Hormone Replacement Therapy Decoded: Why the FDA Removed the Blackbox Warning on HRT

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31:38I also love their red light lamp. I turn them on as soon as it gets dark and I use the big panels, 10 to 20 minutes each day. They are some of the best red light products I have ever used, low EMF on the market. And right now, Bond Charge is having their holiday sale. So you can save a massive 25 % off. Just head to bondcharge.com and your 25 % off code will automatically be added to your order. The sale will end on the 31st of December, 2025. So hurry and don't miss this chance to save on your favorite bond charge products. Right. This is true optimization. This isn't treating a disease state or anything like that.

32:20This is optimizing this, this group of women. And what I was looking at and see was, you know, they weren't on a, uh, a training protocol as part of this study that I can see. And so you're talking about by just giving you this cream I'm improving your run to exhaustion, which I imagine probably the effect of testosterone on the red blood cells, maybe the iron, you know, the oxygen carry capacity, but still like all those metrics moved. And I would be curious to see if they had them both on training protocols, what it could be more pronounced even with the testosterone. Basically, this paper was a randomized control trial in young, healthy women to show the short term testosterone administration.

33:05led to significant increase in total lean mass. And they increase when they say significant increase in total lean mass, 1.9%. And leg lean mass by 2.4 % with type 2 muscle fiber hypertrophy and increase in capillarization. What does this mean? Fiber types change as we age, type 1, type 2, and obviously there's type 2A and these combo fibers. But really for simplicity sake, we have type 1 fibers, which are the long endurance type fibers, which also there is a preferential transition to type 1 fibers as we age. And this is, I was going to make a joke about my dad because he does listen to the podcast, but he's got some type 2 fibers, but we see they become more frail and thin.

33:51And then type 2 fibers, this is what we think about hypertrophy. And there was a preferential improvement in these type two muscle fibers and then increase blood flow and so that's really good for the the young people and then like you talk about that fiber type shift i mean that that's part of the the reasoning or the logic i've always heard of why if you look at like sprinters or you know power sports once you get past the age of 30 35 you usually don't see athletes in that whereas like long distance running you can have people in their 40s going into it yeah because because endurance seems to to kind of stay with those athletes longer than say you know like a Usain Bolt versus uh the Kipchoge would be the best example he just did the New York marathon I mean I think he finished you know at 40 in his 40s top he was a top 20 like you know ran like a 228 something you know some crazy and still and I remember seeing his time I know I remember seeing his time and be like yeah and that that doesn't even get you in the top 10 or top five but he was still able to compete at a high level versus for sprinters i don't know of any sprinter like past the age or males at least past the age of like 35 who are still i actually i hadn't thought about that on yeah when did he stop when did justin gatlin stop sprinting i i don't know how old he was but that's it's a really good point what i thought was also interesting is you know when we're looking at all this data that the randomized control trials showed increase in leg lean mass with a preferential increase in type two muscle fibers, which by the way, friends who are listening to this, you can improve your type two muscle fibers by getting on a great resistance training program.

35:26This could be three days a week. I put that in my book, the new book, which you have over here, Forever Strong Playbook. Love it, great book. Three days a week of doing resistance training. It could be full body. And we put the rep range in anywhere from six to 15, which is a wide rep range, but the whole idea is that you're going to one to two reps in reserve. People will say, oh, well, you should, use compound movements and I get it. And also if someone doesn't feel comfortable doing a deadlift or a squat or some kind of big compound movement and they want to use machines, totally fine. I'm sure you hopefully agree with that.

35:59I agree. I agree a hundred percent. I mean, I think as we age and adjust and I've seen that become more prevalent, that kind of stance, I guess on, you know, some of the Instagram stuff with, because at one point I remember it was very kind of old school. You had to squat, you had a bench, you had a deadlift. And now there's some great human performance professionals doing, hey, you can lunge. You don't have to do that. And thank God, because I'm terrible at squatting. The other thing here was looking at some other papers in postmenopausal women, higher dose testosterone therapy for up to 24 weeks was associated with a dose dependent increase in lean mass.

36:37And this was actually up to 4.4 % and muscle performance. Again, these are short-term studies, I think, especially because the FDA has removed this black box warning. We're actually working on a randomized control trial now with testosterone. That's exciting. That is very exciting, just to show and create a body of literature showing the safety of it. Again, I'm assuming that that's what we're gonna find, but I'll keep you posted. Now, there is a few things that someone has to think about in terms of when would you be concerned about testosterone? If your hemoglobin and hematocrit go up, typically, again, whether it's up to 48%, you know, by 50%, we are decreasing it.

