This is Your Brain on Hormones

Wait, you're listening to Radio Lab from WNYC. One of the reasons that I come to you is maybe 10 or 15 years ago, I read a popular science book. I'm not even going to say the title because I think that it was like somewhat controversial afterwards. And I remember this fact, and I think since I read it, I have wondered if it was true, and I've also told everybody this fact. So this is like my live fact check, which is I read that, as you go through your menstrual cycle, the size or shape or makeup of your brain changes. And I remember reading that and thinking, wait, my brain actually physically is changing, is that true? Okay, there's so much to unpack here. Hey, I'm Molly Webster. This is Radio Lab. And today I can go roll far back. We're going hard on a question that I have been thinking about for years. Totally. It's funny as I've been thinking about this topic, everyone's like, honestly, you should just talk to Emily. Oh, like Emily is a neuroscientist and neuroendocrinologist to be precise. And she is on one of the teams that has been struggling to understand how hormones affect the brain because we had these like, these glimpses, these little flickers of what it could be doing. But to watch the full-pum cinematic view of how this is unfolding, that was a breakthrough. Very recently, Emily's lab came up with an experiment to so precise, so daring, it allowed them to pin down what hormones can do to our brains. And here's the thing, even though the story starts with menstrual cycles, it very quickly gets to the fact that women, men, whoever, we are all at the mercy of a crashing, swelling wash of chemicals inside of us. The chemicals we call hormones. So when we say a hormone, maybe we just define our terms, like when we say hormone, that's a chemical messenger. It's a chemical that is released from an endocrine gland like testes or ovaries. You have adrenal glands sitting on top of your kidneys, you have a thyroid gland. And then once they start producing hormones, those hormones use your circulatory system. Your blood supply is their superhighway. Almost every cell in the body. And when you think about why do we even have hormones? Why is that a thing? Just to make it complicated. Why do we have hormones? Because if you're a multi-cellular organism, if you have more than two cells, those cells need to know how to communicate with one another so that everything's working together and in sync. And nature has figured out a really clever way to do that. There's several ways. But hormones are one way. It just seems like a sloppy way to communicate. I'm going to wash you in a liquid. A synaptic connection where there's a fiber, a cable, and it's sending information from A to B feels like clean and directed and efficient. So why would we choose this bathing method? I think because you can't have wires connecting every single cell to every single other cell. Yeah, it would be like a scary motel. You see the wires around the walls. Right. But we have this blood supply that feeds essential nutrients and oxygen to all parts of our body. And so hormones can just basically make use of what's already there in order to get your spleen talking to your heart, talking to your brain. Think of it like a broadcasting system. They're like the PA for the human body. And they go everywhere your blood goes, including your brain. Which brings us back to the brain question, what are hormones doing up there? The science is really, I'd say, mile one of the marathon. No, inch one, inch one. Wow. We're using pretty archaic methods to understand the function of hormones in the brain. And a lot of it is correlational. Like most of the studies take large groups of people and take one snapshot of their brain and take one blood draw. But that snapshot in time, that's not how the endocrine system works. A fundamental feature is that it ebbs and flows over time. It is not static. In fact, all of its power comes from the dynamism of that system. Like, my body doesn't care if I'm at 20 pg per milliliter of estradiol. It cares that I came from zero and I'm going to 200. So it's not the static level that matters. It's the change. And none of our experiments to date were capturing that change. But something happened in the field of neuroimaging about 15 years ago where somebody was like, wait a minute, I'm actually interested in how individuals change over time. This is a friend and collaborator at Stanford named Rust PoleDrak and he completed a project where he basically scanned himself over a hundred times and just collected everything you could possibly collect. Like, how much caffeine did I have today? And how well did I sleep? And like, did I have an exlima flare up? Like literally everything. This is like my dream. Yeah, yeah. And he, that study really launched this whole new way of thinking about the use of MRI to understand dynamics of the brain. And so we, my group, you know, here we are sitting at UC Santa Barbara. And we're watching all of this great science unfold and all of a sudden it unlocks this, you know, this, it sort of solves this major problem for us because we're like, wait a minute, we can study an individual and track this change. And so I had this brilliant graduate student in the lab. Yeah. Laura Pritchett. Yeah, sorry, let me just, I'm going to modify my headphones a little. And she was like, hey, I have