Dr. Nick Barringer (3:39)

Is. Is that because of your advocacy?

Dr. Gabrielle Lyon (3:41)

No, but what I think has really happened is that up until 2003, women were prescribed hormones. These hormones include estrogen, progesterone, and testosterone. So testosterone replacement therapy has been around for, I don't know, 80 years, very effectively. And then all of a sudden, the Women's Health Initiative came out and that changed the trajectory and people became afraid, both of the hormones and also prescribing. But again, now we get a review. What the science says. What are the logistics? Should women take testosterone? You were asking me, will women grow a beard?

Dr. Nick Barringer (4:18)

That's what I want to know. Will they grow a beard? That's what my wife would want to know. Be like, am I going to grow a beard?

Dr. Gabrielle Lyon (4:24)

No. And if you look at the normal laboratory values of total testosterone in women, it is dependent on age and menopausal status. Also the type of testing used, depending on the assay used, depending on the lab, you might get a higher number or a lower number. And the gold standard is liquid chromatography. Okay, just thought I'd throw that out. So if you're getting.

Dr. Nick Barringer (4:49)

Is that specific? Like, so should that be something when you go to your physician? Yes, it should request. Okay.

Dr. Gabrielle Lyon (4:55)

Yes, it should.

Dr. Nick Barringer (4:55)

Liquid chromatography.

Dr. Gabrielle Lyon (4:56)

That's right. And you should at least find out, is it liquid chromatography? Mass spec. But let's talk about the ranges. Total testosterone ranges. So there's total testosterone and then there is free testosterone. I suppose before we talk about testosterone, we talk about androgens. And androgens, you know, they are also precursors for estrogens, estrone, estradiol, and estriol E3 in pregnancy. But the primary, most well known androgen of them all is testosterone. That's right. Which can aromatize into estradiol in both men and Women.

Dr. Nick Barringer (5:32)

Well, it just seems like men get, would you say, overly worried about that?

Dr. Gabrielle Lyon (5:36)

Totally.

Dr. Nick Barringer (5:37)

Okay.

Dr. Gabrielle Lyon (5:37)

And we test, in our clinic, we do test for estrogen levels in men and men. Estrogen is actually. You know what we should do? We should also do an episode on estrogen in men. Yes, why not? Why don't we just balance the playing field?

Dr. Nick Barringer (5:50)

That's true. Yeah, yeah. Just reverse. We're going to talk about testosterone in.

Dr. Gabrielle Lyon (5:53)

Women and then we're going to estrogen in men. I actually really like this.

Dr. Nick Barringer (5:56)

Yeah.

Dr. Gabrielle Lyon (5:57)

What level of estrogen do we find effective and valuable for men? And that is really between 30 and 50. So if you go and you look typically you will see a range between 30 and 50. If estrogen is too high in men in clinical practice, I have seen that they don't like the way they feel and they might. And again, this is subjective reports of increasing in mood, lability. Maybe they're feeling more emotional or their mood is a bit depressed. And low estrogen seems to kill sex drive in men. So if they're on an aromatase inhibitor, say for example, they go to their doctor and they are getting too high a dose of testosterone, say they are taking 300 milligrams of testosterone a week and some of that testosterone gets converted to estrogen. So the guys, a lot of the bodybuilders, they think, oh well, more is better. More is not always better because it aromatizes to estrogen. And you don't want really high estrogen levels in men. Conversely, you don't want low estrogen levels in men because that can affect bone density. They can get low bone density just like women with low estrogen. They also can have low sex drive.

Dr. Nick Barringer (7:06)

Just, I think, yeah, just let's, let's make sure everybody's hearing that right. Low estrogen, if men get their levels too low, it can suppress their sex drive, bone density, all those sort of issues. So guys taking things that suppress their estrogen kind of willy nilly or in lieu of getting on TRT could be a bad idea.

