The Testosterone Myth Women Have Been Lied To About │ Dr. Susan Hardwick-Smith

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23:20Dr. Gabrielle Lyon:Don't miss it. When I finished residency and then fellowship, I went into private practice. One of the things that we would see is that women had very low free testosterone. And I remember at the time this was I finished fellowship 10 years ago. And there was not a ton of information in terms of dosing. I started dosing women with cream and I would not see their levels move at all. And I was so afraid to go up because everything I read was that women were going to lose their hair, that they were going to get acne, that they were going to get irreversible changes of their clitoris and their voice.

24:08Dr. Gabrielle Lyon:Now, I never saw that in clinical practice. Well, we don't see that in my office. But going back to the dose is the poison, right? With anything, we can get too much of absolutely anything. And so we don't want too much. So one of my missions in life is to help establish how much is too much and how much is the right amount. And so there's a lot we could get into about why blood levels are not always. There's a lot more to just what's floating around in your blood that we can talk about. But yes, we've been taught and I was taught and my colleagues are terrified that testosterone will make you grow hair on your chin and your hair will fall out and you'll have these irreversible changes that you mentioned.

24:51Let me jump forward to a bunch of data that we have about what happens with high doses of testosterone, like too high. Can we define what the landscape is in terms of low, medium, and high doses of testosterone for women? Yeah, tricky. Okay, because it depends. I agree. Well, depends on a lot of things because we've got all these different modes of delivery. Are we talking about a gel, an injection, a pellet? we don't have a patch anymore, but if you could get one, all of those are different. So this is super interesting. I didn't know this either. And the stuff that I didn't know took me years before I thought to myself, and this was in the terms of estrogen.

25:31So you know, estrogen patches, let's just say, I'm using estrogen, because this is something a lot of your listeners are familiar with the dosing. A common estrogen patch might say 0.05 milligrams a day. So great, you're getting 0.05, I'm going to use easy math, multiples of 10, 0.05 milligrams a day of estradiol. That's great. You stick it on. Hopefully you're getting about that much. Actually, you're probably getting maybe 80 to 90 % on a good day. Now the estrogen gel, 10 times higher. Instead of 0.05. Meaning the metrics of the dose. So if you look at the dose, if you're using say DiviGel, you'll be getting either 0.5, that's 10 times higher, or one milligram, put it on your arm.

26:20Okay, so I did that for years. And I, at some point was like, huh, why are the numbers different? Here's something that I learned that was like mind blowing. When you're using a topical gel or a cream, the assumption is that you're going to absorb 10 % of it.

26:37Dr. Gabrielle Lyon:That is a wild guess. Yes, because that's why they dose it 10 times higher because they know you're not going to get it all. Now, that's a wild guess. You might absorb none or you might absorb 50%, but because of evaporation, because of loss on the skin, all these things, right? So any topical gel, including testosterone, and we can talk about dosing, is dosed 10 times higher if it's a gel or a cream than something that's a different method, like an injection, a pellet, because you're actually getting that under your skin. So the assumption is that's actually going to be delivered into your body.

27:12Now, if you're using a gel and the assumption is you're going to get 10%, how in the heck do you know how much you're going to get? You don't. And this is very interesting because our colleagues at Baylor published a study some years ago on this exact problem with men. So this is known in the male urology literature that testosterone gel for men sucks. They don't like it. They don't use it. Hardly anyone uses gel anymore because it doesn't work. At that time, there were two kinds of testosterone for men, androgel and testem. While they're just testosterone, you'd think they'd be the same. The difference between them, and this is why it's so interesting about FDA approval, two different FDA approved testosterone gels for men, just testosterone, vastly different blood levels.

28:01Testem got much higher levels than androgel. Why? Because they put it in a different medium that's better absorbed. Some men, 15 % didn't absorb it at all. 20 % absorbed it too little to be effective. And then the range was all over. Some guys absorb way too much. Like you said, many absorb none. And then out of these two FDA approved products, there was a huge difference. So the idea that you get it's FDA approved, and it's going to be the same the same every day and your blood levels will be stable and perfect is completely wrong. And in the male literature, we know this. So why do we think in women, it's suddenly going to be perfectly absorbed?

28:43It isn't. And I studied that in my own clinic with Baylor. And so we found that that's true. But in the community, we're still being told that gel is perfect and you put it on and everything's great. It's not. What are the delivery methods for testosterone in women? Well, we don't have any FDA approved methods. So here's where we're sort of painted into a corner. In 2019, there was an international consensus published, which attempted to help providers understand how to use testosterone. So this is fantastic that you get, I think, in this particular setting, there were 15 or 16 world experts, and they got together and they wrote down there what they agreed on.

29:28And then they published this thing. What was it called? It's the International Consensus for Use of Testosterone on Women.

29:34Dr. Gabrielle Lyon:It was published. 2019, the Journal of Clinical Endocrinology. Yes. Davis was the lead. That's right. So Australian, she's a world expert in testosterone and various other of her colleagues. So a fantastically educated group of people. Okay, so they got together. Oh, you can imagine I wasn't there. But when you're trying to get 15 or 16 of the brightest minds to agree on anything, there's going to be a lot of consensus. And so it turned out to be sort of wishy-washy and not very much of anything useful, in my opinion. And we'll post it. We'll... Yeah. And also it was seven years ago. Okay. So what they stated based on their opinion, and this is based on their opinion, was that testosterone for women should only be using FDA approved male gel, dividing it somehow into 10 times less, and then getting physiologic levels, which was sort of broadly defined and people disagree.