normal cycles, I have a summer to kill. I don't really have a life. I volunteer to do this. Emily is a philosopher and I am a country bumpkin. That's why I describe myself and no better case subject than me. So our girl, Laura is actually Dr. Laura Pritchett now. Now I'm in Philly for a postdoc. But in 2018, she was a fresh faced grad student in Emily's lab. She had just started studying neuroscience in her undergrad. And she was less feeling dissatisfied. I noticed for like a week after week after week, the papers we were having to read only included male animals. And I would pose this question of, why is this only males? And I would always get this response of, oh, well, females have an a stress cycle, you know, the akin to the human menstrual cycle. And that's just complicated. And it's just a lot. And I was like, what the fuck? Like, yeah, we, you're studying basic features of the brain. You're also taking these findings and applying them to males and females. So the logic's not there. This doesn't make sense. And that seems pretty wack. At the same time, I remember my boyfriend at the time in college, his mom was going through menopause. And I loved her. And she would just talk to me a lot about how she would walk into a room and forget where, why she was there, where her keys were. You put together like a human female going through menopause. And then at the same time, you're seeing study after study after study doesn't have females in it. Like those two things connected for you. Yes, exactly. Then that led me to go, okay, well, how do sex hormones influence the brain in ways that I can measure? And then you were like, I know who can be the perfect study sample. Yeah, me. I was like, I'll just to answer these questions, I'll just roll up my sleeves. And that's, you know, sort of how 28 me was born. Laura named her experiment based on the 28 days it roughly takes to complete a single menstrual cycle. And for each one of those days, she would wake up, go to the lab, spit in a vial. I did saliva and then I would go get my blood drawn. Mario, the phlebotomist, would poke her in the arm. We tried once to get my foot because I was a little too bruised up and I almost kicked them in the face. Yeah. And then I would go straight to a two hour or so MRI. They put her in a brain scanner and she had to lie totally still. We 3D printed a foam head case custom to me and I actually had them put sandbags on my legs and take straps and strap me in almost like a straight jacket? - I can't believe that made you feel better. - Yeah, that's what I'm saying. I'm a weirdo. - So Laura was in there. She was under this blanket of sandbags, and they would scan her entire brain while she was doing a series of mental exercises. - We did no resting state scan, meaning recording my brain as I'm letting my mind wander. And I would look at highly rewarding food for a block of, you know, a minute. I'd look at very neutral images, like a Q-tip, and we looked at still images of porn. I remember there were like men taking selfies with a mirror, and I'm like, give me a romance novel. Like this is not gonna do this for me, but I did that every day. - And Laura did this, spit stick scan, spit stick scan, again and again for a month. - The hardest part was halfway through, where you're like, I've done 15 days of this. Oh my God, there's 15 more. - And with every scan, they were taking a picture of what her brain looked like on each day of her cycle. And then with every task, they were looking at how her brain worked, literally how it was firing, as she moved through that cycle. - Exactly. Did you like look at your data every day, or did you wait till like the end to look at your data? - Yeah, great question. I waited till the end. So we actually decided to start blind in the middle of a cycle so that I would eliminate as much bias as possible. And I also didn't even know where I was at in my cycle, and I remember her, I didn't even know when I was gonna get my period, but I remember a graduate student had to come and give me like a tampon. - When it was all said and done, Laura and her team had all of these images of her brain. And then alongside that, they had what her hormones were doing at the time the images were taken. And when they put those two things together. - Her data were beautiful. When she started to look at sort of relationships between that period when estradiol peaks right around the time of ovulation, she saw this massive increase in functional connectivity across most parts of the brain. - What is functional connectivity? Like what am I visualizing when you say that phrase? - This is really just a measure of brain regions that are talking to one another. Like all the bits of the brain are talking to one another in a way that's more congealed. So it's like everything is just like hyper-connected. Imagine like let's say we wrapped the brain in a string of Christmas tree lights. - I don't know where this is now. - I love it. - We're gonna try it. - Stick committed. - Okay, okay. - We're wrapping the brain in a string of Christmas tree lights. And when estradiol peaks, it's right around the time of ovulation, like all the lights go on. Like the green lights are like really connected to each other and the red lights are all really connected to each other. It's like they're all like working in sync. And then that's so like walking through your