← Keeping It Real: Conversations with Jillian Michaels
Keeping It Real: Conversations with Jillian Michaels
HRT: Unveiling It’s Life Changing Health & Wellness Benefits w/ Peter Attia
01:10:22
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- [00:02]
A
None of this you learn in medical school. So everything we're talking about is not learned in Medical School.
- [00:06]
B
Dr. Peter T. Is back. He is a Stanford John Hopkins, NIH trained physician who focuses the applied sense of longevity with everything he does.
- [00:16]
A
If you go and see somebody and they have their own pharmacy, that's a red flag.
- [00:20]
B
Whether it's his podcast, the Drive and or his book Outlive, which has become a bible for me and. And he joins me today to talk about all things hormone replacement therapy for women.
- [00:34]
A
I gotta make you 14 again, and I'm gonna give you, like, enough estrogen to kill a small pony.
- [00:42]
B
You will get no greater expert on this subject matter to guide you in conversations with your doctor and empower you to take control of your health.
- [00:50]
A
Once a woman hits about 20 or 25, I mean, time to go.
- [00:54]
B
Time to start keeping it real with Jillian Michaels. Peter, I think this is the first time I've addressed you as Peter for your request in our third podcast together. Thank you for coming back.
- [01:08]
A
Thank you for having me.
- [01:10]
B
You're an absolute men. She must want to die. Every time I get a hold of you, I don't let you go. I'm going to do my best to keep this one as concise as possible, but selfishly, I have wanted to pick your brain forever about this. And when I first learned about you, you would think it was like project that you did with Thor, your book, which obviously I'm obsessed with and bought. Which camera am I in here? Outlive. That said, I believe I saw you first on a podcast saying that the Women's Health Initiative study about hormone replacement therapy for women was arguably the most botched study in medical history. And for years I had thought of HRT as just the most deadly and dangerous thing because of that. And I was like, wait, who the is this guy? And I was riveted. And subsequently, I began to obviously learn more about you and become a devotee and worship at the altar. That said, women ask me now these questions about hrt. And while I have some understanding, thanks to you, you are the doctor, the guy. And I wanted to do a show that is essentially a bible for women to educate and empower themselves on what there is to know about this. So my first question just generally is, what is hrt? Is it an anti aging protocol or is it a therapeutic treatment for menopause? And to be dead honest with you, I actually don't know.
- [02:56]
A
You know, it could be thought of as a bit of a semantic question. Right. So it is clearly a Treatment for women going through a transitionary period of their life when their hormones go away, when their natural production of two hormones, but really a third, if we include testosterone but estrogen and progesterone, when the natural decline of those hormones occurs, how can we replace them with hormones given exogenously, which is just a fancy word for given outside the body. From outside the body. Okay, so that's really what it is now. What does it mean to be anti aging? I'm not really sure what that language means, but yeah, you could probably make a case by the end of this podcast that we will have argued that things that occur when a woman ages that are not desirable are slowed. There's no doubt that that's true. So if that makes it an anti aging protocol, so be it. The way I think about HRT is what does it do to improve things that you feel that are getting bad? So I always break things down into things you feel that are bad and things that you don't feel that are bad. And how does it impact both of those? That that might be the easiest way to think about them. So, not surprisingly, maybe we should start with the things that you feel. So it always seems a bit weird when I talk about this because I'm not a woman and I'm not going to go through menopause. And so in that sense it feels like, well, yeah, so, but, but yes, what I'm saying, I guess just to preface this, everything I'm talking about is sort of based on an obsession with this literature over the past decade and treating women. Right. So, you know, just hopefully folks don't come at this thing. What the hell does he know? He's never been through menopause. That's true.
- [04:39]
B
He was like, doctor, I think we're good. You're good here.
- [04:43]
A
Well, but that is your medical degree, I think, covers you, but none of this, you learn in medical school. So everything we're talking about is not learned in medical school. Because remember when I went through medical school more than 25 years ago, that was, first of all, this just wasn't something that was taught. But secondly, as soon as I finished medical school, the Women's Health Initiative, which we will probably talk about, was published. And it basically, I think what I probably said was something to the effect of, it's not just that the Women's Health Initiative was a lousy study. It was interpreted in an abhorrent way and the media was incredibly culpable in failing to hold this horrible reporting of the study to any standard. And what it did, was created a lost generation of women. Right. These women who were born in, you know, basically the late 40s and early 50s and into the late 50s, frankly, who were just completely deprived of HRT. So call it kind of late 40s to mid-60s. That demographic of women have, have largely been screwed horribly by this because they were sort of thrust into. Well, you're just going to go through menopause and there's nothing we can do about it. And that includes the symptoms that we'll talk about, but also these things we can't feel.
- [05:59]
B
Okay, hold on. And you're right. I wanna, I apologize to interrupt you. I must admit a bias and please club me over the head. Just go for it. I want, I need to, you know, give me the perspective of my position will be. Well, we've been doing this for thousands of years. This is ridiculous. Peter. Why do I need drugs?
- [06:20]
A
No, no, Great, great, great question. So we have to understand that things that we've been doing for a thousand years, and it's really 250,000 years, that's how long our species has been around that whole period of time from 250,000 years ago until 100 years ago or 150 years ago when modern medicine showed up. The, the whole purpose of evolution was optimizing for your reproduction. It didn't care if you lived past 40. Yeah, right. It wasn't optimizing for that. Once you produced your offspring and once you transmitted your genetic material evolution, Mother Nature, Darwin had no use for you. So while it's true that women, if they managed to live long enough 50,000 years ago, would have suffered miserably, I would argue they were suffering pretty miserably for a whole bunch of other reasons like the tigers, the lions, the infections, you know, all of the other stuff that is just generally pretty miserable. Menopause was probably the least of their worries there.
- [07:22]
B
You know, the marauding, you know, hordes and. Yes, okay, yeah. The raping, villaging and plundering drugs, those.
- [07:30]
A
Things must have been a little worse than the menopause. You know, it's these goddamn night sweats. Just can't handle this. Yeah, not, not the problem. So. But we're lucky now, right? So in the, in the, in the latter part.
- [07:44]
B
Thank you for the perspective.
- [07:45]
A
Okay. In the latter part of the, of the 19th century and the early part of the 20th century, we, we, we emerged form from the swamp of hell. It was our existence for a quarter of a million years and largely on the basis of sanitation, antimicrobial agents, the development of the light microscope and processes for allowing women to give birth without killing themselves and their babies. We can't ever forget how devastating that used to be. We all of a sudden got to the point where we can live to 80 years old now. And now we have the luxury of worrying about heart disease, cancer, atherosclerosis, pardon me, you know, Alzheimer's disease, osteopenia, osteoporosis. We have the luxury of asking the question, should a woman in her 50s and 60s still enjoy sex? Should she be deprived? You know, should she not have to have night sweats? Should she not have to have brain fog? So again, this is just the luxury we find ourselves in because we solved all of those other problems.
- [08:44]
B
That makes perfect sense. Okay, so back to the symptoms that you, you recognize. And then the things wrong you don't recognize. The symptoms you recognize. We covered. Right. Am I missing anything?
- [08:53]
A
Yeah, the big ones are typically the first things that occur are what are called vasomotor symptoms. These are night sweats and hot flashes, and those are resulting from the reduction in estrogen. So maybe we just take a step back and talk about how the whole hormone situation works in women.
- [09:09]
B
Got it.
- [09:10]
A
Yes, please. So women, um, the, the. We talked about this on a previous podcast, which was that testosterone is still more abundant in women than estrogen, but estrogen is kind of the defining hormone.
- [09:25]
B
Are there three forms of estrogen?
- [09:28]
A
Yes, there's estrone.
- [09:30]
B
Okay.
- [09:31]
A
Estradiol and estriol.