30:36It's something like 50 to 70 nanograms per deciliter. And you brought one of those gels? Did you bring one of those gels? I do. So here's a suggestion. So you can get a tube. This is what is publicly stated as being the best way to do it. But actually, very few people do this for reasons that you'll see in a moment. It's kind of impossible. Get a 50 milligram tube of gel and try to divide it into 10. Well, you can't. And so actually, some of my colleagues are even like, well, it doesn't matter. Just put a blob or another blob, which is fine. But let's just say that is not accurate. So the idea that that's in any way accurate is completely false.

31:19It's a big blob, a little blob, just a blob. And not to say that's wrong. I mean, that will likely make you feel better, but your blood levels are going to be all over the place. Again, if that works for you, I'm not saying that people shouldn't use gel. A lot of my patients do, but just really getting rid of this idea that that is somehow going to end up with stability. And in the consensus, they suggested do this and then get to physiologic levels, which you can't. It's practically impossible or some small percentage might, but most people won't. And then it's only for post-menopausal women who have issues with sex drive, no other things, which has really limited us to be, if I was a young physician looking at this, I'd be like, I can't do that.

32:05That's too hard.

32:07Dr. Gabrielle Lyon:You mean in terms of dosing appropriately for women? Okay. I'm just saying you can't do that. You cannot get male gel divided by 10 and get to physiologic levels. I did the study. The levels are all over the place as they are in MUN. So the studies on MUN show the same thing. Gel does not get to stable levels. Now, interestingly, that consensus said use male gel because we didn't have any other thing. All the studies were actually done on a 300 microgram patch. So a 300 microgram patch is going to give much more stable levels, just like an estradiol patch because it's stuck to your tissue. You're not losing it all over the place.

32:45So it was so much didn't make sense in that consensus. And then all the international societies agreed with it because, you know, what else did they have? I understand why. And then ISWIC, our organization, the International Society for Study of Women's Sexual Health, also agreed with it. And so now everybody agrees with it. And it's like, all right, that's what you should do.

33:07Dr. Gabrielle Lyon:And is that how it's in totality within the landscape? Is that how typically it is? Because we use sub-Q injection for testosterone in our clinic. And I'm curious as to what you see your colleagues, how are they? Are they using the gel because of this consensus statement? Yeah. So if you are someone who is your average physician and you do a lot of things and testosterone isn't like your pain of existence like mine, you will follow those guidelines because that's the only ones that we have. Now, in fact, so in the consensus, it said don't use compounding. Okay, here's where you're getting painted into a corner.

33:54Do not use a compounding pharmacy. Okay. Is that what, okay. I said that. I said, don't use injections and don't use pellets. I'm like, okay, well, if I can't do any of those, then I'm literally stuck with using male testosterone gel, which I'll just reiterate is the worst kind of testosterone replacement for men. So why is that the only one that women are being offered? So in the community, people are not doing that. Like I'm not doing that. I offer patients pellets because I know how to dose those appropriately. And the study that I did, we can talk about showed a significantly more likely way to get to stable levels at six weeks than with gel.

34:30Dr. Gabrielle Lyon:And stable levels, and I'm looking at the levels because I do want to talk numbers because we have a lot of physicians that also listen to this. When you are saying stable levels, are you meaning levels that, for example, again, if the range is two nanomoles per liter of free testosterone, you want to continue to see that as opposed to maybe it's 0.35 and then it goes to five. Is that what you mean? Yes. Well, several things. One is how likely are you going to get to whatever you consider your target range to be at six weeks? Okay, that's one thing. And then how much variability is there around that range?

35:16So our study on gel, and we used a very conservative protocol because I really was wanting to do everything I could to make gel look good, let's just say, and it just didn't. using 5 milligrams a day, which is the lower of the recommended doses in Australia, whereas government approved, 5 to 10 milligrams is acceptable. So we started on the lower end. We took patients who had very low testosterone, so less than 20 nanograms per deciliter starting, gave them either an appropriate dose pellet, which I can talk to you about that, or 5 milligrams of gel, and then we measured it six weeks later. The gel patients, this is a low dose, okay?

35:57Their average total testosterone was 132. Nanograms per deciliter. Now, I don't think there's anything wrong with that. But again, the consensus said you're supposed to get it to between 50 and 70. So how the heck do you do that? With pellets, the average was 92, which in my opinion is a great number. There's a lot of disagreement about that. But more importantly, the standard deviation or the range with the gel was literally from Maine to Mexico. Some people didn't absorb much at all. Some were way too high. Now, I want to say there's nothing wrong with that. I don't want to tell your audience not to use gel, but it's not going to be perfect.

36:33And it's going to take a lot of follow up. So we follow up regularly. Now, if you're just getting it from somewhere and nobody's measuring your blood, it could be way too high or it could be way too low. So we check it six weeks and then we check at least every six months. And then more importantly, ask the patient how they're doing, because there's a whole another line of conversation about blood levels don't really reflect what's going on in your tissue. And then what about safety?

36:59Dr. Gabrielle Lyon:One of the things that clinicians are often concerned about is safety. They are concerned about hemoglobin hematocrit with, again, erythrocytosis. They are concerned about lipids. Cancer, death, heart attack. Yeah, super important. Well, you know, a fantastic bunch of literature we have about that is from the transgender community. As a physician, I spend a lot of time talking to patients about healthy aging. And one of the most important factors is maintaining skeletal muscle. I know it's unsimple, but simple isn't the same as easy. And many people struggle to consistently consume enough high-quality protein to support muscle health, recovery, and long-term metabolic function.

37:46Dr. Gabrielle Lyon:And thank you to one of the sponsors of the show, Perfect Amino. That's one reason why I personally use and recommend Perfect Amino by Body Health. Perfect Amino provides all of the essential amino acids your body needs for protein synthesis and beyond. It is a highly bioavailable form of amino acids. It's easy to take and can be a practical option for individuals looking to support muscle health, especially when meeting protein goals are difficult. Remember, muscle is the organ of longevity, whether you're training hard in the gym or simply focused on staying strong and independent as you age.