menstrual cycle. Like right after ovulation you get this plummeting of estrogen and progesterone starts to dominate the scene. - And during that moment, which is about a week before your period. - You start to see like those lights dim a little bit. And it's not like the brain activity is dimming or like cognitive functions are dimming. It's just like this shift in the basic connectivity structure of the brain. - It's kind of like the structure of the brain is the same. It's just not as in sync. But we also used a really high resolution scan of the hippocampus. So this is the part of the brain that's really important for learning and memory. What we discover it is that this region of the brain and we can actually look at different subfields of the hippocampus. It's not actually one solid structure. It's got all of these little bits and bumps. And that we can see these structures of the hippocampus actually grow and shrink along with the menstrual cycle. I mean like on a rapid time. - Because that one is actually physical. - That one is physical, it's morphological. It is a change that literally like the brain structure is changing across the cycle. - Really? - That's the thing people can wrap their head around. - My takeaway here is that these liquid chemicals in my body are washing my brain and changing it monthly, weekly, daily. But to be sure. You need to essentially squash the endocrine system. And if you squash it. You don't allow those rhythmic endocrine changes to occur anymore, then let's see what happens. - So they basically do the entire experiment all over again. But this time, Laura, I went to our Student Health Center and I said, prescribed me the most common birth control packet you're giving the undergrads. - She went on a drug that suppressed progesterone levels by 97%. - The birth control basically wiped out the hormones in the back half of Laura's cycle. So that progesterone rise. And then she went back to the lab, spits to scan and. - The progesterone dependent changes that we saw on the hippocampus across the cycle were completely obliterated. - So it did give you a chance to say like, look at the data, these bumps we're seeing are because of estrogen and progesterone cycling. - Exactly, yeah. - Okay, so if you're telling me, I can keep telling people that in different points of your cycle, your brain changes. - Yes, wow. - But I think what we need to be careful is in the interpretation of that fact. So we don't know what it means in terms of behavior. So that's where we have to draw the line. It's like, I don't know if this is good or bad. It's just different. - Well, it's funny. I can tell you what that feels like. In my body, it feels like you're making all these connections and you're going so fast. And the world is like a little brighter and I'm quicker. Like I'm like, send, give me an improv troop. Like I would yes and the shit out of the show. You know what I'm saying? And then when what you're saying that the progesterone takes over and estrogen decreases and when I'm like, right before I'm bleeding, I'm like, give me a second. Like yeah, like what was your name? Like, oh yeah. - There were tears. That was a no. I was crying in the parking lot for some reason. As part of the study, Laura was tracking her mood each day. - Like I was seeing the negative affect rise with progesterone rising. So I was seeing it across multiple days. I was like, wow, like this is real. And maybe for me and maybe not for the female across from me. - Laura and Emily did say they can't peg any particular person's mood or cognition to these hormone changes. I mean, the body is freaking complicated. Like estrogen affects dopamine. For me, that might feel really good to get that extra hit of dopamine. But if you're a person who already has a lot of dopamine, it could make you feel awful. So. - Like I think we still need the data to like understand how that is tied to those aspects of cognition. - If you're like a molly brain, when you first hear this research, you're like, oh wow, it's so cool. Like every day that I have had my cycle since doing this story, I'm like, what's my brain doing today? But it also feels like, oh my God, this is the exact thing that people have been saying for millennia. Women are hormonal. Women change. Unlike men, women aren't reliable. - When you like call somebody hormonal, it's like almost always directed at a woman, right? Like it's a pejorative. But like that belives the fact that hormones are in all of us. These are ancient molecules every vertebrates have. Like these are essential. And, you know, men have them too. - But it sort of comes right from the fact of like, our females are changing on this 28 day cycle. It's like, I'm not saying like men don't have hormones, but I think there is a cycle that women are running through. - Right. - I'm not sure if you're about to tell me like, well guess what, men are going through a cycle too. - Yeah, guess what? Men are going through a cycle too. (laughs) - Wait, really? - Yes. - That's right, we're not getting out of this episode without-- - The trending thing is boykibble, right? - A man. We're going inside the male cycle after the break. (upbeat music) - One of the reasons we did 20 and he. - Oh, is that what it was called? 