Dr. Susan Hardwick-Smith 0:00

Testosterone is actually made in far greater quantities than estrogen in female bodies. That’s something that’s often missed. When I found that out, I was like, Oh, what? Like I didn’t know that.

Dr. Gabrielle Lyon 0:13

So it’s been a real uphill battle for women to get access to testosterone.

Dr. Susan Hardwick-Smith 0:18

Yes, absolutely, and I understand why big pharmaceutical companies don’t want to go down that road. Turned out very badly in the past for them.

Dr. Gabrielle Lyon 0:28

What is the role of testosterone in women?

Dr. Susan Hardwick-Smith 0:31

Testosterone’s been associated with men forever. We think it’s a male hormone, that it makes you bulky, it makes you grow hair on your chin. But I didn’t think women made testosterone unless there was some sort of pathology.

Dr. Gabrielle Lyon 0:42

Are there things that are particularly important for a patient to know?

Dr. Susan Hardwick-Smith 0:47

Actually, testosterone improves all the functions of our sexual cycle: blood flow to the clitoris, easier to have an orgasm, reduction in anxiety, depression, and then other things like memory, recall, brain fogs, athletic performance. It makes you perform better.

Dr. Gabrielle Lyon 1:04

The FDA approved 31 products for men as of 2020.

Dr. Susan Hardwick-Smith 1:10

Yeah, so there’s probably even more now with Kyzatrex and so on, but a bunch.

Dr. Gabrielle Lyon 1:13

How many have been approved for women?

Dr. Susan Hardwick-Smith 1:15

Zero. Absolutely none.

Dr. Gabrielle Lyon 1:17

Define what the landscape is in terms of low, medium, and high doses of testosterone for women.

Dr. Susan Hardwick-Smith 1:24

Here’s something that I learned that was like mind-blowing.

Dr. Gabrielle Lyon 1:36

Dr. Susan Hardwick-Smith , welcome to the show. So

Dr. Susan Hardwick-Smith 1:39

excited to be here.

Dr. Gabrielle Lyon 1:41

I met you through our dear friend and colleague Dr. Mohit Khera, who is a urologist here at Baylor, probably one of the leading voices in testosterone, and I would also say his focus is largely on men.

Dr. Susan Hardwick-Smith 1:57

That’s right.

Dr. Gabrielle Lyon 1:57

And you know, women, the focus on women is emerging across all specialties related to hormones. And you personally, one reason I’m very excited to talk about testosterone, you spent 18 years building one of the largest OB/GYN practices, and then in 2020, you left that practice. You had 20 providers at the time, and you launched right into menopause care.

Dr. Susan Hardwick-Smith 2:25

Yes, we know why that happened is because I went through menopause, and being a very prominent OB/GYN, I knew absolutely nothing about it. So when it happened to me, I realized I had absolutely no information to help myself. I’m an athlete. I lost my sex drive, I lost my energy. I felt terrible. It became a real emergency to figure this out. You know, in 2020, that wasn’t that long ago, but the information was even vastly less than we have now. So I left that practice thinking I’d just have a little quiet life, just doing a little menopause practice with me and my nurse practitioner. Well, that’s not the way I roll. So now we have a big practice with three offices, a big virtual platform. We’re growing. We’ve got 12 providers now, looking for more, and it’s really pushing the edges of trying to learn more about how to help women to feel better in midlife. And one of the aspects, not the only one, but a very important one that there’s such a big gap in understanding about, is using testosterone for women. So that’s become a real focus of mine and working with Dr. Keer and Baylor doing studies all about that, trying to figure out a better way to do it, because currently we have very little guidance.

Dr. Gabrielle Lyon 3:35

How much training did you have in testosterone for women?

Dr. Susan Hardwick-Smith 3:40

Zero. The only thing I knew about testosterone was in the context of polycystic ovarian syndrome. So in women who were making too much endogenous testosterone, and that’s a metabolic disease and all kinds of other things happen with that—heart disease, diabetes, so on. We only knew about it in that context. Absolutely nothing about the natural progression of testosterone loss that every healthy woman goes through as part of aging. So, this is something that happens to every single woman, so I think it’s something that we should understand because it’s half the population. Not to say men are also suffering from it as well, but we just haven’t defined how to maximize this for women at all.

Dr. Gabrielle Lyon 4:24

Unusual in the field of medicine to have such an untapped area,

Dr. Susan Hardwick-Smith 4:31

isn’t it?

Dr. Gabrielle Lyon 4:32

In 2026. And the FDA, let’s talk about the FDA. The FDA approved 31 products for men,

Dr. Susan Hardwick-Smith 4:44

Yes.

Dr. Gabrielle Lyon 4:45

as of 2020? 2020?

Dr. Susan Hardwick-Smith 4:49

Yeah, so there’s probably even more now with Kyzatrex and so on, but a bunch.

Dr. Gabrielle Lyon 4:52

How many have been approved for women?

Dr. Susan Hardwick-Smith 4:54

Zero. Absolutely none.

Dr. Gabrielle Lyon 4:57

Okay.

Dr. Susan Hardwick-Smith 4:57

Now, there were a couple of attempts that were turned down, and that’s a really interesting story, a long time ago, and nobody, understandably, has tried again, because one of those companies went broke and the other one just was shot down. And so, it’s not a popular thing for drug companies to want to do this. They’re busy making money on weight loss drugs and cholesterol drugs and ED drugs, and so testosterone for women is just not important in many people’s mind.

Dr. Gabrielle Lyon 5:25

What is the role of testosterone in women?

