such a bigger topic.

Amber Warren, PA-C: So much bigger than that.

Dr. Mark Holthouse, MD: You know? And I think it's important to have this conversation talking about the men's side specifically. Yeah, because there's two genders listening to this, on this audience. And there's always that group that says, yeah, well, I don't want my husband to, you know, become a jerk or lose his temper or treat my the kids poorly or treat me poorly because he's on this stuff.

Amber Warren, PA-C: I think it's the opposite though.

Dr. Mark Holthouse, MD: It is. It is the opposite in my experience.

Dr. Mark Holthouse, MD: And the data is very clear. Um, most guys that are hypogonadal are the ones that are having mood issues and not just depression, but they're curmudgeons. You know, if they're older, they're just a pain to live with. And even the younger ones can just be really not not a party either.

Amber Warren, PA-C: Totally.

Dr. Mark Holthouse, MD: So, um, there is a sweet spot there. And it's not just about giving super physiologic doses. You know, you asked a question about peptides. And so the guys that don't need to lose 20, 30 pounds, uh, where we're going to be using GLP instead we use, um, these growth hormone secretagogues, which it's not growth hormone itself, which is therein lies the beauty. It's basically a naturally occurring, peptide that's been created in a compounding pharmacy to be taken at night, 90 minutes or so after your last meal. And it tells the hypothalamus, the brain, "hey, let's make some, some growth hormone". And then there's another one that you give with it that says, let's let it out, let's release it, as opposed to giving growth hormone itself, which downregulates receptors and can have some dangerous side effects. So what is growth hormone? Why? Why would we ever want to support that? Well, it's secreted during, uh, deep slate, deep sleep at night. And if anyone's worn an Oura ring or a smart watch and looked at their Fitbits, their wearables, and seen how crappy their sleep can be when they've had a lot of stress or whatever.

Amber Warren, PA-C: Or 1 or 2 drinks of alcohol.

Dr. Mark Holthouse, MD: Or. Yeah, that can mess it up too.

Amber Warren, PA-C: Toxic. Toxic.

Dr. Mark Holthouse, MD: Can raise cortisol.

Dr. Mark Holthouse, MD: You come to the conclusion that there's a lot of disruption not only to growth hormone which gets pulsed, dosed every night. That's when it's repairing all your tissues from the damage the day before.

Amber Warren, PA-C: And we lose growth growth hormone as we age. So that's also why this is important.

Dr. Mark Holthouse, MD: Yeah it's a slow road down as well for both men and women along with um testosterone. So those are your two anabolic building hormones that we're losing as we age. Um, women are largely using estrogen as well for muscle, but, uh, it's so important to understand that if you're giving something that's supporting growth hormone, along with optimizing T, it's a fat burner. Basically, it helps burn fat while protecting your structural protein, 13, i.e. lean muscle mass.

Dr. Mark Holthouse, MD: So if you can, um, look at a guy who's like, you know, within 10 pounds of where he wants to be, he's got pretty good body composition on on the measurements that we do, percent body fat, percent lean. And he's really just wanting to get some of the tummy fat off. He wants to lean out a little bit more. Those growth hormone secretagogues are releasing peptides are amazing to do that. In addition sometimes synergistically with optimizing T.

Amber Warren, PA-C: Love it.

Dr. Mark Holthouse, MD: And that's how those hormones were meant to work together.

Dr. Mark Holthouse, MD: Um, so if they're both declining as you age and you can get somebody on something like that in a pulsed fashion, it can be really helpful. And it's not a forever thing like the T. We use these things for two, three months at a time and then take a month or two off. And maybe that's all they needed to get the ball rolling.

Amber Warren, PA-C: Right, yeah. And similar to testosterone I'm blown away. How many people are like oh my sleep. My deep sleep is so much better, which impacts their whole day.

Dr. Mark Holthouse, MD: Yeah, isn't that interesting how structural anabolic hormones help sleep?

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: They're regenerative for our tissues. Evidently, they're doing more.

Amber Warren, PA-C: It's amazing.

Dr. Mark Holthouse, MD: Um, and there's a whole topic about melatonin and why it's high at night and it's antioxidant job in the mitochondria, uh, which is, ironically, where hormones are made.

Amber Warren, PA-C: Made in the mitochondria.

Dr. Mark Holthouse, MD: Yeah.

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Amber Warren, PA-C: So part two of this is what do we do about this? The the lack thereof testosterone optimization or subpar testosterone. So lots of different ways we can replace these guys.

Dr. Mark Holthouse, MD: Yeah.

Amber Warren, PA-C: So tell us the different ways.