28 and he? - Yeah. - Oh, that's hilarious. - Fun fact, this was actually Laura's then partner now husband. - I met Laura first, an intramural softball in graduate school. - His name is Pavel. - Pavel Shabdarenka. I am a scientist. - Shout out to Pavel. - The summer that we met, she had done prior that summer, this study on herself, and I was just taken it back, that someone would do that for science would just stick themselves in a huge magnet for her whole month every day. I mean, immediately, I was. kind of like while I'm in love so when Laura said hey so how do you feel about climbing into the MRI? Pavel said yes but she would always be there by my side every morning they'd get in the car I'd be pulling my saliva like collecting it in your mouth like don't talk just gather spit that's right yeah he'd walk into the lab deposit his spit and Mario would come and take some blood I just love this character of Mario the philbotomist then just like Laura he would lie in the scanner still as can be but for his experiment he did double duty the first 15 days we had a morning scan and a morning blood draw and then 10 days into that 30-day period we also started a 15-day nightly scanning why were you getting scanned twice a day whereas you know the main fluctuation of estrogen happens on a monthly time scale testosterone has sort of a daily rhythm so it's diurnal it's super high in the morning okay super high in the morning and then it drops by anywhere from 30 to 70% at night so for Pavel we really kind of capitalized on this known circadian rhythm where testosterone and progesterone and estrogen are peaking in the morning they're dipping in the evening and we said huh like men have progesterone yeah they have all the bits and you know that we do it just a different concentrations and they you know these hormones cycle in men and so we wanted to understand that like is is the male brain undergoing kind of a similar degree of change after all Pavel's data was collected Emily and Laura had their team combed through it and they saw the punchline is that essentially we see the exact same thing that we saw in Laura that like when these hormones are peaking you see the brain become more interconnected with each other and then when the hormones dip in the evening the brain becomes less interconnected and we see you know the brain is pulsing on this 24-hour scale so when hormones are high it's a little bit bigger and evening it's sort of like tightens up a little bit and we get the crazy part is that we can literally see this you know periodicity this wave if you will happening every single day throughout the entire you know he did 40 sessions across 30 days so it's just this like beautiful rhythm that exists and we can we can measure that that's crazy so it's like that these hormones are are having the same size of fact whether it's happening on a 24-hour time scale or across the 20-day menstrual cycle but wouldn't women also be doing this circadian yes that is true so we're getting circadian 24 and 28 across time and men are more locked into the 24 that's right that's right I feel contradictory then because somehow in you trying to be like look at men are part of this equation too it actually just leaves me feeling like wow my hormones are even more up and down then I thought yeah meaning that like it's a surprise that you have a circadian cycle on top of yeah yeah like you're absolutely right in that this myth of female variability and this idea that we have this kind of like pet family said that even though females have these two cycles studies have shown that they're not inherently more variable than males in fact it might be the opposite here's where stuff gets I think funny it's like you know women have this menstrual cycle and for most women for most of our lives it's as steady as the tides right like you know maybe until we start to get to menopause or if there's like a reproductive condition like short of that like it's it is you know this sort of rhythmic event against this yeah it's this kind of predictable thing that is not so true for for male dominated hormones like testosterone which are famously capricious so testosterone can like spike and dip and it's like super responsive to social stimuli so you can study this in you know in animals who get in a fight and you get these like testosterone surges and then if they're they lose a fight you get like testosterone suppression it's true and humans who aren't even engaged in like you know fist-to-fist combat if they're just watching TV and their favorite team loses you can see testosterone suppression so but that's not happening with like estrogen yeah not as much it's really you know again every you know every sex has every hormone is just the proportions that are different but in you know testosterone which is like on average higher in men it's it's it's much more fickle wow so it's just funny to me that women are the ones deemed as this like unknowable you know it turns out all of our brains are oscillating with these hormones whether it's monthly or daily or fickle or regular all of us have estrogen and testosterone flowing in and the brain gets bigger and more connected and then estrogen and testosterone flow out and the brain gets smaller and less connected brains are built to change they're built to learn they're built to adapt and here we have this mechanism this hormonally mediated mechanism that's allowing our brains to do that if brains did not change that would be the pathology of interest