Dr. Susan Hardwick-Smith 5:28

So, I know your listeners have heard this before, but it’s such an exciting thing to talk about. Testosterone is actually made in far greater quantities than estrogen in female bodies. That’s something that’s often missed, because if you get your blood drawn, the units are different. So let’s just say you got your blood drawn, I’ll just make up some easy math, and your estradiol was 50 and your testosterone was 50. If you looked at those units of measurement, it would require a 10 times conversion to make them apples to apples. So actually, estrogen would be 50 and testosterone would be 500. We just missed that. Like nobody taught me that. When I When I found that out, I was like, Oh, what? Like I didn’t know that. Also, testosterone’s been associated with men. Forever we think it’s a male hormone that it makes you bulky, it makes you grow hair on your chin, and all of these things. As a okay, I was an OB-GYN, as you mentioned, for many, many years. Saw thousands of patients. I thought I knew a lot of things, and I did, but I didn’t think women made testosterone unless there was some sort of pathology, like PCO. I really didn’t think about it. Was never mentioned, nor taught in any way other than in a pathologic point of view: testosterone-producing tumor, PCO, something like that.

Dr. Gabrielle Lyon 6:49

And women, you know, I was talking to Mo, and basically he was talking about testosterone levels in men and that men do not necessarily have to lose their testosterone. Testosterone levels don’t necessarily decline for men. What happens is SHBG, sex hormone-binding globulin, might go up.

Dr. Susan Hardwick-Smith 7:07

Women

Dr. Gabrielle Lyon 7:08

go through menopause.

Dr. Susan Hardwick-Smith 7:10

Yes.

Dr. Gabrielle Lyon 7:10

It’s like Christmas, Tax Day, it’s coming, God willing. Right. Happens to

Dr. Susan Hardwick-Smith 7:15

everyone.

Dr. Gabrielle Lyon 7:16

Happens to everyone. And that those female hormones—again, I think that that’s fair to say. Is it fair to say that they’re female hormones? No, because men also have estrogen, but the estrogen, progesterone, those decline.

Dr. Susan Hardwick-Smith 7:33

Yes. So when we go through menopause, which we all know now is the definition in the textbook is one year after your last period, you know, in reality, it’s just when you stop producing eggs, so our eggs run out. Now we’re not making any estradiol or any progesterone from our ovaries. Still a little bit of that’s produced in peripheral tissue, but the ovaries are done. They’re shut down. They’re not producing any of those two hormones. Now, the ovaries still make a little bit of testosterone. It’s interesting, after menopause, and a little bit from our adrenal gland and then in peripheral tissue. So we do produce a little bit of testosterone. And

Dr. Gabrielle Lyon 8:07

when you say a little bit.

Dr. Susan Hardwick-Smith 8:08

Well, so some some people say, and this is not my experience, but what I’ve read if you look it up, is that women’s testosterone drops by 50%. Somebody made this up. Okay, there’s some studies maybe supporting those numbers, but drops by 50% between age 30 and menopause. Maybe. Well, many of my patients have unmeasurably zero testosterone in their bloodstream, like I was one. So mine dropped by, one could say, 100%. Let’s just say it drops significantly and precipitously, but interestingly, testosterone often often can be measurably zero even 5 years before menopause. Mine was zero when I was 45. So it’s not exactly that it all stops at the same time. Another thing I was taught, or not taught, we just assumed, menopause your hormones all go away on the same day. Well, no, they don’t, and we know now with all this discussion about perimenopause that it’s a 5 or 10-year process of up and down and all over, but testosterone’s often the first one to drop. So many women even they’re having regular periods, maybe they’re 40, 42. So

Dr. Gabrielle Lyon 9:15

testosterone is the first hormone to drop?

Dr. Susan Hardwick-Smith 9:18

In many patients. Now, there I will say there’s enormous variability, but many of my patients, they might be still having periods, they’re perimenopausal, and they present with all kinds of low testosterone symptoms. We can talk about what those are, and And

Dr. Gabrielle Lyon 9:31

what are those?

Dr. Susan Hardwick-Smith 9:32

Well, guess what, they’re kind of similar to what men have: low sex drive, harder to have an orgasm, low energy, gaining fat around the middle, cognitive changes. Now anxiety, depression, and then also brain fog, word recall. Doesn’t that sound like what men say to you when they have low T?

Dr. Gabrielle Lyon 9:50

No. I mean, I just to be frank, the guys in my practice, they I don’t want to affect They are focused on sex. Well, also sex right That is what I hear, yes, that they cannot get an erection or their they feel like they just don’t have what it takes anymore.

Dr. Susan Hardwick-Smith 10:09

Well, yes, and that’s also that’s on the list: so low sex drive and then we you know, women don’t have a visible erectile dysfunction, but lack of blood flow to the clitoris, it actually is a similar mechanism, so women often tell me you know, we talk about testosterone in the context of sex drive all the time, okay, and we can talk about that, but all aspects of sexual function. So it’s harder to have an orgasm. I’m almost there and then it disappears. That sounds like ED to me, right? Or I can’t perform, you know, similar.

Dr. Gabrielle Lyon 10:39

That’s interesting. That’s right, cuz women do get erections. Right,

Dr. Susan Hardwick-Smith 10:41

you just can’t see it,

Speaker 1 10:42

but

Dr. Susan Hardwick-Smith 10:43

but the guy who’s saying, I’m losing my erection, I can’t perform, I’m feeling less virile, all that, very similar. Now, I I know I love Stacy Sims, who says that we’re not little men, but you know, we’re 99% genetically the same. A lot of it is similar, so that list of complaints is my male and female patients, I have a few male patients, all the same stuff,

Dr. Gabrielle Lyon 11:05

right? There was one thing that you and I had been chatting about right before we started recording. You did come in with a massive stack of papers, which is the way to my heart, and Yes. science!