37:21We are recommending a blood donation. This is a bit controversial. The science of elevated hemoglobin hematocrit, again, the science is a bit controversial. Some physicians will recommend a blood donation. Some will not. We typically do a blood donation. What's the alternative? To not, but then your hemoglobin hematocrit rise, but not dissimilar. Again, it depends on how the body responds and we should talk about this. If an individual is not doing an intermuscular injection, so when you do a bolus of testosterone, you get this big bump up and you get erythropoiesis. So you get an increase in red blood cells.

38:00If you do a lower dose sub-Q, say split it up three times a week, the same amount, you don't see the elevation in hemoglobin hematocrit. You know what I can't help but think? All your cyclists and runners listening to this podcast just went, okay, intramuscular next time the marathon's coming up. That's right. I'd never even thought about that. So would that improve performance? Well, it would. I mean, I imagine that's why all the, remember the Tour de France cyclists were taking testosterone? that big scandal you know some years back so I wonder yeah I didn't I didn't know but they must I wonder if they were doing it like around the race so I'm not saying to do that Nick is not saying that so for a normal level typically a hematocrit is again 41 to 50 for men and then females are 36 to 44 percentage again these are non-altitude individuals because if someone lives and altitude, those are higher.

39:01And I think that this is a bit where the controversy comes in, because if we know that people live at high altitude and they have higher hematocrit, should they be not able to be put on testosterone? And so I think there's a lot of conversation that goes in and around this, and I'm hoping that we will see more about this. Now, the high hematocrit level is erythrocytosis. It's red blood cells versus a pathology condition, which is polycythemia vera, which is an increase in red blood cells and other cells. It's kind of across the board. The two are different. And that would be the one thing for testosterone replacement therapy is that people will look, say, okay, well, you have an elevated hematocrit.

39:47We're going to cut back your testosterone or we're going to have you do a blood donation split 50 50. Is that in just to make sure I'm understanding is that because you know one like risk of stroke is that the main concern and then is does that correlate with higher blood pressure naturally with it with that? Possibly so those two things yes. Thank you to our place for sponsoring today's episode. Most people focus on the ingredients they cook with but the cookware matters just as much. Most nonstick pans still contain harmful chemicals like Teflon and other PFAS. One study found that 80 % of nonstick pans contain these forever chemicals.

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41:04We have been using these pans in our family for a very long time. They're ultra nonstick, they clean easy, and buying the set saves you$150 compared to purchasing each piece separately. Stop cooking with toxic cookware. It is very important. Upgrade to Our Place today. Visit FromOurPlace, that's F-R-O-M-O-U-R-Place.com slash Dr. Lion, and you will get 10 % off site-wide. And it comes with a 100-day risk-free trial. I promise you, once you switch to these pans, you will never go back. What else should people be looking at? Well, we also talked about changes in lipid profiles. Yes. So there's an intermuscular testosterone formula that those are associated with a greater increase in hematocrit compared to the gel.

41:59I will say the gel or the patch. So there are other routes of testosterone. There's also an oral lymphatic, so chysetrex. is an oral testosterone, but it's not through the liver. It goes through the lymphatic system. The difference is these fluctuating serum testosterone concentrations. It's the fluctuation that seems to really affect hematocrit levels. But you can account for that by changing the delivery and the delivery schedule, which I think can be really valuable. And I will tell you one other thing. What is another perhaps subclinical risk of testosterone? and this is a pearl for any physician listening or anyone who is reading blood work any health care provider is that we had a patient and we actually saved his life he had pernicious anemia and he was masking it was masking his pernicious anemia and actually it's a very good friend he's a famous navy seal um i could probably talk about him um and he wouldn't care to talk about him all time but yeah he i was like you've got sleep apnea and that's why your hematocrit is going up right So there was this, you don't want to layer on testosterone with someone with sleep apnea.

43:06It could potentially make it worse. But this is a clinical pearl. If someone has underlying anemia, pernicious anemia is a destruction of intrinsic factor in the gut. So it's an autoimmune condition that these people cannot absorb internally. They cannot get B12. It's deadly. It can kill you. And typically, you have to identify it. When you are on testosterone, because testosterone increases erythropoiesis and the generation of red blood cells and is also will mask anemia, can help, quote, treat anemia, it was masking his pernicious anemia. He was having these terrible symptoms of shortness of breath.