well can I just ask a question though I think my takeaway is that the brain is opening in some way when it's bigger or when it's firing in that stronger Christmas tree light like analogy you gave like when it's when it's speaking to itself better that it's opening yeah so like these estrogen rhythms are opening up these windows of of enhanced neuroplasticity and neuroplasticity you probably know this is this idea that the brain is malleable it's open to change and Emily said all sex hormones including estrogen can go into the brain down to the level of the DNA and open it up so DNA is organized in this chromatin structure right so it's actually like pretty tight and closed up like wound tight like he likes and then the helix is like exactly it's really tight right but there but estrogen is one of the factors that that can actually like loosen up the DNA it just it's like it just relaxes a little bit and it can promote you know the production of proteins and then that's the pathway by which learning and all of these great things happen okay but this paper that I just sent you was like I got it like five minutes for the interview so I have no idea what it says I know okay so this is work from tally baron and oh my god it's blowing my mind because this is what the study asked what happens if during that brief fleeting window where estrogen is flooding the system your chromatin is all loosened up it's like it's getting ready for its massage it's on the table it's warm it's like let's go and then you introduce a severe stressor you know blasting loud music you know you're sort of shaking the animal you you know introducing it to odors of its predator if that happens during this period you create a PTSD like phenotype in these animals wow and it's it is long-lasting this study which was done in both female and male mice was an attempt to understand why some people record more trauma than others and one of the takeaways was high estrogen plus stress can produce PTSD then they ask the question okay well what happens in moments of low estrogen what she is suggesting in her data is that actually if you look at the low estrogen periods of the female menstrual cycle that they were immune to these stressors like they had almost like this armor on what this work is suggesting which is so profound is that actually there may be sort of these protective mechanisms of having these beautiful but fleeting windows where you can drive pluscisty but then esters and levels get a little bit lower and you are more resilient to these stressors again pure speculation at this point, the science is so young. I think for me, the thing with this study is that when I think about my period, the moments of high estrogen are the ones that I feel really good in, and the moments of low estrogen are the moments I want to get out of as fast as possible, but maybe at a deep biological level, those moments when we feel are worst. So for me, during my period, maybe for you at the end of the day, those might be moments that are worth sitting in. If you have really high connectivity between regions of your brain, that's really energy dependent. That's Laura again. You could be exhausted. It is funny. Maybe part of what is opening up for me is like, there's so much about, you know, I just finished my period. There's like so much about it where you're like, but I'm just thinking about it in a different way, like as it's almost, it's like a way my body is taking care of itself. Yeah. I think that's a beautiful way of thinking about it. And I think if I teach a class or a guest lecture, I say, what comes to mind when I say estrogen? And it's like Zoe Deschanel's character, a new girl crying and eating ice cream. And it's like, we can move from the stereotypes and be like, wow, hormones are just fucking powerful and they serve a purpose and they're not protective. And if anything, you know, why are we trained to think of the cycle as a source of noise? When in fact, I think it's a source of stability, you know, hormones guide behavior and they do so through this rhythmic action, whether it's across the circadian cycle for males and females or whether it's across something like the menstrual cycle for females. Geez. Are you ever like, damn, our brains 24 hours a day is going up and down, up and down, then every other day it's going up and down, up and down. But I think it's it's like an organizing principle of the brain. It's like, it's, it's creating tiring, but you're saying it's not. I don't know. Like is it tiring for the waves to like, you know, happen on this rhythm? I don't know. Or is it like organizing the system in some really helpful way? Um, I don't know. The, those are the questions that I want to dig into that like, man, we have just like scratched the surface on scientifically. So what make, like just the fact that you could even suggest something like, is it organizing us in a certain way? I'm like, ooh, why did you choose the verb organizing? Why would brain changes be organizational? The brain likes prediction. It likes rhythm. It likes, um, you know, it likes rhythm. You know, like it's, it's, it's, it's like providing a scaffolding or a structure. It's the same thing. Like if you have kids and you let them just like, you know, there's no rules in the house and they could put themselves to bed, whatever they want, or they can eat whatever they want. Like