- [09:35]
B
What's the difference? And does it even matter?
- [09:37]
A
It matters a little bit, maybe. For the purpose of this discussion, I would say leave it rolling. Yeah, Estradiol is the dominant one.
- [09:44]
B
Gotch.
- [09:46]
A
Maybe when we talk about sort of edge cases of hormone replacement therapy, we can talk about the use of estriol. But I think for the purpose of this discussion, women should understand that estradiol is the dominant form of estrogen. And just like we talked about with men, when the gonadotropin releasing hormone from the hypothalamus tells the pituitary to make follicle stimulating hormone and luteinizing hormone, the ovaries make more estrogen. And this is a cycle that occurs. Now, what's really interesting.
- [10:19]
B
And progesterone.
- [10:20]
A
Yep, progesterone. So. So I think the easiest way to kind of picture this, and I did a video on this once, and maybe we can find it and you can link to it somewhere when this podcast comes out, I can insert it. Yeah, it's like a 10 minute video where I actually walk through the Female cycle in hormones. So I show cause for women, it's much more complicated than men because in women you have a rise of follicle stimulating hormone, a fall of follicle stimulating hormone. At the end of the month, you have a luteinizing hormone spike. You have a spike of estrogen that then comes down, followed by a second spike that then comes down. And then progesterone is sort of laying dormant until the very end of the cycle when it rises to prepare for implantation. And unless you're pregnant, it then comes crashing down. And it's the crashing down of the progesterone that leads to the kind of PMS symptoms in women that are susceptible, which is also.
- [11:13]
B
Is kind of related to postpartum as well.
- [11:15]
A
Yes, sorry. And. And it's the. It. It leads to the shedding of the uterus, the lining of the endometrium that leads to the period. So when those estrogen levels are going down, the first symptoms that are going to typically show up for women are these night sweats and hot flashes. Again, those are called vas. Vasomotor symptoms. They will, in most cases go away over time. But. But the variability in how women experience those is remarkable. But I would say most women, long before they become amenorrheic, which is the technical term for when your period stops, they know it's coming because one, their period starts to get irregular. But two, they start to develop these symptoms, right? They're like, oh my God, like I woke up in a total, my sheets were soaked. Or I just get these really hot flashes. Like, if anyone's ever taken niacin or something and knows what that feels like.
- [12:08]
B
Oh my God. Is that what it feels like? Because.
- [12:10]
A
Yes, I take it that's what I'm told it feels like Again, of course not.
- [12:15]
B
Sorry.
- [12:15]
A
Yeah.
- [12:16]
B
Now that genuinely sounds awful if that's in fact.
- [12:19]
A
And then I think the other really big symptomatic component are the sexual side effects. So some of that can be loss of desire, but a lot of that ultimately becomes what's called vaginal atrophy. So that means reduced lubrication. And actually atrophy is a word for shrinkage, right? So a shrinkage of, you know, the sexual organs, basically, what is the net result of that? It generally makes sex painful and undesirable. And so there are solutions to that that do not involve hrt. They're not as effective. But you can use topical estrogen in that case to overcome both of those situations. Again, it's nowhere near as effective as Systemic estrogen, which we'll talk about, which is a part of hrt. Okay, so the third symptom that I think is not uncommon with menopause is kind of like the emotional and cognitive symptoms. And again, it's not the case that every woman will experience every one of these. You can't try to ram this sort of playbook down everyone's throat and say like this is going to happen. But, but women should be prepared to at least experience rain, fog and potentially just, you know, depressive mood. Right? So irritability, all of these sorts of things. Because, you know, it's just hard to overstate how important these hormones are. And even in ways we don't fully understand, I mean, we know we have receptors for them in our brain as well. So it's not just that estrogen and progesterone receptors are found in the reproductive organs, they're also found in the brain. And so therefore it shouldn't be that surprising that when you are losing those hormones, you're going to not just experience reproductive symptoms, you're going to experience cognitive and emotional.
- [13:57]
B
Dr. Lisa Moscone is a neuroscientist, isn't she? With the XX brain for menopause and dementia. And I was like, well, that's, that's scary as hell.
- [14:07]
A
Yeah. But okay, so now we start to get into. So, so if all of those things become the symptoms, now we get into, okay, these aren't symptoms, but these are problems. So yeah, first and foremost is bone health. This just doesn't get enough attention. So the, the probability of a person falling when they're 65 and up is about 25% that you're, you know, once you reach the age of 65, you've got about a 25% chance in your lifetime of having a fall. And somewhere between, you know, 10 to 15% of those falls could be fatal. If you break your hip or femur.
- [14:45]
B
Why is that fatal? And I don't mean to take you down a long path. Is it cause you can't get out of bed? Or like, what is the. And it's like all broke, dead, she's gone. What is that? Is.
- [14:53]
A
There's the, there's the short term reasons because the fatality stats are usually within the first year. And what's ha. So it's not just like you die.
- [15:00]
B
It'S the impact over time of how it limits your mobility and. Got it. Nevermind. I'm with you. Sorry.
- [15:05]
A
Yeah, it's like if you took a 20 year old and put them in bed for a month, they'd recover. When you take a 70 year old and put them in bed for a month, it's very difficult to recover.
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B
That's enough said.
- [15:18]
A
Yeah.
- [15:18]
B
Okay.
- [15:19]
A
So women are disproportionately at risk for falls. They're about 2x the risk because they're, they have less muscle mass, they tend to be, on average, less active, and they have weaker bones. So the reason for this is estrogen is the most important hormone in bone health. So the way bones work is they have little, for lack of a better word, strain gauges in them. So strain gauge is like. It's not an actual strain gauge. That's a term we use in engineering. But a strain gauge is something that detects deformation.
- [15:51]
B
Okay.
- [15:52]
A
So when you pick up something really heavy, your femur, your bones experience deformation. They, they're being shrunk slightly, the body through estrogen. Estrogen is the chemical signal that transmits that information, which is there is deformation to the cells that remodel and build bone. So both for men and for women, estrogen is, hands down the most important hormone in bone health. And this is why women experience a disproportionate reduction in bone strength because they have a sudden loss of estrogen. Whereas in men, the loss of estrogen is a little more gradual as they age because it falls in line with testosterone levels. In women, it's uncoupled. It falls like that. So that's sort of, I would say, reason number one from a medical disease standpoint, beyond a symptom standpoint, then you have the relationship on type 2 diabetes and heart disease and Alzheimer's disease. You referred to Lisa a moment ago.
- [17:00]
B
That one. Yeah. The Alzheimer's disease. I, I and I have the G1 Apoe 4. I'm very mindful of this one, but I. Diabetes. Why?
- [17:10]
A
Well, I don't even.
- [17:11]
B
I don't understand.
- [17:12]
A
Probably for the. Probably because estrogen and progesterone play a role in insulin sensitivity.
- [17:19]
B
They do. Oh, my God. I had. Okay.
- [17:21]
A
And that might explain why women are more likely to gain weight post menopause. But you're becoming more insulin resistant.
- [17:29]
B
Okay, again, I want to beat it.
- [17:32]
A
Yeah.
- [17:32]
B
So I don't want belly fat. Although I must admit, just a little that I, that I've noticed as I've gotten, I've gotten a bit older, but just, just a little, because I've never stored body fat there in my entire life. Unfortunately, it's like lower body and not in the great places like my ass, where I would love it to Be. But now quads, so upsetting. That said, okay, I work out now. I got muscle. I'm doing my VO2 max training like Peter told me to do. I'm doing my strength training like Peter told me to do, which I do. Like a perspective.
- [18:06]
A
All of that's going to help. All of that is going to help.
- [18:08]
B
It'll help.
- [18:08]
A
Yes, absolutely. Yeah. This is not like a one way ticket to hell, but you have to.
