The Period Brain: Understanding Progesterone and Its Impact on Women’s Health | Ep. 593

Full Transcript: Episode 593

Lisa: This is the Fertility Friday podcast episode number 593.

Lisa: I’m so excited to welcome Sarah Hill back to the podcast today. In today’s episode, we are talking about her new book, The Period Brain. And it is absolutely not just another period book. She delves into the science and really important issues as we’ll touch on in today’s episode behind why women tend to feel so bad for half of the cycle. I certainly have a lot to say about that. But what I found most fascinating about Sarah’s book is her deep dive into the science and the way research is done, specifically the differences between men and women and how they’re not taken into account when they do the research. So she really dives into some fascinating details for where our research is lacking and how far behind women have fallen just because of the lack of accurate research on women. And that applies to all different areas from the drugs that are approved on the market to even just basic understanding about how our bodies work. So I feel like this interview provides much a much needed explanation for why as women we often feel so misunderstood, why we often feel that our healthcare providers are not prepared to support us. And I think it’s really validating. It doesn’t make it easier though because it still means that we are misunderstood and we are underrepresented in the research and it does mean that there are many situations where our healthcare providers aren’t necessarily able to support us because literally the research isn’t even there.

Lisa: So with that said before we jump into today’s interview I’m going to quickly share a little bit about Dr. Sarah E. Hill. She is an award-winning researcher, professor, and author of This Is Your Brain on Birth Control, which changed the national conversation about women’s hormones and the birth control pill. And her new book, The Period Brain, is due out in September. So let’s go ahead and jump into today’s interview with Dr. Sarah Hill.

Lisa: Well, without further ado, I’m so excited to welcome Dr. Sarah Hill back to the podcast. Welcome back to the show.

Sarah: Thank you so much for having me back.

Lisa: Well, I’m so excited to have you and we were just talking about how much has happened since we last spoke and of course your new book. I mean, I reached out to you. I was so excited about this topic because I feel like it’s a topic that hasn’t really been addressed well.

Sarah: Yes. Yeah. No, it’s funny because yeah, there’s a lot of talk about estrogen, you know, especially on social media. It’s like we finally have gotten to a place where people understand and are willing to address the fact that women’s hormones cycle, right? And that our hormones matter. And so like we’re there, but the only hormone that anybody’s talking about is estrogen. Yeah. And so I wrote this book because it’s like we know all these like wonderful fantastical functional things that estrogen does like oh estrogen increases at times in the cycle when sex can lead to conception and because of that we feel so sexy and alive and partners find us maximally attractive and all of these things and isn’t it great? And then it’s like and then there’s progesterone and it’s like oh yeah and then there’s that other hormone in that other cycle phase but it’s like nobody really talks about it and like what is that also serving a purpose like what does that hormone do like and so I really got interested in trying to understand this what I always like refer to as like the dark half of the cycle right it’s the cycle it’s the dark half of the cycle both because nobody knows about it because nobody talks about it and it’s also the dark side of the cycle because it’s a time that a lot of women don’t like the way that they feel. And so I wanted to get and sort of unpack like what is this hormone progesterone actually doing, right? And might some of these things serve a purpose? And then also why is it that we feel terrible? And so that’s what the period brain is like really all about. It’s trying to uncover this like dark half of the cycle and try to better understand what it is that our body is up to and then also how we can minimize some of the psychological turbulence and physical turbulence that women experience during this time.

Lisa: Mhm. Well, I was really excited to see your take on it. I mean, I really loved the approach that you took in your first book, This is Your Brain on Birth Control. I mean, it was I love the way that you really delve into the science behind it because it kind of cuts through the noise. It’s not just about what people are thinking about it or what they are saying about it. And then it’s interesting because when you broach some of these topics, there’s a lot of people who have I don’t know whether it’s just a lot of negative opinions about it or they kind of don’t like you questioning these things or whatever it is. But when you just give them the actual science, I feel like there’s not much else that can be said about it.

Sarah: Right. Yeah. Well, it’s yeah. It’s funny because there is a lot of people with very strong opinions about the birth control pill and whether it’s good or whether it’s bad and yeah and I do think that I came in and the message is like it’s good and bad and it’s all about understanding the trade-offs and then figuring out where you land because I mean I really whenever I’ve approached a research topic whether it was a birth control pill or in this case it’s just women’s cycling hormones it’s never been with some sort of an end in mind about what I think other people should be doing. It’s always been something that I’ve approached as like a scientific curiosity and trying to like uncover all of that. And I think that in the process of that and then just presenting the information to people, I think that people are able to take that information and then use it in whatever way best serves their own needs. And that’s my goal, right? It’s like I’m a university professor. I spent my career teaching people and that’s really what this is is it’s like an extension of my educational outreach and yeah and because of this I think that it does cut through the noise because it’s not here’s how I think you should be living your life and here’s what you need to be doing and instead it’s like hey here’s some information for you and like godspeed.

Lisa: I love that and I love that you focused on progesterone. So I mean that hits for me because my kind of first foray into that realm was through the work of Jerilynn Prior with progesterone and bone formation. And it’s unreal when you actually read the research about bone formation because it is all about estrogen and nobody talks about progesterone at all and even how they define HA as an estrogen deficient condition, which is true, but it’s like but there’s no progesterone either, right?