43:46So he's having, he's totally symptomatic. I mean, he had been to the ER multiple times. and so this is a pearl that if someone goes on testosterone it can mask underlying causes of anemia what was it was underlying for the i'm curious for the pernicious anemia he had gut issues shot in the gut or anything he did so he has been shot multiple times but because of his deployments he also had psoriasis he had a lot of conditions i mean he had uh some kind of roundworm as well but forever he will always have to take a b12 shot but the testosterone actually had masked that and i think that what made what triggered you to be like oh i did a peripheral blood smear and i'm extreme if it's one thing that you know people say okay what's one word that defines you or that would represent you and i would say relentless is in that category love it it's just extremely relentless and i care very much for him he was in the same troop as my husband so he's one troop team 10 one troop just like shane and there was no way i was going to let something there was something that i could do about it there was no way that i wasn't going to do it.

44:48And so I was just obsessively going to be like, there's something wrong. Cause you're going to the cardiologist, cardiologist saying you're fine. You're going to the neurologist, the neurologist is saying that you're fine, but you and I both know that it's not psychosomatic. Right. These, these guys, they don't complain unless something's wrong. And usually by then something's like hanging off their body, right? Like, I'm pretty sure that that limb is supposed to be a dach. Yeah. I would say extremely relentless. It's fascinating. And it saved his life. No, that's a great case study. Wow. It absolutely saved his life.

45:20So that kind of goes about, well, how do we think about taking testosterone and what potentially could it mask? So an IM injection, which would be in the shoulder or the butt, or I've got one patient that puts it in her thigh. She's bananas. I'm pretty sure that that hurts a lot. Nick, you and I were chatting. We talked all about testosterone use, a little bit about the history of testosterone use, what it can do for women. However, there are various ways an individual can take and test for testosterone, both men and women. For women, we talked about the cream. We talked about intramuscular injection.

45:53We talked about a sub-Q injection. I think eventually for women, they'll also be able to take an oral lymphatic absorption. Men are also already there in terms of Kysetrex. We talked about the best blood test, and that is a liquid chromatography mass spec. And that's just a technique. We also spoke about the side effects, meaning potential for increase in virulization at supra physiologic doses, supra physiologic doses, meaning it's outside of the normal range for both men or women. And we talked about one of the things that we see in terms of side effects. So there's a virulization that will happen in much higher doses.

46:34We also talked about you wanted to bring up the change in lipid profile, specifically specifically for testosterone versus other anabolic agents. What do you got? Yes. So this is what I found fascinating. So oral testosterone therapy is associated with a significant reduction in HDL cholesterol for women, right? Non-oral testosterone therapy, so the transdermal, injectable, at physiological doses, so we should say that, has been shown to not significantly affect HDL cholesterol in women over the short term and even observational data on exogenous testosterone levels and older women suggest that higher physiological testosterone is associated with higher HDL and lower triglycerides.

47:16So kind of a interesting, you know, stuff to unpack that it's not just testosterone, but it is all about the mechanism of delivery. And I think it's really important because there's a lot of conversation about cholesterol and HDL is the high density lipoprotein and its role is really for transporting cholesterol. You can have a high HDL. People typically think of this as quote good cholesterol, but really it's not good or bad and it's not just the amount of HDL. So if we were to look at the numbers of where we want HDL, which we'll go through, but it's how is the quality and the functioning of that HDL, which I think is really important to look at the functionality and the particle quality.

48:03Someone could do that if they do a Boston heart. And this is looking at some of the databases. This is the American Association of Clinical Endocrinology, and their guidelines are the following, that HDL C less than 40 is an independent risk factor of atherosclerotic cardiovascular disease. And this is ASCVD. And again, this is thinking about plaque, meaning that the HDL is not able to transport the other particles. And so you get this plaque buildup. And that's in both in men and women. And less than 50 milligrams per deciliter is a marginal risk factor in women. So HDL, when we think about a high density lipoprotein, refers to the class of lipoprotein in the blood that's responsible for transporting cholesterol from peripheral tissues back to the liver.

48:59And this needs to be functioning, which is why it got the name of good cholesterol. However, there are certain guidelines. And basically, if someone is taking testosterone, it doesn't seem to negatively impact if they are taking it by injection or topically. Is that what you found? Yes, that is what I found. So oral testosterone therapy reduction, right? Oral if it goes through the liver. Yes, if it goes through the liver, but the transdermal and injectable seems not to affect it. And that's important because you want good functioning HDLs. Now I will say something else, and we've had Dr. Mike Twyman on the podcast many times levels above 80 to 90 milligrams per deciliter is linked to increase in all-cause mortality and increase in cardiovascular disease and that's wait the reverse of what people would think that is the reverse of what well oh you just you just shattered my world i'm so sorry well because because also right in practice you look at cholesterol divided by hdl right for that ratio.