- [18:14]
B
Remember, slow descent into decline. It does seem like you're fucked.
- [18:18]
A
Well, sure, but that's aging, right? Like, the truth of it is that's going to happen and you've always. But we just have to say, like, but, but you know, when, when women experience this sudden drop in hormones, it is going to accelerate a trend towards type 2 diabetes. Does that mean that when a woman goes through menopause she gets type 2 diabetes? Of course not. There are plenty of women who go through menopause who don't get hormones, who don't get diabetes. So we're just talking about, we're just talking about gravitational pull.
- [18:46]
B
Understood?
- [18:46]
A
Y. Okay, okay.
- [18:48]
B
Okay.
- [18:48]
A
Cardiovascular disease. There have been mixed results on these studies, but what I think we can conclude based on the best available, best available evidence today, is that estrogen is protective from future cardiovascular events, doesn't really reverse any cardiovascular disease that is already present. And, and this is where it gets super nuanced and painful. There seems to be a significant difference between if you initiate estrogen during the perimenopausal period, which is when we should be doing it, versus if we start estrogen in a woman a decade or more after menopause. So this is a big part of the injustice of this entire discussion we're having. There's going to be a woman who's listening to us, who's 70 years old, whose bones are brittle, who's at risk for heart disease and maybe dementia, who was part of this lost generation of women who was deprived of HRT 20 years ago when she should have got it in 2004, and she's gonna say, well, sign me up for that. And there is no doctor. I mean, there are some, but there are very few doctors that would be willing to give her estrogen because her quote, unquote window is closed.
- [20:04]
B
Windows closed, meaning the hope of benefits are gone. The bones are already brittle.
- [20:10]
A
No, it's not even so much that people, because we have such a paucity of data for what happens when you initiate HRT that far out, that there is enough concern on the part of doctors to say I'm worried that if I start HRT on you now, there's a risk I'm going to actually make some things worse in you. I'm going to increase your risk of dementia. So.
- [20:35]
B
Okay, so are we leading ourselves into this botched Women's Health Initiative study, then? Because I feel like you had said the women in the study were already botched past the window.
- [20:44]
A
That's right.
- [20:45]
B
Okay, so. So I want to back up for one second and establish what I had thought until you. Oh, my God. Blood clots.
- [20:52]
A
Right?
- [20:52]
B
We're having blood clots.
- [20:53]
A
And there's some truth to that. Oral estradiol does slightly increase the risk of blood clots. Now, I don't know the last time I gave a woman oral estradiol because it's a lousy way to deliver that hormone. It should be given topically. It should be given in a patch. You can give it in a pellet. So there are lots of ways that you can give a woman estrogen that don't involve a pill and that don't have any of those increases in risk. But it is true that estradiol taken as a pill will slightly. It's not a huge increase, but it's. It is. It's a slight increase.
- [21:23]
B
Okay. But it's avoidable, so just don't. Right, well, we'll talk a bit more about that when we talk about the form as well, of, like, what type and patches, creams, noses, vaginal style, the things. Okay. Cancer. Oh, we're gonna. Everyone's getting cancer. Right. So getting blood clots. We're getting cancer. You know, can it cause heart disease? There were all these findings, so much so that I was under the impression that they stopped the Women's Health Initiative because it was so bad, so deadly and dangerous.
- [21:58]
A
Absolutely rabid.
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B
Until you.
- [22:00]
A
Yeah.
- [22:01]
B
So what's wrong about this? How is this so botched?
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A
I've spent so much time trying to deconstruct and understand how this went so bad. I've even had one of the three principal investigators who led the study on my podcast.
- [22:19]
B
Oh, God. That couldn't have gone well.
- [22:21]
A
Well, you know, of the three main investigators, she's the one that's done the closest to amea culpa and acknowledged that mistakes were made. The other two have not come close. So it was actually not a. It wasn't like a brawl. And there were a few moments of. We'll agree to disagree. But I do give her credit for being the one to say, yeah, we kind of botched this, and we should really revisit the idea of hrt, at least under certain circumstances.
- [22:55]
B
How was it botched? So you got the element of the ladies.
- [22:58]
A
So there's two things that get. There's two things that botch an experiment. Right. There's what is the design of the experiment?
- [23:04]
B
Okay. And then the method section of a study.
- [23:06]
A
Yeah. This is like, how do you design it? How did you do it? Okay, okay. And then there's the. How did you interpret it? Remember, it's very important. This is science, is. I have a hypothesis. I have a. It's a guess. Very faint. Feynman famously said, a hypothesis, just a fancy word for a guess. I have a guess. The scientific method, not natural to our species. We didn't do it for 250,000 years. We never had this. We didn't have this tool, but we now have this tool, which is when you have a guess, you can design an experiment to test if that guess will be right or wrong. If the experiment produces an outcome that confirms the guess, we now say that hypothesis was very likely to be correct. There's never anything that's 100% in science. Very important to understand that in mathematics, we do proofs. In science, there's no such thing as proof. There's probability. It's just high, high, high, high probability. Low, low, low probability. Some things are in the middle. Okay, so which of those two? I think the Women's Health Initiative had significant errors in both. Now, the errors in methodology are forgivable. And this is an area where I've become more tolerant in my old age. So the experiment took women and put them into three groups. Any good experiment has to have a placebo.
- [24:23]
B
Yes. Right, right.
- [24:24]
A
These are women who don't.
- [24:25]
B
Saline. They're taking saline.
- [24:26]
A
They're taking something that they think. That's why they're taking it, that they think is the hormone, but it's not.
- [24:30]
B
Got it.
- [24:30]
A
Okay. The second group were women who had undergone hysterectomies at some point in their life. Now, if you have undergone a hysterectomy, you do not need progesterone as part of your HRT regiment. Now, technically, that's true from a cancer perspective, but it's actually not true in general. Whether or not you have a uterus in place, progesterone can still be beneficial. But if you go back to the very beginning of time, when people started playing with hormones in the 50s, they were just giving women estrogen because it was making them feel a hell of a lot better. But then they noticed, oh, these Women are getting endometrial cancer at a higher rate. And then they said, oh, actually, the reason that's happening is we don't have a hormone to oppose the estrogen. And this endometrial lining is getting very, very, very thick. So then they reversed course, started giving women estrogen and progesterone, and lo and behold, that problem went away. So today, the traditional thinking is if a woman has a uterus, she must have progesterone with the estrogen. We're going to talk about how what is done today, which is that doesn't have to be oral progesterone anymore. It can be a progesterone coded IUD if the woman can't tolerate progesterone. So just. We'll come back to that.
- [25:48]
B
Be able to tolerate progesterone nausea or something?
- [25:50]
A
No, usually it's moodiness, irritability.
- [25:52]
B
Oh.
- [25:53]
A
Oh, hot. Okay. What I typically hear my female patients say when they have too much progesterone in them is, I would like to kill my husband is the typical line. So that's. To me, that's a good symptom. Like, that's the symptom. Aha. We have too much progesterone in here. So fast forward to the 1990s. Now, the mainstay of therapy is for women who have a uterus is something called conjugated equine estrogen.
- [26:22]
B
Premarin, pregnant mare urine.
- [26:25]
A
Yes. And mpa, which is a synthetic progestin. Okay.
- [26:31]
B
These aren't bioidentical. Right. Because horses have, like, numerous forms of estrogen and we have three.
- [26:36]
A
That's right. Okay, so you have this conjugated equine estrogen, which we just were using because it was so readily available. It's not like we believed women should be getting horse estrogen, but it was just like, this is the abundant way to get it. So if. If. If a woman circa 1990, was in menopause, she was given and she had a uterus, she was given conjugated equine estrogen and mpa. Synthetic estrogen or horse estrogen, synthetic progesterone. And if she didn't have a uterus, if she had undergone a hysterectomy at some point for any other reason, she was just given the conjugated equine estrogen. Cee. So the Women's Health Initiative study was, we're going to have three groups. We're going to have the placebo group. If you have a uterus, you're going to be cee. You're going to be randomized to either placebo or cee plus mpa, schetrin, and estrogen.