Sarah: No. Well, it was so crazy. So I love her. I think that she is such a like a firecracker of a human being. I mean, she’s so smart and so energetic and she’s been beating this drum for years, saying, “Hey, hey guys, like we have two primary sex hormones, not just one.” And so I just learned so I wrote this book and it’s coming out at the end of September. And so I’ve been like deeply steeped in progesterone. And one thing that I just learned was that in hormone therapy that when people are being given biologically identical hormone therapy that they’re usually only given progesterone if they still have a uterus. And the idea is that it doesn’t matter if you don’t. And so women who are put on hormone therapy if they’ve had a hysterectomy aren’t given progesterone because there’s this idea that with progesterone that the uterus and I stole this from Jolene Brighton. It’s like one of the funniest things I’ve heard and it’s so smart is that they’re treating the uterus like Vegas, right? And they think that like what happens there stays there, which it’s not. It’s like progesterone just like estrogen influences all the cells in the body. And the idea that we’ve somehow have this like idea that it only matters if you need to thin out the cells in the endometrium is just completely nuts. And it goes to show how much of a short shrift progesterone has been given. And as you noted like with bone formation, it plays a really important role. Jerilynn Prior, Dr. Prior has shown in her research that if you just give women micronized progesterone that can be just as palliative as estrogen for treating hot flashes in menopause and perimenopause and is so much safer than estrogen because there’s a lot of women who can’t use estrogen either because they have thrombotic risks. So women who have risks for strokes and blood clots are oftentimes contraindicated against estrogen or women who have estrogen receptor positive breast cancer oftentimes don’t want to have them on estrogen and they’re not given anything. And so they’re just having to like suffer because nobody’s really paying any attention to the fact that she’s got these really beautiful, you know, randomized control trials showing that progesterone is just as effective as estrogen in treating hot flashes. But it’s like nobody talks about progesterone. It’s like just seen as this throwaway hormone. And the other thing that’s crazy about it, and I’m sure you’ve seen this too because Laura Briden’s done a really nice job of amplifying this message as well. But it’s like if you actually look at there’s this figure of the menstrual cycle that we all see where you see this bump of estrogen, this big beautiful bump of estrogen in the first half of the cycle and then you see this big bump of progesterone in the second half of the cycle. And the way that it looks from the picture is that the bump in progesterone is about the same size and magnitude as the bump in estrogen. But the fact is that they’ve got that scaled at a level that’s 10 times the levels of progesterone that are being plotted are at levels that are 10 times higher than the levels of estradiol. And if you actually plotted it and had them both on the same axis, the levels of progesterone are 10 times higher than peak levels of estrogen or peak levels of progesterone are 10 times higher than peak levels of estrogen in the cycle. You never know that from these pictures that we see. And it looks like estrogen is kind of running the show and we have this like really huge levels of this other hormone and nobody’s talking about it. We don’t know what it does and one of the takeaway messages from the book is like no wonder we all feel terrible because no one’s even talking about it.

Lisa: Well, and that graph that you talked about, I mean, that’s one of the most powerful teaching tools that I use because when people see that, all of a sudden, it’s like, whoa, progesterone has entered the chat, right? Like no one realized that. No, no, no. Like there’s if we were to kind of make a joke about it, it would be like the progesterone be hitting the ceiling on the graph, right? Like but we don’t really think about it. And there’s no better example like for the purpose of this conversation I feel like than thinking about PMS. I mean ask any woman who has a really rough time in the post-ov how important progesterone is to her. I mean maybe because we’re not educated about her cycle. She might not understand that it’s the progesterone potentially that is at the root of this issue but ultimately it makes such a big difference. So I mean one of the things that you say in your book is that PMS is not a biological defect, but a predictable response to a system that ignores women’s hormonal reality. Of course paraphrasing potentially here, but this is what we’re getting at. And I would love to hear you just delve into more of that. And one other thing I’ll say is that one of the things that really struck me is how you called out how research is done, right, on men and this whole thing of only focusing on estrogen. And it’s like they’re, this is just my thinking, but it’s like they’re trying to make this, well, men have testosterone, women have estrogen, and they’re kind of just trying to make this like comparison that doesn’t compute, right?

Sarah: No, it’s a one-size-fits-all way of doing research that’s been based around a male ideal. And so just to kind of get into this, when we look at the history of science and research on human beings and even on non-human animals, it all started out with researchers studying men and males, right? So male mice, male rats, human males. And the reason that men were studied first is because nobody cared about women, right? And so you move forward and finally people are like, you know what, we probably should care about women. And so they decided that we needed to include women and then female subjects when we’re talking about non-humans in research. But then they had to deal with the fact that our hormones cycle, right? And that’s another reason that it’s been really convenient to exclude women and females from research is that we do have cycling hormones. And researchers know that these cycling hormones influence everything in the body, right? So they know that if you’re measuring a woman in the follicular phase when estrogen is the primary hormone, you’re probably going to get a different set of responses from a drug treatment or some sort of an intervention than you’re going to get if you measure her in the second half of the cycle when progesterone is the dominant hormone. And researchers know this and because of this they know that they need to find some way right to account for women’s hormonal changes. But rather than making the decision that women’s hormones matter and therefore we can’t really actually understand women until we measure them in each of their major cycle phases, right? When estrogen is the dominant hormone and then when progesterone is the dominant hormone. They made the decision like, well, let’s just minimize the impact of their hormones on outcomes at all and then we can just measure them just like men. And so rather than studying women as women or females as females, what researchers do in animal research, what they’ll often do is ovariectomize the mice or rats. So they’re including females in research to say, “Look, we studied females, but they took out their reproductive organs, so they’re not making any sex hormone.” And so essentially, they’re just like males. And then with human subjects, obviously we can’t do that and get ethical approval. So instead, what researchers do is they only include women in research during the first nine days of the menstrual cycle. So before any levels of hormones are very high and when estrogen is really the primary sex hormone and the only hormone that’s really being released in any quantity at all. And so researchers did this so that way they could keep studying women the same way they’ve studied men, which is in this like one-size-fits-all sort of way. And a lot of this is really steeped in this idea that what it means to be human is to be male. It’s like our ideas about what it means to be a human are all based on one day is the same day hormonally. And any day I pluck you out of a calendar and measure you is going to be the same. Your body is going to respond the same way it would any day that I pluck your body out from a calendar.