Dr. Gabrielle Lyon (7:28)

Yes. And typically we don't recommend aromatase inhibitors, things like anastrozole, and we don't recommend them in high doses. So for example, if someone is getting peripheral conversion, so from their fat cells, they are now converting testosterone to estrogen. But we will give them an aromatase inhibitor at a very low dose to keep that estrogen in check. But it's not the first thing that we're going to do is we're going to try to address their dosing of testosterone first because if their testosterone is too high and they aromatize it too much to estrogen, then we have a problem. Conversely, let's just think about the normal laboratory values because you wanna know. Yes, you wanna know when your wife goes, hey, Catherine. To the doctor and she gets her lab values back and she sees that her total testosterone premenopausal, her number should be, again, this is what the ranges are. Should be 0.3 to 1.6 nanomoles per liter. Or again, I don't want to totally over complicate.8.7 to 46 nanograms per deciliter. And you want to make sure that you're comparing apples to apples. So we're going to talk about both the ranges in men and women with using the same values. Most laboratories will report nanomoles per liter, and that's by liquid chromatography. And in tandem, this mass spec postmenopausal, their total testosterone, this is untreated, is 0.2 to 1 nanomoles per liter, which, let's take a pause. That's not that big of a difference.

Dr. Nick Barringer (9:10)

Right now because it was what, 0.3 to 1.6?

Dr. Gabrielle Lyon (9:13)

Yep. And then postmenopausal, their total testosterone is. Yeah.

Dr. Nick Barringer (9:17)

Okay.

Dr. Gabrielle Lyon (9:18)

What this tells me is that the premenopausal postmenopausal testosterone numbers don't change. And now this is the reference range. Do I believe that this is an ideal number? I don't. And let's talk about free testosterone. So free testosterone is the bioavailable form. And hormones are like children. They can't go anywhere alone. And typically they're bound to things, sex hormone binding globulin. But the free testosterone is what would be considered the most biologically and bioavailable. So a premenopausal free testosterone level would be 5.2 to 26 picomoles per liter, or 1.5 to 7.5 nanograms per deciliter. Postmenopausal women, free testosterone is roughly half.

Dr. Nick Barringer (10:04)

Ah.

Dr. Gabrielle Lyon (10:04)

And that's 2.5 to 13 picomoles per liter or 0.7 to 3.8 nanograms per deciliter. How do we make sense of this? And why should a woman consider testosterone? And number one, is it safe? I would argue that it is safe. When would we be concerned about testosterone? Really? There's two reasons why. And then we'll kind of then double back to all of hormone replacement therapy. What would be a red flag as to who should not start hormone replacement therapy? But testosterone alone is what I would Consider from my professional opinion. Again, I'm not giving anyone medical advice. Please see the disclaimer. But this is for educational purposes. Thank you to Manicura for sponsoring today's episode. Winter means more time indoors, more travel, and if you have kids, a new bug cough or sneeze every other day. I like keeping my routine simple. And manicora has become something I reach for almost every morning. And why do I love it? It is rich and creamy. It tastes delicious. I either take it right from the spoon or I use these little packs. It coats my throat. Tastes amazing. Now, what makes manicora special is where it comes from. Their beekeepers work in this remote forest of New Zealand where the bees collect nectar from the manuka tea tree. Yeah. So cool. And this plant is naturally rich in bioactive ingredients. So basically, the honey that you have ends up with three times more antioxidants and prebiotics than regular honey. And because it contains mgo, which is a rare antibacterial compound, Manuka honey has benefits that you don't get from other honeys. And all you need is one teaspoon to get the most out of these amazing bioactive ingredients in manuka honey. And now it's easier than ever to try manicora honey. Head to manakora.com doctorlion to save up to 31% plus $25 worth of this free starter kit, which is amazing. I have one. It comes with this massive jar of manuka honey that is go to M A N U k o r a dot com DRLION and save 31% plus $25 worth of free gifts. Testosterone is a safe medication. It is produced in the body. It is very valuable for a lot of things. It's very valuable for sex drive. It is also very valuable for energy maintaining lean mass. It is important that we don't isolate it to one thing. So, for example, we think about testosterone and we think about muscle mass, but there are testosterone receptors all over the body. There are estrogen receptors all over the body. It's not just, oh my gosh, I'm going to give you testosterone and then you're going to grow a beard and muscles. It's not going to happen.

Dr. Nick Barringer (13:03)

So there's no concern. That would be like a much higher dose, right when you start seeing those.