Dr. Mark Holthouse, MD: Yeah, weight loss. It's that same list. It's literally not just weight loss but, um, losing body fat. The data is really clear on whether you look at pre-diabetic data or diabetic data. You lose weight. You lose weight. That's great. But if you lose body fat, both subcu and particularly visceral fat, that's probably the number one way you can naturally raise your T.

Amber Warren, PA-C: Cool.

Dr. Mark Holthouse, MD: Uh, number two would be exercise. Number three is going to be right in there. Close, third is that diet that we talked about which is avoiding those processed foods and spiking your sugar. And then lastly would be getting good sleep and managing that cortisol. If you get less than five hours a night of sleep for more than a week, guys, there's a JAMA study 2011 showed drop their T by as much as 15%.

Amber Warren, PA-C: Wow.

Dr. Mark Holthouse, MD: So glad we didn't know that in school, right?

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: I don't know that I got five hours of sleep for four years in med school.

Amber Warren, PA-C: Yeah, your levels dropped quite a bit. It's good you know what you know now.

Dr. Mark Holthouse, MD: Right?

Amber Warren, PA-C: So for those guys who are saying. Yeah, yeah, doc, I've checked those boxes or I'm working on it, I'm getting there. But my levels are still 300 and I feel like garbage.

Dr. Mark Holthouse, MD: Yeah.

Amber Warren, PA-C: Then how do you choose who to replace and how you replace them?

Dr. Mark Holthouse, MD: Yeah. So then it's a matter of choosing them. Are they a good candidate? Basically the hard contraindications are breast cancer or active prostate cancer. We do treat guys with low stage and grade prostate cancer when we're co-managing with urology now all the time, if they have obvious symptoms. If their PSA aren't stable or there's something changing on their their pet Psma Pet scans or their MRIs then you got to hold off. You got you got to have stable prostate cancer before you can treat them. Breast cancer, certainly a hard no. Um, if they haven't had a heart attack or stroke in the previous six months, they don't have an active clot. History of a clot is a relative contraindication. I don't use that as a hard no.

Amber Warren, PA-C: Okay.

Dr. Mark Holthouse, MD: Um, it is for estrogen, but not for for T.

Dr. Mark Holthouse, MD: Um, and they've got symptoms, you know, that list of symptoms, you know whether they're mental, physical, sexual, metabolic, abnormal labs, fatty liver. Um so safe. They've got symptoms. And then you look at their physical exam. You know, do they have a lot of belly fat? Do they have, um, the, uh, acanthosis nigricans, which is the pigmented, uh, hyperpigmented creases on the skin in pre-diabetics. Do they have evidence of high cholesterol on their on their eye exams and on their labs? So you're looking for signs. Physical signs. Do they have changes? Do they have increased breast growth? You see all these guys that have breasts that are growing and it's like, what's going on there? They got way too much estrogen. Um, you feel and check their testicular size. Sometimes there's problems there. They're soft, kind of squishy and not firm. Normal testicle. There can be problems, not just from infections and mumps in the past, but there's all kinds of other things that could be going on with them. Uh, with toxins. Do they have a history of undescended testicles? You know, or is there a problem with, um, toxic burden? What's their job? Are they a firefighter? Are they a farmer, or are they, you know...

Amber Warren, PA-C: Where did they grow up?

Dr. Mark Holthouse, MD: Where do they grow up? Where downwinder are they getting their water from a well? It's, you know, full of phthalates, which we know does a number on, um, your, your in utero and in utero levels of T. Do they drink out of plastic water bottles or get a bunch of BPA, you know. Handling receipts? Um, where we get those things? These are all known endocrine disruptors. So, you know, you ask all these things in this history, it's a quite an elaborate history.

Amber Warren, PA-C: Yes it is.

Dr. Mark Holthouse, MD: You got to go through mood and everything. Physical exam. Um, so they're a good candidate. You're going to obviously then look at labs and I usually look at total and free testosterone the first time. And if it's abnormal, we know we're going to have to repeat it. So as long as it's on another a separate day and they're not acutely ill with some illness, um, you bring them in ideally fasting before 9 or 10 a.m., you check a second one. And on that second round I'm going to add, you know, probably PSA if they're older, I'm going to check estrogen. I'm going to check LH, FSH, blood counts, liver. I'm going to basically want to know okay. It's not only confirmed now, but are they safe to treat and are they primary or are they secondary hypogonadal. And that's what all those other tests help me know. And then you decide with them okay. You're a good candidate. You've got symptoms. Your labs are there or not. Sometimes again it's optimizing and the labs are more irrelevant. But there are certain things you have to make sure on the labs that aren't contraindications. Do you have a wonky PSA? If so, you're probably going to have to do a rectal exam, or at least an ultrasound or MRI. Clear the prostate first. Make sure you don't have a nodule.

Amber Warren, PA-C: Right.

