What Is Perimenopause? | Dr.Sara Gottfried & Dr. Andrew Huberman
00:00:00.000 | To me, this problem is not just menopause.
00:00:06.300 | What's more interesting is to talk about perimenopause.
00:00:10.200 | So perimenopause is the period of time before your final menstrual cycle.
00:00:16.040 | And for most women, depending on how attuned you are to the symptoms, it can last for 10
00:00:21.960 | years.
00:00:22.960 | So I'm still in perimenopause.
00:00:24.240 | It's been like 20 years because I've been tracking it so carefully.
00:00:29.360 | It usually gets kicked off by having your cycle get closer together.
00:00:32.600 | So that can happen in your 30s or your 40s.
00:00:35.580 | You go from 20 days to 25 days, that sort of thing.
00:00:39.160 | You may notice that you start sleeping more poorly because progesterone is so important.
00:00:42.720 | You talked about that with Kyle.
00:00:45.120 | You may notice it as more anxiety, difficulty sleeping.
00:00:48.380 | And that probably is related to the estrogen receptor.
00:00:52.120 | So your alpha is estrogen receptor, alpha is angio.
00:00:58.000 | It increases anxiety.
00:00:59.520 | ER beta is associated with an anxiolytic activity.
00:01:04.600 | And then there's a total of about six estrogen receptors now.
00:01:08.040 | There's the G-protein coupled estrogen receptors, and those are mixed, anxiolytic, anxiogenic.
00:01:15.360 | So there's this whole period of perimenopause, and what's most fascinating to me, and we've
00:01:21.120 | got to talk about this either today or another time, is that there is this massive, massive
00:01:27.080 | change that happens in the female brain that people are not talking about enough.
00:01:32.840 | And so looking at the work of Lisa Moscone at Cornell, from starting around age 40, there
00:01:41.200 | is this massive change in cerebral metabolism.
00:01:44.600 | So you can do FDG PET scans, you can look at glucose uptake, and there's about, on average,
00:01:50.840 | a 20% decline from premenopause, up to like age 35, to perimenopause, to postmenopause.
00:02:01.680 | The women who are having the most symptoms in perimenopause and menopause, the hot flashes,
00:02:06.080 | the night sweats, the difficulty sleeping, those are the ones who have the most significant
00:02:10.760 | cerebral hypometabolism.
00:02:12.240 | - So it's almost like a, I don't want to scare people with this language, but it's a low-level
00:02:21.040 | or let's call it pseudo-dementia of sorts.
00:02:24.400 | - Yes, it seems to be a phenotype that you can then map to Alzheimer's disease, because
00:02:31.080 | that's Lisa Moscone's work.
00:02:32.600 | She's looking at, okay, Alzheimer's disease is not a disease of old age, it is disease
00:02:37.760 | of middle age.
00:02:38.960 | But are some of the biomarkers that we can define that can tell you what your risk is?
00:02:44.320 | I've got a mother and a grandmother with Alzheimer's disease, you can believe I am all over this
00:02:48.880 | data.
00:02:49.880 | - And insulin resistance.
00:02:50.880 | - Huge part of it.
00:02:51.880 | - Insensitivity, as we talked about it before, seems to be somewhere in there, which I think
00:02:58.480 | when that idea first surfaced, a few people were like, "Really?"
00:03:00.720 | But then of course, right?
00:03:01.720 | I mean, the brain is this incredibly metabolically demanding organ.
00:03:05.320 | You deprive neurons of fuel sources, or you make them less sensitive to fuel sources,
00:03:11.280 | they start dying, they certainly start firing less.
00:03:13.440 | It makes perfect sense.
00:03:14.440 | And I think now it's, thanks to Lisa's work, work that you've done and talked about quite
00:03:19.640 | a lot in your books and elsewhere, I think has really highlighted for people that metabolism
00:03:26.840 | and metabolomics is going to be as important as genes and genomics when it comes to dementia,
00:03:33.920 | perhaps especially in women, is it safe to say that?
00:03:37.400 | - I think so, because we believe that the system is regulated by estrogen.
00:03:46.960 | So the decline in estrogen starting around age 40, 43 is kind of the average, seems to
00:03:52.520 | be the driver behind cerebral hypometabolism.
00:03:55.560 | The way I describe it to my patients is it's like slow brain energy.
00:04:00.720 | So you walk into a room, you can't remember why, you just notice that you can't manage
00:04:05.120 | all the tasks the way that you once could.
00:04:07.520 | Things are just a little slower.
00:04:09.800 | And I say that to women and they're like, "I have that, help me."
00:04:15.080 | So this is then circling back to WHI, where women are scared to death of taking hormone
00:04:21.280 | therapy.
00:04:22.640 | And we've got all of these women that are marching toward potentially a greater risk
00:04:27.080 | of Alzheimer's disease, and they have this opportunity in their 40s and their 50s to
00:04:32.240 | take hormone therapy, and they may not be offered it.
00:04:36.160 | Because the typical conventional approach based on WHI is to say, "Unless you're having
00:04:41.560 | hot flashes and night sweats that are severe, I'm not going to give you hormone therapy."
00:04:45.600 | And I just want to call that out.
00:04:47.040 | I would say, "No, that is not the way to approach it."
00:04:51.440 | However, the concept right now in conventional medicine is that hot flashes and night sweats
00:04:58.280 | are these nuisance symptoms that we will take care of temporarily, maybe with a little bit
00:05:03.520 | of estrogen progesterone or a birth control pill, because it's given a lot.
00:05:07.040 | - Or that they pass.
00:05:08.040 | - Or that you just suck it up, suck it up.
00:05:11.120 | It doesn't matter that you're not sleeping anymore.
00:05:14.780 | Turn down the temperature in your room.
00:05:17.280 | And that's not right, because hot flashes and night sweats are a biomarker of cardiometabolic
00:05:24.280 | disease.
00:05:25.280 | They are a biomarker of increased bone loss.
00:05:28.960 | They are a biomarker of changes in the brain.
00:05:32.860 | So many of these symptoms that occur in perimenopause are not driven by the ovaries, they are driven
00:05:37.640 | by the brain.
00:05:38.480 | [music]