it is high chaos in the house and nobody's happy and nobody functions well. But like you put a little bit of structure, you put a little like organizational structure and then all of a sudden like shit flows better. And maybe that's what hormones are doing. It's like laying down these like fundamental rules, these organizing principles for the brain that can like, that help it function at its most, you know, at its highest level. I don't know. I'm totally speculating here. But yeah, yeah. But, but now we get to at least ask the question of like, is that pulse doing anything that the brain likes or that like helps us in some way? Yeah. Wow. That's a, that's a cool word pulse like brain pulse. Like it's working out up there. Yeah. It's like the heartbeat of something, right? It's like the vital sign. It's like you think of like the ch-chunk-chunk-chunk of like the heartbeat monitor. Like maybe this is the endocrine system. It's like, it's pulsing on these different rhythms and then it's creating these echoes throughout the rest of the body that's like, oh, cool. Like here's the rhythm we get to dance to. And it's, that's what I mean when I am thinking about this sort of organizational framework. It's like, I think it's creating that rhythm for then the whole body to get in sync to. Hmm. I think I'm having this question of the brain is such a regal and like commanding object, right? Like you kind of know how much work it's doing in your body, even though it's part of you, it kind of feels like other, like there's, there's a way in which it just has a, it's all powerful. And so then when I hear something about the brain changes, I'm like immediately like, wow, like awestruck. Yeah. Oh my god. I think that that idea that the brain is like this regal thing is a myth. I actually think it's an organ like every other part of our body. Like I think the, the way we can show that hormones influence aspects of the brain suggest that I don't know, we're all just kind of these like, you know, big buckets of chemicals walking around. And we think we have control. But like, no, we don't. Like I yelled at that person because I'm a hangry. And I, I don't even know if I buy into free will. If I'm being totally honest, I don't know. I mean, I think that there's ways we can gain free will. But like by and large, we are also just like big biological sacks of stuff. And I'm hoping that I'm a big biological sack. But if I know that, if I say it out loud, then I could maybe do a little bit more with the sack. Like I could push it to the left and push it to the right, even if only an inch. That's my, that's my, that's my wish. I do think an understanding of the system allows us to control it. In fact, I was just on a call earlier this week talking to there's this incredible researcher out of Caltech. And he's developing continuous hormone monitors. So we, you know, we have the glucose monitor where we can track. Yes. And now they're starting to develop technology where either from sweat, which seems difficult. But even in like interstitial fluid, you can create a glucose-like monitor that can just give us this kind of constant readout of hormones. I mean, imagine if we could get like a second by second or even just hour by hour readout, we can just watch and observe and see the patterns play out. But that's so huge. I mean, think about the images of Pluto that we had 100 years ago where it's this like grainy little blip in the, you know, in the sky. And now we can see the individual like craters and then you like this idea of let there be light like like being able to see a phenomenon in, you know, incredible detail is the start where all of the breakthroughs happen. This episode was produced by Monomet Galker and me Molly Webster. It was fact-checked by Diane Kelly. I want to thank Sorn Wheeler, Pavel Shepter Enka, Emily Jacobs and Laura Pritchett. Emily hangs out at the University of California Santa Barbara. You can find Laura and Pavel at the University of Pennsylvania in Philadelphia. And you can also find all of Laura and Pavel's data online. Go to open neuro dot org. That's open. N-E-U-R-O dot org props to Laura for making all of her data public. Also a huge shout out to Catherine Woolley, whose original research on sex hormones and the brain was foundational to all the stuff we're talking about today. If you find yourself with some spare time, go to radiolab dot org slash the lab and sign up for our members only. Access you'll get ad-free listening, special content. It's fun over there. And that's it. I'm Molly Webster. This is radiolab and the next time I see you, I'm going to ask, where are you at in your cycle? Hi, I'm Gabby. I'm from the Bay Area, California and here are the staff credits. Radiolab is hosted by Lulu Miller and Let's Have Nossar. Soren Wheeler is our executive editor. Sarah Sandbach is our executive director. Our managing editor is Pat Walters. Dylan Keefe is our director of sound design. Our staff includes Jeremy Bloom, W Harry Fortuna, David Gabel, Maria Paz Gutierrez, Sindu Nain Assambundan, Matt Kielte, Mona Morgauker, Annie McEwan, Alex Neeson, Sara Kari, Natalia Ramirez, Rebecca Rand, Joanna Stroghets, Anisa Vica, Arian Wack, Molly Webster, and Jessica Young, with help from Gabby Santas and Maya Applebeam Milamed. Our fact checkers are Diane Kelly, Emily Krieger, Natalie Middleton, Angelie Mercado, and Sophie Semi.