Testosterone Replacement Therapy with Dr. Rand McClain: Rational Wellness Podcast 349

Dr. Rand McClain discusses Testosterone Replacement Therapy at the Functional Medicine Discussion Group meeting on February 22, 2024 with moderator Dr. Ben Weitz.  

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Podcast Highlights

4:33  Some of the most common symptoms men complain of that might indicate the need for testosterone replacement therapy are a lack of energy and a lack of libido.  Other symptoms include cognitive problems, sleep problems, and difficulty improving your body composition. 

6:06  Testosterone and prostate.  Dr. McClain feels that testosterone therapy does not increase the risk of prostate cancer risk, though estrogen might increase prostate cancer risk, as well as cancer of the breast, cervix, and uterus.  Dr. McClain feels that while testosterone does not increased prostate cancer risk, the metabolite, dihydrotestosterone is related to prostate problems.  And placing a man on Lupron for metastatic prostate cancer makes the man miserable.

10:18  PSA.  While androgen deprivation therapy for prostate cancer will lower PSA levels, but Dr. McClain argues that PSA is not an effective test to screen for prostate cancer risk and the American Urological Association no longer uses it as a cancer screening tool.  Dr. McClain also mentioned that he has several patients who have had a PSA level above 13 for most of their adult lives and based on multiple biopsies and multiparametric MRI, they do not have prostate cancer.  And some patients have a normal PSA and have been found with prostate cancer. 

21:34  Transdermal testosterone.  Dr. McClain feels that transdermal testosterone is a good option for females but not for males.  Men do much better with a timed release version of an injectible testosterone.

22:42  Free vs Total Testosterone.  If free testosterone is low because the Sex Hormone Binding Globulin is high, we can lower SHBG through a high protein diet, by taking stinging nettle, with estradiol, or by using a small dosage of an anabolic steroid.


Dr. Rand McClain is a Doctor of Osteopathy and a Regenerative and Sports Medicine specialist.  Dr. McClain is a leader in alternative and regenerative medical treatments at his Regenerative and Sports Medicine Clinic in Santa Monica, California.  He utilizes various anti-aging therapies in his practice, including Bioidentical Hormones, stem cells, peptides, hyperbaric oxygen, cryotherapy, and nutritional supplements. He wrote a best-selling book, Cheating Death in 2023.  His office website is psrmed.com.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure.  Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website. DrWeitz.com. Thanks for joining me and let’s jump into the podcast.

                                                Welcome everybody. It’s a small group tonight. Since after the pandemic, we’re not getting quite the number of people showing up in person, so please tell your friends. These meetings are great networking and trying to bring the functional medicine community together. So we meet on the fourth Thursday of every month, and please join some of our upcoming meetings. Our next meeting is March 28th on an Integrative approach to Cancer with Dr. Nalini Chilkov. And April 25th is Dr. Maggie Ney on bioidentical hormone replacement. So I encourage everybody to ask questions. And after you ask the question, we’ll repeat it. And if you’re not aware, we have a closed Facebook page, the Functional Medicine Discussion Group of Santa Monica. So please join that so we can continue the discussion. I’m recording this event and you can see it on my Rational Wellness Podcast, and so please check that out. And if you do like watching it, please give me a positive review on Apple Podcasts or Spotify. And our sponsor for this evening… Oh, there we go, is Integrative Therapeutics. So Steve, would you come up and tell us about a few of the Integrated products?

Steve:                                   Hi there. This isn’t really our wheelhouse, but we do have a really nice product called Testosterone Formula that has Panax Ginseng, Ashwagandha, Tribulus, a few other things that have been in clinically significant doses. So that’s a top-ten product for us. And then the big news is the cortisol manager is now allergen free, so it’s not news to you, but. So we’ve turned it into a capsule, removed the soy, removed the mag stearate and titanium dioxide, so it’s much cleaner. That’s kind of going to be a trend for us is, if you guys are aware that some of the ingredients that are typically in tablets are being phased out in California. We don’t have two different products for California versus other states like the Prop 65 warning. All of our products are Prop 65 compliant. Is that right, 65?

Dr. Weitz:                            Yes.

Steve:                                   So we’re changing a lot of tablets into capsules where we can’t do that. We’re removing those ingredients anyway, and that’s going to be all over the country. So that’s kind of it for now.



Dr. Weitz:                            So our topic for tonight is hormone replacement with Dr. Rand McClain. Dr. McClain is a regenerative and sports medicine specialist who works with patients at his regenerative and sports medicine clinic in Santa Monica. Dr. McClain is an osteopathic physician and a bestselling author of Cheating Death. Dr. McClain is an expert in hormone replacement therapy as well as with regenerative medicine. So Dr. McClain.

Dr. McClain:                        Thanks for the introduction. By the way, I know it’s billed as a male hormone replacement therapy session as it were, but I deal with female and male hormones, so I imagine you guys might’ve figured that out. So ask away, really. And I don’t want to take any thunder away from the gals coming a week from next or…

Dr. Weitz:                            A couple of months. Yeah. That’s fine.

Dr. McClain:                        Couple of months. Yeah, please. As matter of fact, I was telling Doc earlier tonight that I started practicing with females being the larger percentage of the population for the longest time before it flipped on me. And now I think more than ever, women are getting the gyp in terms of attention to the therapy they need. So anyway, ask away, please.

Dr. Weitz:                            So I’ll start with the questions.

Dr. McClain:                        Okay. Sorry. Please.

Dr. Weitz:                            Let’s start with men. When you see a man in your office and they come in complaining, what are some of the complaints that would make you think about prescribing testosterone for men?

Dr. McClain:                        That’s an easy one, most people complain about a lack of energy. That’s probably number one on the list. With males and females, though libido is an issue, people are still in their thirties and wondering why that magic has gone away. Sometimes it’s cognition and that makes sense if you think about the light bulb not getting enough energy, it’s not a problem with a light bulb, it’s just you’re tired all the time so how can you think straight.  Body composition is the one that comes up too, because you know what you do, especially a lot of the patient population I have here in California, they work out like we all do in Southern California, and the tricks that used to work, something as simple as not having beer for three weeks or whatever brings your abs back, but not anymore. And you’re wondering why if I’m doubling up my cardio, can I not get the results anymore? Well, you don’t have the leverage of testosterone. So those are just a few of the ones that bring people in really.  Trouble sleeping too for a totally different reason that testosterone tends to be nature’s antidepressant. And for a lot of people, it’s hard to get a good night’s sleep if you’re worried about the 2.3 kids and a mortgage and don’t have the ability to, like you did when you were 20, to shut off your brain and say, “Be quiet. I’m going to go back to sleep and handle this in the morning.” So those are a few.

Dr. Weitz:                            So when you see a man, let’s say a guy comes into your office and they’re interested in possibly getting on hormones, when do you think this person shouldn’t be on hormones? What are some of the risk factors, reasons why you wouldn’t want to prescribe testosterone, say to a certain guy?

Dr. McClain:                        If he or she’s really bent on feeling bad, then I won’t give them any medication. But really if you’re referring to the potential side effects, the potential side effects are, first of all, things that we can control and typically do not reflect testosterone per se, but a metabolite testosterone called dihydrotestosterone. That’s the bad guy. And men have known about that for a while for accelerating hair loss. Women for acne. That’s why we used to prescribe spironolactone, which is actually a diuretic, but it has a secondary benefit to females to block the conversion from testosterone into dihydrotestosterone. So that’s an easy fix if you think about it, if you’re one of roughly the 20% that does get acne, or not only hair loss in the head, but hair in the wrong places, it is driven by dihydrotestosterone and we can just block the formation thereof and you’re happy.

                                                So those are really the… Now you might read about, if you go on Dr. Google, some of the side effects that have been presented over the years or contraindications, for example for men, prostate cancer, oh, it’s going to give you prostate cancer. Legend. I challenge you as would Abraham Morgentaler, who really did a lot of the leading research, along with guys like Dr. Larry Lipshultz, to find a study that actually proves that. It’s been legend for probably 80 years now, and we actually know that testosterone’s protective to the prostate rather than the other way around. It’s the estrogens men and ladies have to worry about, again, a metabolite testosterone. But we can control those because we’ve identified that the estrogens you got to look out for, and write it down if you guys are planning on being on jeopardy, but the 16a-hydroxyestrones and the 4-hydroxyestrones definitely are associated with cancer of the breast, cancer of the cervix, uterus, but also the prostate. So that’s what we want to watch out for as metabolites.