Sarah: And with women, it just doesn’t work that way. But science never designed research that includes women to actually understand women, right? Because if they were actually trying to understand women, they would measure us at different times in the cycle so that way they could find out how our bodies and our brains react to different types of interventions depending on which of the primary hormones is dominant, but instead they’ve just minimized the impact of our hormones on outcomes at all. And what this means is that adding women into research isn’t actually being done in a way that helps us understand women. And instead it’s just being done in a way that allows us to pat ourselves on the back and say, “Look, we’re including women in research. Look at all this and it’s ludicrous and it’s preventing us from understanding women.” And it’s also now muddying the water and making it so we can’t really understand men either because the other thing that happens in research that a lot of people aren’t aware of is the fact that now that there are these mandates that you have to include females in research. And so researchers are like, “Haha, okay, that’s great. We’re going to include women during the first couple of days of their cycle when hormone levels are low.” But then what they also don’t do is they’re not including sufficient numbers of males and females to be able to test for sex differentiation. And so now you’ve got this data that’s collected on some women and men. And it’s never even looked at whether or not there’s going to be sex differences in any outcomes, which is absolutely ludicrous because we know that there’s sex differentiation throughout the body. It’s like as time goes on, people in fields ranging from like cardiology, so heart doctors are starting to understand that men’s and women’s hearts and their cardiovascular systems don’t always respond the same way to the same types of treatments, right? To immunologists who are beginning to learn that the way that male and female bodies deal with things as simple as bacterial threats differ, right? But we’re beginning to understand that there’s sex differentiation throughout the body and that we’re not testing for this. And then when we’re including females in research or women in research that we’re only looking at them when they’re in the sort of under the beautiful spell of estrogen, it’s no wonder that we feel terrible, right? Because not only have we dismissed and sort of minimized the impact that our hormones have on all kinds of outcomes, making women not really appreciate just how much of a remodeling project their body is doing every cycle as they shift between these two different hormonal states. But it’s also it’s created these like guidelines for living, right? From everything ranging from how much sleep we need to how many calories we need, what sexual desire is supposed to look like, what our side effects for medications are supposed to look like, that are all one-size-fits-all, right? And so they’re all based on either men or on women in the early phases of the cycle. But the fact is like that’s not how we work, right? We’re cyclical. And so when we apply these guidelines for you know what we should be eating and what sexual desire is supposed to look like and what our side effects from our medications are supposed to look like that have been taken from the follicular phase when estrogen is dominant they don’t always apply to the luteal phase and the fact is that it makes many of us feel miserable and one of the examples I give of this in the book is this idea that we need to have x number of calories every day you know it’s like our resting basal metabolic rate requires that we have x number of calories a day. And all of us have been force-fed this since we’re a kid, right? You need this many. If you have this activity level, then this is the number of calories you need a day. And that’s all well and good if you’re a man. But for women who cycle, your basal metabolic rate increases between 7 and 11% when you’re in the luteal phase of the cycle. And that means that if you’re somebody who eats 2,000 calories a day, you’ll need between an additional 150 to 200 calories a day. Right? This is not something that women are told about. And the result of that is when they’re following these like one-size-fits-all set of nutritional guidelines that we’ve all been given is that women are feeling hungry, tired, angry, having food cravings, and then they see their kids’ Halloween candy, right? And then they go crazy because they’re hungry and they’re not feeding themselves. And then they get mad at themselves, right? And then there’s this whole narrative that so many women develop over the experience of being given guidelines that don’t fit their bodies where women have this idea that their body is the enemy, right? And that their body is the thing that’s standing in the way between themselves and meeting their goal because they don’t understand why their body is working against them. And they don’t realize that they’re working against their body by doing what they’re told they’re supposed to be doing. And it’s because all of us have been told like this is what it means to be human. You need this many calories a day. You need this is what like I said this is what sexual desire looks like. This is what your medication side effects look like. This is what the symptoms of your chronic illness look like. And for women it changes across the cycle. And so most of us feel crazy about half the time because the way that we’re responding and our body is responding to things isn’t the same every day. And we really need to wrap our arms around that idea and get comfortable with the fact that our hormones matter, which is why I love the work that you’re doing. I love the work that other people in the space are doing. It’s like it’s about time that we have this awareness of how important these things are.