- [27:22]
B
But this conjugated synthetic forms.
- [27:24]
A
Technically, there were four groups because you had two placebos. You've had a placebo, you had basically divide them. Uterus, no uterus, and then placebo, C, E plus mpa, placebo, C, E only. Okay, so that makes sense.
- [27:37]
B
Yep.
- [27:37]
A
I'm kind of confused. That. So. So now the question became, what happened in the study? So the first a hell in a.
- [27:45]
B
Handbasket, they all dead like flies. And we.
- [27:48]
A
The first. The first thing women have to realize when they're. When we're talking about hormones today is I've never prescribed cee or MPA in my life, and I don't know anybody who does.
- [28:00]
B
So that's changed. Now it's bioidentical, meaning it matches the human forms of estrogen.
- [28:05]
A
That's right. Now, when we give women estrogen, we give them the actual hormone that their body made. And when we give them progesterone, we give them the actual hormone their body made. The only exception to that is oral contraceptives, where we still use synthetic hormones. Okay, so we can talk about that if anybody cares. But to just put a pin in it, the reason synthetic hormones are used for oral contraceptives is they have a much higher binding capacity for the receptors. And when you're giving a woman an oral contraceptive, your only goal in life is to make her stop ovulating.
- [28:38]
B
Well, that actually answers one of the questions, which was, what's the difference?
- [28:42]
A
Yeah, so that's totally different.
- [28:44]
B
Kind of a big difference.
- [28:45]
A
Right. So putting that aside, when we treat women for menopause and perimenopause, I'm sure there are some doctors out there who are still using the old hormones, but I don't know any of them. The doctors that I would know would never dare. You just wouldn't do it. Doesn't even make sense. So that's one of the huge limitations of the study. And again, I've asked this question point blank of the investigators. Why did you design a study with such lousy hormones? And in their defense, they said, because at the time, most doctors were still using them. And you know what? I'm going to give them a pass on that. I think that's fair.
- [29:24]
B
Fair.
- [29:25]
A
The next aspect of the experiment that really was lousy, I have also become a little bit more understanding of, but much less so, and that is that the women in the study, by definition, couldn't be symptomatic. Their argument, if we allowed, if we did this in young women, women who are perimenopausal and menopausal who are just entering, they're going to be all symptomatic. Well, no woman who is symptomatic would agree to be in a study where she runs the risk of getting the placebo because then she can't get hormone replacement therapy. She's going to be miserable. They're going to drop out of the study. We're going to have no study. So. Because at the time, HRT was viewed as a given. Of course, you give women hormones.
- [30:12]
B
Right.
- [30:13]
A
All the epidemiology said, hrt is wonderful. Women do so much better on hrt. So when the NIH came along to fund the Women's Health Initiative, what their initial goal was is, we just really want to make sure this isn't causing more heart disease and breast cancer. Even though all the epidemiology says it's great, it's wonderful, it's amazing. And they were like, we're never gonna be able to enroll in this study. Like, they. This was a billion dollar study, by the way. I mean, it's an enormous study. And they said, the only way we're gonna do this is if we get a bunch of women who are so far out of menopause that they won't know the difference if they're getting the placebo or the. Of the treatment.
- [30:53]
B
Okay.
- [30:53]
A
It's further confounded by the fact that many of those women did receive HRT when they were younger.
- [30:59]
B
Got it.
- [31:00]
A
So it's. It's an absolutely abhorrent, filthy cohort of data. That sucks.
- [31:06]
B
Wow, what a shit show.
- [31:09]
A
But then it gets worse because all of that is just prelude to how bad this is going to get.
- [31:15]
B
We're not done talking about how bad.
- [31:17]
A
Oh, no, no. God, no. So now we get to. Now we get to the main course.
- [31:21]
B
The first time I started talking about.
- [31:22]
A
It, okay, the study design was merely the amuse bouche. You haven't had the entree. The entree is how this study was interpreted. The lies that people had to tell themselves to make sense of the data.
- [31:37]
B
So I usually see this the other way, Peter, and forgive my bias, but usually it's like, oh, the drug companies are funding it. Of course the drug companies want you on their drugs. You know, it's usually the other way. Not the, you know, don't take drugs. I've never seen a don't take drug study.
- [31:52]
A
That's a fair point. Well, Nancy Reagan had a couple of those, but fair. So so what happens? So there are many things they're looking at. Colon cancer, heart disease, diabetes, osteoporosis, osteopenia, et cetera. But the thing that got all the attention was breast cancer. So let's talk about that. There's a thing called relative risk, and there's a thing called absolute risk. So let's pretend your risk of getting food poisoning if you go to that particular restaurant over there, the risk that it happens is 1%. So if you would go there a hundred times, you would expect to get food poisoning one of those times. Okay. I come along and I say, I now have. Let me make the math easier. 10 times. So it's 10%. This is obviously crazy. You have a 10% chance of getting food poisoning if you go there. So if you go there a hundred times, you're going to get food poisoning once. But now I say, jillian, I have a magic drug that I'm going to give you that is going to reduce the risk of you getting food poisoning. And let's find out how much it happens. So you. I get a whole bunch of people in a study where the base rate of getting the food poisoning is 10 out of 110%. But after the study is done, you guys only get food poisoning five out of a hundred times. That's pretty good, right? Okay, so what's the relative reduction in the risk of food poisoning? It's 50%. Would you agree?
- [33:29]
B
Yeah.
- [33:30]
A
You went from 10 cases in 100 to five cases in 100. What's the absolute reduction in risk? It went from 1% to 0.5% or, you know, one in this case, because I boosted the signal, it went from 10% to 5%. So it's a 5% reduction in absolute risk. So you go back to the way I phrased it at the outset when I said you had a 1% risk, and I took you down to a 0.5% risk. That would still be a 50% because it's half of relative risk reduction, but it would be a half percent absolute risk reduction. And then there's a number that we like to think about called the nnt, the number needed to treat, which means how many people do you need to treat to appreciate that that risk benefit? And it would be 200. Right. Because the NNT is the reciprocal of the absolute risk reduction. So just keep that in the back of your mind as we talk about this.
- [34:28]
B
Basically saying they blew these numbers way out of proportion.
- [34:33]
A
So what were the numbers? So what happened in these two groups? So there's Two parallel experiments. There's the conjugated equine estrogen with placebo for the women with no uterus, and then there's the estrogen and the MPA with the versus placebo for women with a uterus.
- [34:50]
B
Right?
- [34:51]
A
Okay. In the group that got the conjugated equine estrogen alone versus placebo, the risk of breast cancer went down by about one case per thousand.
- [35:04]
B
Okay.
- [35:05]
A
And the relative reduction was about 20%.
- [35:10]
B
Okay.
- [35:10]
A
So there's a reduction in the risk of breast cancer in that group, both in absolute terms, although it's trivial, and relative terms. It didn't quite.
- [35:19]
B
It didn't go up.
- [35:20]
A
It didn't quite reach. It didn't go up. It didn't reach statistical significance at the conclusion of the study. It did 15 years later. Cause they followed these women overall. So there is a small but real reduction in the risk of breast cancer in women who were getting conjugated equine estrogen only in the women who were getting both conjugated equine estrogen plus mpa, the risk of breast cancer went up just slightly. It went up from four cases per thousand to five cases per thousand, which, if you can do the math, what's 5 divided by 4 minus 1 times 100?
- [35:58]
B
Oh, shit.
- [35:59]
A
25%.
- [36:00]
B
Don't do this to me right now.