Dr. Weitz:                            Well, I get that. I hear you and I’ve seen the studies that show that testosterone doesn’t increase the risk of prostate cancer, but there’s got to be some relationship because we know that patients who have advanced prostate cancer are often treated with androgen deprivation therapy. So somehow blocking testosterone has some benefit in inhibiting prostate cancer growth.

Dr. McClain:                        I’m glad you brought that up because that’s the saddest part of what I’ve seen with this association that’s been misplaced, because again, it’s not the testosterone itself, it’s the metabolites that cause the issues. Of course, cut out testosterone, you don’t have any more dihydrotestosterone, you don’t have any more of this estrogen made from testosterone. So it does work sometimes. Sometimes it doesn’t however, because you do lose the protective benefit of testosterone. And you put a guy through even more torture because ladies who are meant to have a pretty high level of testosterone can even, sorry, estrogen, beg your pardon, can attest to when it’s too much feeling not so good. Guys are not meant to have estrogen. And what little remains in the relationship, I should say, to the zero testosterone makes a guy miserable. And it’s not only that we’re cutting that off, but we are actually giving them Lupron. And so the estrogen levels can go way higher than they’re supposed to and guy’s miserable on top of having stage four prostate cancer. It’s really terrible. So I hope you were teeing me up for that answer, but yeah.

Dr. Weitz:                            Yeah, I generally think you’re right, but still there’s got to be… I mean you definitely see PSA levels go down when they get on the Lupron.

Dr. McClain:                        Are you teeing me up again? I think you are. PSA has never been and never will be a cancer screening tool. It can be useful for prostate cancer if you’ve had a radical prostatectomy because obviously if there’s any prostate tissue left over, we have an issue. But prostate specific antigen has been touted as a cancer screening tool since the guy invented it and went to committees that sort of glossed over the fact that it really had no relationship. The guy who invented the tool actually, to detect prostate specific antigens, first went to The Wall Street Journal and then nobody listened. He was screaming, “Don’t use my tests to screen for cancer. That’s not what it’s for.” So he had everything to lose, so to speak, and nothing to gain from that. Actually ended up writing a book called The Great Prostate Hoax.  But finally, I believe it’s official, the American Urological Association no longer uses it as a cancer screening tool anymore because they realize it doesn’t work. You can have prostate specific antigen elevations because you passed a large stool the day before, you had sex the day before, you rode your bike the day before and essentially manipulated the prostate so that it would express more prostate specific antigen. But it could be that those numbers are elevated simply because you have a large prostate or the three, I think, things I mentioned earlier.

Dr. Weitz:                            I would argue with that. I think that PSA is not as accurate a measurement as we’d like, but if a guy presents in your office with a PSA of 20, very highly likely has prostate cancer. Now you can have small changes, you can go from two to three or three to four, and that could be something benign. But I think very large changes in PSA are likely caused by prostate cancer.

Dr. McClain:                        The studies don’t bear that out. And in clinical practice, which I can speak to more so than the studies, I have two good friends who maintain a PSA somewhere above at least 13 for most of their adult life. And one of them has been through five biopsies of the prostate, which are not without risk and are no fun. They do not have prostate cancer as evidenced by the biopsies, but also through multi-parametric MRI, which allows you to visualize the prostate. So again, it does make some sense that you could expect to find a cancerous prostate associated with an elevated PSA because typically it’s going to be larger, right? Cancer grows out of control or undifferentiated cells. So a higher PSA could be related to that. But again, if it’s also because of enlargement for a benign reason, then you can’t necessarily say that is a sign. It’s pathognomonic, we would say, right, for prostate cancer.

                                                So it does jive if you see a high PSA in certain cases. But then again, we have cases where the PSA was normal and we found prostate cancer. So I don’t use it as a tool. Actually, what I do use it for is a tool to manipulate insurance companies with their rules and say, “Hey guys, if it’s over four, let’s get a multi-parametric MRI so we can actually see what’s going on there.” You can visualize a lesion as small as three millimeters if you send it off to a special place in Holland, but even five millimeters is pretty small, and if we catch it early enough, we have about a 97% cure rate with prostate cancer. So that’s the name of the game. But I know I’m getting off topic with the PSA.

Dr. Weitz:                            Oh no, that’s fine. I mean it’s an important topic. Prostate’s an important topic. Why don’t we talk for a few more minutes about prostate? What do you think about localized prostate treatments?

Dr. McClain:                        Like [inaudible 00:14:40]?

Dr. Weitz:                            Like using the HIFU or some of the other techniques to… Let’s say you have a localized prostate cancer, localized to say one lobe of the prostate and after the MRI and it’s a lower grade, let’s say a Gleason six using a localized therapy as opposed to radical prostatectomy?

Dr. McClain:                        The jury’s still out. I have some patients that have gone through with that and so far so good. I would expect nothing but success if the entire lesion was removed and the margins, etc. Because it does make sense. And of course you can preserve a good portion of the prostate so that the patient is not harmed in any way by a loss of prostate function because it’s gone. So I think there’s a lot of potential for success there for people that don’t want to do what we call watchful waiting to see if it’s in a section like that that you can isolate, and it’s not near the edges of the prostate, some people like to just watch to see if it’s going to grow any further. But some say, “Hey, let’s get rid of it.” And that’s a procedure that seems to be working well so far. But they’re new so we don’t have long-term studies that can say, “Hey, when I removed it with this particular technique, I had a 20-year survival rate or more hopefully. But it makes sense

Dr. Weitz:                            Obviously when anybody gets that treatment, you don’t just forget about it and you got to be monitoring them carefully. So you’re going to prescribe testosterone to a man. What type of treatment do you typically recommend?

Dr. McClain:                        That’s kind of easy too. I like to joke self-deprecatingly that a monkey could do this if he gets enough practice because believe it or not, the starting dose is typically the same. I was sharing the story with the 83-year-old woman with you before and early in my career I made the mistake of saying, well, gosh, she’s 83, maybe I should cut back on the dose a little bit. And boy did I get an earful when six weeks later she was complaining that, hey, it hadn’t kicked in and it’s not doing anything for her. And it ain’t like she has a whole lot of time left. She wants to get to the garden and have enough energy to do her gardening. So I learned early on that, at least at the start, and it’s rare that I would say this, but one size does fit all. And then you can adjust it from there depending upon someone is what I call a cheap date or an expensive date, they need more or less. And we can adjust that roughly 90 days.  But the interesting thing about testosterone replacement, and I’m assuming you’re talking about testosterone because the ladies need estrogen modulation as well, and progesterone perhaps, depending upon each individual. But with testosterone, you’re trying to get to a therapeutic minimum threshold and remain above that rather than find a sweet spot like you would say thyroid where you’re looking for the same reference intervals with exogenous thyroid that you would with the body producing its own. With testosterone, you’re not looking for that. And we’ve known that since roughly the 1950s, although that’s not widely published either anymore or at least known. But you get to that level, stay above it, and you’ll be fine. Well, I should say you’ll have resolutions of the symptoms that you’re trying to resolve. So that’s one thing that’s unique about testosterone.

                                                So you can start with that dose and then, as always, ask the patient how he or she is doing in roughly, I wait 90 days because it takes six weeks. We don’t know why it works this way with certain antidepressants too, but at six weeks they’ll feel better typically, the symptoms will resolve. But you go through what I call a honeymoon period, because the body, and I know I make myself into a nerd even more so every time I say this, but it’s really cool if you think about it, you can’t make more keys, so you make more locks with the same keys, you make more receptors, it’s called upregulating receptors, to take care of the business of not having enough testosterone around. Well, now we fix that with replacement therapy. So it takes the body a while to downregulate the receptors, and in that time you enjoy the benefits of having what would be considered more testosterone effect.

                                                So roughly 90 days I like to check back in. And then again, how are you doing? That’s the most important thing. Have the symptoms resolved? If not, what isn’t there for us yet? And then look at the labs, arguably secondarily, to see, okay, do you have more testosterone than you need? Do you have less than you need? Again, in combination, most importantly with the symptoms, because you don’t treat numbers. And I see plenty of patients… And Morgentaler, by the way, deserves credit for this because early on I read his material and he would give a cutoff. Do you remember those days when 450 total testosterone… By the way, they weren’t even looking at free testosterone, which is important because the free is what is real to you. That’s what’s available for use. But 450 nanograms per deciliter or below, then you’re a candidate. If not, you’re not. Well, what if you’re 447? You’re out of luck? Let’s try measuring again. Let’s try that again. Anyway, and what happens once you’re above or below that range for other reasons?   So he has come around along with at least 20 other experts in the field worldwide. They published a consensus in 2016, they published through the Mayo Clinic, basically saying what I’m now repeating, you treat people not numbers. And if someone is symptomatic and they don’t have a ridiculous testosterone of say, 1200, which is very, very high, then treat them whether it’s 450 or 650 if they’re suffering from low T symptoms. So anyway, I’ll stop there.