50:07So those higher numbers like 90, 95 is always going to keep it within, you know, under that five or you might be a three, 2.4. So they'd be classified as low risk. But you're telling me that no, that doesn't necessarily put you at low risk. That is correct. And that's why a Boston Heart or additional testing, looking at the particle quality, looking at ApoB, looking at all these other markers rather than these isolated ratios and independent markers, I think it's just really important because people typically think that 60 or higher is considered to be protective. And yes, it is 60 to 70 and potentially even higher than that.

50:47But one just has to make sure that the functionality of the HDL is good. And that becomes important. And listen, during perimenopause and menopause, we see a lot of shifts of cholesterol, LDL cholesterol, HDL cholesterol increase in ApoB has to do with these, you know, this relationship between estrogen and these transporters. But the reality is we have the ability to test for it. And testosterone within physiological ranges don't seem to have a negative impact. Other anabolic agents can, depending on the agent, meaning if we're talking about anabolic steroids. And one of my goals is to really help dissolve this stigma that anabolic steroids, even the word anabolic steroids, seems to have with people because anabolic agents can be very helpful when clinically indicated.

51:38And again, not all of them affect LDL cholesterol or HDL cholesterol. There's a normal physiologic process, but I'm really glad that you brought that up. And if people are going to go on testosterone, you want an entire panel. Someone gets a baseline panel of free and total testosterone, sex hormone binding globulin, estradiol, progesterone. They should also include a thyroid panel. They should also include an iron and a ferritin, really looking at all of these things, luteinizing hormone, follicle stimulating hormone, everything. And also, so for the women, but also men should have comprehensive panels as well.

52:19How often, so you put somebody on testosterone, then how often are you following up with panels? You get a baseline, make sure that everything is where it should be, see what we're looking at. And then four weeks after, we also get a baseline as to where they are so that we know if we move it up or down. You know, because you don't just start testosterone, men and women just all of a sudden feel great. It takes time. And typically we want to give people at least four weeks. But you still, even if they haven't gotten their full effect, you do want to start monitoring. And then of course, a CBC.

52:51You know, some people just get a hemoglobin hematocrit, which again, we talked about hematocrit as the oxygen carrying capacity, the red blood cells, but you really want to get a full spectrum. So it's baseline, four weeks after, you allow them to go for a period of time. And then we check in another three months to make sure that they are where they should be. And once someone is stable, every six months, anywhere from four to six months, you know, you want to keep your finger on the pulse. What can a woman expect, right? Who's, you know, you determine she's, she's low testosterone or maybe other hormones.

53:28You put her on this, this hormone profile, like, you know, what and when can she expect kind of the changes you see? And I would love to hear your like most dramatic change or patient you've had over the years. The most dramatic change. And there's one patient in particular I'm thinking about. It wasn't just testosterone. So we use low dose terzepatide. And this was really about, you know, she had very low sex drive, low libido, felt like she had lost a ton of muscle. And again, testosterone is not FDA approved for muscle mass. It's not, quote, recommended for body recomp, which is fascinating because we know sarcopenia is really dangerous for people, which is sarcopenia is defined as loss of muscle mass and function.

54:09We think about it as something for aging, but it's not a disease of aging. and one of the most dramatic transformations that I've seen was this woman she had always been training she's 60 this woman is a beast she's incredible and what we did is she had low libido low recovery a ton of joint pain and we optimized her hormones and her testosterone dose you know we're not talking about 20 to 30 milligrams a week so typically the testosterone dose is you know one-tenth of a male dose. It was dramatic for her, and we used a low-dose trisopatide. This was able to help curb her appetite. She's training a ton, just extremely hungry.

54:55Very low dose, starting dose, and then optimize her testosterone, progesterone, and estrogen. I mean, her body transformation was unbelievable. This was a woman who never wanted to get on the scale ever. And you know, she's like running ultras. Wow. Her body fat percentage is 16 % now. And it's not effort. It just seemed that we were able to put everything into place. And this took six months. And again, everything is within range. We're not talking about pushing super physiological numbers. She's able to recover. She's sleeping. So one of the things that we see is that women that are going through perimenopause, menopause aren't sleeping.

55:36They're not recovering. you add progesterone oral progesterone not cream but oral progesterone it seems to affect as a GABA agonist in the brain allows women to sleep estrogen we know estrogen is great for bone and brain function there are estrogen receptors on muscle again i don't think it's the primary driver but just the combination and then sub-q testosterone injection with a tiny little bit of terzapatide and this woman it dramatically has changed her life that's awesome you talk about the physical but then also like what about the cognitive what did she report two things mental freedom from thinking about food and her body weight this is a woman who had been obsessing about how she looked and performed for 30 years and we took that off the table and it just completely transformed her life it was probably one of the most fulfilling moments i mean and again we see this there is so there's the cognitive process a cognitive thought process I've got brain fog and I'm tired.