Dr. Susan Hardwick-Smith 11:15

Science, because

Dr. Gabrielle Lyon 11:17

again, it’s always evolving, and especially in 2026, people believe often that we should have a lot of this stuff figured out, and it is a little bit of an embarrassment, I think, in the sciences, health sciences, that we don’t know as much as we should about females and testosterone. And I’d ask you, Why do you think that is? And you had brought up that the FDA had approved 31 testosterone products by 2020 and zero for women. You also said that this was a sequence of regulatory decisions that you can trace back to Intrinsa in 2004. Yeah. And I don’t want to spend a ton of time on it, but history seems to be very important for when we reflect on where we are today.

Dr. Susan Hardwick-Smith 12:01

It’s it’s super interesting. So people often ask, as as you’re asking, Why don’t we have an FDA approved testosterone for women? And it it it truly doesn’t make sense, although kind of does. Let’s look at this. So Procter & Gamble produced a patch for women. They called it Intrinsa. Very low dose. It was 300 micrograms a day, which is We’ll talk about dosing later, but let’s just say very low dose patch. Now in studies, the randomized controlled trials on testosterone for HSDD used a 300 microgram patch.

Dr. Gabrielle Lyon 12:34

HSDD is hypo-

Dr. Susan Hardwick-Smith 12:36

Yeah, hypoactive is also known as sex drive, right?

Dr. Gabrielle Lyon 12:38

hypoactive sexual desire disorder. Yeah, so

Dr. Susan Hardwick-Smith 12:41

there’ve been a number, at least six, probably more, randomized controlled trials done on testosterone for treatment of HSDD in postmenopausal women, all kinds of caveats. They used a 300 microgram patch. Now we don’t have that now cuz it’s not available. However, Intrinsa was a 300 microgram patch. There was a lot of data, randomized controls trials showing that it was indeed helpful for HSDD. So, Procter & Gamble pro- you know, sent it up to the FDA, and it was universally turned down. Now, this was in December of 2004, 18 months after the Women’s Health Initiative debacle had scared everybody into thinking hormones will kill you. Okay, so the I also like the psychology around this. So, I’m trying to put myself in their shoes. So, at this point in time, the climate of that time was hormones will kill you, especially women. Right. Hormones will kill women. Right. So So, it was turned down, even though there were very solid RCTs showing that it was helpful, because there was a concern about cardiovascular risk. Okay, first of all, transdermal patches are not associated with cardiovascular risk. We can talk about that, but let’s let’s look at what happened with male testosterone. Up until last year, there was a black box warning showing saying that the opinion was that testosterone for men increased cardiovascular risk. They passed that right through and just said, Well, it might give you a heart attack, but take it anyway. Now, it doesn’t. Now that it doesn’t. We know now the TRAVERSE trial, that black box warning was removed last year. But point being, in that environment, the requirement for this safe, natural hormone at a very low dose, which had been shown in many RCTs to help sex drive, had to be so perfectly safe. They wanted Procter & Gamble to go back and do five more years, which would have cost them $300 million. They just said no. We can’t afford it, so they withdrew their NDA and just went away. Now, a few years later, a gel was called LibiGel was also put up, and similar didn’t meet a favorable opinion. And that company called BioSante you’ve never heard of because they went broke.

Dr. Gabrielle Lyon 15:03

So it’s been a real uphill battle for women to get, would you say access to testosterone? Yes,

Dr. Susan Hardwick-Smith 15:10

absolutely. And and I I also also I can I can understand why big pharmaceutical companies don’t want to go down that road. I mean, it turned out very badly in the past for them, and it’s a this is a bioidentical, naturally occurring molecule, so Will you define

Dr. Gabrielle Lyon 15:27

define bioidentical? So testosterone,

Dr. Susan Hardwick-Smith 15:30

meaning if you were a chemist, it looks exactly like the testosterone that we make in our body, as opposed to some other types of anabolic steroids or other things, right? So this is just testosterone. Now, you cannot patent a naturally occurring substance, right? So that’s a problem for drug companies that want to make money, and they need to pay for their R&D, understandably. It’s an expensive process, for sure, and their studies, and you got to get the money from somewhere. So the only way it can be patented is patenting the delivery system, like a fancy patch or some kind of spray applicator or something like that. So nobody wants to do it, and and then no one’s going to pay for it. So we’re we’re somewhat stuck, and we probably will be for some time with not having an FDA-approved product.

Dr. Gabrielle Lyon 16:17

Is FDA approval necessary for women being prescribed testosterone?

Dr. Susan Hardwick-Smith 16:22

No. I jumped in and just said no, because no, it isn’t. Now, FDA approval is terrific. However, so many things we do in medicine are off-label. FDA approval is wonderful if you can get it. It indicates that there have been strong studies done and a good case for safety. Although we all know, I mean, not just testosterone, but I enjoy watching TV ads for drugs, and you see all the fine print at the bottom. These are FDA-approved drugs, but it’s like might kill you, you could go blind, da da da. The fact that an FDA approval is there doesn’t mean that something is without risk,

Dr. Gabrielle Lyon 16:59

right?