Dr. Weitz:                            Yeah, for those who aren’t familiar, Abraham Morgentaler is a world-famous researcher and doctor who’s written a lot of papers about the safety of testosterone and argued and shown in papers that testosterone doesn’t increase the risk of prostate cancer, and it’s even safe in some cases with patients who’ve had prostate cancer.

Dr. McClain:                        It’s actually been used, a very small study, I will say, in NF-15 to treat prostate cancer. They called it bipolar testosterone use where they put people on, they took them off, put them on, albeit it a small dose and it was transdermally applied, but it worked. So yeah, he’s been a great proponent of testosterone use and making sure that a lot of these rumors were dispelled. But again, in that consensus statement, he incorporated the expertise of those worldwide. So that’s one of the reasons I mentioned it, because it’s not just him.

Dr. Weitz:                            What about transdermal testosterone?

Dr. McClain:                        So that’s a good option for females, and I can’t tell you why it works for females but not males, except that it just doesn’t work as well when it comes to resolution of symptoms. Guys tend to do much better on an injectable where you’re using what we call an esterified form of testosterone, a time-release version. And it is more than just effectiveness, which is defined one way differently than efficacious is because effectiveness implies compliance. And guys and creams don’t work well, certainly don’t work well with me, I hate shaving as it is. Obviously you do too, look like you got [inaudible 00:22:18] today. And I joke, and I don’t mean to sound… this is going to sound sexist, but my wife, I drop my candy by not invested in Sephora because she loves creams and gels and stuff like that every day. But compliance is an issue in and of itself. But beyond that, as I’m trying to say, it’s much more efficacious in men to use the injections rather than the cream. But for females, it seems to be no difference.

Dr. Weitz:                            You mentioned free testosterone versus total testosterone. And so if the free testosterone is low often because the sex hormone binding globulin is high, how do you address that?

Dr. McClain:                        So if that’s the only issue, in other words, it doesn’t appear that the gonads, whether they’re ovaries or testicles, are producing insufficiently if there’s plenty there, but it’s just a matter of getting that free testosterone up. We can lower SHBG through a couple ways. One is to maintain a high-protein diet. The other is to keep… And this is for a male now-

Dr. Weitz:                            How does a high-protein diet help?

Dr. McClain:                        That’s a good question. I don’t think we know the mechanism of action, but maybe you do?

Dr. Weitz:                            I don’t.

Dr. McClain:                        I don’t know anybody who does, but we’ve observed that. Well, I got one for you. Let me skip to stinging nettle. It’s a supplement, right, stinging nettle?

Dr. Weitz:                            Yeah, stinging nettle roots.

Dr. McClain:                        Yep. Right.

Dr. Weitz:                            Not stinging nettle because then you’re wondering, how did they figure that one out?

Dr. McClain:                        No, stinging nettle root, excuse me. That tends to lower SHBG. So does maintaining estrogen, and we use estradiol, the most prevalent in a male and female, as a surrogate marker for all those. So if we can get the estradiol in a male down to about 15 to 20 picograms per milliliter, roughly below 21 or 22 to be more precise, he will drop the SHBG and typically we’re looking at an average of about 2% free testosterone will be available, therefore. There’s one other way to do that that I’m aware of, and that’s to use a very, very small dose of what we refer to as an anabolic steroid.

                                                Which by the way, segue, unless you tell me not to, an anabolic steroid is simply a… a lot of the ones are derived from dihydrotestosterone molecules that I talked about earlier, but don’t have anything close to the same effect. As a matter of fact, the opposite. Because all you have to do with a molecule is change one ligand. It can look very similar, but change one little post here and it can change the effect demonstrably. As a matter of fact, anabolic steroids that are used by women, not just female athletes who are trying to win a race, but for example, for females who have estrogen-sensitive cancers and need the effects of testosterone to feel better, but don’t need the risk of it converting to something that can harm, they’re magic. And they have less side effects like we were talking about earlier, hair in the wrong places, losing hair in the right places, getting acne, than would dihydrotestosterone, even testosterone itself.  So testosterone, estrogen, they’re all steroids, we know that, right? Because they’re made from cholesterol. Okay, just want to make sure. But adding a small dose of an anabolic steroid, something that would have no effect anabolically, in other words, the way that is intended to be used otherwise, will lower SHBG also. So those are the four things I just mentioned, right, the ways to lower SHBG.

Dr. Weitz:                            Let’s see, what about other male hormones like DHEA, androstenedione?

Dr. McClain:                        So I’m a big proponent of if you want to go from LA to San Francisco, don’t go via New York. A lot of physicians were using, for example, progesterone in the hopes that it might convert down the cascade to testosterone in the early days. No one wanted to touch testosterone, even though we had some really cool studies with testosterone in females. One of my favorite was a depression treatment study where they used it on, I think it was 50 females and at least 85% were able to resolve their depression using testosterone. I thought that was pretty interesting, especially back in the fifties. What happened with testosterone is one other subject, meaning the period between then and now. But I’m sorry, I’m getting sidetracked. What was your question?

Dr. Weitz:                            Oh, I was asking about supplementing DHEA or other male hormones like androstenedione.

Dr. McClain:                        The problem with that is they can convert to things you don’t necessarily want. And while they’re-

Dr. Weitz:                            DHEA, that’s pretty safe, isn’t it?

Dr. McClain:                        Well, it can convert very easily to any of the others. It depends upon the individual. Unless you use 7-keto DHEA because, of the three DHEA metabolites, that one will not convert to another androgen or estrogen for that matter. So that one’s safe. But yeah, the others can convert just like they were trying to use progesterone back in the day hoping it would convert, but not knowing if it would or not, and everyone’s different. Some people, the ladies unfortunately, would not convert. They’d blow up. That’s one of the side effects of too much estrogen, you get bloated and moody or really, really tired because progesterone can convert to, particularly if it’s oral dihydroprogesterone or 5alpha-Pregnane, which works on the GABA receptors, those same receptors that you’re trying to activate when you have a shot of whiskey or a Valium or a Xanax or something like that. So yeah, you can run some risks doing it that the indirect way by using some of these other substances that you don’t know where they might end up.

Dr. Weitz:                            I think it’s generally thought that DHEA in women will convert into testosterone, but not likely in men.

Dr. McClain:                        I don’t know what the statistics are when it comes to polling and seeing what’s going to convert to what, particularly with regard to gender. What I’ve observed is in men, yeah, it tends end up spoiling your estrogen control. In females though, what I’ve found is that it either stays as DHEA or will turn into another antigen because when I add DHEA to the regimen for whatever the reason might be, we can go into that if you want, but I see acne development and sometimes hair loss, so I’m a little resistant to use DHEA unless it’s 7-keto DHEA, and even then I don’t unless I have to.

Dr. Weitz:                            Let’s say a 30-year-old guy comes into your office and let’s say they have the symptoms that would indicate the need for a testosterone, and let’s say their total testosterone level is 250. Are you hesitant to use testosterone in a younger guy because now he might be on testosterone the rest of his life, might affect his fertility?

Dr. McClain:                        So you asked actually a few questions in there. The first thing I would address is whether they’re 30 or youthful… that’s not the right word. If they’re what we would normally be considered early candidates for therapy, the first thing I would check to see is whether it’s indeed primary or secondary. Meaning is it the testicles that aren’t working anymore or is it a signal to the testicles that’s not working anymore? So if there’s something like a what’s called a pituitary micro adenoma, which is the fancy way of saying you have a little growth in the pituitary, and typically they’re benign, they’re not often found, but you could also have damage to the pituitary. Say this guy was a fighter and had been concussed too many times. Once it’s enough, sometimes. Been in a motor vehicle box and whatever it might be, we can do an MRI of the brain to visualize the pituitary and see if there’s something called an empty cell. It doesn’t appear to be there anymore.