Dr. Gabrielle Lyon (13:08)

The biggest concern is virilization. If we dose testosterone, which is very. It is highly androgenic, meaning testosterone is androgenic, meaning it will affect, it can affect virialization, hair growth, clitoral enlargement at higher doses versus and we're not going to talk about this in too much detail. Other anabolic agents like nandrolone, which is an anabolic steroid, which is FDA approved for anemia of chronic disease. It's used in osteoporosis. This agent is highly anabolic versus androgenic. And I think that that becomes important. Again, we're talking about this overview of hormone replacement in females. Underneath hormone replacement we've got estrogen, progesterone, testosterone. This is what the body would make. This is over in one category. And then we have muscle building and anabolic agents in the other corner. And these agents are things like nandrolone and oxandrolone. Oxandrolone, also known as anavar, which is not typically used anymore but was used back in the day. You and I talked about this for burn victims and maintaining lean mass and muscle. Anavar or oxandrolone, is an oral agent. So again, it was, I don't want to say taken off the market because places still make it, but it isn't used so much in a practicing physician environment because of the increase in liver enzymes, which it does seem to increase liver enzymes versus say a nandrolone seems to have a better safety profile. And nandrolone is an anabolic agent or anabolic steroid, which people are, they hear it and then they get very upset. But again, anabolic steroids or androgens, androgen derivatives, there is a place for them in clinical use. So when we think about the normal laboratory values for men, and I think that this is best used when we think about age reference range for a healthy non obese male, age 19 to 39 years old, typically the total testosterone is. And again, These numbers are funny, 264 to 916 nanograms per deciliter. And this is.

Dr. Nick Barringer (15:36)

Yeah, that's a big. A lot of variability.

Dr. Gabrielle Lyon (15:39)

Yeah, but also, what, 264. And on the low end, by the way, the low end, if you are considered low testosterone, it's dependent on geography and it's also dependent on what organization you're looking at, which is fascinating. So the low number of testosterone might be different. In Italy, what they would consider as a cutoff is low. So it's geography dependent, which signals to me that it's not a hard and fast biological number. But there's a level of interpretation then. So for free testosterone, the most robust recent data that, you know, we have using mass spec or liquid chromatography, the reference range is 184 to 749 picomoles per liter for healthy non obese men, age, you know, 19 to to 39. And that's a free testosterone number. And technically there's data to suggest that free testosterone declines with age and increasing bmi, which makes sense because you then are aromatizing and BMI is the wrong way to look at it. So body mass index, but body fat percentage that can decrease testosterone. Okay, let's talk about some of the risks. Who should not go on hormone replacement therapy? First of all, this is all context dependent. You work with your provider. It is a personal decision. Here is what is typically recommended as red flags. Active breast cancer or active cancers. Undiagnosed, unworked up. If someone has not worked up, vaginal bleeding and stroke. Those are the things where you would give you pause. And it's not that many. Active cancer, undiagnosed bleeding. Why are you having some kind of vaginal bleeding and recent stroke.

Dr. Nick Barringer (17:33)

Wow. I mean that's pretty straightforward.

Dr. Gabrielle Lyon (17:35)

And then when you look at why there are benefits. So now switching back. So we kind of covered this idea of testosterone and androgens. Androgens are a precursor for estrogens in women's bodies. The most well known androgen that we talk about all the time is testosterone, which aromatizes to estradiol. And then there are less important androgens. And when I say less important, perhaps things that we don't always test for, although we do in our clinic dhea and you pulled a paper that we're going to talk about. And androgens are directly secreted by the ovaries and adrenal glands in women. Let's talk about menopause treatment and the benefits of that. And this is really from my understanding why they removed this black box warning. When the FDA puts a black box warning on something, it really makes people pause and it limits the use of these medications and it scares people and for a reason. A black box warning is a. It's a major problem, major risk. The reason the black box warning for hormone replacement therapy happened was from the Women's Health Initiative. It's an outrage for many years and it's gotten more and more pronounced, which is why they reevaluated the data and took the black box warning off. And the following has found to be important and these are the benefits of, of menopause treatment and ideally right before you're going into menopause. So around this transition is the best time. A woman could always be treated. But again, her risk of heart disease, as estrogen declines, her risk of heart disease goes up. Her risk of Alzheimer's disease. Again, Alzheimer's two thirds are in women and of course there are changes in lipids that happen and osteoporosis. So benefits of hormone replacement therapy include a reduced risk of all cause mortality fractures. HRT has also been associated with a 50% reduction in heart attack risk. Wow, sign me up. 64% reduction in cognitive decline. 34% lower risk of Alzheimer's. This episode is brought to you by Body Health. Something changes in your mid-30s that no one talks about and it's called anabolic resistance. Your muscles become less responsive to the signals from protein that trigger growth and repair. This can make hitting your body composition tough. This is why beefing up your protein intake at each meal becomes important often why I say hit 30 grams of protein now? Not everyone wants to eat all of that in a meal. This is where strategic supplementation becomes important. Body health's perfect amino provides essential amino acids like leucine. With less than 20 calories per serving. It's particularly useful for lighter meals like lunch or when using plant based protein shakes. When total protein is sometimes limited. I use it to balance the protein quality of my meals, especially when I'm busy traveling and my meals are lighter on protein. Perfect amino has the appropriate ratios that stimulate muscle protein synthesis and aids in recovery without adding a ton of food volume and calories. If you're focused on your muscle, then this is one of the muscle centric tools that works great. You can check out Body health's perfect amino using the link in the description. And if you'd like to try it, you can use the code Lion20 for 20 off your first order.

