Dr. Peter Attia

I agree.

I agree.

I'm really happy to hear. We're following your playbook already. So yes, we almost always start with estradiol and we muck around for a while till we get it right. That's why I saved it for last, by the way, because it's the hardest, in my opinion, in my experience to get right. Then we fiddle with progesterone and then testosterone if they're not already on it.

I'm really happy to hear. We're following your playbook already. So yes, we almost always start with estradiol and we muck around for a while till we get it right. That's why I saved it for last, by the way, because it's the hardest, in my opinion, in my experience to get right. Then we fiddle with progesterone and then testosterone if they're not already on it.

But to your point, some women are coming into perimenopause already on testosterone. Okay, let's talk about estradiol. There are two other estrogens. Estradiol is E2, but there's estrone, E1, and there's estriol, E3. Now the FDA only has a battery of approved products around the second estrogen, which is the dominant estrogen.

But to your point, some women are coming into perimenopause already on testosterone. Okay, let's talk about estradiol. There are two other estrogens. Estradiol is E2, but there's estrone, E1, and there's estriol, E3. Now the FDA only has a battery of approved products around the second estrogen, which is the dominant estrogen.

There's no FDA-approved product for estrone, and there's no FDA-approved product for estriol, but there are plenty of compounded opportunities around that. In fact, the most common of them is referred to as biest, biestrogen, which is an 80-20 mix of estriol and estradiol. What is your take on why that product exists? Do you view that as a reaction to the WHI? I mean, how do you think about it?

There's no FDA-approved product for estrone, and there's no FDA-approved product for estriol, but there are plenty of compounded opportunities around that. In fact, the most common of them is referred to as biest, biestrogen, which is an 80-20 mix of estriol and estradiol. What is your take on why that product exists? Do you view that as a reaction to the WHI? I mean, how do you think about it?

We don't use it at all. I have used it occasionally in the past, probably about 10 years ago, largely in women who were terrified of HRT. And to your point, it was viewed as, look, if you buy the argument, and this is a biochemical argument, there's no human data that demonstrate what I'm about to assert.

We don't use it at all. I have used it occasionally in the past, probably about 10 years ago, largely in women who were terrified of HRT. And to your point, it was viewed as, look, if you buy the argument, and this is a biochemical argument, there's no human data that demonstrate what I'm about to assert.

And again, I say this because one can look at a whole bunch of biochemical charts and tables and talk themselves into anything being true. But there are biochemical arguments to be made that estrone, and in particular one of the metabolites of estrone, and I think it's 4-hydroxyestrone, is the estrogen that is driving breast cancer.

And again, I say this because one can look at a whole bunch of biochemical charts and tables and talk themselves into anything being true. But there are biochemical arguments to be made that estrone, and in particular one of the metabolites of estrone, and I think it's 4-hydroxyestrone, is the estrogen that is driving breast cancer.

So in an estrogen-sensitive breast cancer, given that you have so many estrogens, is it more likely that one is responsible than another? And so the answer is, oh, some of the data suggests it's 4-hydroxyestrone. Well, estriol has no biochemical path to even get there. In other words, there are no series of enzymes that can convert estriol into 4-hydroxyestrone.

So in an estrogen-sensitive breast cancer, given that you have so many estrogens, is it more likely that one is responsible than another? And so the answer is, oh, some of the data suggests it's 4-hydroxyestrone. Well, estriol has no biochemical path to even get there. In other words, there are no series of enzymes that can convert estriol into 4-hydroxyestrone.

And of course, there are pathways that will turn estriol weakly into estradiol. So maybe you get a little bit more. So there's a long-winded way of saying no reason at all from an evidence perspective to use it. We don't use it, have not used it in a decade, but that was my half-baked argument in certain situations. And in fact, I did use it once in a woman who had breast cancer.

And of course, there are pathways that will turn estriol weakly into estradiol. So maybe you get a little bit more. So there's a long-winded way of saying no reason at all from an evidence perspective to use it. We don't use it, have not used it in a decade, but that was my half-baked argument in certain situations. And in fact, I did use it once in a woman who had breast cancer.

was adamant that she needed hormones. Symptomatically, she really seemed to. Wanted it very badly. And I felt that this was a reasonable compromise. For what it's worth, she got insanely better on the biased. How much of that was from the estriol? How much of that was from the estradiol? I have no idea.

was adamant that she needed hormones. Symptomatically, she really seemed to. Wanted it very badly. And I felt that this was a reasonable compromise. For what it's worth, she got insanely better on the biased. How much of that was from the estriol? How much of that was from the estradiol? I have no idea.

Yeah. And you mentioned this earlier. I think this is one of the biggest limitations of how I talk about this thing, medicine 2.0, which is very few people are conditioned to ask the question, what is the risk of not acting? We have a reasonable idea of what is the risk of doing X? What is the risk of doing Y? Although in this particular example, we seem to get that patently wrong.

Yeah. And you mentioned this earlier. I think this is one of the biggest limitations of how I talk about this thing, medicine 2.0, which is very few people are conditioned to ask the question, what is the risk of not acting? We have a reasonable idea of what is the risk of doing X? What is the risk of doing Y? Although in this particular example, we seem to get that patently wrong.