                                                We can also look at some of the hormones that are supposed to be sent by the pituitary to the testicles that say, hey, make some testosterone. Luteinizing hormone is what we’d be looking for. We can do a stem test if we don’t trust just seeing what levels come up, we can give them ACG. In other words. We can give them enclomiphene. There are certain drugs that we can use, in other words, to identify and differentiate between secondary versus primary. Because yeah, if it is secondary, then most guys, at least that I’ve observed, tend to want to keep riding that wave of natural production for as long as they can just because, for another reason, rationally or not, it sounds good. “Hey, I want to keep using mother nature for as long as I can,” is typically what I hear, even though oftentimes the results won’t be as good because, by definition, 35 is the start of what we call peri andropause, like when we talk about peri menopause for females. So you’re getting close to where the testicles are going to say, “We’ve set the pace here long enough. Okay? We’re done. If you have procreated by now,” or whatever your theories are as to why it starts to peter out, that’s when it happens typically.   But stress can bring it on more quickly too, males and females. So that’s the other thing I have to look at with this 30-year-old, is there physiologic damage or is the guy working three jobs, not getting but four or five hours of sleep a night and we need to correct a few things that will right the ship without having to add any drugs?

Dr. Weitz:                            Or they’ve got a significant exposure to environmental estrogen?

Dr. McClain:                        Absolutely. Sure.

Dr. Weitz:                            This phenol A, we can go on and on about all the environmental estrogens and other things that could affect-

Dr. McClain:                        Yeah, just being overweight. We know that fat is a big producer of estrogen because inside and around fat, you have aromatase enzymes which convert testosterone into estrogen. So again, another just pretty simple thing to look at and go, well, hey dude, let’s work on, see if we can drop a few lbs here of fat and correct the situation.

Dr. Weitz:                            As we’re discussing. Do we have questions? Yep.

Speaker 4:                           I have one. So with a patient that wants to stay natural, what do you do for them?

Dr. Weitz:                            Okay, so let me just repeat the question. The question is, for a patient who has symptoms of low testosterone and let’s say you measured their total testosterone and it’s low?

Speaker 4:                           Yes or on the lower end.

Dr. Weitz:                            Right. So in other words, shorter giving hormones, what else is in your toolbox to help these patients?

Dr. McClain:                        Well, to be clear with your question, are we talking about skipping hormones or skipping any type of drug treatment? Because there’s a big difference.

Speaker 4:                           Well, let’s say skipping any type of drug treatment first.

Dr. McClain:                        Then you try and figure out what could be causing the low testosterone, the things we mentioned, and this is all part of the history. I mean, if you’re a practitioner, you know this is where we get it all, or 80% of it, let’s find out what’s going on. Is stress the issue? Is this person carrying way too much fat? Is there again, a problem with pituitaries or some sort… Prolactinoma is another one. I mentioned a microadenoma. There’s different things that could affect him physiologically that wouldn’t involve drugs to fix. Sometimes they go in, they usually go in through the roof of the mouth and they find something on the pituitary and they scrape off this little piece and things go back to normal, so to speak, the function of the pituitary anyway, and its effect on Luteinizing hormones.

                                                So yeah, you do some detective work and find out what could be the cause. Again, like you said, I skipped it and I shouldn’t, and I almost did again, but environmental exposures. This guy lived next to power lines, he’s lived next to a chemical factory. I mean, these are all important things. He’s a mechanic. So exposure, believe it or not, to oil, if he’s not using gloves, I mean that was the only way of doing it. I mean, we didn’t do that when we were working on the car. Come on, that’s a nerd who puts on gloves. Well now you better because long-term exposure to just motor oil can really mess you up.

Dr. Weitz:                            Now what about for the patient who has symptoms of low testosterone? Let’s say they do have low testosterone, but they don’t want to go on testosterone. What are the other drug treatments that you’ll use and what protocols do you find effective?

Dr. McClain:                        So even if the gonads are not working as they should, so to speak, like they did when they were 20. It should, that’s not the right way to put it. But we can still get the last bit of work out of them by using things to stimulate them to produce more testosterone such as luteinizing hormone, actually not analogs, but homologs, HCG human chorionic gonadotropin, it’s so close in nature, we have to call it a homolog rather than analog. That’s something that you would inject anywhere from two times a week or more typically to override the system and tell the testicles to do more work. The other way to do that is secondarily by blocking the perception of estrogen, something called SERM, selective estrogen receptor modulator. Tamoxifen is one that’s well known because it came to the floor with a treatment of estrogen-sensitive cancers.

Speaker 5:                           Is anastrozole the same like tamoxifen?

Dr. McClain:                        No. Anastrozole is an aromatase inhibitor known typically as Arimidex anastrozole the brand, but either one works to lower estrogen directly or the perception of estrogen tamoxifen in clomophene indirectly, and therefore if testosterone is low, the pituitary, speaking what they say, anthropomorphologically will say, “Hey guys, let’s send a signal to raise testosterone.” However, if testosterone’s high because estrogen is made from testosterone, you can block estrogen all day long and the body says, “Talk to the hand,” because testosterone’s still high, it’s not going to send a signal. So it only works when you have low testosterone present, and that’s a relative term, right? When I say term and relative assessment, it’s low for your body or not. So if you block estrogen, the pituitary will send a signal to produce more testosterone in the hopes that that’ll happen and the estrogen will right itself too. Does that make sense, the way it works? It’s secondarily, bottom line

Dr. Weitz:                            When prescribing… I’m sorry, did you have a question Roxanne?

Speaker 6:                           Yeah. How are you?

Dr. McClain:                        Hey, good. How are you doing?

Speaker 6:                           So good to see you.

Dr. McClain:                        Likewise.

Speaker 6:                           Do you have any experience using medical grade around therapy suppositories for PSA issues? I’m asking because I once attended a lecture with a urologist who specialized in this type of disorder, if you will, she worked down in Orange County. I sent a couple male patients when they had their PSA come in with a odd problem and they claimed it worked very well for them. So I hear what you’re saying about the injections. I certainly hear about compliance. But this is… I don’t know that they’re going to stick something up their butt either, but it works supposedly very well.

Dr. Weitz:                            Let me just try to repeat that question. So-

Speaker 6:                           This doctor down in Orange County, she’s a urologist, she was specializing in male disorders. And her primary way of treating was she actually manufactured them, but they do sell them, they’re medical grade aromatherapy suppositories. The theory is that they work transdermally very close to the area you’re trying to treat rather than swallowing something or applying something close to the area. So anyway, I just [inaudible 00:39:22].

Dr. Weitz:                            So the question is what about the use of aroma-

Speaker 6:                           Aromatherapy.

Dr. Weitz:                            … aromatherapy suppositories to-

Speaker 6:                           Treat PSA?

Dr. Weitz:                            … to treat IPSA?

Speaker 6:                           Yes.

Dr. McClain:                        I don’t know enough about it. I can only speculate that when you’re using things like that, there’s chemicals in what we refer to as the aromatherapy ingredients, which can include a lot of things, right? Herbs and things that are typically fragrant, you’re talking about aromas. And that they’re-

Speaker 6:                           [Inaudible 00:39:55].

Dr. McClain:                        So the quality is better. You’re not going to have some contaminants and you might have a higher concentration, but the point being that there’s chemistry involved there and because you’re putting it close to the prostate, it might affect… I remember, I don’t know if you walked in when I was talking about the PSA and what it’s for, but it would block, at a minimum, the theory would be would block the release of prostate-specific antigens into the bloodstream. What that means is open to interpretation. Okay? Is it shrinking the prostate over time so there’s less prostate to dump these antigens into the bloodstream? I don’t know. I can only speculate. And I don’t know. I haven’t heard about it, but it sounds like something that might be effective.

Speaker 6:                           [Inaudible 00:40:46] mechanism either. All I know is that these two patients came back, claimed that that was their primary mode of therapy and seemed to work for them. And it’s quite popular in France and Germany [inaudible 00:40:59].

Dr. McClain:                        Well, we don’t know if it was treating prostate cancer. We just saw the observation was that the PSA went down?

Speaker 6:                           Yes.

Dr. McClain:                        That’s plausible. I can see that happening. There was something there that shrunk the prostate or stopped it from… It could have been just quelled inflammation because that’s enough to release more prostate-specific antigens into the bloodstream. So that’s plausible. I just don’t know enough about it. I’ve never heard of that.

Speaker 6:                           Theoretically [inaudible 00:41:22].

Dr. McClain:                        Yeah, it’s definitely plausible.

Dr. Weitz:                            So what about potential risk for cardiovascular disease with testosterone therapy?