Dr. Nick Barringer (21:11)

Do you think that reduction in Alzheimer's, since that's the, you know, the type 3 diabetes is because it, if I understand correctly, it reduces the risk of metabolic syndrome or the incident of metabolic syndrome.

Dr. Gabrielle Lyon (21:21)

I think it's a great point. I think it's twofold. Again, this is just my professional opinion. There are estrogen receptors in the brain. Estrogen. I think the longer the span of lower estrogen, the greater the risk of cognitive dysfunction. And I do think that there is a relationship between insulin resistance in the brain and estrogen. I don't know the exact mechanism. And I also think that when women indirectly are on hormone replacement therapy, they're more likely to be training and exercising. And so they're having a lower insulin resistance peripherally, which then I think can account for a lower risk of Alzheimer's. Again, correlation is not causation. But I do believe, again I train in geriatrics and during the time that I was in training. So I finished my geriatric fellowship in 2015. From 2013 to 2015, right around that time, they were exploring intranasal insulin use to lower insulin resistance in the brain. It didn't pan out. It's not a treatment for Alzheimer's. But one of the things that they had not been exploring at the time, which they have now begun to look at more so frequently, is estrogen use in the brain. So it's not just insulin resistance, because if you would then give insulin, you would think that there would be a reversal or a pause or some kind of treatment. So that doesn't happen. And it's probably the synergistic effect.

Dr. Nick Barringer (22:46)

What about hysterectomies? You know, you're talking about all these issues, and I'm thinking about those. Those poor women that have those early on. So. So I imagine that puts them at greater risk for Alzheimer's and all those diseases you mentioned.

Dr. Gabrielle Lyon (22:58)

And think about all the women that weren't treated. When you get. There's a hysterectomy, there's a total hysterectomy, and then there's a hysterectomy where you just take the uterus and leave the ovaries. And hopefully most women, again, it just depends on what the diagnosis is, that if they still keep the ovaries, they're still producing hormones. But if you do a total hysterectomy, and we've had many patients like this, we put them on hormone replacement, which is the full spectrum. And, you know, right now the conversation really is estrogen and progesterone. Women, I think, are still really afraid of using testosterone, and I can appreciate as to why. But testosterone in women is really important, and it's important for a number of reasons. We should pull up a few of the studies. So there was one study. Let's pull up that. That study on younger women because, again, women think, okay, well, testosterone, it's just after I go through postmenopause, my postmenopausal experience. But, you know, if we look at the values of premenopausal total testosterone and postmenopausal women, it's not that different. But free testosterone does seem to be the. The biggest change. And then looking at what is some of the data on testosterone use and women. Let's look at some of the studies. And there was one in particular that I really liked looking at younger women and the use of testosterone administration. So this is a randomized controlled trial. This is the effects of moderately increased testosterone concentration on physical performance in young women. A double blind randomized placebo control trial. And this was in the British Journal of sports med 2020. And so what this was is this was a double blinded, meaning both parties didn't know what they were. Randomized placebo controlled trial. It was 48 healthy, physically active women age 18 to 35.