Dr. Mark Holthouse, MD: And then you're going to talk about what the different modes of delivery are. Basically you've got creams, gels, roll ons, things that you can stick to your gum, which I don't recommend. Gum in your mouth, not chewing gum. Um, Nasal sprays um more commonly are going to. The most common is gels and creams. Probably the most effective are the injection.

Amber Warren, PA-C: Yep.

Dr. Mark Holthouse, MD: Uh, and there's 4 different types that you can do there. And then pellets. The injections are the least expensive. They're more apt to give you a roller coaster, um, on the dosing and side effects and needing to go donate blood because a lot of guys, when they do injections, they get a really big overshoot. And then their bone marrow makes too many red cells, which can thicken the blood. And you got to go donate blood, which we often will see that with the injectable more so than pellets.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: Pellets are every six months on guys. Every four on the gals. Um, pellets are great. You put them in and you can kind of forget about it. If the dose didn't last or you didn't get the pop you wanted. You do a complimentary booster at a month, and depending on the labs and their symptom relief, you make choices for the next pellet, what you're going to do. Usually by the the first couple of times they they have a pretty good idea.

Amber Warren, PA-C: So advantages over pellets over like the injectable.

Dr. Mark Holthouse, MD: So yeah it costs a little bit more.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: But the advantages of pellets you don't have to give yourself a shot twice a week.

Amber Warren, PA-C: Right.

Dr. Mark Holthouse, MD: Um, you avoid a lot of the roller coaster. A lot of weightlifters prefer injectable over pellets because they feel like the pellets fade.

Dr. Mark Holthouse, MD: That's because it was dosed improperly. And that's something that's easy to solve for by going up on the dose.

Amber Warren, PA-C: My other argument to that would be that that testosterone is synthetic. It's actually testosterone cypionate.

Dr. Mark Holthouse, MD: Yes.

Amber Warren, PA-C: So it's not nearly as natural for those that are interested in that like pellet form would be.

Dr. Mark Holthouse, MD: Pellets come from ground up yam.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: Uh, and it's actually testosterone. The injectable cypionate is a synthetic prohormone. Kind of like levothyroxine or synthroid is for the thyroid, it's T4 that has to get converted to T3. Well, cypionate has to go from the shot where you gave it to your liver, get converted to testosterone before it can go and tag the receptors. Um, so there's advantages on side effects. Uh, convenience. Um, uh, if if cost is the only thing that they care about, injectables is probably going to be the way they go. If convenience, consistency of dosing, um, not having to hassle with going and donating blood and not being as worried about, um, some of the downstream metabolites, uh, are a concern, then pellets are probably the way to go.

Amber Warren, PA-C: Okay.

Dr. Mark Holthouse, MD: Um, creams and gels are most guys. It's not what they enjoy doing.

Amber Warren, PA-C: It's just a pain.

Dr. Mark Holthouse, MD: Yeah.

Amber Warren, PA-C: Most of them you need to apply twice a day, right?

Dr. Mark Holthouse, MD: Yeah. You got to wait.

Amber Warren, PA-C: What guys are gonna do that?

Dr. Mark Holthouse, MD: Hours. Yeah. You gotta wait four hours before you can take a bath, shower.

Amber Warren, PA-C: You don't want to get it on your wife or your kids or your pets.

Dr. Mark Holthouse, MD: You dose. Your pets. Everybody. And you got to use your own hand towels and watch what you touch after. And yeah, it's really easy to contaminate people that don't want that testosterone. And that's that tends to be pretty pricey.

Amber Warren, PA-C: Yeah, yeah.

Dr. Mark Holthouse, MD: The gels are all that you can get through, um, regular pharmacies. They don't do creams. That's got to be through compounding. And compounding is much less expensive for testosterone topical than having to pay full price for testim and androgel and. Um, the other thing I didn't mention is there are there are three FDA approved oral, long acting testosterones that are out there, and I've always been a little gun shy of those because of the history of that being absorbed through the liver and then creating problems in the liver. Uh, they have, uh, testosterone undecanoate, which is a long acting ester of the testosterone, both in injectable and in oral forms. Now that have gotten away from first pass liver metabolism, meaning they don't get absorbed through the liver, they get absorbed through the lymphatic channels in your small intestine, bypassing the liver. Um, you know, they're new. They are associated with hypertension, albeit the studies are pretty, um, minimal. I mean, it's it's like 2 to 2% or something, 2 to 5% that get actually a bump in blood pressure. But if you're part of that 5%, I'm just like, man, I don't need any any help with battling high blood pressure.

Amber Warren, PA-C: Right.

Dr. Mark Holthouse, MD: You know, with the bulk of people, majority of people having it in our culture as they get older. Um, but that certainly is an that's an option. The problem is, again, to get that paid for, you have to qualify. Meaning most of the guys that are here to optimize, they're going to end up coming out of pocket.