38:25Dr. Gabrielle Lyon:Giving your body the building blocks it needs is an absolute non-negotiable for your long-term health. Go to bodyhealth.com and use the code LION20 for 20 % off your first order. That's bodyhealth.com, code LION20. I was just looking at the transition literature. It says the target testosterone level for hormone therapy from female to male is, it says 320 to 1 ,000 nanograms per deciliter, which corresponds to a normal physiological pathological male range represents roughly a 10 to 30 fold increase from a typical female premenopausal level. Yeah. So this is a great population to study because if you, as I do, we all have a concern, okay, is this safe?

39:24Is it going to cause cancer, heart attack, increase in red blood cells that could potentially cause an issue? All of the concerns that we might have, increase in breast cancer, these are legitimate questions to answer. So there are studies lasting as long as 50 years. There's one from Amsterdam that looked at 50 years of transgender data. There's one from Japan lasting 10 years. There's actually several lasting 10 to 20 years looking at what happened given transgender men very, very high doses of testosterone. Here's the bottom line. Nothing bad happened. No increased risk of death from anything.

40:01Improvement in muscle mass, obviously. in bone mass. And erythrocytosis was minimal and did not result in any problems. Now, just like men getting testosterone, potentially, you could increase your number of red blood cells. Actually, that's not the same as hematologic diseases like polycythemia vera. It arguably isn't even important. We know now in the male literature that there is no association with cardiovascular disease. So I can be very comfortable from that literature saying that the safety is understood. So it won't kill you. It won't give you cancer. Now, we don't give those

40:42Dr. Gabrielle Lyon:high doses. What about the effect on, is there an effect on the lipid profile? If you take it orally, yes. So just like all the things we've learned, right? Now, not counting chysotrex, it has a different pathway, but the old types of testosterone had an adverse effect on LDL went up, HDL went down. So this is very similar to in all of the data we know about some type of not by mouth form of hormones, because these are tough on the liver, let's say, and they do adversely affect the liver profile. And that whole pathway is what potentially increased the risk of heart disease. We know that's not the case anymore, because we don't use it that way.

41:20So if you took these 50 years of transgender patients and gave them way massive doses of testosterone, they didn't have heart attacks.

41:27Dr. Gabrielle Lyon:And this is, and I'm looking here at this data here, it says that the typical starting dose is 50 milligrams sub-Q weekly for someone who is transitioning. 50 milligrams sub-Q weekly. And so I don't take care of a lot of men, but men, I know, sort of 50, 100, even up to 300. And then you measure their blood levels. But so we know what happens with high doses of testosterone in the trans community. It's safe. Now, do they get virilizing symptoms? Yes, because they want to. So we don't want that high. But I think that's answered the safety issue. I'll also say it whatever people's opinions are about pellets.

42:06Gary Donovitz, who is the founder of BioT back in the day, published data with over a million pellets, like a million pellets. Now, I don't particularly agree with the dosing protocol they use, but let's just say it was safe. There were no safety issues. Other big studies looked at NHANES data over 10 years and showed no increased risk in any major adverse cardiac event. Actually, a decrease in women who are under 50. So lower PE, lower heart attack. In women over 50, it was the same. So there have been these massive studies looking at millions of patients. And I think we can just put the safety question to rust.

42:49It's safe. Now, any side effects we have are, I would say, we call them nuisance side effects. Talking about these things like losing your hair, deepening your voice. A nuisance side, like it's a nuisance.

43:01Dr. Gabrielle Lyon:Yeah, so it won't kill you, right? Now, these things also don't happen overnight. I'll tell you about a patient I saw a couple weeks ago. She came in from a different place, and she had significant male pattern baldness. I mean, really, really terrible for her. It was very bad. Now, she'd been given very high doses of testosterone over a period of eight years. What was the delivery mechanism? Pellet, very high dose. Okay. So dose is the poison. Again, her blood levels were 800. Now, that did not happen overnight. It took eight years. So I never blamed the patient. However, I said, why did you keep going back?

43:39And she said, well, I felt great. So here's the thing, like your hair will not fall out overnight, your voice won't deepen overnight, your clitoris doesn't grow overnight. This is like prolonged high doses. It takes transgender patients years to transition. Just like if someone's worried about a heart attack, you don't take a medicine and have a heart attack. It takes years for that plaque to build up. So if you're being followed, that won't happen. Kind of like when people say statins cause diabetes, not if you're following them. If you saw that trend, you would do something.

44:12Dr. Gabrielle Lyon:What about as we're talking about these numbers? What about the numbers, the baseline evaluation for what women are? As we know, in medicine, the quote, average is an average number of what testosterone would be in the population, and we know that the majority of people are not exercising and are potentially, they have a higher body fat and a lower muscle mass. How do you think about what the numbers should be? Well, the number is different for each patient. So let's talk about blood levels. Now, if I get my blood drawn and I go to Quest, let's just say our typical LabCorp, whatever lab, for someone my age, if you look at the reference range, it might say something like, normal testosterone is zero to 30, 40, something like that.

45:07It'll say something like that. Now, that reference range, as you mentioned, is just based on what people have. It's in no way, like any lab, an optimal range. So I think labs in general, we need to move away from the reference range of what 90 % of people have towards what's actually optimal for the patient. So I mentioned the consensus was saying, okay, let's try to get to levels of 50 to 70 nanograms per deciliter. That logic came from that's what 20 year olds have typically. But being higher, what's wrong with that? Well, possibly nothing. Because women typically, so my experience, which is massive, as you know, our patients typically feel bust.