Dr. Susan Hardwick-Smith 17:00

Like it, and I love this idea that it is actually not true that Hippocrates said first, Do no harm. That was a mistranslation. Doing nothing often is really harmful. Like every drug or every intervention that has any significant benefit is potentially going to have a few side effects, so we weigh the risks and benefits. But what drug doesn’t have a few side effects? Look at the package insert.

Dr. Gabrielle Lyon 17:23

And then I think what we also have to recognize, which I know that we’re going to get to, is if you choose to do nothing, and again, there is the art of medicine, which is where off-label usage comes in, for example, testosterone, the risk of not providing a hormone that could possibly be beneficial, for example, estrogen is not FDA-approved for memory and cognition.

Dr. Susan Hardwick-Smith 17:53

Yes, or or reduction in heart disease, which which we know very well. That’s a massive reduction in heart disease. So, talking about estrogen, as you know, the the package insert only says it’s good for a few things: osteoporosis prevention, vasomotor symptoms, and genitourinary symptoms. That’s it. But we know estrogen has a 100 other benefits, similar to testosterone. So the the most of the studies done on testosterone looked at sex drive, HSDD, and yes, that was beneficial. But if they’d asked them other questions, they would have found that it was beneficial for a lot of other things. And like you mentioned, I do have a stack of studies, and there are studies showing benefit from head to toe. So I totally agree with you. Doing nothing is often very harmful.

Dr. Gabrielle Lyon 18:42

And what is, if you were to give your top three surprising facts of how testosterone specifically benefits women, what would they be?

Dr. Susan Hardwick-Smith 18:53

So, let me give it a good try. So, I’m just going to go from top to bottom of the human body. Yeah, the big

Dr. Gabrielle Lyon 18:59

ones, you know. Yeah.

Dr. Susan Hardwick-Smith 18:59

So, I was surprised about this. So, let’s just say we all know that it improves sex drive. Actually, testosterone improves all the functions of our sexual cycle: blood flow to the clitoris, easier to have an orgasm. So, I was surprised, and there’s this fantastic study that our friend Louise Newson published in 2024 about the cognitive benefits of testosterone. Now, I knew that because that happened to me when I started testosterone, and my patients tell me the same thing. They use words like optimism, motivation, I feel like myself again. Yes, I want to have sex, but I also want to play pickleball, I want to go out to dinner, I feel like I want to engage with the world. So, cognitive benefits, so reduction in anxiety, depression, and then other things like memory, recall, brain fog, so brain stuff. Okay, on a related note, there’s some really interesting studies. This is just from like last year, looking at patients with Alzheimer’s or specifically with APOE4, endogenous levels of testosterone, when they’re lower, that means what you make in your own body, is associated with a higher incidence of Alzheimer’s and worse testing if you do have Alzheimer’s. So, brain stuff, all right, that’s one. Coming on down, breast cancer. Very much looks like testosterone reduces the incidence of breast cancer. Now, we can’t say that with certainty, but that nothing in There’s not a piece of data showing that it increases it, and a lot of data pointing to it might decrease the incidence of breast cancer. So, that’s exciting. And then, okay, you love bones and muscle, so do I. Undisputable and kind of obvious that testosterone reduces muscle loss, improves the ability to gain muscle, great for bone health. This was a fun one I just read this weekend: osteoarthritis is improved. I mean, everything is improved, I’ll just say, and nothing gets worse if I’m going to put a big caveat: if it’s dosed appropriately. It’s safe, and we can talk about how we know it’s safe. Benefits are massive. The downside is pretty much nothing if it’s dosed properly.

Dr. Gabrielle Lyon 21:10

Do we know the mechanism of action in terms of osteoarthritis, things of that nature?

Dr. Susan Hardwick-Smith 21:19

Yeah, maybe. I don’t know if we know anything. Like, I’m always hesitant to say I know anything, but the theory about that one that was interesting is that, similar to estrogen being helpful for plantar fasciitis and frozen shoulder, these bioidentical hormones have massive anti-inflammatory properties. Right? So, that might Yeah, so that might be the mechanism. Point being, it doesn’t cause problems and it potentially has a lot of benefits. So then I’m going back to why don’t we consider using it?

Dr. Gabrielle Lyon 21:50

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Dr. Susan Hardwick-Smith 23:51

all.

Dr. Gabrielle Lyon 23:51

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. Now, I never saw that in clinical practice.

Dr. Susan Hardwick-Smith 24:10

Well, we don’t see that in my office, but, you know, 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. Let me jump forward to a bunch of data that we have about what happens with high doses of testosterone, like too high. And that’s Can we

Dr. Gabrielle Lyon 24:57

define what the landscape is in terms of low, medium, and high doses of testosterone for women?

Dr. Susan Hardwick-Smith 25:05

Yeah, tricky. Okay, cuz it depends Oh, well, depends on a lot of things, cuz 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, in the stuff that I didn’t know. Took me years before I thought to myself, and this was in the terms of estrogen. So 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 .05 I’m going to use easy math, multiples of 10. .05 mg 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 .05,

Dr. Gabrielle Lyon 26:07

Meaning the metrics of the dosing. The dose.

Dr. Susan Hardwick-Smith 26:10

So if you look at the dose, if you’re using say, Divigel, you’ll be getting either .5, that’s 10 times higher, or 1 mg. Put it on your arm. Okay, 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. That is a wild guess! Yes, cuz 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. Now, 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 Testim. Well, they’re just testosterone. You think they’d be the same. The difference between them, and these are this is why it’s so interesting about FDA approval, two different FDA-approved testosterone gels for men, just testosterone, vastly different blood levels. Testim 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? It isn’t, and 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.