- [36:02]
A
It was a 24% increase in the relative risk of breast cancer. Seems massive unbearable until you realize it went up by one case in a thousand, 0.1%. Furthermore, that was an increase in the risk of getting breast cancer. But when you looked at mortality from breast cancer, there was no difference. And interestingly, that result has also persisted 20 years later. Twenty years later it's gone down a little bit. It went from 24% to 20% increase in relative risk. And the absolute risk remains at 0.1%. Now, if I were transported back in time, looking at those data, the first thing I would say is estrogen alone has about a 20% reduction in risk. Estrogen plus MPA has about a 20% increase in risk. Neither of these have a clinically significant change in breast cancer. Would your conclusion at that moment. Well, let me ask you, what would you conclude? Explain the difference. Let me reframe the experiment. What if the this group was cookies give you less breast cancer, right? Cookies and carrot give you more breast cancer. What do you think?
- [37:24]
B
Well, I would just remove the carrot, right?
- [37:26]
A
So interestingly, I think any person with an IQ above of 82 would look at the results of that experiment and at least hypothesize that it was the.
- [37:35]
B
Carrots that caused the problem.
- [37:37]
A
That might have been the problem. Right. I mean, of course, right? Like, I've only been thinking about this for 15 years, but it would appear to me that it's not funny. I don't mean that the CAA only group or the CEE only group, the SG only group, has a reduction in risk. The estrogen group goes up a little.
- [37:58]
B
Bit, remove the progesterone.
- [38:00]
A
So either there's only two explanations here, right? Either there's something about the women who have a uterus that is making them more likely to get breast cancer, or what I would call the Occam's razor explanation is it's actually the mpa, it's actually the synthetic progestin that's driving up the risk. But instead, two headlines emerged. The first was, breast cancer risk increase with HRT is 25%. Now, that's technically almost true. There was a 24% increase in the relative risk of breast cancer, but it's not entirely true because it was only in the group getting this other treatment. And the second headline that emerges is estrogen causes breast cancer despite the fact that there is nothing anywhere in the Women's Health Initiative at all that says that estrogen had anything to do with this. And Those results persisted 10 years later and 20 years later at the reevaluation of those patients.
- [39:09]
B
Wow.
- [39:10]
A
So even if in fact it was.
- [39:13]
B
Quite the opposite, it actually reduced risk slightly.
- [39:16]
A
That's right. So even if we think it makes sense to give women conjugated equine estrogen and MPA today, and nobody really does, what I like to tell women is look at a minimum, your risk is probably going up by 0.1%. And let's evaluate that increase in risk against all of the benefits that come with it.
- [39:43]
B
Right. And in addition, can I ask you, like, family history? I don't have a family history of breast cancer. If I did, would it matter?
- [39:51]
A
It might, right? A little. So we still live in an estrogen phobic world. There's no doubt about it. We still live in an estrogen phobic world. So we have to sort of be able to.
- [40:01]
B
The estrogen positive cancer conversation, right? Then it's like, well, early onset cancer diagnosis is up massively and X percent of it is digestive tract stuff. And then X percent of it is hormone positive stuff, estrogen breast cancer being top of your list. So then you're like, oh, estrogen positive.
- [40:18]
A
Yeah, but remember when we did the program and we talked about TRT for men, we talked about the role of testosterone. See, there's a real analog between how testosterone works in prostate cancer and how estrogen works in breast cancer. Yes, it's quite a different thing to say if you have a raging prostate cancer, pouring testosterone on it will make it worse. That might be true. Just as if a woman has breast cancer and it is a raging and it is estrogen sensitive, if you give her estrogen, you might wake worse. That's an entirely different proposition from saying if you take testosterone, you will get prostate cancer, which has been demonstrably demonstrated to not happen. And I believe that it is pretty clear that giving estrogen does not cause breast cancer. Now, if you have a woman who is high risk for breast cancer, you would take a lot of steps to make sure that you are evaluating her and screening her. Got it. And, but the truth of it is, if you look at the data very carefully, it is not clear that estrogen would have any role in the initiation of breast cancer. And by the way, like, you can even just look at this in a crude way, which is if testosterone was driving prostate cancer, young men would be getting it, of course, but it's old men, it's men with low testosterone that are getting it.
- [41:43]
B
And I've subsequently heard that.
- [41:45]
A
And it's the same as true with breast cancer.
- [41:46]
B
That's what I'm just gonna say that I remember hearing that thinking like, I don't get it, but I'll circle back later, talk to somebody about it at a later date.
- [41:54]
A
On average, not always on average, women are getting breast cancer when they have less estrogen than when they have high estrogen. So you had this perfect storm of lousy study design, very poorly interpreted study, and then media that really loved the idea that this was a contrarian finding here. All that time you thought HRT was good for you.
- [42:19]
B
So can I conclude after this whole talk that really there's no negative side effects for perimenopausal women with HRT outside of potentially a family history of breast cancer, where I should be monitored by my doctor to just screen me regularly in the event something develops. So not because of this, but in the event, and that this doesn't accelerate or act as an accelerant on the breast cancer.
- [42:45]
A
I have yet to see a valid piece of data that suggests to me that HRT will increase the risk that a woman dies of breast cancer.
- [42:54]
B
Can I jump to the next conclusion? Would all women benefit from hrt?
- [42:59]
A
Yeah, that's an interesting question. My knee jerk response to a question like that is no, because I think it's very difficult to say all fill in the blank anytime in medicine. So again, my intuition is that the answer to that question is probably no. But what I think is really valuable is the idea that every woman should be offered the discussion. And that's again, so we're sitting here more than 20 years after this study was published and it's hard to know because I live in a bubble, right. Like I live in a bubble where I, you know, as a doctor that.
- [43:38]
B
Knows everything, you know, and I say this only so I don't.
- [43:40]
A
Yeah. I don't know how bad it is. It's pretty bad in the real world. I don't know what fraction of women are not even given this opportunity to have the discussion. And that's just if that's right, that is, that is a tragedy of epic proportions.
- [43:55]
B
And here's what I mean. So as a 50 year old woman with many friends in this age range, I generally have to be the one when they're telling me their whole world is falling apart, which happens all the time, to then say, hey, you know, watch what Dr. Tia says about this and then go talk to your doctor. I think I've done that 10 times in the last three months. And it's even the friend of the friend, you know, so it's like my friend, then their friend and she's like, oh, talk to Jill. Then Jill says the same thing and then they go talk to their doctor. And, and I'll be honest, I don't even, I haven't even had this conversation with my doctor yet. And I, what is it? An internist?
- [44:36]
A
I think, I think there are great internists that can do this. I think there are great gyns that can do this. You know, historically this would fall in the purview of your, your, your primary care physician or your gynecologist. And look, don't.
- [44:52]
B
Peter.
- [44:52]
A
No. Yeah, I don't even know.
- [44:53]
B
Like, I've also.
- [44:54]
A
But just as we would have a urologist or a really good primary care physician should be able to manage TRT in men. I know for a fact.
- [45:03]
B
Or your obgyn.
- [45:04]
A
Yeah. And I know for a fact that there are great examples of both of those types of doctors that do this, there are also hormone clinics that's become quite vogue. And I just think, well, I think it's all going to come down to like who the people are. I, you know, I've seen some that I think are doing good work and I've seen some that are absolutely ridiculous. You know, they're giving women herculean doses of estrogen. They have this thesis that says, I gotta make you 14 again, and I'm gonna give you, like, enough estrogen to kill a small pony. And I think that they're potentially doing harm in that regard. So. And they're. And they're loading them up on, you know, massive doses of testosterone and growth hormone and doing all sorts of crazy things. So you just. Because someone's got a clinic, I think you gotta kind of hear out their philosophy a little bit.
- [45:49]
B
Of course.
