How Menopause & Estrogen Impact Brain Function | Dr. Mark D'Esposito & Dr. Andrew Huberman
00:00:00.000 | - Are there any sex differences, male-female differences
00:00:05.000 | in sort of these dopamine levels, working memory,
00:00:10.320 | injuries, concussion, like things that would direct people
00:00:18.360 | toward different routes of treatment given that, you know,
00:00:22.680 | maybe there's more susceptibility in one case,
00:00:24.560 | maybe less susceptibility,
00:00:25.740 | maybe certain neurotransmitters are more effective
00:00:27.820 | in improving symptoms in men versus women.
00:00:32.280 | Do you see that in the clinic?
00:00:33.780 | - Yeah, that's a great question.
00:00:36.600 | There was Emily Jacobs, who's a professor
00:00:39.440 | at UC Santa Barbara now in the psychology department,
00:00:42.540 | when she was a graduate student in my lab,
00:00:44.200 | studied the role of estrogen on working memory
00:00:47.680 | and dopaminergic function.
00:00:49.600 | And what she brought to my attention at the time,
00:00:51.560 | and it was embarrassing that I didn't know,
00:00:53.720 | was that the frontal lobes are full of estrogen receptors.
00:00:57.340 | There's probably more estrogen receptors
00:00:59.200 | in the frontal lobes than any other part of the brain.
00:01:01.800 | - In men and women.
00:01:02.640 | - Estrogen boosts dopamine.
00:01:04.360 | So higher estrogen levels correlates
00:01:07.280 | with increased dopamine levels.
00:01:10.440 | And there was some anecdotal evidence
00:01:12.920 | that in postmenopausal women who were put on estrogen
00:01:16.600 | that their working memory improved,
00:01:18.560 | and there was a kind of evolving link
00:01:20.740 | between estrogen and frontal lobe function.
00:01:23.000 | She did this amazing study where she studied
00:01:25.960 | healthy Berkeley undergraduates at two points in time
00:01:28.960 | during their menstrual cycle when estrogen was at its lowest
00:01:31.280 | and what was its highest, and she also genotyped them
00:01:35.200 | for this enzyme they were talking about
00:01:36.920 | to know if they were sort of lower or higher
00:01:39.120 | on the dopamine level, and then put them in the scanner
00:01:43.240 | and measured frontal lobe function,
00:01:44.800 | and showed that there was a clear,
00:01:47.440 | the frontal lobe function was modulated
00:01:49.900 | by where they were in their estrogen cycle.
00:01:51.700 | When they were low estrogen, they were low dopamine,
00:01:54.160 | and if they were low estrogen and low dopamine to start,
00:01:56.680 | they really had decreased frontal lobe function
00:01:59.760 | and decreased working memory ability.
00:02:01.640 | So it fluctuated based on this interaction
00:02:04.760 | between estrogen and dopamine,
00:02:07.120 | suggesting that not only is dopamine important,
00:02:10.040 | but hormones are clearly important,
00:02:13.160 | and they work synergistically.
00:02:15.800 | So as we're developing this cocktail,
00:02:19.220 | we certainly have to bring hormones into the equation
00:02:23.840 | and learn more about it.
00:02:25.460 | There's just so little information
00:02:27.080 | about hormones and cognition.
00:02:30.640 | - Yeah, one of the themes that's come out
00:02:32.280 | of some of the episodes we've done with MDs
00:02:34.280 | who specialize in endocrine health
00:02:36.360 | is that for both men and for women,
00:02:38.840 | optimizing estrogen levels is really important
00:02:42.360 | for cognition and vascular function.
00:02:44.120 | I think people mistakenly hear,
00:02:46.360 | okay, testosterone, men, estrogen, women,
00:02:49.320 | obviously both hormones are present in men and women.
00:02:51.540 | In fact, I think, I know that testosterone levels in women
00:02:56.400 | are actually higher than their estrogen levels
00:02:58.560 | when you sort of use the same units of measure.
00:03:03.560 | It just so happens that they still have lower testosterone
00:03:06.800 | on average than the typical male,
00:03:08.800 | but that men whose estrogen levels are too low
00:03:12.280 | suffer cognitive defects and vascular defects.
00:03:16.240 | So this idea that more testosterone,
00:03:18.000 | lower estrogen in men is the ideal,
00:03:21.480 | and it just doesn't hold, it doesn't hold.
00:03:25.280 | I mean, unless you want to be dumb and have a heart attack,
00:03:28.040 | it just doesn't hold, very interesting.
00:03:32.220 | Do we know what estrogen is doing there?
00:03:33.800 | Is it, it's specifically raising dopamine.
00:03:37.080 | We don't have to get into the synaptic biology,
00:03:39.000 | but it's so interesting.
00:03:40.740 | - Yeah, it's actually boosting dopamine activity.
00:03:43.740 | - So it's making more dopamine available.
00:03:46.240 | - Yeah, yeah, it's really amazing.
00:03:49.960 | And to think about it sort of fluctuating,
00:03:54.960 | certainly during the menstrual cycle,
00:03:56.400 | we can think about how much it fluctuates
00:03:58.040 | in an individual woman over 30 days,
00:04:00.000 | but then you can think across individuals,
00:04:01.960 | you can think about how much it can account
00:04:04.480 | for individual differences.
00:04:05.800 | So not only sort of knowing your dopamine level,
00:04:08.600 | but just knowing sort of estrogen and serotonin
00:04:11.960 | is really going to be important.
00:04:13.800 | - Interesting.
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