Dr. Nick Barringer (24:56)

Wow. 18.

Dr. Gabrielle Lyon (24:57)

I know. 10 weeks of treatment. And again, that's a short treatment course. 10 weeks of treatment. Because we don't think about cycling testosterone like someone would think about cycling an anabolic. 10 week of treatment with 10 milligrams of testosterone cream daily or a placebo. Everybody completed the. The study, which is unusual. And the primary outcome measures, what did they look at? They looked at anaerobic performance. So the wingate test. I've actually never done one of those.

Dr. Nick Barringer (25:25)

Oh, you're not missing anything.

Dr. Gabrielle Lyon (25:28)

The only time I've ever seen your face is like, that is when we're talking about rucking. 10 milligrams of testosterone cream daily. Primary outcomes were aerobic performance measured by time to exhaustion. And then the secondary outcome was anaerobic performance. Wind, gait and muscle strength. Squat jump. And it looks like they did a knee extension and a counter movement jump, which I don't know what that. Do you know what that looks like?

Dr. Nick Barringer (25:54)

Yes. You. You jump down and you jump up and you can either reach up and like hit something up high, and that's how they measure the vertical, or there's a pad that'll measure your time in the air and it'll calculate it from that.

Dr. Gabrielle Lyon (26:05)

Mine would be zero.

Dr. Nick Barringer (26:06)

You got a vertical, you got. You got hops.

Dr. Gabrielle Lyon (26:08)

Are you kidding? Come on. And then they looked at hormone levels and body composition by DAXA address, and here were the ranges. So this is 10 milligrams a day, which, you know, I remember when I started 10 years ago and we were prescribing testosterone cream, we were so concerned. Again, this was during this wave of the Women's Health Initiative where we couldn't find a lot of providers that were prescribing and we would start with 0.5 milligrams of testosterone.

Dr. Nick Barringer (26:38)

That do anything? No. Okay. Yeah.

Dr. Gabrielle Lyon (26:41)

But we were so concerned with increasing. And then I remember when, when we got to 2.5 milligrams, we were so worried. Like, whoa, we're really worried. Again, this is all topical, a topical delivery system. And right now, I would say it depends on the provider, but maybe on average it's 5 milligrams a day. Five is absolutely reasonable. Might not even be enough because it depends on skin absorption. 5mg a day of some kind of testosterone cream, and this was 10 milligrams of testosterone cream daily. And what they found was the serum Testosterone increased from 0.9 nanomoles per liter to 4.3. So it went from 0.9 to 4.3 in the testosterone supplement group in the running time to exhaustion. This increase saw a correlation of testosterone increase, but they found that it also increased their time to exhaustion by 21 seconds.

Dr. Nick Barringer (27:41)

That's significant.

Dr. Gabrielle Lyon (27:42)

That's a lot.

Dr. Nick Barringer (27:43)

That's a lot.

Dr. Gabrielle Lyon (27:44)

It came out to 8.5%, which doesn't sound like a lot, but can you imagine being able to push 21 more.

Dr. Nick Barringer (27:50)

Seconds, especially if you're chasing your kid? Yeah, yeah.

Dr. Gabrielle Lyon (27:53)

But seriously.

Dr. Nick Barringer (27:54)

Right.

Dr. Gabrielle Lyon (27:54)

And this is in testosterone group, compared with the placebo and the wingate average power, which increased by 15.2 watts in the testosterone group versus 3.2 watts.

Dr. Nick Barringer (28:06)

Yeah.

Dr. Gabrielle Lyon (28:07)

So this is performance. 15.2 watts. I mean, I'm assuming that that. Is that significant. I mean.

Dr. Nick Barringer (28:14)

Yeah, yeah. I mean, if you look at performance, if you were an athlete, that could be the difference between being on a podium and not. And you know, and then for daily life, that. That's also, again, being able to keep up with your kid or not keep up with your kid.

Dr. Gabrielle Lyon (28:26)

Yeah. And also to be clear, maybe it's not significantly different between the two groups. So if the wingate average power was increased by 15.2 watts in the testosterone group compared with 3.2 watts in the placebo group, maybe that's not significantly different because it looks like this is a low P value. But like you said, if it's chasing a kid or some performance. It also says there was no significant change in the counter movement jump, which would make sense. Right. Is that a true. That seems like that's a skill that you would.