- [45:49]
A
And ask, like, how are you managing this? What is your philosophy around, you know, the use of these hormones? And what hormones do you use? You know, do you have a. Here, I'll give you a big red flag. If you go and see somebody and they have their own pharmacy, that's a red flag.
- [46:03]
B
That is a red flag. Why is a compound. Why?
- [46:07]
A
Because I think it's a conflict of interest. I don't think a doctor should be prescribing a medication to a patient when they make money on the medication.
- [46:18]
B
Oh, but you're okay with compounded hormones?
- [46:23]
A
We don't tend to use them because I always prefer to have an FDA product. The quality assurance is so much higher.
- [46:31]
B
But it's still bioidentical.
- [46:33]
A
Yes, we use bioidentical estradiol, of which there are many FDA approved products, and we use bioidentical progesterone. That is an FDA approved product. Now compounding runs rampant. Some compounding pharmacies are really good.
- [46:52]
B
Some have certain standards. Right. And then others.
- [46:54]
A
There's two standards of them.
- [46:55]
B
That's right, yes. Okay. Which is a separate issue, but nevertheless.
- [46:58]
A
I did a whole podcast on this.
- [46:59]
B
Topic, by the way, which we'll link to guys, which absolutely people should check out, especially because of what's going on with ozone. So I strongly recommend on any and all subject matters to check that out because there is a big difference, as far as I can tell. And you need to know what you're dealing with.
- [47:15]
A
Yeah. Compounding pharmacies are the wild west, which is to say there's some good and there's many bad. Got it. But when in doubt, always opt for an FDA approved product, even if you have to pay a little bit more for it.
- [47:27]
B
Got it. Okay, so now then, explain to me, if you can, how long. So I remember talking to Dr. William Lee about something, and his mom had gotten cancer, right? And it's because they. According to him, I think one of the elements was they left her on HRT for ever Nobody ever took her off. Why would you ever come off? How do you know when to come off?
- [47:55]
A
So there's no good evidence to answer this question. And so what.
- [48:01]
B
Okay.
- [48:01]
A
What most doctors are doing is having. If they're. I think if you're a good doctor, what you're doing. When a woman has been on HRT for a decade, which seems to be. So if you. If you look at the people who were staunch opposers of HRT that are kind of coming around to it now, they're. They're doing so with many fences still, right? They're saying, okay, maybe the Women's Health Initiative was wrong. Maybe HRT is not, you know, the worst thing in the world, but you must start it immediately. I agree with that, by the way.
- [48:36]
B
Oh, that's going to be my next question.
- [48:38]
A
In fact, you should start it during perimenopause. You don't want to wait until you're fully in menopause. But we'll come back.
- [48:42]
B
Yeah, we got to come back.
- [48:43]
A
And then they would say, and you really should. You really shouldn't do it for more than seven to 10 years now. If you push and ask why, they'll say, because of the risk of breast cancer. To which I then say, what risk of breast cancer? They'll say, you know, the Women's Health Initiative. And I say, right, but the Women's Health Initiative didn't really show an increase in breast cancer.
- [49:02]
B
Right.
- [49:03]
A
It showed that CEE plus MPA increased the risk of breast cancer by 0.1%, but didn't increase fatality of breast cancer. Is that the risk you're talking about? They'll say, yes. And I'll say, so that's the reason we're telling women to stop at 10 years.
- [49:19]
B
What is the reason?
- [49:21]
A
That's the reason.
- [49:22]
B
Oh, God. So the mantra now, if I've been.
- [49:27]
A
On this, the mantra of HRT today. So we went from, this is amazing.
- [49:33]
B
Everyone's on it, right?
- [49:34]
A
Then we went to, you'd be better off rubbing cyanide on your inner lip. And now we are minimum effective dose for the shortest period of time. And don't tell anyone and hold your breath while you're taking it.
- [49:47]
B
Yeah. Is that. That's not where we should be?
- [49:51]
A
I don't believe so.
- [49:51]
B
So that's where we are.
- [49:53]
A
Which is an improvement over, don't ever touch this stuff.
- [49:56]
B
What if I'm at a window of seven years? Do I keep it rolling or do I, like, is there a. What do I.
- [50:01]
A
You know, again, this is not a particularly Compelling answer. But I do think every. I hate saying this because it sounds like such a stupid cop out. Every case has to be evaluated individually.
- [50:11]
B
Fair.
- [50:12]
A
You know, my view is that if a woman really understands what benefits she's getting from it and understands what the risks are, potentially most women tend to say, I would like to stay on this, thank you very much.
- [50:26]
B
So the risks don't accrue over time?
- [50:30]
A
No. And again, I think there's some very confusing data on brain health where the Women's Health Initiative showed that there was an increase in the risk of Alzheimer's disease in these women who started it very late. Now, today, we don't really know what to make of those data, although there are data that show the opposite, that if you actually start HRT early, you improve brain health.
- [50:56]
B
It's all that Dr. Lisa Moscone stuff.
- [50:57]
A
That's right. So there's also some data that show women with an APOE4 gene disproportionately might benefit from estrogen. Because remember, we have to acknowledge that Alzheimer's disease is a very asymmetric disease. It afflicts women twice the rate of men.
- [51:16]
B
And this is arguably the reason. Right. The estrogen.
- [51:20]
A
I think this is a big part of it. Because that delta of 2x cannot be explained by the delta in life expectancy.
- [51:27]
B
Right.
- [51:28]
A
In other words, mathematically, it's not the case that because women live longer, that's why they have twice the rate of Alzheimer's disease.
- [51:34]
B
We get it at younger ages anyway. It doesn't matter. It's not like we're getting it at 100.
- [51:38]
A
You can get it at the most. The most obvious thing is, is, is that something about the sudden loss of hormones and maybe estrogen more than progesterone, but. But possibly both would play a role in that. So I can just tell you that for. For most of our patients who are at that point in time where you're.
- [51:59]
B
Not ripping them off of it based on, based on an arbitrary number of.
- [52:03]
A
Seven to 10 years, you're definitely not ripping them off it. And when we have that discussion and try to present the data, because the data are the data, like, you know, I want people to be very familiar with all this stuff. I mean, I used to keep copies of these studies. I used to keep a copy of the Women's Health Initiative and all of its published subsequent studies on my desk. Just because this is back, you know, when I was, when my practice was in person and before it became a virtual practice. And. But so that if a person is sitting There I'm going to be able to show, you know, this is the data. Like, you can look at the tables and figures, too. You be the judge.
- [52:34]
B
Yes.
- [52:35]
A
So. Yeah, so. So I. I think that it's. I think it's overly cautious to just say we should arbitrarily stop HRT 10 years out or 7 years out or whatever it. Because again, when you push, push, push on that argument, they just say, no. But look at the whi. These women that were older, they had bad outcomes, and it's like, yeah, they, A, they were on a different hormone, B, they started very late, and B, these were very unhealthy women. That's yet another element of that study.
- [53:06]
B
That is what you're talking about. That is they already had all these health issues.
- [53:10]
A
That's right, yeah.
- [53:13]
B
Okay, so now I've got a series of questions that I'm going to link together because I'm hoping it will flow. When do I start? You said perimenopause. I kind of don't know what that means. In other words, I should be in perimenopause. I'm 50, but I don't have symptoms. So is that me?
- [53:29]
A
Yeah, you might not be right. So perimenopause is a vague idea that is like, there's a set of symptoms which I'll never be able to rattle off because some of them are obvious and some of them are not.
- [53:40]
B
And I should just be like, you're 50. You're in perimenopause. Like, surely, Jill, you are.
- [53:43]
A
Nope, nope. Definitely not.
- [53:45]
B
Okay.
- [53:46]
A
Yeah.
- [53:46]
B
So we're on a blood test.