Dr. McClain:                        That was another myth and part of why I referenced the 2016 consensus that was led by Morgenthaler because that was one of I think nine resolutions that dispelled various things like that. There is actually a correlation between low testosterone and coronary artery disease, low testosterone and type 2 diabetes, low testosterone and osteoporosis, as I said earlier, low testosterone and prostate cancer, low testosterone and colon cancer. So yeah, more what legend to dispel. And the good cardiologists, the ones that are hip, up-to-date so to speak, will say just that. They used to say, “Oh boy, stay away from that testosterone.” Now they say, “Well, no, fine, keep going. You’re doing fine.” And it makes sense even if it’s not a direct mechanism, if you’re healthy otherwise, you’re exercising, your heart’s probably going to benefit from it rather than the other way around.

Dr. Weitz:                            Well, one of the mechanisms by which theoretically it could cause cardiovascular problems is it’s well known that men who take testosterone therapy are going to see an increase in red blood cell hemoglobin hematocrit production, so therefore your blood gets thicker and potentially that puts you more at risk for a heart attack or a stroke.

Dr. McClain:                        So with testosterone replacement therapy, dosages that are not super physiologic, not bodybuilder doses, we’ll call them, no dispersion toward bodybuilders, but with replacement dosages, we don’t have that issue. When you see elevations in hemoglobin hematocrit and red blood cell count, in my experience, there’s two reasons for that. Almost, I’ll say, and I used to bean accountant before, I’m a doctor, so presumably I’m honest and conservative, I would say 99% or more of the time it’s related to sleep apnea that hasn’t been diagnosed yet. And it makes sense if you think about it because… Real quick, the other one is a JAK2 gene mutation, which is very rare.

                                                But as people age, they tend to have issues with sleep apnea. Even people as skinny as olive oil can have sleep apnea. They don’t have necessarily a big neck, but the soft tissue of the palate starts to collapse over the area, whatever the reason is. And so hemoglobin and red blood cell counts tend to rise because basically you’re training in your sleep, the same training effect you’re looking for when you go into oxygen debt on a treadmill, but you’re doing it for hopefully at least seven to nine hours a night. That potential rise is modulated by the decrease in testosterone that happens about the same age, and so they cancel each other out and the typical primary care physician goes, “Yeah, everything looks fine. If you’re a male, your hemoglobin is 15.5, red blood cell count’s below five and everything’s hunky-dory.”

                                                And then you have the testosterone, which is absolutely necessary. You can become anemic without enough testosterone. That’s the opposite of high H&H. And you put the testosterone in the engine and all of a sudden, oh look, that doggone testosterone’s causing a problem. Hemoglobin’s going up, red blood cell count’s going up. It’s that testosterone. No, it’s the undiagnosed sleep apnea. And you treat the sleep apnea and hemoglobin hematocrit come back down.

                                                Now, if you do use super physiologic dosages, well above TRT levels, you’ll typically see a bump of about at least, it’s roughly one point of hemoglobin. That’s strictly because you’ve got way too much testosterone in the system, the idea of, what do you call it, stoichiometry, right? A plus B equals C, as long as B is not a limiting factor. You [inaudible 00:45:25]. That does apply, but 100% of the time, or almost I should say, I said 99%, above 99% it’s because of sleep apnea. We treat the sleep apnea and it comes back down. Otherwise, and I know this is a crummy example and people do it all the time, and I’m doing it now, medicine is much more complicated than this, but if it were the case that high testosterone levels caused high H&H, like we’re talking about that every 16-year-old kid would have hemoglobin or red blood cell count off the charts. It doesn’t happen. It’s because you’ve got a stressor, lack of oxygen at night, that’s causing this.

                                                The other point though is that the one issue I will agree on, if it does go high like that, and again, it’s not because of testosterone, it’s because of sleep apnea, but if you do have high H&H and the blood viscosity, you’re talking about the blood thickness goes up. That is not good for the heart. It’s kind of akin to hypertension in the way the heart has to work harder, the left ventricle, and you’ll get the wrong kind of enlargement of the heart, not an athletic heart. But that’s bad, just like hypertension’s bad, but it does not lead to stroke. And the hematologist, a good one will stand up and go, “I agree, stop calling viscosity the same as stickiness.” At a certain level of thickness, then yes, I can’t deny if you had a hemoglobin, and I’ve had a patient like this in my practice of 23 because he had [inaudible 00:46:57] an autoimmune disease and a hematocrit of whatever is associated, three times that, then you might be at increased risk of a clot formation. But there’s a huge difference between viscosity and stickiness.  But I will agree with you or whomever you’re citing as well, blood thickness at that level becomes a problem over the long term if you don’t treat it, but it’s not linked directly to testosterone for the reasons I explained.

Speaker 5:                           On that subject, the local hematologist friend suggested every three months to do phlebotomy. What do you think about that?

Dr. Weitz:                            So the question is, should patients who take testosterone get a therapeutic phlebotomy periodically?

Dr. McClain:                        My opinion is generally no unless you’re having symptoms associated with it. So what I’ve found in my practice simply is for a male, again, with a hemoglobin of roughly 18.5 and above, and a commensurate hematocrit, which is really more related to the thickness, and that’s a general multiplier of three. Patients will say get up out of a chair, and whoa, I need an extra beat or two literally of the heart to get the blood from the legs up to the head. Well, that’s a reason to go ahead and treat, so to speak, with a therapeutic phlebotomy.

                                                But otherwise, and your hematologist friend, I’d love to hear what he responds to this, because I learned about this from a hematologist, and I apologize, I don’t remember his name because he deserves credit, but what about the stem cells in your bone marrow that you’re taxing, you’re using up every time you bloodlet, your body says, okay, great. Now I got to start over again. And until you fix the reason, again, 99% of the time in my experience it’s sleep apnea for the elevation, your body’s going to come right back and make more, and so unless you have a reason, meaning symptomatically, to treat it, then I don’t recommend a therapy to phlebotomy. Again, for the reasons I said I’ve never seen an issue with clots because of it, and you’re taxing your long-term stores, as it were, of stem cells and bone marrow that are going to be needed to make those cells again.

Dr. Weitz:                            Another common effect of testosterone therapy that I’ve seen is you typically see the HDL level come down quite a bit. Isn’t that an increased risk for cardiovascular disease?

Dr. McClain:                        Another loaded question. But thank you. So the HDL decreases typically because of what comes with most therapy for a male. Okay? I haven’t seen it with a female necessarily, but with males, we have to modulate the estrogen downward so that you don’t have side effects of excess estrogen. When that happens and you err on the side of oversuppression, you will see HDL drop. Okay? No doubt. The poison as it were, is in the dose, so you have to modulate the estrogen effectively so you don’t drop the HDL. Does that-

Dr. Weitz:                            Wait, hold on, hold on. So you’re saying the reason why the HDL drops is because estrogen goes up? You’re saying higher estrogen levels-

Dr. McClain:                         No.

Dr. Weitz:                            No. Okay.

Dr. McClain:                        No. Estrogen levels are, it’s iatrogenic. We give them too much of an AI, for example, to modulate estrogen too low. It’s oversuppression estrogen that does it. That’s what I’ve seen.

Dr. Weitz:                            So low estrogen is reducing HDL levels?

Dr. McClain:                        Yes.

Dr. Weitz:                            But that’s not from testosterone. You’re saying that’s from?

Dr. McClain:                        It’s what comes with therapy, that we’re trying to modulate the estrogen downward. And a matter of fact, aromatase inhibitors get blamed for it. Oh, I can’t take anastrozole, that’s bad for you. Try not taking it, and then you got to have surgery or remove breast tissue. I mean, I’ve heard some crazy stuff.

Dr. Weitz:                            But without taking an aromatase inhibitor, don’t you see HDL levels come down with testosterone therapy?

Dr. McClain:                        No. If you use a super physiologic dose, I’ll see LDL levels go up. But I don’t see HDL levels go down. If it goes untreated, meaning you let estrogen rise, there’s no reason for an HDL to drop. Anyway, that’s just been my experience. Now, a huge can of worms you opened up, and I’ll be brief because I’m not a cardiologist, is does that affect your risk of coronary artery disease specifically?

Dr. Weitz:                            Sure. Yeah.

Dr. McClain:                        Okay. My answer is no, and I will protect myself a bit, although I’ll accept it as my own dogma as it were. But Marc Penn, and I have it on a Zoom tape because it was during COVID, Marc Penn is one of the leading cardiologists in the world, he used work with Cleveland Clinic, but I have him quoted as saying 95% of cardiologists, not just primary care physicians, don’t get this right. Cholesterol is not what drives coronary artery disease. Inflammation does.