Dr. Nick Barringer (28:58)

Yeah. A little bit lower body power coordination. Yeah.

Dr. Gabrielle Lyon (29:01)

And then squat jump. And then surprisingly, there wasn't a change. And also knee extension, there was no change. What I'm wondering. And again, I don't have the lab values here. What I'm reading from this paper again that there was an improvement in the aerobic capacity that seemed to be helpful this running time to exhaustion. But the other thing was the total lean mass for the change in baseline again. And I think that this is what has pushed people to not take testosterone. And the total lean mass. This is not skeletal muscle. This is all mass. These are all organ systems. Was 923 grams for testosterone group. And 135 grams for the placebo group. And the mean change in lean mass in the lower legs was roughly 400 versus 100. So four times increase in. Again that's not a huge amount, 398 grams. But I do think that this highlights that there is an effect of testosterone in increasing the aerobic capacity as well as lean mass in young physically active women. Now if we take a pause, what this highlights is really an effect on body composition. Those are higher doses than we typically see in clinical practice. It seems to also improve lean mass. Again, I'm not saying that anyone needs to take this, but looking at some of the data, it's nice to see young healthy people as well because I think a lot of when we think about a lot of the medications and hormone replacements are typically in older or unhealthy or pre diabetic type people. It's nice to know do healthy people benefit as well as less healthy people. Thank you to Bon Charge for sponsoring this episode of the show. And if you've been following me for a while, you know that I take light exposure seriously. Why? Because it impacts your sleep, your hormones, your mood, your ability to recover and focus. It doesn't just affect you, but it also affects your kids. And that's why I use Bon Charge. They've created science backed tools that help balance our modern industrialized lives. From harsh indoor lighting to too much screen time. Their blue light blocking glasses are a nightly ritual for me and my kids. Borrow mine. They help calm my nervous system, protect my circadian rhythm, especially, especially if I just happen to look at my screen, which we all know that never happens. I 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 Boncharge 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 31st December 2025. So hurry and don't miss this chance to save on your favorite Bond Charge products.

Dr. Nick Barringer (32:15)

Right? This is true optimization. This isn't treating a disease state or anything like that. This is optimizing this, this group of women. And what I was looking, I didn't see was, you know, they weren't on 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. But still, like all those, 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.

Dr. Gabrielle Lyon (32:56)

Basically, this paper was a randomized control trial in young healthy women to show the short term testosterone administration led 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's 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 the. 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 and then type two fibers, this is the what we think about hypertrophy. And there was a preferential improvement in these type 2 muscle fibers and then increased blood flow.

Dr. Nick Barringer (34:01)

And so that's really good for the young people. And then like you talked about that fiber type shift. I mean, that's part of 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 endurance seems to kind of stay with those athletes longer than say, you know, like a Usain Bolt versus 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 2, 28 something, you know, some crazy. And I remember seeing this.

Dr. Gabrielle Lyon (34:44)

You really work on that speed.

Dr. Nick Barringer (34:45)

I know. I remember seeing his time and being like, yeah, and that's. 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.

Dr. Gabrielle Lyon (34:59)

I actually, I hadn't thought about. Yeah, Justin Gallon Gatlin. When did Justin Gatlin stop sprinting? 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 were looking at all this data that the randomized control trials showed increase in leg lean mass with a preferential increase in type 2 muscle fibers, which by the way, friends who are listening to this, you can improve your type 2 muscle fibers by getting on a great resistance training program. This could be three days a week. I put that in my book, the new book, which you have over here. Forever Playbook.

Dr. Nick Barringer (35:31)

Love it. Great book.

Dr. Gabrielle Lyon (35:32)

Three days a week of doing resistance training. It could be full body and we put the rep range in anywhere from 6 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.

Dr. Nick Barringer (35:59)

Agree. I agree 100%. I mean, I think as we, we age and adjust and I've seen that become more prevalent that, 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.

Dr. Gabrielle Lyon (36:19)

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. And 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 controlled trial now with testosterone.

Dr. Nick Barringer (36:51)

That's exciting.

Dr. Gabrielle Lyon (36:52)

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 going to 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. We 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.