45:47Now there's a lot of variation when their levels are sort of 50 to 120. I can say mine, if mine's sort of 80 to 100, I feel really great. If it drops below that, I can tell something's not right. Now, there's different ways to do blood work. And we can talk about, you know, standard versus LC-MS and all the things. Standard testing, your average lab is going to use what's called ELISA. It's the standard type of testing, which has got some problems that can pick up things that are not there. It's not as accurate as we think. This other type of testing called LC-MS.

46:22Dr. Gabrielle Lyon:What is the error rate on ELISA? So if someone is listening to this, what I really want to get out of, or what I want listeners or viewers get out of this is to understand testosterone's role in women. We've touched on where the barriers have been, which it seems as if it's more of an administrative challenge and then very expensive to do multiple randomized controlled trials. However, we do see it done in men. So there's a little bit of a disconnect there. But also to empower them. As you and I both know the information landscape is vast and there are nuanced questions that should be asked and there should be a platform for people to learn about that and that's really what we're trying to do I believe in this episode and so as you are listening or watching this you're thinking okay I'm pulling out my lab work and as a woman who's postmenopausal or perimenopausal I'm looking at the free testosterone.

47:21Dr. Gabrielle Lyon:And my free testosterone shows zero, 0.0. Yeah, well, let's talk about free testosterone. All right. So in this consensus, and I want to go back to the ELISA versus LCMS, because we did a study on that too. So let's just for your listeners say there's different ways to measure hormones in the blood, and none of them is perfect. We have this, I had this idea that when you draw the blood, whatever the lab says is exactly correct. It's not. Now, I've done this and others have too. I've drawn my blood every two hours and I get different numbers because if you did, yes, we did all, we do all kinds of fun stuff in the office.

47:59It's not the same all day. The labs machine is different at different times. It's a guideline, right? So we need to look at the lab value as a guideline. That's really tricky.

48:09Dr. Gabrielle Lyon:I think that that's really tricky for physicians and also patients because trust is important. And if they're looking at their level. If a guy comes into our clinic or a woman and their testosterone is 200, you want to say, okay, yes, I believe that this number is 200. Well, we need to lighten up on that a little bit and understand. I love this about you. So you go, if you went into, I'm sure you've done this because you did a bunch of science. You go into a lab and you see these machines and they're feeding blood in and it's spitting out a number, it's not perfect. There are many, many things that can cross-react in different ways.

48:51And then not to mention your own blood level changes during the day. But let's just say there are, you want to fit within a certain guideline. First, I want to say free testosterone. So in the consensus, which all of us are supposed to follow, they specifically say, do not look at free testosterone for women because the number is so low that it's practically impossible to measure. You have to use something called equilibrium dialysis. Like most labs can't even do this. So in fact, if you're getting a free testosterone from 99 % of places, it's not actually being measured. It's being calculated.

49:23So they get the total testosterone, which we already know is less than perfectly measured in the first place. Measure a hormone called SHBG, which binds testosterone, and then try to do some math, which is calculating using how much is bound to protein, SHBG and albumin. and then guess how much is free? Well, that number is not accurate as a calculation. So the recommendation is don't look at free testosterone because it is not, talk about not far from accurate, that is so far from accurate. So there's no consensus about what free testosterone should be for women. We're barely even understanding what total should be.

50:02So for those who are not, if you're somewhat a beginner as a patient or a doctor, I just look at total. I look at total, maybe just eyeball the SHBG. But the fact is the number is so not that important. Because we were trained, any blood test, that you draw your blood and that is magically showing what your tissues are being exposed to. Not the case. Lots of examples about how blood levels and tissue levels are not the same. We've got androgen receptors that have different levels of function from pleomorphisms and things. We've got different levels of proteins that are binding. There's also testosterone production going on within the cell that isn't even measurable in the blood.

50:45So it's a guide. So here's what I say. What the best number is for you is the number at which you feel well without having any side effects. I don't really care what that number is, honestly. Typically, it might be somewhere from 50 to 120. But now if you came in to see me and your level was 150 and you said, I feel fantastic. I have no side effects. I would say carry on. Carry on with your life. Right. You're doing great because it's safe. You feel well. What is the problem?

51:16Dr. Gabrielle Lyon:I appreciate what you're saying. And I just pulled up some of this data. And this was ELISA and other immunoassays for testosterone have significant accuracy limitations, particularly, as you were saying, at low concentrations found in women. and they define lower track. I do think it's very important that we have definitions, especially in medicine, typically less than 100 nanograms per deciliter. They also show poor correlation with the gold standard method, the gold standard method, which is liquid chromatography, tandem mass spectrometry, which is LC-MS. Yeah, okay, let me tell you about - Rolls off the tongue.

51:59Dr. Gabrielle Lyon:Uh-huh. This is what I read. Okay, so I actually looked up like, where did this information come from? where we were told that LCMS was like dramatically more accurate than ELISA. Now, ELISA has gotten better over the years, but not perfect. We did another study with Baylor where we took 99 women, we just did this in January, and we drew their blood, same blood draw, same day, same moment, and we sent it to test for both. We said test ELISA and LCMS, same patient, same day. Not significantly different. Oh, really? There was a small change. So in the patients who were not on testosterone, LC-MS generally read a little bit higher, but by six nanograms per deciliter, a tiny bit higher, not clinically significant.

52:40In the patients on testosterone, the difference was an average of 22. Now, yeah, read a little bit higher, but that doesn't change my management. So for a doctor who's in practice and they don't have access to LC-MS and all this fancy stuff, ultra-sensitive everything, it's not going to change your management.