                                                So let me jump ahead and say if someone has extant coronary artery disease, then yes, we found that lowering cholesterol is very helpful, whether it’s through statins or some of the new drugs they have or just dietary changes. But if they do not have extant coronary artery disease, which is driven by inflammation, but evidenced by extant coronary… plaque in the arteries, then to lower cholesterol makes no sense to me or apparently 5% of the cardiologists who actually understand this, like Marc Penn says they should, and there’s so much evidence to that. I don’t want to go into it too much because I am not the cardiologist, not the expert, but it makes sense to me.

                                                If you look at textbooks even that go back in time and show the lumen of an artery or lumen of a vein for that matter, there’s not that much difference. It makes no sense that cholesterol coming through the lumen would be causing the problem. You can look at the changes in the intima versus the media and you can see the way hypoxia is what the issue becomes and the way the body reacts and starts growing vessels into the media to try and make up for the hypoxia. At any rate, I’m sorry. I’m way out of my league here in terms of being able to explain this like a good cardiologist.

Dr. Weitz:                            No, no, no. You’re totally explaining this. In fact, I just had a discussion this afternoon [inaudible 00:53:40].

Dr. McClain:                        You’re on the same page. Oh yeah, you went into finer details.

Dr. Weitz:                            And We had a discussion about hypertension for the podcast, and the focus is all on the endothelium and the glycocalyx, and that’s really what sets up cardiovascular disease.

Dr. McClain:                        Hypertension causing the inflammation, and then you have the brick and mortar, as it were, of the cholesterol being there that is part of what the body uses to treat-

Dr. Weitz:                            The inflammation and the [inaudible 00:54:07] stress, it damages the lining on the artery, the endothelium, the glycocalyx.

Dr. McClain:                        But it’s not the cholesterol itself. And I would posit one thing here too, that if it were the case, then hopefully you guys were having this discussion too, why is it that people with high cholesterol, or anybody, why is… And by the way, I’ve seen, and I can tell you a good story if you want to hear, I have three individuals with perfect lipid panels. Forget about triglycerides. Their cholesterol was 80 LDL 60 HDL plus or minus two in all three patients. I told you I was a CPA before, so I’m prone not to lie or exaggerate, I’m just telling you. Because I went back and looked and I couldn’t believe these super healthy guys had, one of them had 99% blockage in, they called the widow maker, the left anterior descending coronary artery, and the other two had 98% blockages. All three were on their way to go do something, some form of exercise, and their wives talked to them into going to the emergency room and they survived. But they had this great physique. They were all into exercise and eating right, et cetera.

                                                The point being, they didn’t have crazy cholesterol numbers, but they all had major plaque. If cholesterol was a problem, how come there’s no plaque in the veins? Think about that one for a second. Going back to what you said, hypertension drives this. You can’t have that kind of pressure, one way anyway, in the veins. You can have the arteries and where it’s tortuous, you have a curve, in other words, that turbulence causes the inflammation. That’s the start where the cholesterol is used to block it off and go through the body’s processes, right, but it doesn’t cause it is my point.

                                                So the point to your question is if testosterone were to raise, which I’m not saying it does, but if it were, it would not drive directly the formation of plaque. Only if someone had an issue. By the way, people that… I shouldn’t do anything. You just talked about those three guys, the epitome of health, one thing, they don’t tell you, the cardiologists, is there are other ways that you have no control over that can seed inflammation in the arteries. How about a GI bug when you were 30? How about an abscess tooth when you were 25 and couldn’t afford to fix it, right? That can seed in the heart. And we know that already. Think about it. Oh, this patient has a heart murmur. I’m going to do a dental procedure. You got to take some prophylactic antibiotics. How come? Because there’s a connection there folks. And so something you have no control over could have led to the formation of plaque and then the cholesterol adds to the problem.

                                                That’s the pitch for energy and being proactive about everything we can do to find out beforehand. So energy, meaning carotid alpha and ultrasound to see if there’s plaque there, whether you’ve been the epitome of great health or not. All right, I’ll stop.

Dr. Weitz:                            Do you [inaudible 00:57:11] patients get a coronary calcium scan?

Dr. McClain:                        I do not. As a matter of fact, it upsets me when they do because the calcium score is, to my mind, a waste of time. There is some correlation, obviously it means there was plaque there at one time, but it’s been calcified, it’s been walled off. It’s old news. And there’s really nothing you can do about it anyway. Soft or fibrous plaque, however, is new news. It’s a current problem and there are things you can do about it including reducing cholesterol and inflammation, et cetera. So-

Dr. Weitz:                            Do you have your patients get a CT angiogram with artificial intelligence?

Dr. McClain:                        I ask them to do a coronary CT angiogram with and without contrast so I can see everything, not just the calcified plaque. I start though with a bilateral carotid Doppler ultrasound… And by the way, I can’t take, I’m saying this as this is what I do, but I’m not a cardiologist, but I do take note of what people like Marc Penn say, Stefan Ruehm over here at UCLA, our famous driven, important head of cardiothoracic imaging at UCLA for 30-something years, and it hasn’t changed. A bilateral carotid Doppler ultrasound to evaluate the intermediate thickness here will let us know if there’s a problem typically because there’s 95% correlation between what we see here and what’s in the coronary arteries of the heart. So it’s a good first pass, non-invasive, takes 10 minutes if they’re slow, and if there is something there, then I say, yeah, let’s do the gold standard, I would call it as a coronary CT angiogram with and without contrast.

                                                The calcium score is too misleading. I can, without breaking any privacy laws, tell you, I was one that had the abscess tube that I nodded on when I was in my twenties. In my early thirties I had plaque in the carotids. Early thirties, I didn’t care. In my fifties, I knew too much and I went and had the coronary CT angiogram with and without contrast, I still had the calcium here. I had a little bit in my heart, but I had not a speck of soft or fibrous plaque in my arteries. Otherwise. Did I treat as though I had coronary heart disease that needed cholesterol lowering drugs, whatever? No. Why? I didn’t have any other of inflammation that I could see. I knew it was from 20 years ago, I assume, I should say for good reason. And so why would I lower cholesterol just because of that, something that it’s done? Lowering my cholesterol would do nothing for that calcified plaque. Does that make sense?

Dr. Weitz:                            Yeah. The point that he’s making, if everybody’s not following, is that when you have plaque in your arteries, after a period of time, the body will calcify that plaque. And generally speaking, calcified plaque is considered stable, whereas soft plaque is considered potentially unstable, can break off and can lead to a myocardial infarction or a stroke.

Dr. McClain:                        Thank you.

Dr. Weitz:                            Jeff?

Speaker 7:                           Are there variants of testosterone in the organs? Just [inaudible 01:00:20] like we have with the thyroid, we have reverse thyroid, active, inactive. Is testosterone just [inaudible 01:00:28] across the board testosterone or are there some variants?

Dr. Weitz:                            You’re talking about therapy or testing?

Speaker 7:                           Testing.

Dr. Weitz:                            Testing? Well, we have total testosterone and you have free testosterone.

Dr. McClain:                        Are you thinking about different forms of exogenous testosterone? For example, you might’ve heard of testosterone cypionate versus testosterone enanthate or propionate, is that what you’re talking about?

Speaker 7:                           Well, both of them. What’s the difference between those three exogenous versions of it? And then also, so we just have total testosterone and then what was the other version?

Dr. Weitz:                            Free testosterone.

Speaker 7:                           Okay, so which one’s the active form.

Dr. Weitz:                            The free testosterone.

Speaker 7:                           Okay. That’s what that’ll find then? So the inactive one would be the total minus?

Dr. Weitz:                            Yeah. It’s bound up with proteins that bind it like albumin and sex hormone binding globulin.

Speaker 7:                           So what therapies are there to help? Maybe just increase the free testosterone by increasing the binding protein.

Dr. Weitz:                            Dr. McClain addressed that, I think before you came in, but maybe-

Dr. McClain:                        Real quick though, to review. High protein diet, keeping your estrogen modulated below, roughly you’re estradiol sensitive at about 21 milligrams per milliliter or below, stinging nettle supplementation, or a very, very small dose, what would normally not be used for anabolic effect, but an anabolic steroid in a small dose will also lower your SHBG.

Dr. Weitz:                            If you do that, they won’t be crying at movies.

Speaker 8:                           I have a question then. What about the European testosterones? I work at a gym and a lot of the bodybuilders there take all kinds of different things that-

Dr. Weitz:                            I think you’re talking about anabolic steroids?

Speaker 8:                           Is that a difference?