Lisa: I mean, there’s so much of what you said that I don’t even know if I can unpack, but I feel like so when I’m looking at research, I’m often looking at menstrual cycle research, and my gripe is that they’re not tracking cycle parameters in a way that makes sense or that, right, like certain things like that. But you just took it to a whole other level in terms of educating us about how research is done with the mice with the ovaries removed or with what you said about how they just only test women for whether it’s medication, side effects, things like that at the one time of the cycle. I was being interviewed this recently and I was in a room with all these men because like the men were the ones doing the AV equipment and the lighting and all that and I was talking about how they only recently started studying females and female animals even and they were shocked and all these questions from the men were just like what are you talking about but it’s like in name it’s lip service only based on what you’re saying and I’m still there when you said that that really hit and resonated and it’s just it’s just so deep and vast. How little we know. I know that that’s a weird way to say it, but like how little we know is so like it’s ridiculous.

Sarah: No, it is. No, it really is. And I mean, honestly, like one of the things I write about in my book is that science needs a do-over. Like we just need to we need to scrap the way that we’ve been doing it because I mean it was it was all based on the idea of a male body and it doesn’t work for a female body and instead they’ve just tried to shoehorn the female body into this like one-size-fits-all prototype and it just doesn’t work for us and the result is that we’re never studying women as women. We’re studying women from a tiny little moment in time that makes up about 20% of our lives. And that means that 80% of the time our body isn’t responding to the way that it’s being tested. And so it’s no surprise at all that when you look at medications like 80%, something like 80% of new drugs are pulled from market the first year of use because of unanticipated side effects on women. 80%. And so I mean that means that anytime a new drug comes out and you’re trying it as a woman, you don’t know it, but you’re part of a trial because they’re just like throwing it out there because it got approved because the studying women in this really tiny moment in their cycle didn’t respond poorly to it. But the fact is our bodies metabolize things differently across the cycle. Metabolism changes, our immune system changes, our inflammatory processes change. I mean there’s a million things that we don’t know. Nobody’s even thought to test some of these things. Like for example, we know that during the luteal phase that progesterone because it’s immunomodulatory, it shifts us from a pro-inflammatory TH1 type of immune response to a more anti-inflammatory TH2 type of response. I’m guessing that this means that there’s an optimal time in our cycle to get an immunization, but nobody has looked at that. But it’s like it’s totally nuts. I mean, it’s just totally nuts when you think about the implications that recognizing that our hormones matter, like the implications of this on the ways that we could vastly improve things like surgical outcomes, the immunity developed from immunizations, etc., etc., etc., and the way that we metabolize drugs and our side effects from drugs. And nobody has thought to do this because everybody wants to just push forward with the status quo because it’s easier and cheaper to do. But the easy and cheap isn’t the right way to do it and it’s going to be a way that all but ensures that women are never understood.

Lisa: Well, easy and cheap for them, very expensive for us.

Sarah: Yeah. No, exactly.

Lisa: I want to hear your thoughts on something because it occurred to me that I’m always looking at menstrual research and there’s a lot of interest in this area of kind of cyclical changes. So there are a lot of research studies out now about like you said the metabolism changes whether women are sleeping differently at different times of their cycle whether they are processing their food differently or whether their natural cravings go up and things like that but I feel like even that gives a false sense of security or a false sense of understanding we think that they’re making so much progress but these are studies on that thing they’re not what actual drug companies are doing to determine if their products are safe for us or appropriate for us at different times of the cycle. So I feel like you’re hitting on something huge like are you the first person to be talking about this?

Sarah: I don’t know that anybody else is talking about this really loudly and but it’s so funny because in science we call it procedural inertia, right? And it’s like where you get handed down from your research mentor like a way to do research, right? And then you just keep doing things the way that they’ve done them because you’re told this is the right way to do it and so you just do it without really thinking about whether or not this makes any sense. And I think that for me because I kind of came into the world of neuroendocrinology from a background in evolutionary biology. So my background was always very steeped in understanding the evolutionary processes that have shaped sex differentiation. So my whole background is on sex differences and like how the fact that because women are the ones who give birth and have to deal with pregnancy and all this that this sort of puts us on a different evolutionary path than the male path because we’re each having to solve different sorts of adaptive challenges just based on our different reproductive biology. Right? So my background has always been on like as an undergraduate and a young graduate student was very much all about sex differentiation and like deep appreciation for the ways that males and females differ. And then I go into the world of neuroscience and neuroendocrinology and I see that the way that they’re studying females or women is just by focusing on this little tiny narrow window in time and never actually looking at what about them makes them different and instead just trying to make them fit like men in a research design. I was like this doesn’t make any sense at all. Like what and it’s the gold standard. That scene is the gold standard because you’re keeping hormones consistent and like isn’t that great? We’re controlling for this extraneous variable, but this extraneous variable is like our lives. It’s like if you’re a woman, you know, it’s like that’s your life, that extraneous variable. And it is — I mean, it’s just so nutty to me. And so I don’t know anybody else who’s speaking about this about this particular issue, but it is something I think like needs to be shouted from the rooftops because I think that it’s like I think even some of the scientists who are doing this if they actually sit with it for a minute and say like do you think that this is going to actually help women understand themselves like as they live? No. No. No, it’s not. No.