Dr. Gabrielle Lyon 28:55

What are the delivery methods for testosterone in women?

Dr. Susan Hardwick-Smith 29:00

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 their what they agreed on, and then they published this thing.

Dr. Gabrielle Lyon 29:29

What was it called?

Dr. Susan Hardwick-Smith 29:30

It’s The International Consensus for the Use of Testosterone in Women. It was published

Dr. Gabrielle Lyon 29:34

2019, The Journal of Clinical Endocrinology. Yes, and so Davis was the lead. That’s right.

Dr. Susan Hardwick-Smith 29:38

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 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.

Dr. Gabrielle Lyon 30:07

And we’ll post it. We’ll

Dr. Susan Hardwick-Smith 30:09

Yeah, and also it was seven years ago. Okay, so what 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, it’s something like 50 to 70 nanograms per deciliter.

Dr. Gabrielle Lyon 30:40

And you brought one of those gels, did you bring one of those gels?

Dr. Susan Hardwick-Smith 30:43

I have I do. I have a so here’s here’s a suggestion. So you can 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 mg 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. It’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 just really getting rid of this idea that that is somehow going to end up with stability. And in the consensus, they 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 postmenopausal women who have issues with sex drive, no other things, which has really limited us to be If I’m If I was a young physician looking at this, I’d be like, I can’t do that. That’s too hard.

Dr. Gabrielle Lyon 32:07

Mean in terms of dosing appropriately for women?

Dr. Susan Hardwick-Smith 32:11

Okay. I’m just saying you can’t do that. You cannot get male gel, divide it by 10, and get to physiologic levels. I did the study. The levels are all over the place, as they are in men. So the studies on men show the same thing. Gel does not get to stable levels. Now, interestingly, that consensus said use male gel cuz we didn’t have any other thing. All the studies were actually done on a 300 mcg patch. So a 300 mcg patch is going to give much more stable levels, just like an estradiol patch cuz it’s stuck to your tissue. You’re not losing it all over the place. So, there 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 ISSWSH, our organization, the International Society for the 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. And

Dr. Gabrielle Lyon 33:07

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

Dr. Susan Hardwick-Smith 33:22

you

Dr. Gabrielle Lyon 33:23

see your colleagues. How are they? Are they using the gel because of this consensus statement?

Dr. Susan Hardwick-Smith 33:29

Yes, Yes. So if you are someone who is your average physician and and you do a lot of things and testosterone isn’t like your bane 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 we’re getting painted into a corner. Do not use a compounding pharmacy. Okay,

Dr. Gabrielle Lyon 33:56

Is that what Okay.

Dr. Susan Hardwick-Smith 33:57

said that. It 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 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.

Dr. Gabrielle Lyon 34:31

And stable levels, and I’m 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. Yes. 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, Mhm. you want to continue to see that, as opposed to maybe it’s 0.35, and then it goes to five. Do you- Is that what you mean? Well, so

Dr. Susan Hardwick-Smith 35:03

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? So that’s one thing. And then how much variability is there around that range? So our study on gel, and we use a very conservative protocol, because I, you know, I really was wanting to do everything I could to make gel look good, let’s just say, and it just didn’t. Using five milligrams a day, which is the lower of the recommended doses in Australia, where it’s government-approved, 5 to 10 mg 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 appropriately dosed pellet, which I can talk to you about that, or 5 mg of gel, and then we measured it six weeks later. The gel patients, this is a low dose, okay? They Their average total testosterone was 132 Now,

Dr. Gabrielle Lyon 36:01

per deciliter.

Dr. Susan Hardwick-Smith 36:02

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 it it’s not going to be perfect, and 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 at 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 nother line of conversation about blood levels don’t really reflect what’s going on in your tissue.

Dr. Gabrielle Lyon 36:58

And then what about safety? One of the things that clinicians are often concerned about is safety. They’re concerned about hemoglobin hematocrit, with again, erythrocytosis, they are concerned about lipids,

Dr. Susan Hardwick-Smith 37:14

cancer, death, heart attack. Yeah, super important. Well, you know, a fantastic bunch of literature we have about that is from the transgender community.

Dr. Gabrielle Lyon 37:23

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Dr. Susan Hardwick-Smith 39:16

Yeah, so this is a great population to study because if you, as I do, we all have a concern, okay, is this safe, is 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 giving given transgender men very, very high doses of testosterone. Here’s the bottom line: nothing bad happened, no increased risk of death from anything, improvement in muscle mass, obviously, and 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 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 high doses. What about the

Dr. Gabrielle Lyon 40:42

effect on, is there a an effect on the lipid profile? If you

Dr. Susan Hardwick-Smith 40:46

take it orally, yes. So just like all the things we’ve learned, right? Now, not counting Kyzatrex, it has a different pathway, but the old 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. So if you took these 50 years of transgender patients and gave them way massive doses of testosterone, they didn’t have heart attacks.

Dr. Gabrielle Lyon 41:27

And this is, and I’m looking here at this data here, it says that the typical starting dose is 50 mg subQ weekly for someone who is transitioning. 50 mg,

Dr. Susan Hardwick-Smith 41:37

yeah,

Dr. Gabrielle Lyon 41:38

subQ weekly.

Dr. Susan Hardwick-Smith 41:40

And so, I don’t take care of a lot of men, but men I know sort of 50, 100, even up to 300, so 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 whatever people’s opinions are about pellets, Gary Donovitz, who was the founder of BioTE 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 and I think we can just put the safety question to rest. It’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

Dr. Gabrielle Lyon 42:59

Oh, nuisance side Yeah, like it’s a nuisance. Yeah, so it won’t kill you, right?