Dr. Weitz:                            Yeah, so basically anabolic steroids are in science is taking the testosterone molecule and manipulating it to try to have more of the say, muscle building effects, the anabolic effects without some of the other androgenic or the effects you don’t want.

Speaker 8:                           Yeah, so there’s, and I don’t know the names well, but-

Dr. Weitz:                            I think there’s a lot. Why don’t you talk about it?

Dr. McClain:                        No, go ahead. Are there names you might recall or come close? I can help you there.

Speaker 8:                           I don’t know the name, but he was saying that it cannot convert into estrogen or DHT because the way molecules are designed.

Dr. McClain:                        Right. So testosterone conversion, meaning the development, these anabolic steroids from testosterone is maybe considered maybe some of the initial molecules. But what we’ve taken now, and I mentioned this earlier, the DHT derivatives, I call them three cousins. And the names you would’ve heard at the gym, I’ll tell you, even though the generic are what’s out there… Actually, there’s one brand that’s still out there called Primobolan, which is a DHT derivative, the others, Anavar and Winstrol, are no longer available in this country. Winstrol is available for veterinary use, I beg your pardon. But those are three molecules that started as a dihydrotestosterone molecule. And then by adding or subtracting those little ligands I was talking about, just one sometimes, it turns into a totally different molecule in terms of the properties like he was referring to where DHT we talked about earlier can drive the hair growth on your ears and stuff, if you’re a guy. Maybe even if you’re a gal, we forget, women and men have hair in the same place just women a lot less.

                                                But the Anavar, for example, one of these cousins that is made from that initial dihydrotestosterone molecule has roughly eight times more effect on muscle tissue growth, the anabolic effect we’re looking for, but I don’t know the percentage. It would vary upon the side effect, but much, much less effect on the hair growth. We were talking about the unwanted hair growth or the acne, and that’s why ladies often use, whether it’s in sport, or like I said, someone who has estrogen sensitive cancer will use one of those products because of the lack of the androgenic side effects, the bad ones that you don’t want the hair in the wrong place and stuff.

                                                Now, just because he brought it up as well, you might hear other names of the form in which testosterone is being held. It’s being bound up purposely, designed by an ester. I don’t know if you remember your double bonded oxygen from high school chemistry? But basically it takes more energy to break off these binding molecules so that over time some of that testosterone, no longer bound, the free testosterone will be released. So it’s a time-released form that enables you to apply it weekly, for example.

                                                The ones in Europe, I think you mentioned Europe, there’s one over there, it’s actually technically available here, but try finding it. Undecanoate, which is a much stronger bond, and so it takes even longer to release and enable you to go at least three weeks without having to shut. So that might be what they’re talking about, these different esters I mentioned earlier, cypionate, propionate and enanthate, that boils down to testosterone though, not an anabolic steroid, which is different… It really is a different substance altogether because it’s rare you can say this, but every anabolic steroid, we can say that in life much less in medicine, every anabolic steroid will raise LDL. I mean that’s what you were talking about, and lower HDL. Hands down. Some more than others. Whereas testosterone, when used appropriately, meaning not super physiologic dosages, doesn’t do that.

Dr. Weitz:                            Does testosterone therapy promote longevity?

Dr. McClain:                        We can’t say that for sure. There’s a lot of things we can’t say but can only conjecture about longevity based upon what we see with other markers we believe are biomarkers for good health and longevity. But it seems to improve what we call our health span, our time on the planet that’s healthy based upon the biomarkers we use. We see, and we talked about earlier, about how it makes sense, if you’ve got more energy to exercise, let’s say because of testosterone, well that’s going to improve your health. And so whether it’s a direct cause of testosterone affecting these biomarkers or indirect because you’re doing all the right things more because if nothing else, you have the energy to do it, we believe the testosterone is going to prolong our health span.

Dr. Weitz:                            On this theme of longevity. It seems to me that there was a period of time where the longevity space, it was very popular to recommend testosterone, growth hormone, things like that because the thought was, as you get older, you lose muscle, you lose bone, you don’t replace your cells as quickly, and things that promote growth are beneficial for longevity. And recently those things have sort of fallen out of favor. And a lot of the emphasis in longevity has been on trying to reduce things that promote growth. So for example, you have Dr. Valter Longo saying that you should have a lower protein intake because you want to have a lower IGF-1 level because you want to reduce things that cause growth because anything that promotes growth is going to increase cancer risk. So the key to longevity is an inhibiting growth. And then you want to inhibit mTOR, which is more of a growth signal. So you want to use things like rapamycin, all these things are to inhibit growth and that being the key to longevity.

Dr. McClain:                        That’s great. And that’s the reason I wrote the book because yeah, it ties together all these concepts. You’re absolutely right. That’s where we’re headed. And I think that the answer is, like so many things, I mean we talked about, you and I, before we started on our thesis and finding the right dose with, and I always get his name wrong, but he’s over at USC, the ProLon diet guy.

Dr. Weitz:                            [Inaudible 01:09:13].

Dr. McClain:                        Right, right. Sorry, I’m terrible with names. But he makes a point. But it’s retrospective and so many retrospective studies. You can poke a billion holes in, in the ones that support what you want or not. But my opinion, because it’s only opinion, we don’t have enough lifespans to observe yet to be able to make a conclusion for certain with the right kind of studies prospective, et cetera. But if you’ve got someone who’s riding a desk all day, why do they need extra growth hormone/IGF-1? Just so you know, growth hormone loan gets released first. When it hits the liver, then the liver makes IGF-1. And arguably IGF-1 does most of the yeoman’s work and credit goes all to growth hormone.

                                                But anyway, if you’re working in oil rig, I think you probably are going to have a problem with the ProLon diet and Longo’s concepts of low IGF-1 because you need the regeneration. Whereas if you’re riding a desk, what do you need that for? I almost, and it’s a terrible analogy, but it’s the only one I can think of off the top of my head, but if you’ve got some bacterias in a dish and you load it up with a bunch of sugar, well they’re going to grow out of control. And of course the propensity for cancer exists more in that situation than if it’s very lean in there in terms of fuel, no bacteria can grow. Again, that’s a terrible example, but if you don’t need it, then it doesn’t make sense to have it and there’s a potential for things to go awry, and that’s the desk jockey. Whereas if you’ve got a guy working the oil rigs, he needs as much help as he can get. So you got to find the balance between the right amounts.

                                                Isn’t that the key to what we all want and what we all try and do as physicians, you got to find the right balance for the individual. And that’s why I… I’ve never gone back and looked at any of these things, but I think about what I said, I go, why did you say that so sweepingly? Because you got to be careful. You can’t always make such general statements because it’ll come back and bite you because you have so many different circumstances. And that’s where I think, and not to give us credit, it’s just understand where we’re coming from, we as physicians, that’s our job, we got to figure out what works for you, the individual.

                                                So I appreciate his work and I mean that most sincerely, I think he’s got a point, but for certain individuals it works, whereas for certain it doesn’t. And so there are people, I mean if someone were to break a femur and I think they could probably use some growth hormone to help them heal. At least the surgical one for sure, and possibly also for bone unionization. But yeah, I mean I can go on and on and I’m not sure I’m really addressing your question, but-

Dr. Weitz:                            Yeah, no, it’s okay. Look, it’s a complex concept.

Dr. McClain:                        It is. And you can’t oversimplify it.

Dr. Weitz:                            And I think clearly there’s got to be a balance. It’s clear that as people get older, suffering from sarcopenia, the loss of muscle, there’s a lot of people whose life ends because they fall and break their hip and never recover.

Dr. McClain:                        Number three on the list.

Dr. Weitz:                            Yes. So there’s no doubt that being able to have regenerative power is being able to replace your cells, being able to maintain your muscle mass, your bone mass, those are key longevity from a certain perspective. On the other hand, too much growth is potentially going to increase the growth of cancer. So there’s got to be a balance and exactly how you find out what that balance is. I don’t think we quite know, but.

Dr. McClain:                        Well, and if I may, because you brought it up and I think it’s going to become more relevant as people look into the latest research, which is exactly what you say, the reverse of growth and the mTOR antagonism. And if you think about that, it’s like our night and day cycles where we go out and we exercise, we do what we do all day, and then we rest at night. We have too much of that daytime activity and not of nighttime activity. And I could liken that as probably another terrible example to growth hormone versus mTOR. And you got to give your body time to clean up the mess. I use the restaurant example where if all you did was sling food all day, eventually the pots and pans are going to pile up, they’ll become dirty and the food won’t be clean.