Lisa: And then how deep does this go? Because how many women are on contraceptives? How many women are past cycling? How many like there’s other variables as well. So I guess the like hundred million dollar question is based on all of what you’ve seen and what you wrote about, do you have any — I’m sure you have ideas of how this could be better. I don’t know that anyone has a silver bullet.

Sarah: Yeah. No. So I mean for me in the last chapter of the book I make some like I say like here’s what we need to do because I really do think that science needs a do-over. And I think that there are two things that we really have to take the spotlight. The first is understanding that sex differentiation exists throughout the body and that we need to get rid of this idea of bikini because people talk about bikini medicine, but bikini medicine is nothing more than an outcome of bikini science, right? Because science has all been done with this idea that the only differences between men and women are the parts of the body that are covered by a bikini, right? Hence bikini medicine and then bikini science. But that’s just not true, right? And the more research that gets done, the more deeply we can’t deny the fact that there’s sex differentiation throughout the body. And so we need to as researchers go into studying men and women with the assumption that there might be sex differences. So I don’t think that researchers should be allowed to have study designs that don’t have sufficient numbers of each male and female participants to be able to effectively test for sex differentiation in outcomes because sometimes there won’t be sex differences in outcomes. So let’s say you’re looking at something like I don’t know a pulmonary function and there’s something where there’s not sex differentiation. Great. But that should be the researchers should have to demonstrate that there’s not sex differences. We can’t make the assumption that there’s no sex differences. That shouldn’t be the null hypothesis. The null hypothesis should be there are differences and that we have to show otherwise if we’re going to get away with only including males or only including females or lumping them together without testing for sex differentiation. So that’s the first thing. Second thing that needs to change is that women and females need to be studied as women and females. And that means that we need to be studied at each of the major phases of the cycle. And this is obviously we can get and I’m sure you do, it’s like we can get a lot more fine-tuned than that, right? Again get into the cycle as like four phases and then there’s this and this and this but at a minimum looking at women when the primary sex hormone is estrogen and women when the primary sex hormone is progesterone I think will go a long way and then obviously moving forward you know as we move forward in the world so one you know it’s like study understand that there’s sex differences throughout the body and you should test for them two study females as females right and study at each of the major phases of the cycle and then so those are like my two like let’s if we do this I think we’re doing pretty well and then as we move forward I think because women are I mean we’re a moving target we also have pregnancy lactation perimenopause menopause we need to really start to understand the limitations of our understanding of women when we’re not studying them in the different phases right like of life and so eventually I think that we also need to with some of the things that we’re testing if we’re interested in intervention and especially if it’s an intervention for menopausal women, then we need to be studying menopausal women obviously or not so obvious apparently.

Lisa: Yeah. No, that’s what I mean because it’s like even with things like they’ll test things on women like cycling women and then tell pregnant women that these things are fine because they don’t go through the and usually the way that they make that determination is whether or not it goes through the placenta. But it doesn’t consider the fact that the pregnant woman herself is a different version of herself, right, than she is when she’s not pregnant. And so determining whether or not something is a good idea for a pregnant woman to be taking. The only litmus test shouldn’t be just whether or not it passes through the placenta, right? It’s also that her body is different and is it safe for that body. And these are questions.

Sarah: Well, the hormone levels during pregnancy are just not the same at all.

Lisa: Yeah. No. Wildly higher. Yes. Much higher. And yeah and again changing your body at the same time. I know people refer to perimenopause as like the second puberty. I refer to pregnancy as the second puberty because your body literally changes. I mean I got new breasts like your brain is different like right. And then it’s you got a totally different situation going on. There’s even research on how it can rejuvenate the cervical crypts. Like it’s just a whole situation.

Sarah: Yeah. No, your body goes under like a major remodeling project with pregnancy and it changes you forever as noted. And in fact, there’s this really I have to tell you about this. I know you’re going to love it because it’s like it’s really cool research. But there’s this idea out there because you know that women get like the rates of autoimmunity are just like through the roof relative to men. And there’s this hypothesis out there that I think is so cool and I think that it’s spot on and it’s essentially the pregnancy prevention hypothesis. And it’s like or the pregnancy hypothesis and it’s this and that is that throughout most of history humans spent a lot of time pregnant. Women did because we didn’t have birth control and presumably women weren’t charting and cycling you know and doing all the things. And so women spent a lot of their time pregnant a lot more time than they do now. And they’ve done some average numbers of years that women spent pregnant by looking at contemporary hunter gatherer groups and I mean several years of our life spent pregnant. And there’s this idea out there that because progesterone is like this very powerful anti-inflammatory immunomodulatory hormone that one of the reasons that we may be seeing so many such a high rate of autoimmunity in contemporary women is because we’re not pregnant so much and that we no longer have this brake pedal that was being pressed on our immune system for all of these years that we spent pregnant. And the result is that we have this unchecked inflammatory pro-inflammatory type of an immune response which could be contributing to the really high rates of autoimmunity that we see today. Which I think is a really interesting hypothesis. And I also think what’s really interesting about that is that especially for women who are on the pill who don’t they don’t get to experience progesterone. They just get those synthetic progestins which are not the same thing and they don’t have these same beneficial effects in the body. Is that what if we gave these women micronized progesterone while they’re on the birth control pill and see whether or not we can’t start to cut back on some of these lowering the rate of autoimmunity specifically in these groups because we do know that the birth control pill is also linked with a greater risk of developing autoimmune disorders. So anyway, just another really sort of interesting thing that it’s like pregnancy absolutely remodels our body, right? And has all these different types of effects, including putting the brakes on our immune system.