Dr. Susan Hardwick-Smith 43:02

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 8 years.

Dr. Gabrielle Lyon 43:21

How was How What was the delivery mechanism?

Dr. Susan Hardwick-Smith 43:23

Pellet, very high dose. Okay, so dose is the poison. Again, her blood levels were 800. Now, that did not happen overnight. It took 8 years. So I never blame the patient. However, I said, Why did you keep going back? And 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.

Dr. Gabrielle Lyon 44:12

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?

Dr. Susan Hardwick-Smith 44:46

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, or typical Labcorp, whatever lab, for someone my age, if you look at the reference range, it might say something like normal testosterone is 0 to 30, 40, something like that. It’ll it’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 best, now 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. It can pick up things that are not there. It’s not as accurate as we think. This other type of testing called LC-MS. What is

Dr. Gabrielle Lyon 46:22

the error rate on ELISA? So as someone is listening to this, what I really want to get out of, or what I want listeners or viewers to 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 control 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, and my free testosterone shows 0, 0.0. Well, let’s talk

Dr. Susan Hardwick-Smith 47:26

about free testosterone. All right. So in this consensus, and I want to go back to the ELISA versus LC-MS because we did a study on that, too. So let’s just, for your listeners, say there’s 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 2 hours, and I get different numbers because of You did? Yes, we did all We do all kinds of fun stuff in the office. It’s not the same all day. The The lab’s machine is different at different times. It’s a guideline, right? And so we need to look at the lab value as a guideline. That’s really

Dr. Gabrielle Lyon 48:08

tricky. I think that that’s really tricky for physicians and also patients, because trust is important. Yeah. And if they’re looking at their their level, if a 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 I love this about you, yes. Yeah, so so you

Dr. Susan Hardwick-Smith 48:35

go If you went into I’m sure you’ve done this, because you did a bunch of bench 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. And then, not to mention, your own blood level changes during the day. But just 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. So, 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. It’s a calculation. So, the the recommendation is don’t look at free testosterone, because it’s not that 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. So, for for those who are not if you’re somewhat a beginner as a patient or a doctor, I just look at total. Look at total, maybe just eyeball the SHBG. But the fact is the number is so not that important because that, you know, we were trained at 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 polymorphisms 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, so 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

Dr. Gabrielle Lyon 51:11

life.

Dr. Susan Hardwick-Smith 51:11

Right, you’re doing great, because it’s safe, you feel well. What is the problem?

Dr. Gabrielle Lyon 51:16

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 low, which 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 that. Rolls off the tongue.

Dr. Susan Hardwick-Smith 51:59

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 LC-MS was, like, dramatically more accurate than ELISA? And now, ELISA’s 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 LC-MS, 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 6 nanograms per deciliter, a tiny bit higher, not clinically significant. In 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, ultrasensitive everything, it’s not going to change your management. It

Dr. Gabrielle Lyon 53:00

doesn’t change the management. It doesn’t.

Dr. Susan Hardwick-Smith 53:01

So clinically, you know, I get it from a scientific point of view, yes, LC-MS is probably more accurate. I would just say probably because how do you know? Like, how do if you how do you know what the truth is, and which one’s closer? What about salivary? People

Dr. Gabrielle Lyon 53:14

will talk about

Dr. Susan Hardwick-Smith 53:15

salivary testing. Yes, way less data on that. That that’s not been studied by any in any good resource to be better than anything. I I get the point. I mean the idea is that what’s in your saliva is is free from protein binding, but just not clinically useful, and very very confusing, and expensive. Yes. So, again, because the level is not particularly important, it isn’t, because I have some patients Now, I I use 50 in my office. If if you’re coming in and drawing your blood, and And you

Dr. Gabrielle Lyon 53:48

don’t check free testosterone? You check total? Well,

Dr. Susan Hardwick-Smith 53:51

We do.

Dr. Gabrielle Lyon 53:52

You You do, okay. Okay, because you’re doing studies. Because we’re doing studies. But, we’re we’re

Dr. Susan Hardwick-Smith 53:55

really doing it for research purposes, not for does not change clinical management. Because what’s your free testosterone supposed to be? Well,

Dr. Gabrielle Lyon 54:02

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 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, I 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, again, it’s kind of this back and forth, even if there’s plausibility that a testosterone above 1000 is perfectly fine.

Dr. Susan Hardwick-Smith 54:44

Yeah.

Dr. Gabrielle Lyon 54:44

But, I I don’t know.

Dr. Susan Hardwick-Smith 54:46

Yeah, so there So, 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 a 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. Let’s go back to that. That is a miniscule 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

Dr. Gabrielle Lyon 55:46

talk about that? Because tachyphylaxis, I 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, or you’re even starting to see it with GLP-1s,

Dr. Susan Hardwick-Smith 56:02

Right, you don’t don’t feel it anymore.

Dr. Gabrielle Lyon 56:04

You do not feel it anymore. Can you touch on tachyphylaxis, please?

Dr. Susan Hardwick-Smith 56:08

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. Many of our patients say this. Like the first two to four weeks, they’re like, Oh my god, I feel amazing. I’m having sex dreams. 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.

Dr. Gabrielle Lyon 57:03

downregulate, and that’s exactly what we see. Is

Dr. Susan Hardwick-Smith 57:06

Yeah.