- [53:48]
A
Yeah, I've heard you talk about blood tests. Yeah, well, we'll talk about the blood test also.
- [53:51]
B
Like, you have to go on a certain day of the month or something.
- [53:54]
A
Yep, yep. But before we do that, what are those symptoms? Right, so, okay, so are periods getting more spaced out? Are they getting heavier? Are you gener. Are you becoming more moody, more irritable? Are you getting any of the vasomotor symptoms? So, yeah, yeah, no. So I'm saying, like, you go through that list and that's how you sort of do the math. Now, from. From a biomarker standpoint, the first thing that we start to see is a rise of FSH on about day five. So that's our window. That's. That's the most consistently reproducible time to check estradiol, FSH and LH levels. So if day. We define day one as the day the period starts.
- [54:34]
B
Oh, so like, right when it ends, kind of A thing is when you want to check it.
- [54:37]
A
Yeah. Depending on it. If it's a. But even if you just spotted for two days, we would still check you on day four or five.
- [54:44]
B
Okay.
- [54:44]
A
If you had a heavy period that went six days, we would still check you on day four or five.
- [54:48]
B
Common knowledge, Peter.
- [54:49]
A
Yeah. And then we would look at what is your fsh. And what you're going to see is if you're. If you're. If you're a young woman, if you're a woman who's got a regular cycle, your FSH on that day is going to be like 2 or 3 or 4 or 5. As you get more and more towards menopause, that FSH starts to really ratchet up, and there is no defined cutoff, at which point I would say you're perimenopausal or menopausal. But I will tell you that once a woman hits about 20 or 25.
- [55:18]
B
I mean, time to go. Time to start.
- [55:21]
A
To me, that would. I would add that to the list of. Yeah, we're.
- [55:24]
B
So that's a pretty good indicator. So now I want that blood test. No one's offered it to me. And I have. I have great doctors, maybe because I'm not bitching. So.
- [55:34]
A
So, yeah, I mean, in their defense.
- [55:36]
B
I mean, they're really good doctors.
- [55:37]
A
If you're totally asymptomatic and you're not hitting any of the nine symptoms that we would typically see in perimeter menopause, I think it's reasonable that they're not losing sleep over what your FSH is on day five.
- [55:48]
B
Okay. Yeah. Now, so that's a great benchmark. It's quantifiable. Fantastic. Testosterone. Okay. So all I tried to do is block this. And the reason is because I've had breakouts my whole life. I had PCOS as a kid. And I say as a kid because no symptoms really, outside of. Gynecologist recently ordered a pelvic ultrasound and lining was a little thicker than she wanted. It was a whole fricking cancer scare. And they did a biopsy, and it was nothing. Nevertheless, this is like a thing of mine. It's linked to PCOS and all this shit. So all I do. And I told you I turned into, like, a little bulldog, which I fricking hate. And I'm the person that arguably doesn't exist, where I do, you know, three squats and I get thighs this big that everyone's like, no, it's not a thing. It kind of does happen to me.
- [56:42]
A
So you really Picked the wrong thing. You should have been a bodybuilder.
- [56:45]
B
I know, but I hate it. And then we. I hate. It's so weird. Cause I'm such a boy, but I kind of don't want to look like one. I feel like I have the brain of a man, but I don't really personally want to look like a man. Not that there's anything wrong with that. So. And hair, I want to keep my hair. I don't want pimples all over my face. And I ended up. I tried Accutane twice in my life. My body would break through it. Nevertheless, here we are. And my dermatologist and my gynecologist put me on spironolactone and it works. And it's like what medications you're on. And I love saying none except. And I'm like, but not cause I'm unhealthy, just cause like I break out. So I block the shit. I'm like, I do not want this dht. Don't want it. And then I'm like, is then I Do we need to replace testosterone?
- [57:40]
A
No, we don't. Yeah, we don't need to. And, and again, when do you know if you do well again? Like if you're. If your libido is tanking and you're having a hard time putting on muscle mass and your testosterone is demonstrably and measurably low.
- [57:52]
B
So when do you test for that? Can you. At the Same day as F. FS8.
- [57:56]
A
It's less relevant. You can test it any day. But yes, if you're going to go through the trouble of testing a woman, I'm gonna look at her fsh, her lh, her estradiol and her testosterone and free testosterone on that same blood drop.
- [58:08]
B
And what should it be for a woman, number wise? What's our window?
- [58:12]
A
Yeah, so for women we would typically see a total testosterone. And it depends on. This is another important point. I am really adamant that these hormones, both for men and women, are only checked using something called LC Ms. Liquid chromatography and mass spectroscopy. And they're. So if you go to LabCorp, you can have your doctor specify LC Ms. Testing for estradiol and for testosterone. And that's really important because the enzyme based assay for those hormones is really quite inaccurate. And it's remarkably inaccurate in people who are taking supplements and things like that. So we see. We see. I mean we.
- [58:56]
B
A million supplements.
- [58:57]
A
Yeah. So you, unless you're getting an LC ms, you can throw the numbers out. Just means Nothing. So, so if we're going to go through the trouble of doing all of that and you're getting a proper LC ms, I would say a normal testosterone for a woman could be anywhere from 50 to 100 nanograms per deciliter.
- [59:16]
B
Okay. Remember, so much lower than men. It's.
- [59:19]
A
Right. Men would be, you know, five hundred to a thousand would be normal. And then a free testosterone would be probably 1% of that. And the reason is women have much more sex hormone binding globulin.
- [59:35]
B
Okay.
- [59:35]
A
So. So they're going to have a lower free testosterone. The lower percentage as free. So they're free might be, you know, like one to two or something like that.
- [59:46]
B
Okay. Is there a way to get the androgenic effects that you mentioned of like, muscle maintenance and bone density?
- [59:53]
A
Anabolic.
- [59:53]
B
I'm sorry, I'm sorry. Anabolic. With, without the androgenic of like face.
- [59:58]
A
No. And so with, with, with women, the two most common symptoms of testosterone replacement are acne and hair growth. With women, though, there's another trick which is you don't have to give.
- [60:08]
B
What's my trick?
- [60:09]
A
Well, it's not, it's. It's. It's just you can give them DHT instead of. Oh, sorry, I'm sorry, dht. You can give them dhea. DHEA is a precursor to testosterone. It's a. It's another.
- [60:22]
B
If I want to go to the vitamin store and I can buy. You can't.
- [60:25]
A
You can. In the US DHEA is legal over the counter.
- [60:28]
B
Should you not be doing that then?
- [60:30]
A
No, no, I'm just saying that there's a. There's an interesting difference. So it's, it's because, again, men think DHEA is a great way to boost testosterone, but it's not in men because DHEA only boosts the testosterone that's produced by your adrenal glands. So in the case of. And by the way, it does the same in men and women. But the difference is if a Guy's testosterone is 300 and he takes DHEA, it goes from 300 to 330. Doesn't make a difference. But if. Exactly. If a Woman's testosterone is 30 and she takes DHEA and she gets 30 more, she goes to 60, she's normal. So DHEA is actually a pretty cool trick for women to replace testosterone without taking testosterone. But again, I just don't recommend you do this without having a person who knows what the heck they're doing.
- [61:19]
B
People are messing around with this stuff all the time and that's it's. Like, even, even. Even when people ask me, what are you taking? I'm like, well, I take fish oil. Talk to your doc. All this stuff interacts with different drugs. You don't know what your levels are in your blood. Like, always, always talk to your doctor and have them look at your.
- [61:36]
A
Hopefully you've got a doc that cares enough about this stuff.
- [61:40]
B
Yeah.
- [61:40]
A
Which is you have to be a little curious because you're not learning this stuff in the normal channels. Like, you sort of have to, you know, do a little after school learning.