Lisa: Oh my goodness. I mean, that is so fascinating. And to add more to that, for women who aren’t cycling, who aren’t pregnant all the time, how many of them are actually getting optimal progesterone? I feel like this brings us back to the topic of PMS. I mean, I just I spend my days observing charts and you know what I mean? Kind of looking at it through a different lens. And what you can see when you’re looking at these symptoms through the lens of the chart is that there’s often signs of low progesterone, whether it be short luteal phase spotting, whether it be lower temperatures or a sharp drop of a temperature too soon or whatever it is that coincide with a lot of these PMS symptoms. So then from that perspective, like to add more to it, even the women back in the day who were not pregnant all the time, they probably had more stable cycles. They probably maybe the environment was a little bit less stressful for them and maybe they were able to actually just live their lives through having sufficient progesterone in the luteal and maybe that also had some level of protective effect.

Sarah: Yeah. No, for sure. I mean when you look at the contemporary environment it’s like the number of things that are stacked against ovulation I mean it’s pretty profound and I was and I write about this in my book but I found in my own research because we do this cycle research you know we’re looking at the effects of women’s cycling hormones and on their different types of psychological and behavioral outcomes and when I first started doing this research and we would have women in and it was only women with regular cycles right so who felt pretty confident that they were ovulating regularly and they were all healthy, all healthy weight, etc. And we would be studying these women in the lab and we would get failure to ovulate in about 30% of our sample every single time they’re measuring it. And these women’s cycles look normal, right? Like so they’re the same. They’re not skipping a day or they’re not too long and they’re not too short and they’re just not ovulating. And that’s I mean, that’s crazy. 30%. And when I talk to my colleagues because at first I thought we were just doing it wrong. I thought we were like messing up something and I talked to my colleagues who study the same thing and they find the same rates. It’s about 30%. And I mean and that’s like that’s insane. And it’s like you noted. I mean it’s like stress, social isolation, right? All like these types of things. Not getting enough sleep, not taking care of your body, not eating enough. These kinds of things can lead to these failures to ovulate which then you don’t get all of the really wonderful benefits of progesterone across the cycle and that also is associated with worse mood outcomes.

Lisa: Well, this is I’m so — like I feel like there’s a hundred directions we could go in. I mean, what are the implications then for your average woman who just feels like her period sucks? There’s still I think we’ve come a long way. It’s been just amazing to see how the conversation has shifted around the menstrual cycle over the past 20 years. I keep asking how old am I? But it’s really interesting because when I first learned about charting and about cycle tracking, no one was talking about it. There was no such thing as a podcast, right? There was none of this stuff going on. There was no social media either. But things are so different now. Like people are talking about it. Women are kind of putting it out there. But my question would be like are people feeling better?