52:59Dr. Gabrielle Lyon:It doesn't change the management. It doesn't. So clinically, I get it from a scientific point of view. Yes, LCMS is probably more accurate. I would just say probably because how do you know? How do you know what the truth is and which one's closer? People will talk about salivary testing. Way less data on that. I would agree. That's not been studied by any good resource to be better than anything. I get the point. I mean, the idea is that what's in your saliva is free from protein binding. But just not clinically useful and very, very confusing and expensive. So again, because the level is not particularly important, it isn't.

53:40Because I have some patients. Now, I use 50 in my office if you're coming in and drawing your blood. And you don't check free testosterone? You check total? We do.

53:52Dr. Gabrielle Lyon:Because we're doing studies. But we're really doing it for research purposes, does not change clinical management. because what's your free testosterone supposed to be? Well, is there a number where you're like, wow, 200? Say a woman comes in and you know that at 300, let's just say, let's pick a number, at 300, she's going to have symptoms. And it might not be immediate, as you said. It might take some time. Is there a number where you go? So for me, I can say that if I'm looking at the guys and I'm looking at a reference range, And again, depending on who you are and depending on how you practice, I like to see the guys in a normal range, even if there is plausibility.

54:37Dr. Gabrielle Lyon:Again, it's kind of this back and forth. Even if there's plausibility that a testosterone above 1 ,000 is perfectly fine. Yeah. But I don't know. Yeah. So this is just my clinical sixth sense that you develop after years of being a doctor. I typically and my providers are taught that we want their testosterone after treatment to fall between, say, 50 and 120. Now, if it's slightly outside of that, great. If it's way outside of that, I will tell that patient, like, at this level, your risk of having side effects is really starting to go up. I don't recommend that we continue. Let's drop down. There's also this data that's so important with the very low dose patch.

55:21Let's go back to that. That is a minuscule dose. Those patients had very minimally increased levels of testosterone and in RCTs had a significant improvement in sex drive. So we know benefit occurs at quite low doses. My opinion is you really don't need those high doses to get benefit. And in fact, at super high doses, it can overwhelm the receptors. You get this thing called tachyphylaxis where it just stops working. Can you talk about that?

55:47Dr. Gabrielle Lyon:Because tachyphylaxis, as someone who is, if someone was listening to this, and they are, again, either a patient or a physician that felt really good at a starting dose of something, we're even starting to see it with GLP -1s. Right. You don't feel it anymore. You do not feel it anymore. Can you touch on tachyphylaxis, please? Yeah. Well, I'll just tell you what I understand from my clinical practice, what I've seen. So if you take someone like me who had a testosterone that was measurably zero, and I got a reasonable amount of testosterone, and it increased my level to, say, 100-ish, and I feel great.

56:26Many of our patients say this, like the first two to four weeks, they're like, oh, my God, I feel amazing. I'm having suck streams. I'm lifting heavier weights. I feel great. Because going from zero to high normal is a massive change. So your androgen receptors have been seeing nothing, and all of a sudden now they're happy and full and doing their job. Well, if you keep going up on the dose, the receptors, my understanding of how tachyphylaxis works is that the receptors just get saturated and they downregulate because they're trying to create homeostasis, obviously. They just want to shut everything down.

57:03Dr. Gabrielle Lyon:So they downregulate, and that's exactly what we see. Yeah. And I first, again, men getting testosterone 10 years ago was relatively more common, at least. And I remember seeing these guys where they're at 100 milligrams a week, and then they're at 150, and then they're at 200. And then what you find is they're always pushing for that. You're sort of chasing a high. You're chasing a high. Yeah. So I tell my patients this may or may not be appropriate, but it's like this is not cocaine, right? This is a natural hormone. We're not trying to make you feel high, although you might feel so good the first few weeks, similar to when women start on estrogen and all of a sudden they're sleeping and their hot flashes are gone.

57:49They feel amazing. Now, after a time, they're just going to feel kind of normal. So I'm sitting here with all three hormones in my body and I feel amazing, but it's also kind of normal. I'm not chasing a high. So the patient I mentioned who came in with male pattern baldness, she admitted she was like chasing a high. She's like, I just felt good. So I kept getting it and I kept getting it. And then, you know, over eight years, all her hair fell out. Yeah. So let's not do that. So I loosely say 50 to 120, you know, and then if a patient's a bit higher, we'll just say, well, how are you feeling?

58:24and watch out for these side effects, which are nuisance side effects, easily reversible. If they do happen, you get some couple hairs on your chin or some oiliness, drop it down. Because we know it's safe, it's not going to kill you. If a patient wants to play with that, I think it's her choice. So if you said to me, I feel really good. What if you said, I feel really good and I've got a couple of hairs, but I'm seeing my obstetrician. Skin's a little oilier, but I'd like to take care of that with some products. So carry on. Why are we being so paternalistic about telling women, you can't do that?

59:03And what other avenue do we tell people they can't do that? You get to choose. It's safe, right? So if it's not safe, I'll advise you against it, but it is safe.

59:13Dr. Gabrielle Lyon:We all remember what a freshly cleaned room smells like, straight chemicals. As I think about it, I used to touch this stuff with my hands directly. And the more we learn, the more we understand the whole body burden of these compounds over time. We all have, frankly, enough to worry about cleaning products should not be one of those things. And I remember when people thought I was crazy because I was really concerned about all of these cleaning products. I get it. The essential oils might not clean everything, but on the other hand, I'm not sure that we need these very aggressive cleaning products.

59:49Dr. Gabrielle Lyon:And typical cleaning products use chemicals that leave synthetic fragrances and other endocrine disruptors as well. There's also harsh organic compounds on your countertop floor, your sheets that kids sleep on. These chemicals accumulate over time, forcing your body to carry that burden. And that's why in our house, we use Branch Basics. Their premium starter kit It uses one plant and mineral-based concentrate to replace every single toxic cleaner in your house. It has zero fragrance and zero endocrine-disrupting chemicals. It handles everything from our laundry to our kitchen counter without compromising our health.