                                                So you got to let the cell heal itself, so to clean up the mess and get ready for the next day. That makes sense. Again, some of these things that make sense, don’t necessarily [inaudible 01:13:53] medicine at all, but really I think is where we’re headed with this, which is, hey, you don’t just do growth hormone all the time. Just like we have seasons where we might exercise more, work longer days versus the opposite, there’s a time and a place for everything. And if we focus only on the growth, human growth was the founding youth for a while, we realized not so much, and not the repair mechanism, what we call autophagy and the activation of mTOR… or sorry, the antagonism, then we’re going to have a problem like the kitchen example. And that’s I think where we’re headed to trying to figure out what that is for each individual, but changing direction more toward focus on the repair or the autophagy we were talking about.

                                                And you have guys leading the way with this that it’s interesting. Sinclair, who is, I’d say the first third of his book is worth three. The rest of it’s more activism. But his perspective, like all of ours are going to be, it’s a little slanted because if you read between the lines, he exercises maybe once a week. And exercise in and of itself, I call it the great equalizer, will activate these same things that we’re talking about rapamycin will do. It helps activate the systems of clean up the mess once you go to bed versus again if you don’t do anything but sit all day. So I guess what I’m trying to say is we’re on one end now the other, and I think we’re going to find a happy meeting in there. That again goes back to, well, depends upon the individual or what he or she does. Sorry.

Speaker 7:                           Touching on exercise. So we learned recently the last few years about muscle contraction, produce musculin, it’s a hormone that muscles secrete. Is there any correlation or anything that you’ve noticed about increased exercise and the secretion of musculin and its relationship with the testosterone?

Dr. Weitz:                            So the question is there’s a hormone… I am not aware of this. This is some new data. A hormone secreted by muscles known as musculin?

Speaker 7:                           Yeah.

Dr. McClain:                        Don’t know that one either. It sounds like it works on the muscle, they’re calling it musculin. But I don’t know the effect. But to your question, without knowing what muscle it is, does muscular activity affect testosterone production?

Speaker 7:                           Okay. So yeah?

Dr. McClain:                        I don’t think we can say that for sure. As a matter of fact, too much activity using your muscles too much, can actually reduce your production of testosterone. But don’t take that the wrong way, let me finish and say this, that I see a lot of pro athletes, a lot of even college athletes that are in such great competition that they’re overtrained. And that stressor like any other overstressor, I guess I should say, will cause a decrease in production of testosterone. So a lot of these athletes that you see oftentimes don’t have the testosterone that you would think because they’re overdoing it. But again, the concept of hermesis keeps popping up. The proper balance of exercise tends to make you healthier and tends to at least get you to whatever your point is on the scale, the highest level of testosterone that you can make for you because you’re in the best health.

Dr. Weitz:                            But I think heavy weight-training has been shown to increase testosterone levels as well as growth hormone levels, I think.

Dr. McClain:                        Well, I would argue that has to do again with how much work it takes. When you say heavy lifting, if you’re talking about literally heavy weights, you can’t lift heavy weights to the point where you’re releasing… An endurance athlete might go for three or four hours and produce a bunch of cortisol, which is not necessarily conducive, excess cortisol is what I’m implying, to testosterone. But someone who goes in and does a 45-minute weight workout, probably that’s the sweet spot. And so yeah, I can see how those results would be, I’m not saying they’re skewed, but would represent, oh yeah, these people are all super healthy and have higher level testosterone than that Tour de France athlete who’s climbing hills six hours a day.

Speaker 7:                           Maybe this discussion’s more for Dr. Penn. You look like you’re in good shape. What does the research say about how many times a week to work out and how long for having optimal levels of the different estrogens and testosterone?

Dr. Weitz:                            Yeah, I mean it depends on the study, but I think from what I’ve seen, doing an hour of exercise a day, five, six days a week, I think is considered a pretty good level.

Speaker 7:                           Yeah, I’m sure it is.

Dr. McClain:                        Well, to add to that, as Woody Allen said, what was it, 95% of the success there just showed up. To what intensity level you take is going to be dependent upon the individual too. Would you say, Doc?

Dr. Weitz:                            For sure. Yeah. Obviously weight training, cardiovascular exercise, flexibility training, balance are all important components of exercise.

Speaker 7:                           Have you seen some studies, because I know you’re big on of course, exercise and exercise chiropractor, studies that have taken a bunch of athletes and they help do a certain kind of exercise and other ones and what the results show in their energy levels [inaudible 01:19:38] I’m not sure you ultimately measure.

Dr. Weitz:                            Yeah, I think as far as hormone levels, weight training has been shown to be especially beneficial, especially heavier weight training or intense weight training. Endurance athletes like marathon runners typically will have lower testosterone levels. Women marathoners will have lower estrogen levels. So I think more than a certain amount of exercise, especially endurance exercise, tends to decrease hormone levels.

Speaker 7:                           I know somebody who’s training be a triathlete and he’s in his fifties. Do you think [inaudible 01:20:23] to recommend additional testosterone and estrogen as he’s training for the triathlete competition? But you’re saying that these people who are overdoing over training he’s in, he’s got three different trainers, but really push him-

Dr. Weitz:                            Yeah, I think the reality is it is great to exercise probably for ideal long-term health training and running a marathon is probably bad, not good, unfortunately.

Dr. McClain:                        I would say almost definitely, not even probably, I’ll go on the limb there. Over training is not your friend. And to run a marathon and really any sort of competitive sport these days, you’re probably not giving yourself the best shake when it comes to health span, that healthy longevity. But that doesn’t mean you shouldn’t necessarily do it. Obviously that gets philosophical because hey, maybe you just enjoy it and you live a little bit longer just because you’re happier. But physiologically, when you go to those extremes, you’re beating yourself up. Now, I will say this real quick. There are three things that we have definitively linked health and longevity. One is a higher VO2 max, another is grip strength, and the third is muscle mass.

Speaker 9:                           How do you dose Primobolan for women and men?

Dr. Weitz:                            Can you speak up?

Speaker 9:                           How do you dose Primobolan for men and for women?

Dr. Weitz:                            How do you dose Primobolan for men?

Speaker 9:                           And women?

Dr. McClain:                        So Primobolan is an anabolic steroid I referred to earlier that’s a DHT derivative, and it’s injectable, which is definitely an advantage, I believe, over an ingestible because it bypasses the liver, obviously. So it would depend upon what the, let’s say female is interested in doing a course. And I don’t mean to put the question back on you, but feel free to give me a specific example, but in general, whether it’s male or female, it’s, okay, what are you doing this for? Are you 80 years old and at risk of a fall? Are you 40 years old and trying to compete in the CrossFit Games? In which case we have a no whole other perspective on that and legalities and that sort of thing. But physiologically, medically speaking, roughly, Primobolan typically comes in 100 milligrams per ml, and a male might dose anywhere from 100 to 200 milligrams per week. Whereas a female would do about one-tenth of that as a general rule.

Speaker 9:                           So a woman who’s already in menopause who uses testosterone cream can’t really get the testosterone up or doesn’t like the side effects of the DHT, wants to try anabolic instead?

Dr. McClain:                        Well, the problem with Primobolan is it’s not legal in this country. It would be considered a contraband. And it is terrible because it leaves our choices to orals, which in this case would be oxandrolone would be my choice because that is legal. And that, you wouldn’t have the side effects because it cannot… well, some side effects because again, even though it’s a DHT derivative, it doesn’t have those androgenic side effects and it cannot convert to estrogen. So bloating is an issue with testosterone because you’re, I call it a converter, you’re converting to a lot of estrogen to begin with, then that’s an option.

Speaker 9:                           And that dose?

Dr. McClain:                        For oxandrolone, typically we will start with about five milligrams twice a day, and then there’s the expensive date that requires more, I call it the fitness model dose, closer to five milligrams three times a day or split twice a day, however it works for you. It’s got a very short half-life of nine hours so you definitely want a divided dose. And because it’s got such a short half-life, you can’t look at the numbers and determine, oh, it’s too low a dose. I hear that all the time. It’s not even showing up. And you can’t use the numbers for that.

Dr. Weitz:                            All right, any final questions? Okay, thank you. Thank you [inaudible 01:24:55].

Dr. McClain:                        Thank you very much. Thank you guys for listening.

Dr. Weitz:                            Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a five star ratings and review. That way more people will discover the Rational Wellness Podcast.  And I wanted to let everybody know that I do have some openings for new patients so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions, or for an executive health screen, and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way. And that usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing, and we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective. So if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at (310) 395-3111, and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.


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