Dr. Nick Barringer (37:39)

What's the alternative to not?

Dr. Gabrielle Lyon (37:41)

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 intramuscular 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. If 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.

Dr. Nick Barringer (38:12)

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.

Dr. Gabrielle Lyon (38:22)

I'd never even thought about that. So would that improve performance? That's a.

Dr. Nick Barringer (38:25)

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.

Dr. Gabrielle Lyon (38:33)

Yeah, I didn't, I didn't know.

Dr. Nick Barringer (38:36)

But they must have wondered if they were doing it like around the race. So I'm not saying to do that.

Dr. Gabrielle Lyon (38:41)

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 in altitude, those are higher. And 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 1 thing for testosterone replacement therapy is that people will look, say, okay, well, you have an elevated hematocrit. We're going to cut Back your testosterone or we're going to have you do a blood donation. Split 50. 50.

Dr. Nick Barringer (39:52)

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?

Dr. Gabrielle Lyon (40:02)

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 non stick pans still contain harmful chemicals like teflon and other PFAs. One study found that 80% of non stick pans contain these forever chemicals. And another study showed that a single scratch can release thousands of plastic particles into your food. That was enough for me to switch. Our place makes high performance toxin free cookware. So you'll never have to question what is getting into your your meals which is really important. Their four piece cookware set is the simplest way to upgrade your entire kitchen. You'll get two always pans and two perfect pots in mini and full sizes. Those four pieces replace a whole stack of cookware and you can sear, saute, fry, bake, boil if you do those kinds of things. And what I appreciate is that the performance is excellent. We have been using the these pans in our family for a very long time. They're ultra non stick, 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. And upgrade to our place today. Visit from our place. That's F R O M o u r place.com Dr. Lyon 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.

Dr. Nick Barringer (41:50)

Yes.

Dr. Gabrielle Lyon (41:50)

So they there. So there's a intermuscular testosterone formula that those are associated with a greater increase in hematocrit compared to the gel. I will say the gel or the patch. So there are other wraps of testosterone. There's also an oral lymphatic. So Kaiser tracks 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 the fluctuation that seems to really affect hematocrite 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 sub clinical risk of testosterone? And this is a pearl for any physician listening or anyone who is reading blood work, any healthcare provider is that we had a patient and we actually saved his life. He had pernicious anemia and he was masking it. It was masking his pernicious anemia. And actually it's a very good friend. He's a, he's a famous Navy seal. I could probably talk about him and he wouldn't care because I'm all the time. But he. I was like, you've got sleep apnea and that's why your hematocrit is going up. Right? So there was this test. You don't want to layer on testosterone with someone with sleep apnea could potentially make it worse. But this is a clinical pearl. If someone has underlying anemia, pernicious anemia is a destruction of the 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. So he's having. He was 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.

Dr. Nick Barringer (43:58)

What was it? What was the underlying for the. I'm curious with the pernicious, he had gut issues. Shot in the gut or anything he did.

Dr. Gabrielle Lyon (44:04)

Okay, 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 some kind of round worm as well. But forever, he will always have to take a B12 shot. But the testosterone actually had masked that.

Dr. Nick Barringer (44:20)

And I think that what made what triggered you to be like, oh, I.

Dr. Gabrielle Lyon (44:24)

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.

Dr. Nick Barringer (44:34)

Love it.

Dr. Gabrielle Lyon (44:35)

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. And so I was just obsessively going to be like, there's something wrong because 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.

Dr. Nick Barringer (45:01)

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.

Dr. Gabrielle Lyon (45:09)

Like, I'm pretty sure that that limb is supposed to be a dash. Yeah. I would say extremely relentless.

Dr. Nick Barringer (45:14)

Fascinating.

Dr. Gabrielle Lyon (45:15)

And it saved his life.

Dr. Nick Barringer (45:16)

No, that's a great case study. Wow.

Dr. Gabrielle Lyon (45:18)

It absolutely saved his life. So 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, 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. We 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 Kaisertrex. 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 virilization at supraphysiologic doses. Supraphysiologic 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 the virilization. That will happen in much higher doses. We also talked about. You wanted to bring up the change in lipid profile specifically for testosterone versus other anabolic agents. What do you got?

