This is Your Brain on Hormones

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2:29Wait, you're listening. Okay. All right. Okay. All right. You're listening to Radiolab. From WNYC. See? Yeah.

2:46One 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. And there's so much to unpack here.

3:48Hey, I'm Molly Webster. This is Radiolab. And today... I can go real 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. Emily is a neuroscientist, a 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 cinematic view of how this is unfolding, that was a breakthrough.

4:33Very recently, Emily's lab came up with an experiment 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 a hormone that's a chemical messenger it's a 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 um yeah and then once they start producing hormones the those hormones use your circulatory system, your blood supply is their super highway.

5:45They hit, you know, almost every cell in the body. And that's when you think about like, why do we even have hormones? Like, why is that a thing? Just to make it complicated. Just to make it complicated. Like, why do we have hormones? Because if you're a multicellular organism, if you have more than two cells, those cells need to know how to communicate with one another so that like everything's working together and in sync. And nature's figured out a really clever way to do that. And there's several ways, but hormones are one way. It just seems like a sloppy way to communicate. Like I'm going to wash you in a liquid, like a synaptic connection where there's, you know, a fiber, a cable, and it's sending information from A to B feels like clean and directed and efficient.

6:37So 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 where 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 it's like 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.

7:19Which 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 are 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.

8:04Like, my body doesn't care if I'm at 20 picograms 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.

8:24but 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 um this is a friend and collaborator at stanford named russ poldrak 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 eczema 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.

9:10And 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 is 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. Yep. 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.

9:52That's how I describe myself. 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 left feeling dissatisfied. I noticed for like 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 asterisk cycle, you know, akin to the human menstrual cycle.

10:32And that's just complicated and it's just a lot. And I was like, what the fuck? Like, 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 whack. 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 why she was there, where her keys were. Oh, 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.

11:17Like 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 28andMe 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.

11:57Mario, 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 straitjacket. 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, like, blanket of sandbags. And they would scan her entire brain while she was doing a series of mental exercises.

12:42We did a 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 would 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 going to 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?

13:29And 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. And 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 I didn't even know when I was going to get my period.

14:09But 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 like massive increase in functional connectivity across most parts of the brain. Wait, what is functional connectivity? Like, what am I visualizing when you say that phrase?

14:53This 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.

15:14Imagine, like, let's say we wrapped the brain in a string of Christmas tree lights. I don't know where this is now. We're going to try it. Stay committed and keep going. Okay. We're wrapping the brain in a string of Christmas tree lights. And when Estral peaks, it's right around the time of ovulation. It's 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, so to like walk you through your menstrual cycle, right? Like right after ovulation, you get this plummeting of estrogen.

15:47and 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 discovered is that this region of the brain, and we can actually look at different subfields of the hippocampus.

16:30It's not actually one solid structure. It's got all of these little bits and bops. And that we could see these structures of the hippocampus actually grow and shrink along with the menstrual cycle. I mean, like on a rapid time scale. So 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 a 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.

17:13And 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, prescribe 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, spit stick scan, and... The progesterone-dependent changes that we saw in the hippocampus across the cycle were completely obliterated.

17:59So 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 you're telling me I can keep telling people that at different points of your cycle, your brain changes. Yes. Wow. But I think where 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 it's like 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 like the world is like a little brighter and i'm quicker like i'm like send send give me an improv troupe like i will yes and the shit out of this show you know what I'm saying?

18:53And then when what you're saying, the progesterone takes over and estrogen decreases, and when I'm like right before I'm bleeding, I'm like, give me a sec. Oh, like, yeah, like, what was your name? Like, oh, yeah. There were tears. I remember that was a note. 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. And 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.

19:44I 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.

20:27Women 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 belies the fact that like hormones are in all of us. These are ancient molecules. Every vertebrae has them. Like these are essential. And, you know, men have them too. But it sort of comes right from the fact of like ours females, however, you know, 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.

21:09I'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. Wait, really? Yes. That's right. We're not getting out of this episode without... The trending thing is boy kibble, right? A man. We're going inside the male cycle after the break.

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23:09Shout out to Pavel. The summer that we met, she had done prior that summer this study on herself. And I was just taken aback that someone would do that for science or just stick themselves in a huge magnet for a whole month every day. I mean, immediately I was kind of like, wow, I'm in love.

23:32I've climbed the Eiffel Tower. So when Laura said, Hey, so how do you feel about climbing into the MRI? Pavel said yes. She would always be there by my side. Every morning they'd get in the car. I'd be pooling my saliva. Like collecting it in your mouth. Yeah. 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 phlebotomist.

24:10Then, 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 timescale, testosterone has sort of a daily rhythm. So it's diurnal. It's super high in the morning. I did not know that. Okay. Super high in the morning. And then it drops by anywhere from 30 to 70 percent 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 let's men have progesterone oh yeah they have all the bits and you know that we do just at different concentrations and they you know these hormones cycle in men and so we wanted to understand that?

25:20Like, 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 comb 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 like 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. At evening, it sort of like tightens up a little bit.

26:00And we get the crazy part is that we can literally see this, you know, curiosity, 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 measure that. That's crazy. So it's like these hormones are having the same size effect, whether it's happening on a 24-hour timescale or across the 28-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. That's right. And men are more locked into the 24.

26:44That's right. That's right. I feel contradictory then because somehow in you trying to be like, look, men are part of this equation too. It actually just leaves me feeling like, wow, my hormones are even more up and down than I thought. Yeah. Meaning that 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... Emily 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.

27:30Here'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. Again, 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.