1:00:32Dr. Gabrielle Lyon:The only thing I wish it did different is if it would actually clean itself, but it doesn't. Branch Basics is available at Target, Amazon, and branchbasics.com. You can get 15 % off the premium starter kit with code DrLion at branchbasics.com. That code is DrLion for 15 % off. What about within the hormone space? Are there things that are particularly contentious that it's important for a patient to know? Oh, my favorite one is about pellets. so pellets have developed a certain reputation and I understand why they have a very interesting history they've been around since the 1950s and as you know they are actually FDA approved for men so pellets are a fantastic delivery method testapel FDA approved for men since the 1970s been around forever it doesn't come in doses appropriate for women it's just one dose so and what is that dose 75 milligrams so men would typically get you know eight to ten of them now A woman could get one, possibly.

1:01:39I'll tell you about how we dose it. I get 50 milligrams, so that would be too high for me. It's really expensive. The main prohibitive thing with pellets is that they cost a fortune. The Testopel does. And what is the brand name? Testopel, yeah. Testopel. Yeah, so it's great, and a lot of guys like it. You put them in, and then they're good to go for five months. I don't use them, but our friend Mo Cara does, and he's like, Yeah, it's a great option for some men. So men have pellets. So let's just say they're FDA approved. It's a safe and understood delivery method. But we don't have any FDA approved testosterone, pellets or otherwise, right?

1:02:19Now, pellets got associated with some a bit shady kind of behavior. And I... What do you mean? Well, so back in 2011, a company called BioT, which is not a bad company, but I think they really were doing some groundbreaking work and trying to move the needle forward. The owner at the time, Gary Donovitz, came up with a protocol for dosing pellets for women, and you could go to a weekend course in Dallas and learn how to do it. So a lot of people did that, and they'd get, you know, 24 hours of training, and now they're giving pellets in their esthetician office or whatever, without any understanding really of endocrinology or anything.

1:03:01That dosing protocol was unarguably way too high. That's the dosing protocol that got my patient's hair to fall out. Well, because of that, a lot of doctors, a lot of my colleagues think that all pellets are like that. Well, and I agree that, you know, before I met Mo, I was one of those providers that

1:03:21Dr. Gabrielle Lyon:I thought that too. Pellets were irresponsible. And we're seeing patients with significant side effects. Like the one that I mentioned. So yes. So going back to the doses, the poison, yes, that dosing regimen was unarguably too high, and doctors and other clinicians were using it who had no understanding of endocrinology. They were just putting them in and didn't know what to do about side effects and so on. So that went south a bit. Now, it doesn't mean that you want to throw the baby out with the bathwater, because pellets are a really fantastic way to deliver hormones. I have one in my bottom.

1:03:58We have a different dosing. And no, there will not be a show and tell. Well, because you can't see it. I'd be happy to, you can't see it. A size of a piece of long grain rice. A 3.2 millimeter in diameter, right? Tiny, tiny, tiny. Like a piece of jasmine rice, all right? So it lasts for three months. So for me, that's a great choice. I don't tell people what to do, but just to say that it should be on your list of choices, in my opinion. But the dosing is what's important. So in the study that I mentioned we did with gel versus pellet, I mentioned the average testosterone level was 90, which is very reasonable at six weeks after a pellet.

1:04:35I see. Versus in the BioT program, it would be 300 or higher. And actually, they trained doctors to get testosterone. The goal in that program was to get to levels of 250 to 350. I went to the training just to see and was like, wow, that's interesting. That's what they're teaching. No wonder pellets have a bad reputation. but not all pellets are the same. So we source ours now from a company called Pharmakao in Dallas. Actually, a lot of the scientists from BioT left and went over there. It's an interesting story. You can get whatever dose pellet that you want to. And so we developed in our office a different dosing regimen.

1:05:19And I don't know if it's the right one, but it works very well. We dose 0.8 to 1 milligrams per kilogram. So I use 50 milligrams because I'm 55 kilos. And so we round down. And then personally, I've been doing that for eight years. And I have no side effects. I feel great. My sex drive is great. My muscle mass is great. My bone density is the same as a 25-year-old. Maybe that's also partly from estrogen, but it helps. I feel better. And my levels are not too high and everybody's happy.

1:05:51Dr. Gabrielle Lyon:The absorption kinetics, which basically we started out by talking about delivery systems of testosterone for women. There is gel and cream. Yes. People can get compounded cream, right? Yeah. Wherever they go to get their hormones, injection, and pellets. And the next layer to that, because we are talking about testosterone, do you think it matters the kind of testosterone used, whether it's enanthate or cipionate? Well, other than injection, these others are just testosterone. So the enanthate, sipionate would be in an injection, does not matter. So again, this is interesting. I didn't know this either.

1:06:45I have heard some influencers say, oh, that's not bioidentical testosterone, so therefore it's bad. Actually, the sipionate or the molecules cleaved off, so it does appear as testosterone in your bloodstream. So if you measure your blood after a T-sipionate injection, you will see elevation of testosterone because the sipionate's been cleaved off. So it's just, that's absolutely fine. They're all fine. Get it any way that you want to. So I have no, I, if you want to do an injection twice a week, sub Q, great. And people say, well, the dosing hasn't been identified. Well, kind of, we've all agreed.

1:07:20We give 10 times less than the male dose. So instead of starting at 50 a week, we'd start at five a week. And we typically do 2.5 twice a week, tiny, tiny dose, and then measure it six weeks later. So whatever dose you use, take the male dose, divide it by 10, and off you go. So I think the dosing has been established with that logic, knowing that we don't really know what blood levels you will get to as an individual. So we check it six weeks later, but nothing bad happens in six weeks. You're not going to grow an extra arm in six weeks. These are things that happen over years. So I do tell my patients, whatever we're starting on, it is an experiment with an N of one.

