To me, this problem is not just menopause. What's more interesting is to talk about perimenopause. So perimenopause is the period of time before your final menstrual cycle. And for most women, depending on how attuned you are to the symptoms, it can last for 10 years. So I'm still in perimenopause.

It's been like 20 years because I've been tracking it so carefully. It usually gets kicked off by having your cycle get closer together. So that can happen in your 30s or your 40s. You go from 20 days to 25 days, that sort of thing. You may notice that you start sleeping more poorly because progesterone is so important.

You talked about that with Kyle. You may notice it as more anxiety, difficulty sleeping. And that probably is related to the estrogen receptor. So your alpha is estrogen receptor, alpha is angio. It increases anxiety. ER beta is associated with an anxiolytic activity. And then there's a total of about six estrogen receptors now.

There's the G-protein coupled estrogen receptors, and those are mixed, anxiolytic, anxiogenic. So there's this whole period of perimenopause, and what's most fascinating to me, and we've got to talk about this either today or another time, is that there is this massive, massive change that happens in the female brain that people are not talking about enough.

And so looking at the work of Lisa Moscone at Cornell, from starting around age 40, there is this massive change in cerebral metabolism. So you can do FDG PET scans, you can look at glucose uptake, and there's about, on average, a 20% decline from premenopause, up to like age 35, to perimenopause, to postmenopause.

The women who are having the most symptoms in perimenopause and menopause, the hot flashes, the night sweats, the difficulty sleeping, those are the ones who have the most significant cerebral hypometabolism. - So it's almost like a, I don't want to scare people with this language, but it's a low-level or let's call it pseudo-dementia of sorts.

- Yes, it seems to be a phenotype that you can then map to Alzheimer's disease, because that's Lisa Moscone's work. She's looking at, okay, Alzheimer's disease is not a disease of old age, it is disease of middle age. But are some of the biomarkers that we can define that can tell you what your risk is?

I've got a mother and a grandmother with Alzheimer's disease, you can believe I am all over this data. - And insulin resistance. - Huge part of it. - Insensitivity, as we talked about it before, seems to be somewhere in there, which I think when that idea first surfaced, a few people were like, "Really?" But then of course, right?

I mean, the brain is this incredibly metabolically demanding organ. You deprive neurons of fuel sources, or you make them less sensitive to fuel sources, they start dying, they certainly start firing less. It makes perfect sense. And I think now it's, thanks to Lisa's work, work that you've done and talked about quite a lot in your books and elsewhere, I think has really highlighted for people that metabolism and metabolomics is going to be as important as genes and genomics when it comes to dementia, perhaps especially in women, is it safe to say that?

- I think so, because we believe that the system is regulated by estrogen. So the decline in estrogen starting around age 40, 43 is kind of the average, seems to be the driver behind cerebral hypometabolism. The way I describe it to my patients is it's like slow brain energy.

So you walk into a room, you can't remember why, you just notice that you can't manage all the tasks the way that you once could. Things are just a little slower. And I say that to women and they're like, "I have that, help me." So this is then circling back to WHI, where women are scared to death of taking hormone therapy.

And we've got all of these women that are marching toward potentially a greater risk of Alzheimer's disease, and they have this opportunity in their 40s and their 50s to take hormone therapy, and they may not be offered it. Because the typical conventional approach based on WHI is to say, "Unless you're having hot flashes and night sweats that are severe, I'm not going to give you hormone therapy." And I just want to call that out.

I would say, "No, that is not the way to approach it." However, the concept right now in conventional medicine is that hot flashes and night sweats are these nuisance symptoms that we will take care of temporarily, maybe with a little bit of estrogen progesterone or a birth control pill, because it's given a lot.

- Or that they pass. - Or that you just suck it up, suck it up. It doesn't matter that you're not sleeping anymore. Turn down the temperature in your room. And that's not right, because hot flashes and night sweats are a biomarker of cardiometabolic disease. They are a biomarker of increased bone loss.

They are a biomarker of changes in the brain. So many of these symptoms that occur in perimenopause are not driven by the ovaries, they are driven by the brain.