Sarah: Well, no. You know, I think that when women start to learn this stuff, I do think that it helps everybody feel better. I think there’s a lot of people who are still feeling pretty bad. And I think that the answer to those women is one is just like understand what your body is doing. And so one of the reasons that I wrote the period brain is I really wanted to understand like what like what is the body up to in the luteal phase like like why is it that we experience some of these experiences that we all have that make us feel less than ideal. And so understanding what your brain and your body are actually trying to do as your body is shifting from a state that’s optimized for sex and conception and then switching into a state that’s optimized for implantation and pregnancy. The body does undergo a little mini remodeling project every single month as it goes between those two states and understanding what your body is doing and why it has the experiential effects that it can. So like for example I explain some of the things that go on in the brain that can lead to kind of low-key feelings of lack of motivation, right? Because we do get our brain changes the outside world to seem less rewarding to us so that way we’re not chasing rewards all the time because we do need to conserve energy. It’s a very metabolically expensive time in the cycle. Our body is remodeling tissue which ends up being an incredibly expensive thing to do. And so our body is oriented toward energy conservation at this time, making us sleepier, making us less sort of outwardly facing, turning our energy inward. And understanding some of these things or the changes in sexual desire that many women experience in the luteal phase which is when sex becomes less about like this sexy act that you have to have and instead becomes something that is a tool of connection and so it’s like serving a different set of motivations which means that it’s also going to impact relationships. Educating yourself about what all of that is and I think I do a pretty good job of I lay all that out in the period brain in the new book and then also understanding that there’s a lot about our current environment that is eroding our sort of resilience to hormonal changes. Right? So as you and I talked about at the beginning of the hour, the luteal phase is this time of just intense hormonal change because I mean, you have these huge rises and falls of progesterone that are again like 10 times higher than the levels of rising and falling of estrogen in the first half of the cycle. And you’re also getting a rise and fall of estrogen in the second half of the cycle as well. And so it’s this time of huge hormonal change. And for most of history, we lived in a way where we had a lot of resilience to any type of internal or external stressor. And that’s been eroded by our modern environments. Right? There’s a lot of things that erode at our resilience or the resilience of our cells to be able to quickly adapt to internal changes. And given that you have all of these huge hormonal changes and with these hormonal changes come changes in neurotransmission. So just for example we know that progesterone when it gets broken down in the body turns into this really lovely metabolite called allopregnanolone and it has this really nice relaxing effect on the brain and it can be very kind of almost almost soothing. It’s like this like really nice hormone, but when it’s going up and down and you’re not your cells aren’t able to adapt to those big changes of up and down, it can feel really terrible because imagine that you’re a neurotransmitter and you’re getting bathed by this like inhibitory relaxing effect and all of a sudden it’s gone and you’re like trying to find it and everything feels crazy. That’s a lot of what’s happening because of the ways that our environment has minimized our cells’ plasticity and ability to quickly adapt to different types of hormonal and different types of neurotransmission changes. And so another thing that I recommend is just taking steps to try to increase your resilience to hormonal changes to try to make these changes that we experience even though they’re still noticeable, less like you’re careening off a cliff and feel more like you’re just sort of riding, you know, riding a soft wave. And so and these are just like the basic pillars of health, right? So it’s like not eating processed foods and moving your body and getting morning sunlight so you can set your circadian rhythms and that way you’re able to get enough sleep, right? Listening to your body when it’s telling you it needs sleep and rest to be able to take that time to restore. Having a community around you, which is one of these things where I think that like on one level I think everybody knows that stress is bad for them. Like if you ask people like, “Hey, is stress good for you?” and they’ll say, “No, it’s not.” And so we all know that, but I don’t know that most people know just how bad it is. I mean, just in terms of like the way that it erodes at our hormonal health and the way that it erodes at our ability and resilience to things like hormonal changes because when we don’t have a village, like if we don’t feel social support and we don’t feel safe, like a that’s going to interfere with ovulation because our bodies don’t like to ovulate if they don’t feel like the world is a safe place to be able to have a pregnancy. And so it erodes at that. But then it also it increases inflammatory activity because anytime that we see the world as dangerous or too much for us to handle, which is how we feel when we’re stressed, our body releases inflammatory activity as a way to be able to be ready and on guard in case you become injured. Because historically, the times that we felt stressed were times when physical danger was a potential threat. Right. And even though that’s no longer true, we still have the legacy of our ancestors. And so when we get stressed out, it increases inflammation and inflammation erodes at our cellular plasticity. And so anything that we can do to just sort of build on the basic pillars of health I think are incredibly important. And they really can do a huge service in terms of increasing our resilience to hormonal changes and allowing ourselves to ride that wave and have it feel minimally unpleasant.

Lisa: I just love this conversation so much and being a podcaster for many years. I feel like I’ve had the privilege of interviewing so many different incredible minds talking about similar topics in a very different way. And I feel like this is one of the first times I’m hearing about kind of like the brain science, right, behind what’s happening in our cycles. And yeah, it’s a really fascinating conversation for me. I’m sure our audience is loving it as well. And I mean, I think it’s amazing. And in some ways, it almost makes me sad that we have to do this much to be heard, right? Like women have been saying these things in different ways for so long, but we really do need the researchers to pull the science on it and to call it out so that we can actually get something done about it.

Sarah: Yeah. No, I think it’s sad. It’s sad that it takes somebody having to come and pull out a chart and a list of references for people to listen because it’s like, yeah, this is the stuff that women have been talking about for years and it’s nobody was really paying any attention or thinking that they were crazy. And it’s only recently that even like the medical community, it’s like for a long time doctors would whatever you know it’s must be in your head. And I think now doctors are finally starting to understand that the science that they’re being trained on is very limited. And so I have seen like one positive change I guess I’ve seen is that I do think that doctors are more like look women have been studied very well. So like I’m listening to what you’re saying. I don’t know what to do about it, but at least I believe you and I feel like that’s at least a step in the right direction. I mean, it’s and obviously we need to go a lot further because just sympathy only goes so far. It’s like at some point you want to fix the problem. But I really think that trying to get a handle on the fact that our cycles matter and as our hormones change, it changes the way that we experience our bodies and that affects everything ranging from, like I said, it’s like things like our emotional states, our ability to manage stress, right? The way that our sexual desire manifests, the way that we respond to drugs for chronic conditions, the symptoms we have of chronic conditions. I mean, all of these things can change across the cycle and women aren’t told about any of them. And so instead, they just kind of feel like they’re crazy. And so my one hope that well, one of my hopes, right? So one of them is that we totally we give science the do-over that it needs in order to best serve the needs of women. But also I want women to have the tools that they need themselves to be able to just start to really get a handle on their body’s relationship to their hormonal changes and then how that impacts the things in their lives that are really important to them. So in the book for example I talk about the ways that progesterone influences everything, right? And so and really starting to track. So for example, if you’re a woman who has a chronic condition, because one of the things I talk about in the book is how our symptoms of chronic conditions change across the cycle. And for some women, they find that their medication doesn’t even work as well during certain points in the cycle. And so if you’re a woman with a chronic condition, whether it’s a mental health condition like ADHD or whether it’s a chronic health condition like asthma, a lot of times women will notice breakthroughs in their symptoms where they’re not being managed very well by their drugs. And there is some research on certain types of conditions where doctors have now recognized that this is in fact something that happens and that women might need additional they might need additional care during the last two weeks in their cycle because that’s generally when most women have worsening of different types of symptoms that they experience. And so for example with things like asthma, it might mean that you have more than one type of treatment that you use during the second two weeks of your cycle because this is a time when many women, I think it’s something like 80% of asthmatics experience premenstrual worsening and they define premenstrual as anywhere between 2 weeks to a week before your period starts. A lot of women experience luteal phase worsening of asthma related symptoms and so getting that extra care so during that time you don’t feel like you can’t breathe can be really helpful.