1:07:59Now millions of other people have done it, but I can't tell you what your blood levels will be. I can tell you, for example, that our average blood level was 90 with a pellet and 130 with gel, but you could be different. So let's just see and then adjust.

1:08:14Dr. Gabrielle Lyon:That leads me to something I do want to talk about is when you think about how you are dosing. And again, there's a lot of people that are using various ways to get it. You know, obviously pellets, sub-Q injections. Do you think that there is a way to think about conversion? If someone is listening to this and they go, okay, well, gosh, I've been using the gel. And you pull out your small little tube, which is hysterical if you have it. I have no idea how anyone would be able to dose it. And they want to switch. Is there comparable conversions? Kind of. However, going back to what we talked about with the absorption through the skin being so incredibly variable, and we also talked about the fact that gel is dosed 10 times higher than a pellet.

1:09:04So let me tell you about me. I could use 5 milligrams a day of gel. So think about this. I'll try to do easy math. Now, I have a 50 milligram pellet in my bottom, which is going to last approximately 100 days. This is easy math. So I'm getting 10 times less per day in the pellet than I would be if I put the gel on my arm. So if we use that 10 to 1, yes, gel 10 times higher, pellet or injection 10 times lower than the gel. Now, will that end up with the same numbers? Who knows? Because we really don't know how much the gel you absorb. It's fairly reliable how much of a pellet or injection you'll absorb because it's in your body.

1:09:43You're not losing it through evaporation or anything else. That being said, everyone's metabolism is different. I'm sure you've seen you give 50 milligrams to one person and another, and they'll have a vastly different response. So you have to follow patients. So if you're going in clinic where they just say, here you go and see you next year, that's where you get into trouble, potentially. But if you have your blood drawn, say, six weeks after initiation of whatever it is you decide, have it manipulated. And then we check twice a year ongoing. going, if you're on any kind of hormones, we check twice a year because labs are available.

1:10:20Why not? We want to take the best care of our patients and make sure that everything's optimal. And then to be very honest, in our practice, we do not see any adverse side effects because we manage it that closely. We just don't see those things that people are talking about.

1:10:35Dr. Gabrielle Lyon:What about, so someone's listening to this and they go, well, you know what? I don't want to take hormones and they want to age al natural, can they take action to mitigate that decline in testosterone? I wish we could. I tried actually when I was as funny when I was in my mid forties and this was happening to me. I had the idea because that was popular at the time that I would just sort of get through it. Kind of like I tried having a baby without an epidural. I changed my mind in the middle. So I do yoga, I do meditation, I'm like, I can get through this and brain juice myself through it. I think a lot of women say that.

1:11:15Yeah, I tried. You can't. You cannot use your mind to elevate your hormones. I tried. I like really tried. Didn't work. They were still zero. So I'm happy that I did that experiment, though, because I actually do know what it feels like to be in a hormone depleted state. For whatever reason, I decided to sit there for six months, and then decided to do an experiment with the alternative and quit my job, like I said, because it was like, okay, this is really important. You know, when you look at the

1:11:44Dr. Gabrielle Lyon:literature, there is no supplement or nutrition that, again, that I've seen evidence for, that will raise and maintain testosterone in women? Well, the only one I can think of is if you take DHEA orally. I tried this, by the way, in my green juice experiment. At what? Something like 100 milligrams? The highest dose I could get. I'm like, let me go to G and C and C. I think I did take 100 milligrams. So with 100 milligrams of DHEA for six weeks, my testosterone went from zero to 40. So it went up a little bit, but it wasn't enough to move the needle. And actually studies on DHEA, there are some show that you cannot get enough to improve any symptom, particularly HSDD or sex drive.

1:12:32It will elevate it a little bit. Maybe it has some cellular benefit that's not noticeable, but as far as making you feel better, good luck, highly unlikely. I think it's an important point because

1:12:45Dr. Gabrielle Lyon:if people want to feel better and the end result is if we are going to go through the aging process, How can we do that in a way where we have agency? And people will spend years trying to do alternative therapies. This is not one of those areas. And I appreciate you as a provider who sees patients willing to discuss that because it misleads people for a very long time. And then five years pass, they're still waiting to feel better, and they don't even remember what feeling good is like. Well, you know, with this particular hormone, I think then I won't, I can't pick my favorite. Honestly, estradiol is freaking amazing.

1:13:27Like all the things that we know now that it does, but I'll just say that's largely not argued about anymore, right? We know all the amazing things that does. Testosterone, let's talk about in your field. muscle mass bone health which leads to reduction in dementia and all the offshoots that you have written about and talked about for your whole career about how important that is we have a natural hormone that we know and i would just say we do know reduces the risk of sarcopenia and osteoporosis what is wrong with that not to mention all the other things like sex drive which is just fun. I mean, so in my buckets of health, listen, on this show, people bring all

1:14:08Dr. Gabrielle Lyon:kinds of things to the show. We right. I love Amy Perlman. I love Amy Perlman's bag of tricks. When I look at buckets of health, and people often say, oh, nutrition, movement, sleep. I add fun to that and sucks. Like why are you having a good time when we're older, enjoying ourselves. And part of that is physical intimacy, and play. And here's another point that I love, I wish I could go back and do these studies again. All of these randomized control trials, and I mentioned there's at least six good ones, probably some smaller ones as well, that randomized patients to testosterone patch, which we don't have anymore, versus placebo.