Dr. Gabrielle Lyon 57:06

that 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 mg 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 next. They’re sort of chasing a high, yeah. They’re chasing a high. Right. Yeah.

Dr. Susan Hardwick-Smith 57:30

So I I I tell my patients this. It 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, they 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. And 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? And watch out for these effects, which are nuisance side effects, easily reversible. If they do happen, you get some a 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 I if 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 aesthetician, skin’s a little oilier, but I’d like to take care of that with some products. Carry on. It’s it’s why are we being so paternalistic about telling women you can’t do that? In 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.

Dr. Gabrielle Lyon 59:13

We all remember what a freshly cleaned room smells like: straight chemicals, you know? 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. 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 the 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 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. 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 DR LYON at branchbasics.com. That code is DR LYON 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?

Dr. Susan Hardwick-Smith 1:01:06

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’re actually FDA-approved for men. So pellets are a fantastic delivery method. Testopel, FDA-approved for men since the 1970s, been around forever. Doesn’t come in doses appropriate for women, it’s just one dose. So, And what is that dose? 75 mg. So, men would typically get, you know, 8 to 10 of them. Now, a woman could get one, possibly. I’ll tell you about how we dose it, that I I get 50 mg, 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 the pel- the Testopel does.

Dr. Gabrielle Lyon 1:01:53

And what is that the brand name?

Dr. Susan Hardwick-Smith 1:01:55

Testopel, yeah, so Yeah, so it’s great, and a lot of guys like it. You put them in and then they’re good to go for

Dr. Gabrielle Lyon 1:02:02

Testopel. 5

Dr. Susan Hardwick-Smith 1:02:03

months. I don’t use them, but our friend Mo Carrera 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? Now, pellets got associated with some, ah, a bit shady kind of behavior, and I

Dr. Gabrielle Lyon 1:02:27

What do you What do you mean?

Dr. Susan Hardwick-Smith 1:02:28

Well, so back in 2011, and a company called BioTE, which is not a bad company, but and I think they really were doing some groundbreaking work in 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. That 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

Dr. Gabrielle Lyon 1:03:16

I agree that, you know, before I met Mo, I was one of those providers that I thought that too. pellets were cuz

Dr. Susan Hardwick-Smith 1:03:24

irresponsible and were

Dr. Gabrielle Lyon 1:03:25

seeing patients with significant side effects women.

Dr. Susan Hardwick-Smith 1:03:29

like like like the one that I mentioned. So, yes. So, going back to the dose is the poison, yes, that that dosing regimen was unarguably too high, and doctors and other clinicians were using it who had no understanding of endocrinology and didn’t, you know, 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. We have a different dose And

Dr. Gabrielle Lyon 1:04:00

know there will not be a show and tell. Well, cuz you can’t

Dr. Susan Hardwick-Smith 1:04:02

see it. I’d be happy to. You can’t see it. The size of a piece of long grain rice. A

Dr. Gabrielle Lyon 1:04:07

3.2 millimeter in diameter, right?

Dr. Susan Hardwick-Smith 1:04:11

Tiny, tiny, tiny. Look like a piece of jasmine rice, all right? So, it lasts for three months. So for me, that’s a great choice. I 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 this 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.

Dr. Gabrielle Lyon 1:04:35

I see.

Dr. Susan Hardwick-Smith 1:04:36

Versus in the BioTE program, it would be 300 or higher. And actually, they train 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 we source ours now from a company called FarmaKeio in Dallas. Actually, a lot of the scientists from BioTE 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 a different dosing regimen, and 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, 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’s 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.

Dr. Gabrielle Lyon 1:05:51

The absorption kinetics, which basically we started out by talking about delivery systems of testosterone for women.

Dr. Susan Hardwick-Smith 1:06:01

Mhm.

Dr. Gabrielle Lyon 1:06:02

There is gel and cream.

Dr. Susan Hardwick-Smith 1:06:05

Yes.

Dr. Gabrielle Lyon 1:06:06

People can get compounded cream, right, at their wherever they go to get their hormones, hormones, injection,

Dr. Susan Hardwick-Smith 1:06:17

Yes.

Dr. Gabrielle Lyon 1:06:18

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 cypionate?

Dr. Susan Hardwick-Smith 1:06:33

Well, other than injection, these others are just testosterone. So the enanthate, cypionate would be in an injection. Does not matter. So again, this is interesting. I didn’t know this either. I have heard some influencers say, Oh, that’s not bioidentical testosterone, so therefore it’s bad. Actually, the cypionate or the the molecule is cleaved off, so it it does appear as testosterone in your bloodstream. So if you measure your blood after a T cypionate injection, you will see elevation of testosterone, cuz the cypionate’s been cleaved off. So it’s just it’s that’s absolutely fine. They’re all fine. Get it any way that you want to. So I 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 we give 10 times less than the male dose. So instead of starting at 50 a week, we’d start at 5 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 1. Now 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.

Dr. Gabrielle Lyon 1:08:14

That 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 I’ve no idea how anyone would be able to dose it, and they want to switch. Is there comparable conversions?

Dr. Susan Hardwick-Smith 1:08:52

Kinda. 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. So let me tell you about me. I could use 5 mg a day of gel, so think about this. I’ll try to do easy math. Now, I have a 50 mg pellet in my bottom, which is going to last approximately 100 days. Of course, 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 10:1, 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 of the gel you absorb. It’s fairly reliable how much of a pellet or injection you’ll absorb because it’s in your body. You’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 mg to one person and another, and they’ll have a vastly different response. So, you have to follow patients. So, if you’re going to a 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. If you’re on any kind of hormones, we check twice a year because labs are available, why not? We want to take the best care of our patients and make sure that everything’s optimal. And then I- 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.