Dr. Nick Barringer (46:43)

Yes, so. So this is what I found. Fascinating. So oral testosterone therapy is associated with a significant reduction in HDL cholesterol for. 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 in older women suggests that higher physiological testosterone is associated with higher HDL and lower triglycerides. So kind of interesting stuff to unpack that it's not just testosterone, but it is all about the mechanism of delivery.

Dr. Gabrielle Lyon (47:25)

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 will 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. Someone 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 as cvd. 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. And 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, is that what you found?

Dr. Nick Barringer (49:20)

Yes, that is what I found. So oral testosterone therapy reduction, right?

Dr. Gabrielle Lyon (49:26)

Oral. If it goes through the liver.

Dr. Nick Barringer (49:27)

Yes, if it goes through the liver. But the transdermal and injectable seems not to affect it.

Dr. Gabrielle Lyon (49:32)

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.

Dr. Nick Barringer (49:52)

People would think that is the reverse of what? Well, oh, you just shattered my world.

Dr. Gabrielle Lyon (49:58)

I'm so sorry.

Dr. Nick Barringer (49:59)

Well, because also in practice, you look at cholesterol divided by HDL, right, for that ratio. So those higher numbers, like 90, 95 is always going to keep it within, you know, under that 5, or you might be a 3.2.4. So they'd be classified as low risk. But you're telling me that, no, that doesn't necessarily put you at low risk.

Dr. Gabrielle Lyon (50:21)

That is correct. And that's why 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. But 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. And 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. Men. And also. So for the women, but also men should have comprehensive panels as well.

Dr. Nick Barringer (52:19)

How often. So you put somebody on testosterone, then how often are you following up with panels?

Dr. Gabrielle Lyon (52:24)

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 it, 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. You 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, 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, every anywhere from four to six months, you know, you want to keep your finger on the pulse.

Dr. Nick Barringer (53:20)

What can a woman expect, right? Who's, you know, you determine she's, she's low testosterone or maybe other hormones. You put her on this hormone profile like, you know what and when can she expect kind of the changes do you see? And I would love to hear your like, most dramatic change or patient you've had over the years.

Dr. Gabrielle Lyon (53:38)

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 tirzepatide. And this was really about. 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. We 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, 1/10 of a, of a male dose. It was dramatic for her. And we used a low dose tirzepatide. This was able to help curb her appetite. She was training a ton, just extremely hungry, very 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.

Dr. Nick Barringer (55:13)

Wow.

Dr. Gabrielle Lyon (55:14)

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 supraphysiological 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, they'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 tirzepatide. And this woman, it dramatically has changed her life.

Dr. Nick Barringer (56:05)

That's awesome. You talk about the physical, but then also, like the. What about the cognitive. What did she report?

Dr. Gabrielle Lyon (56:11)

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. Cognitive thought process of I've got brain fog and I'm tired. And then there are people that are just super tough, and regardless if they're tired or not, they're still executing. And that was her. But from a cog. 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 she has. I mean, this is something that consumed her for 30 years.

Dr. Nick Barringer (57:01)

Wow. And what's so, you know, fascinating about listening to that is the descriptors. You told me at the age of 60, I am willing to bet 99.9% of physicians would be like, you're 60. It's just part of getting older. Right. It's just the expectation.

Dr. Gabrielle Lyon (57:17)

100 miles. You know, this woman outlifts me. She puts four plates, and we start alternating her. 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. And 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 screw for 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 believe muscle is so important, but we don't, not even clinically indicated, to say, you know what you need testosterone. Women 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 is 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. There'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.

Dr. Nick Barringer (59:13)

So DHEA you can get is 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 worried about needles or the stigma of testosterone. Could 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 what I found was this, you know, review is 21 studies, and it does seem to move the needle. So testosterone by 24 points, estradiol by nearly 8. 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.

Dr. Gabrielle Lyon (60:11)

I think it's a great question. And I typically test DHEA sulfate in all my blood markers and I will say that when women are on androgens, testosterone, etc. 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 5 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 there 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. But 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.

Dr. Nick Barringer (61:33)

Right?

Dr. Gabrielle Lyon (61:33)

But what would it be compared to 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 Barringer, 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. Both 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 push ups does Nick really do?

Dr. Nick Barringer (62:25)

Not a lot.