- [61:49]
B
Okay. So how do I know if I need progesterone if I have a uterus?
- [61:54]
A
Yep. So if you have a uterus, you have to have some form of progesterone if you're taking estrogen.
- [61:59]
B
Got it. Because otherwise you will experience the lining.
- [62:01]
A
Of your thickness check. So our strong preference is that women take what's called systemic progesterone, a pill. They take oral progesterone. And the reason for that is progesterone does a lot of good that goes beyond just opposing estrogen at the endometrial lining. So for most women, it improves the quality of their sleep. That's probably the single most important thing that they experience with progesterone. It also improves mood. If you get the dose right. If you get the dose wrong, it doesn't.
- [62:33]
B
Right. That's when you want to kill your estrogen.
- [62:35]
A
That's right. For most women. It increases hair thickness.
- [62:38]
B
Oh, my heaven.
- [62:40]
A
Yeah. And then obviously you get the protection against the endometrium. It also plays an important role in bone health during perimenopause.
- [62:49]
B
So now I understand this whole component. And we all know when to get tested, what to look for, quantifiable numbers that it should be at least these two together.
- [63:00]
A
Yeah. And when you're giving estrogen, you're treating. So this is much more art than science, to be clear. Right.
- [63:08]
B
So I was gonna say what's the right dose?
- [63:10]
A
Right, exactly.
- [63:11]
B
That's the art.
- [63:12]
A
So don't know. Right. We can give you ranges. Progesterone is typically between 50 and 200 milligrams orally before bed every night. So how do you know where on that spectrum to be is not. Because you're measuring progesterone levels in the blood. That's not particularly helpful. You can measure them in the urine, but I would argue it's not really necessary. My view is only change one hormone at a time and treat to symptoms within a known range of the hormone. So you need at least 100 milligrams of progesterone to give you the endometrial protection.
- [63:46]
B
Got it.
- [63:47]
A
So then the question is, where do you need to be? 1001-251501-75200. That's going to be. While holding everything else constant. We tweak there until we find the right dose. Okay, so that's progesterone. We're not doing anything off blood markers with estradiol. Let's just assume we decide we're going to put a patch on you or something like that.
- [64:09]
B
This would be my next question. You've got like vaginal nose stuff. Patches, pills.
- [64:15]
A
Yeah. So again, it all depends on what you're trying to accomplish. But my preference is a patch.
- [64:20]
B
Really?
- [64:20]
A
Yeah. Okay.
- [64:21]
B
What if I'm just trying to accomplish all this awesome stuff like my hair and my mood and my body fat and, and all the things? Like there's not just. Isn't everybody trying to accomplish the same stuff?
- [64:35]
A
Yeah, I mean, I think so, but again.
- [64:38]
B
Oh, I get like vaginal lubrication.
- [64:40]
A
Yeah. If you, if you give vaginal estrogen, you're not getting it throughout the body. You're just trying. You're just doing that. The only reason you would use vaginal estrogen is probably in a woman who doesn't want to take systemic hormones but wants to do everything to kind of mitigate the sexual side effects.
- [64:57]
B
But we already established that that's there's really no significant risk.
- [65:02]
A
True. But there are still obviously many women and their doctors who are still really afraid. And this is kind of like they're dipping their toe in the water under.
- [65:10]
B
Ah, thank. Got it. You like the patch, you said so.
- [65:14]
A
We like the patch. In women, it's easy to titrate. Right. So it's an F. It's a beautiful FDA approved product that gives a consistent level of absorption. And, you know, you basically titrate it by trimming the side. I mean, first of all, it comes in different doses. Well, it comes in different. It comes in different doses. And then you would say you go half patch, quarter patch, et cetera.
- [65:32]
B
I got it.
- [65:33]
A
And you change the patch every three days.
- [65:34]
B
Okay.
- [65:35]
A
And the biomarker we look at there. So first of all, symptoms matter the most. But we get guidance from your FSH and to a lesser extent, the actual estradiol level. But mostly the FSH symptoms matter, as.
- [65:48]
B
In the alleviation of symptoms. Not like, oh, God, you've developed a horn on your head.
- [65:54]
A
No, you can give a woman too much estrogen. So the The. The most common two things that you see with excessive estrogen are mood irregularities. But again, that could be the progesterone, which is why I don't want to be ingesting these two hormones at the same time. Because you can. If. If a woman is having irritability or depression, how do I know if it's that she's got too much or too little progesterone, Too much or too little estrogen? So just tweak one hormone at a time. And then the second thing is breast tenderness. That's pretty unique to estrogen and not testosterone and not progesterone.
- [66:25]
B
Part of the reason I'm grimacing when you're talking is simply because all of the nuance. I hate to say this, but I. I just don't think the majority of doctors know about or understand. I don't think they're even testing women on this fifth day like you talk about. I. I don't think they're even considering the. The testosterone component. Yeah.
- [66:51]
A
So look, there's gotta be doctors that are watching this. There's gonna be women that are watching this that are gonna send it to their doctors.
- [66:57]
B
Okay.
- [66:57]
A
Some of those doctors are gonna be like, that guy's an idiot. I don't have time for this. Sure. And some of them are gonna be like, you know what? I'd like to learn more about this. Maybe I should pay attention to this. So, you know, it's not a great answer in the sense that it doesn't solve the problem tomorrow, but Rome wasn't built in a day, and we are kind of. We do have to rebuild a new medical system.
- [67:16]
B
Is there? So essentially, I guess the question becomes. And I started to learn that through talking to all of you guys. Your care comes down to a partnership with your doctor. So you come in and you can ask all these questions, and you have a relationship with your doctor, a doctor you trust, a doctor that listens to you, a doctor that takes the time, and a doctor that doesn't just write this off. Like the guy in Miami that was like. Like, what test do you want? You even talking about? Okay, so what day do you want your blood work, genius? And I was like, seriously? Are you kidding me? You know?
- [67:52]
A
Yeah. I mean, look, that. You just have to get a new doctor. Like, that's not. That's not. I don't. You're not. I'm not gonna spend time interacting with that person, trying to convince them they've already shown their hand. And there's a. There's a level of arrogance there, and there's a. A level of intellectual laziness that's going to preclude having any kind of meaningful relationship. So let them go off and do their thing. Wish them well, and you just got to find somebody else. Now, the real challenge here is just as much as we have people on that side of the ledger, people that I just call, you know, firmly, firmly entrenched in the Medicine 2.0 system, unfortunately, you got a lot of insane quackery on the other side, where people that just want to give every woman every hormone and they fashion themselves as longevity gurus. And there's a real problem there as well. And so what happens is part of this guy's reaction is to these buffoons, and these buffoons are, in part, a response to this guy. And so the challenge is nobody really likes to be in the middle because it's a lonely place, and you have to take a long time to explain what's going on, and you have to spend a lot of time learning. So it's. So I do think politics. Yes. I think that's actually a fantastic analogy.
- [69:12]
B
Check out all the links we sent you guys in the comments here. Check them all out as discussed. Listen to the drive. Peter's podcast is an invaluable resource. The book has a ton of this stuff in there. Get the book, which. Mine's signed because I had the book, but, oh, my God, I got a really nice long letter. Jillian, I'm going to read. I haven't read it yet. Jillian, I hope this book plays a small role in your quest to help people live longer and better lives. And here's to your very best Centurion Decathlon. I love you madly. Thank you. And you're very welcome. I mean, and like, by the way, every woman in our office has a crush on you. Your poor wife. Add one. Add one. But, like, I'm safe. I think her military safe. Just let her know I love him, you know, but. So I would. I would probably turn the tables for you.
- [70:02]
A
Very well. Thank you.
- [70:05]
B
Thank you so much for watching. If you enjoyed the podcast, please, like, comment, subscribe, and share. And make sure to let me know what guests you want to see on in the future.