Dr. Gabrielle Lyon 1:10:35

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 au naturel. Can they take action to mitigate that decline in testosterone?

Dr. Susan Hardwick-Smith 1:10:52

I wish we could. I tried, actually. When I was- it was funny, when I was in my mid-40s 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 was- I do yoga. I do meditation. I’m like, I can get through this and green juice myself through it. I think a lot

Dr. Gabrielle Lyon 1:11:14

of women say that.

Dr. Susan Hardwick-Smith 1:11:15

Yeah, I tried. You can’t. You You cannot use your mind to elevate your hormones. I tried. I like really tried. It didn’t work. They was 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 6 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.

Dr. Gabrielle Lyon 1:11:42

You know, when you look at the literature, there is no supplement or nutrition that, again, that I have 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, at the highest, the highest dose I could

Dr. Susan Hardwick-Smith 1:12:10

get. I’m like let me go to GNC and see. I think I did take 100 milligrams. So, with 100 milligrams of DHEA for 6 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 there you cannot get enough to improve any symptoms, particularly HSDD or sex drive. It 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.

Dr. Gabrielle Lyon 1:12:42

I think it’s an important point because 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 5 years pass, they’re still waiting to feel better, and they don’t even remember what feeling good is like.

Dr. Susan Hardwick-Smith 1:13:18

Well, with this particular hormone, I think then I won’t, I can’t pick my favorite. Honestly, estradiol is freaking amazing, like 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 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 I will 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

Dr. Gabrielle Lyon 1:14:07

this show, people bring all kinds of things to the show.

Dr. Susan Hardwick-Smith 1:14:10

We Right. I know. I I loved Amy

Dr. Gabrielle Lyon 1:14:13

Pearlman’s Amy Pearlman’s

Dr. Susan Hardwick-Smith 1:14:14

bag of Tricks. tricks. When I look at buckets of health, and people often say, Oh, nutrition, movement, sleep. I add fun to that and sex. Like, what why having a good time when we’re older, enjoying ourselves, and part of that is physical intimacy and play. And here here’s another point that I love. I wish I could go back and do these studies again. All of these randomized controlled trials, and I mentioned there’s at least six good ones, probably some smaller ones as well, that randomize patients to testosterone patch, which we don’t have anymore, versus placebo, and then they asked them in these standardized questionnaires questions about sex drive, because, you know, 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 I feel better. So, my patients say, Yes, my sex drive is better, but my all of my drive is 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. I 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.

Dr. Gabrielle Lyon 1:15:51

You I know that you also have a book that is coming out, which we’ll have you back in to on to talk about, which is Create Her. Is that link available for us now, or is there That is.

Dr. Susan Hardwick-Smith 1:16:02

So, there is a pre-order link. We’ll put that there. Not coming out till February, but It’s okay. We’re going to put it

Dr. Gabrielle Lyon 1:16:07

1. 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, what am I going to do now? No amount of exercise and training Listen, maybe training will definitely improve muscle mass,

Dr. Susan Hardwick-Smith 1:16:37

maybe

Dr. Gabrielle Lyon 1:16:37

it improves short-term increase in testosterone, but the reality is we will have a decline in hormones. It’s 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? That this is

Dr. Susan Hardwick-Smith 1:17:01

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. So 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

Dr. Gabrielle Lyon 1:17:18

And where does the other 50 come from?

Dr. Susan Hardwick-Smith 1:17:19

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 use, 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 We need Yes, 21-year-olds, and I was one on the pill. My sex drive was great. My testosterone was probably zero. So that points to the It 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.

Dr. Gabrielle Lyon 1:18:05

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 PCOS.

Dr. Susan Hardwick-Smith 1:18:19

Yeah, so the androgen-blocking drugs like spironolactone or finasteride is going to potentially limit how much testosterone’s 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 it blocks it altogether. That patient might need a little bit more to overcome that barrier. So these are the nuances where we can sort of say, I also have patients on birth control pills who use testosterone, 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 LC-MS 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 see what’s happening. See how people are feeling. Use some of these standardized questionnaires before and after treatment, and you will see dramatic improvements in their well-being.

Dr. Gabrielle Lyon 1:19:28

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?

Dr. Susan Hardwick-Smith 1:19:49

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. You know, 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. So, let’s move away from this consensus that’s so restrictive, and be a bit more creative, you know, within safe boundaries. And the people that are saying that gel is the only way, you know, there it’s not. And dose pellets appropriately, 0.8 to 1 mg/kg. 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 great.

Dr. Gabrielle Lyon 1:20:37

And also potentially have a long athletic career as you have done. Is it 44 long, I I’m sorry, nine full-distance Ironman races and

Dr. Susan Hardwick-Smith 1:20:53

35 half, yeah. I know that’s an embarrassing number, but since you asked me. Yes, we can do hard things and 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. It makes you perform better. What is wrong with that? I’m not in the Olympics. Give me some.

Dr. Gabrielle Lyon 1:21:26

But you could be. Maybe. I’d have to stop

Dr. Susan Hardwick-Smith 1:21:30

taking testosterone, though. So,

Dr. Gabrielle Lyon 1:21:31

Dr. Susan, thank you for all that you are doing and not making testosterone just the male hormone.

Dr. Susan Hardwick-Smith 1:21:37

It’s not. Well, I’m delighted to be