Dr. Mark Holthouse, MD: It's going to be hundreds and hundreds of dollars a month to buy the oral version of T. So those are out there and available now.

Amber Warren, PA-C: Okay. Okay. So interesting.

Dr. Mark Holthouse, MD: Yeah.

Amber Warren, PA-C: So who's a good candidate?

Dr. Mark Holthouse, MD: Oh, man. Um, so we don't want to give it to guys that are still wanting to have kids. Because if you give testosterone to any guy, it'll shut down the ability to make sperm. So.

Amber Warren, PA-C: But we have options for those guys.

Dr. Mark Holthouse, MD: We do.

Amber Warren, PA-C: We do.

Dr. Mark Holthouse, MD: Yeah. We have options. There's prescription options for those guys where if you've got low T and you're symptomatic with Clomid and and clomiphene now through the compounders, which has less estrogenic side effects and HCG injections are out there and they work great.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: If you're looking to get your numbers up around 800. Anything above that, that's about where they peak out. You got to go to T. So if it's a guy that doesn't care about siring any kids in the near term, uh, a question I get often is if I start testosterone at 35 and I get, God forbid, get remarried in my young thing wants to have a family in my second term. Uh, time around here. What about that? Well, you're you're able to stop that, and things will come back online. The synthetics, don't hold your breath. It may not.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: Um, it can take months, you know? And after pellets, it can take upwards of a year for for the sperm counts to come back. But, um, for everyone else. Yeah, you can use testosterone. And, um, that client that's got those symptoms, whether it be metabolic dysfunction, whether it be sexual side effects, whether it be just, hey, I need more cognition. I want to get rid of my brain fog and improve my focus, my stamina, my recovery time. Um, I want to build more muscle. I want to lose belly fat. We know testosterone is really good at helping you lose fat and gain muscle.

Amber Warren, PA-C: Yeah. Or you just don't want to follow in your father or grandfather's footsteps of having an MI at 60. Right?

Dr. Mark Holthouse, MD: Exactly. You know, we used to think it caused prostate cancer. Now we know that's not true. Doctor Huggins. 1941, won the Nobel Prize for doing a bogus study on dogs. 80 years later, we're finally finding that to not be true. And now we're realizing that it not only doesn't cause heart attacks and strokes like we thought, the FDA label hasn't even caught up yet. Uh, the new traverse trial that was just released a year ago in July has a it's powered enough statistically to now show it doesn't cause heart disease, doesn't cause prostate cancer. And in fact, we think that it actually helps prevent heart attacks. Yeah. So amazing when you think about the number one cause of death in this country being cardiovascular disease.

Amber Warren, PA-C: We have tools, very safe and effective tools to decrease that statistic. Yeah. Reduce that risk. It's amazing. Yeah. Anything else you find that is important or pertinent to share around this topic of male hormones and optimization?

Dr. Mark Holthouse, MD: I think you really did a good job, Amber, at kind of exposing the fallacy of thinking that it's a one it's one issue.

Amber Warren, PA-C: Yeah

Dr. Mark Holthouse, MD: It is. It is one hormone on a dance floor of dancers.

Amber Warren, PA-C: Yeah.

Dr. Mark Holthouse, MD: And if you don't pay attention to who else is out there that can knock you over and, and, um, you know, you're spending money on these things. Uh, and you want them to be effective. Um, you may not need it. There may be some of these other players that you can get to first. You may only need to work on weight loss and the right kind of exercise and change, tweak your diet just a little bit and not need them.

Amber Warren, PA-C: It can be enough.

Dr. Mark Holthouse, MD: Might be all you need. I have seen guys raise their testosterone by 50%.

Amber Warren, PA-C: Wow!

Dr. Mark Holthouse, MD: Within six months with lifestyle changes not touching a supplement.

Amber Warren, PA-C: And that's truly the beauty of functional integrative medicine. And what we get to do every day, right, is you can try A, B, and C first before you have to rely on D. D is always an option, but we don't have to go there initially, especially if that's not your desire. Our job is to meet you where you want to be met and try and reach your health goals together. So yeah, it's it's wonderful. Well, men and women alike, we hope you share this with your brothers and your dads and your colleagues and coworkers. And because this is a message we want. We definitely want out there. And we talked in the female version about how no one should have to suffer in silence. And it's true for our for our guys too. So yeah, thank you, Doctor Holthouse. Thank you for those of you that tuned in.

Dr. Mark Holthouse, MD: Thank you. You're welcome.

Amber Warren, PA-C: Thank you for listening to the Functional Medicine Foundations podcast. For more information on topics covered today. Specialties available at the FMI Center for Optimal Health and the highest quality of supplements and more go to funmedfoundations.com.