1:14:46And then they asked them in these standardized questionnaires, questions about sex drive, because studies, they have one endpoint. And all of them had an improvement in sex drive. Well, I know for sure if they had asked those same patients an additional set of questions about, we mentioned earlier, like how do just life drive? I feel better. So my patients say, yes, my sex drive's better, but all of my drive's better. It's easier for me to go to the gym. I want to socialize. I want to try new things. I just jumped out of a plane. I'm going on a trip to climb up a mountain. I didn't want to do that before.

1:15:22I was sitting on the couch just eating ice cream and feeling sorry for myself. So the cognitive benefits are not just sex drive. Sex drive is a mood and it affects all of our mood, not just that one part. That's an important part, but it's much more than that. I often tell patients, like there's not some tiny part of your brain where the testosterone molecule just attaches and that's your sex drive locus. It's the entire mood. It's the whole, it's everything in our cognition.

1:15:51Dr. Gabrielle Lyon:you I know that you also have a book that is coming out which we'll have you back in on to talk about which is create her is that link available for us now or that is so there's a pre-order link we'll put that there not coming out till February but we're gonna put it in and it's called create her aging into the healthiest version of yourself before we wrap up one of the things that I did want to mention is that there seems to be a few drugs that can potentially lower testosterone in women. And why do I want to bring this up? Because perhaps if someone is thinking, okay, well, gosh, these ladies just ruined it for me.

1:16:30Dr. Gabrielle Lyon:What am I going to do now? No amount of exercise and training. Listen, maybe training will definitely improve muscle mass. Maybe it improves short-term increase in testosterone. But the reality is we will have a decline in hormones. It is an unfortunate part of aging. But medications that lower testosterone. If someone is on these medications, again, it's something to think about. Oral contraceptives, they increase sex hormone binding globulin. Would you agree with that? Oh, absolutely. So I love birth control pills. I have 21-year-old girls and they're very useful in certain populations. But they shut down your ovaries.

1:17:09So let's think about how they work. They prevent ovulation. So your ovaries are not producing hormones and about 50 % of our testosterone comes from our ovaries. Not only that, but the testosterone...

1:17:18Dr. Gabrielle Lyon:Where's another 50 come from? Adrenal glands and then just intracellular production. So like you mentioned, that protein we talked about, SHBG, goes up when you're taking birth control pills. So whatever small amount of testosterone you have left is not freely available for you. So it pretty much shuts it down. And this is an interesting thing. I wondered this. How come 21-year-olds have such great sex drive when their testosterone is often zero? It's because they're 21. Like they don't need all the things we do. We don't have that resilience anymore. We need, yes, 21-year-olds and I was one on the pill.

1:17:50My sex drive was great. My testosterone was probably zero. So that points to, it's very complex, right? It's not just testosterone is the only thing. It is complicated. Right, sex drive is so complex. But as we get older, we need all the help we can get. So we're not 21.

1:18:06Dr. Gabrielle Lyon:Also, spironolactone, that blocks androgen receptors. And it seems to partially inhibit testosterone. Synthesis is that, are you in a kind of alignment with that? and it's used for hirsutism and PMOS? Yeah, so the androgen-blocking drugs like spironolactone or frenasteride is going to potentially limit how much testosterone is available to your androgen receptors. Now, I have some patients who are using testosterone, and perhaps she's one who has oily skin and is also taking spironolactone. So it's not black and white that blocks it altogether. That patient might need a little bit more to overcome that barrier.

1:18:43So these are the nuances where we can sort of say, I also have patients on birth control pills who use testosterone, a small subset. We just need more because we're understanding that most of it's not bioavailable. So that's in the nuance once you've sort of understood the basics. But for providers, I would really just stick with measure total testosterone. Doesn't much matter if you use LCMS or ELISA, just the best you can do. And then use your judgment. If a patient feels well and she's not having side effects and it's some kind of reasonable number, get some experience in your clinic and see what's happening, see how people are feeling.

1:19:21Use some of these standardized questionnaires before and after treatment and you will see dramatic improvements in their well-being.

1:19:28Dr. Gabrielle Lyon:Dr. Susan Hardwick-Smith, it is a pleasure to have you on. I'm excited to have you back. You are doing a lot of great work in the field that needs a voice because it is really underappreciated, this role of testosterone in women. Do you have any last closing thoughts? Well, I'm so delighted to have been able to share this with your audience because it is such a gap that we can potentially help people to feel better. I went into medicine to help people to get well and feel better. And this is an opportunity to do that, that a lot of providers and patients are missing. And the data is right in front of our nose.

1:20:07So let's move away from this consensus that's so restrictive and be a bit more creative within safe boundaries. And the people that are saying that gel's the only way, it's not. And dose pellets appropriately, 0.8 to 1 milligrams per kilogram. come see us we know how to do that you can get testosterone safely and not have any of those side effects dose is the poison don't throw the baby out with the bathwater and and you'll feel

1:20:36Dr. Gabrielle Lyon:great and also potentially have a long athletic career as you have done is it 44 um long i so i'm sorry, nine full distance Ironman races and... 35 half. Yeah, I know that's an embarrassing number. But since you asked me, yes, we can do hard things and fun things. We should, right. So if you're developing sarcopenia and osteoporosis, and you can't move because you have no energy and you've got no drive, you're not going to do those things. So I think this is a massively important topic for those issues, athletic performance. It's performance enhancing. That's why you can't take it in the Olympics.

1:21:22It makes you perform better. What is wrong with that? I'm not in the Olympics. Give me some. But you could be. Maybe. I have to stop taking testosterone, though.

1:21:31Dr. Gabrielle Lyon:Thank you for all that you are doing and not making testosterone just the male hormone. It's not. Well, I'm delighted to be here.

1:21:43Thank you.