56:37And then there are people that are super tough. And regardless if they're tired or not, they're still executing. And that was her. But did her cognition improve? I would say yes, but she never complained about that. What she complained about was just constantly feeling uncomfortable in her skin and just really obsessive about how she looked and performed. And this is something that consumed her for 30 years. wow and what's so you know fascinating about listening to that is the descriptors you told me at the age of 60 i'm willing to bet 99.9 percent of physicians would be like you're 60 it's just part of getting older right it's just the expectation 100 miles you know this woman this woman outlifts me she puts four plates and we should all train here she puts four plates on that sled plus so she wraps the sled around her weight plus kettlebells 90 pounds of kettlebells I mean, this is extraordinary.

57:30And so we don't, you know, we think about testosterone replacement therapy for men. Nobody blinks an eye. Yeah. Men will come in. I have low libido. I have low muscle mass. I have brain fog. The hair is falling off my legs. Oh, you need to refer testosterone here. Let me just put it in the water. But a woman comes in and is like, oh, I'm not feeling well, blah, blah, blah. And it's, oh, well, you know, it's in your head. Maybe you need an SSRI. But we don't think, and again, I, you know, believe muscle is so important, but we don't. not even clinically indicated to say, you know what, you need testosterone.

58:01Women aren't even thinking about that. Similarly, just how men aren't even thinking about estrogen, which is equally important for men and women. And we have a lot of work to do, but the goal of this episode is what is testosterone? How is it being prescribed? What are the benefits? Where's the safety? What do we begin to think about it? And from a clinician standpoint, who is perhaps listening to this, I think in the next five years, we're going to begin to see FDA approved usage. And just because something isn't FDA approved, it can still be used quote off label, which means you review the benefits and the side effects and what it's clinically indicated for and what it's not.

58:41There's one more aspect about testosterone that I think is important is there is a use of testosterone vaginally, estrogen, progesterone vaginal. And why is this? Because this tissue atrophies and nobody wants that, right? Because that's just not ideal, increases risks of urinary tract infections. Before we wrap up this episode, I did want to talk about DHEA because you brought it up and I think that it's something that's important. And I'm just going to pass that over to you. So DHEA you can get as a dietary supplement, right? That's in that category. You don't require a prescription. And so I was wondering about if an individual is a little wary, maybe they're, you know, worried about needles or the stigma of testosterone.

59:32Could they consider or would you consider like higher dose DHEA to increase things like the estradiol and testosterone because it can go either way right in their body and and what i found was this you know review is 21 studies and it does seem to to move the needle so testosterone by 24 points uh estradiol by nearly eight but it took higher doses of 50 milligrams or more to produce those results especially adults over 60 so so my question to you would be do you guys use dha in practice? Are you, you know, seeing people take it or? I think it's a great question. And I typically test DHEA sulfate in all my blood markers.

1:00:18And I will say that when women are on androgens, testosterone, et cetera, that we see a decrease in DHEA. So whatever the pathway is, it seems to pull it forward. And in clinical practice, we might use five to 10, maybe 20. Typically, I haven't gone up to 50, I would just move them to use testosterone, or I would, again, as a practicing physician, there's obviously a discussion, maybe they want to use it, maybe they want to use DHEA versus testosterone, but I would certainly be open to it. And I do think that where the real magic of DHEA, which DHEA may have some anti-inflammatory effects, where I think that there is benefit is if someone is on testosterone therapy, also adding in DHEA again, because I see that the DHEA levels seem to decrease when people are on testosterone, maybe, you know, it's shutting something off or something of that nature.

1:01:14But what else did they find in the study? Anything else of relevance? Because it's interesting. So there's 21, this was a review of 21 studies and it did move the needle. It did increase estradiol and it seemed to increase testosterone. Again, one would argue is 24 points enough. That's a lot for a dietary supplement. right but what would it be um compared to uh testosterone but again it seems like all of these things are dose dependent there is use for dhea they do use intervaginal dhea by the way well dr nick berenger we have covered how women can utilize testosterone without getting quote too jacked too hairy no beards no beard free and we are at a new frontier in medicine where people are really advocating.

1:02:02Both clinicians and patients are starting to advocate for themselves. And we appreciate you guys and hope you enjoy this episode. And if you want to hear more, hopefully you are involved with the behind the scenes super cast. And that is our private community where you can listen to these episodes ad free and ask questions and find out how many pushups does Nick really do? Not a lot.

1:02:30Thank you.