Lisa: Oh my goodness. I mean I could talk to you all day and then probably all week. We’ll have a little retreat have a mini retreat where we just sit and ask each other questions. But this is I mean on the one hand like it’s amazing what a time to be alive, right? Like this is being talked about in big platforms now. We’re actually getting all this information out here and on the other hand it’s like women have been saying these things for so long.

Sarah: I know.

Lisa: So but it is it is truly amazing. I am so thankful for you and for the work that you’ve done in this area I just love the topics that you touched on today and obviously they need to be shouted loud and wide and long from all of the places so that we can inspire the change that needs to happen clearly in science I mean I’m sure that I’m generally outraged so I don’t know if my outrage counts but I’m sure that we have plenty of listeners that are outraged to think that they’re taking medications that were only tested on a part of their cycle and we just have literally no information about how it affects you for the other half of your life. You know what I mean? Like it’s completely insane.

Sarah: Insane.

Lisa: So as we draw this interview to a close, I would just love to hear your final thoughts. I mean, for someone who tuned in and thought they were just going to have a run-of-the-mill conversation, but got their mind blown over and over and over again, where does she start or just I guess I don’t know. I’m sure you have plenty of words of wisdom for us.

Sarah: Yeah. So I mean, the first thing is just really understanding your cycle. And I’m assuming that most listeners who know about cycle charting and all the wonderful things that you do know that like keeping track of what’s happening with yourself hormonally is like the first is really the first step in everything. And starting to get not only a feel for what’s happening as you’re doing your charting, but using that and then also evaluating how you’re feeling, checking in with yourself, right? And starting to learn your own different patterns within the cycle. So when it comes to everything that’s important to you, so things like your mood, sexual desire, performance at work, appetite, your workouts, are you having side effects from the medications that you’re taking, right? These are things that I think that starting to track regularly across the cycle can be incredibly important just in terms of understanding the way that your body responds to hormones. Because even though there are some patterns that we tend to see that are pretty reliable between women, each woman’s relationship with her hormones is a little bit different. And it’s like good to get a handle on what yours is. And just to give a quick example, even though most women feel great near ovulation, there’s about 10% of the population that feels the worst right near ovulation. And which is like one of these things we don’t have an answer for it, but if you know that about yourself, then you know when to put in the safeguards. And so starting to understand your relationship with your own hormones, I think is really important. Number two, obviously I’m going to have a plug for my book, The Period Brain. I really do try to unpack for women everything that’s happening in the body in the second two weeks of the cycle. So that way they can actually have a road map of what the luteal phase is supposed to be about and that way they can understand what’s happening in their body. Because I found that when I have language to describe what’s happening to myself, it’s really easy to talk myself out of feeling things I don’t want to be feeling and also being able to communicate with people around me to be able to make sure that I’m able to recover from whatever it is that I’m going through. Whether it’s just having a moment or if I’m having difficulty with sleep or exercise or whatever, it’s something I can talk about and I’ve got language for it and it makes sense. And so checking out the book I think is also helpful. And then lastly, it’s really believe your body. I think one of the things that has disheartening about all the conversations that I’ve had with women over the years and through my research and just through conversations with readers and others and friends is how many women have an adversarial relationship with their body. And I think that a lot of that is because we all have been fed this one-size-fits-all idea about what it means to be human. And so even when we’ve been following all the rules that we’ve been told that we’re supposed to follow to have good health and good nutrition and good rest and good friendships and so on and so forth, that most of these rules have been created for male bodies and they don’t always work for our bodies. And the result is that we’ve had a lot of times where we felt like we were doing what we’re supposed to and our body was rebelling and then we learned to distrust our body. And so like another thing that I think is really important is to try to start to reestablish a new and trustful relationship with your body where you start to believe what it’s telling you and then use that as a guidance for the path forward, right? And so starting to develop a trusting, loving relationship with your body, listening to what it’s telling you and then sort of going from there.

Lisa: That is incredible advice and I highly recommend for anyone who found this conversation interesting like run to like pull out your phone now and grab the book. And one of the reasons I’m saying that as well is because Sarah your approach to writing and research is just very different. So even if you’ve read a whole bunch of books on the menstrual cycle and those types of things, you’re not getting that same book. This is a very different approach and I feel like you never disappoint with your just the rigor, your approach and your creative mind. I love that you just you’re thinking about these things and you’re wanting to figure out why and you’re doing it right and that’s what makes your books very unique, very interesting, very informative and I really mean that because I’ve seen a lot of like a lot of books come across my desk, right? I’m guessing that’s true.

Sarah: Yeah.

Lisa: So this definitely isn’t just your regular book but you can tell by our conversation like these are topics that really haven’t even been broached. So I mean, just congratulations. I’m so thrilled to be able to support you and in getting the word out.

Sarah: Thank you so much. It’s always such a pleasure. I have so much fun talking with you, Lisa, every time.

Lisa: Me too. Likewise.