Hidden Symptoms of PMDD & PMS: How Progesterone, Birth Control & Brain Chemistry Shape Your Mood | Dr. Sarah Hill

26:07And so our body will just say, enough, because it doesn't want the body to completely fall apart because that is what will happen. The reason that salmon fall apart after swimming upstream is because of cortisol release. Constant cortisol release literally makes the body fall apart. And so the body will just shut it down. If there's chronic exposure to glucocorticoids, it's like, all right, enough, no more stress for you. and then the system gets shut down. And with the pill, when you have these progestins that are stimulating these cortisol receptors, it's making the brain and body think that it is in a state of trauma, right?

26:41Like chronic exposure to stress. And so the body seems to be shutting it down. And this is consistent with what we tend to find with women on the pill because they have these really high levels of glucocorticoid binding globulins in their bloodstreams that are essentially the liver saying, no more cortisol for you, right? And this is the reason we get that blunting. And that blunting, at first it might sound like, wow, that's great. Then you don't experience stress. But of course, that's not what happens. That would be nice, but it's not the reality. Yeah, not the reality because cortisol is how we cope with stress.

27:11It's how our body mobilizes resources. So that way we can deal with things that are meaningful, again, whether bad or good. And so when you blunt that, you're actually blunting your ability to recover from stress. You're blunting your ability to manage stress. or blunting your ability to sort of smoothly move from situation to situation because cortisol is part of how we adapt to our environment. And so it minimizes your ability to adapt to the environment. And this, of course, can cause problems, right? This can cause problems with mood because when you aren't able to cope with your environment, I mean, that causes anxiety, which ultimately leads to depression, right?

27:47It also can create issues with our ability to cope with hormonal changes. And so one of the things that I write about in the new book, The Period Brain, is I talk about the, you know, when we look at women who tend to suffer from really bad PMS and PMDD, many of them have a history of trauma or they have a history of having blunted HPA access response. And what seems to be happening when you look at all the pieces together, the puzzle seems to be revealing a picture where these women aren't able to cope. They don't have what I refer to in the book as resilience to hormonal changes. Because when our hormones are going through rapid periods of change, our body and our brain are going through rapid periods of change.

28:32And there's a lot of adaptation that has to go on. There has to be adaptation in terms of our hormone receptors, right? So receptors for things like estrogen and progesterone. But also, there has to be a lot of plasticity in terms of things like our GABA receptors, because allopregnanolone levels for naturally cycling women are rising and falling during the second half of the cycle in ways given that they stimulate GABA receptors in the brain, our brain has to be able to adjust to those things. Cortisol is the master coordinator of adjustment, right? It's saying mobilize resources to help us deal with this change, right?

29:07We can think of it as a hormone that helps our body cope with change, right? Because that's kind of one of the principal elements of stress. And hormonal change is a form of stress, right? Because it's something that is an event that our body needs to cope with. And that's generally the way that we define stress. And so when you're lacking what I call like HPA access tone, right? Like when you've got like a really nice dynamic cortisol response, like when things are stressful, get big cortisol release. And when things are not, it goes back to normal. When you're lacking that and have that blunted response that we see in women who've experienced trauma or women who've been on hormonal birth control.

29:44This can diminish your ability to navigate smoothly between hormonal transitions. And the luteal phase of the cycle that lasts two weeks of the cycle when you have this huge ebb and flow of the sex hormone progesterone, right? And the rise and fall of progesterone happens at levels that are 10 times higher than the rise and fall of estrogen. So even though we all see that little menstrual cycle map that shows this like big shift in estrogen in the first half of the cycle. And then this, you know, just slightly larger shift in progesterone, those things aren't drawn to scale. And the y-axis that's showing levels of progesterone is actually scaled at 10 times higher than the estrogen side.

30:26And so we have this huge increase and huge decrease in progesterone during the luteal phase. And you also get a big increase and decrease in estrogen that many people don't really pay any attention to because they're always focused on the estrogen shift that happens in the first half of the cycle prior to ovulation. And that's a lot of adjustment that our brain and the rest of our body is having to do to cope with that rise and fall of hormone. And again, this isn't just with our hormone receptors, it's with our GABA receptors in our brain because they're getting this big rise and fall in allopregnanolone.

31:00And if you're not able to adjust to those changes quickly, it's going to make you feel messed up, right? And what we tend to see is that a lot of women who experience PMDD, that's exactly what's happening when they've done studies. These are usually done using animal models and just looking at their ability of their neurons to like sort of increase and decrease GABA receptors as needed and modulate their GABA receptors in response to that rise and fall of allopregnanolone. And it suggests that it's compromised, right, in these women. And so they're not able to, like, sort of gracefully navigate their way through the luteal phase.

31:39And the result of that is they feel absolutely terrible. I want to zoom out a bit because you said, like, your brain's changing across the menstrual cycle. But something you, well, let me just say, I also appreciated that graph in your book because I think you had on their like arbitrary units of like how we always present the menstrual cycle and the way as we're having this conversation like we always present it this way so that the patient can wrap their head around it but i as you're saying it i mean i do think some clinicians have taken it as fact like they're like fact this is exactly what it looks like good energy in good energy out

32:20storm zero sugar 200 milligrams of caffeine and immunity support storm energy for life right now in your book you said estrogen acts like miracle grow in the brain so tell us how that plays out in terms of brain function and behavior yeah so estrogen essentially primes your brain to be its most alert sensitive self right and the reason for this is like this is a period in time when sex can lead to pregnancy. And there is no better time for your brain to roll out the red carpet in terms of your sensory acuity than during this time, because you're essentially choosing who your genes are going to be intermingling with in the next generation and future generations beyond that.

33:04And so the process of evolution by selection, this process that has shaped our brain and shaped us to be the way that we are as human beings, has shaped us to be incredibly sensitive to the environment, and particularly cues related to mate attraction during this time in our cycle. And what we tend to see is that women are more alert, they're more energetic, and they get new dendritic spines on their neurons. So their sensory... For people who don't know what that is. Yeah, yeah. So our neurons, we always think about the brain as being this like lump, Yes, we do.

34:07pop out of neurons, and they're there to be more sensitive to any information that's coming in, right? So the more of those that are out, the more sensitive we are, and when they retract, the less sensitive that we are. And the reason our brain isn't always rolling out the red carpet is that that's incredibly metabolically expensive to have all of these dendritic spines that are very aware of even fine-tuned differences in scent and fine-tuned differences in appearance. And this is what we find in women when they're in the estrogenic phase of the cycle, particularly prior to ovulation. You get like women are able to tell the difference between really small differences in things like cues, for example, related to testosterone.

34:49So we find that when women are in the estrogenic phase of the cycle, they're better able to determine and notice just noticeable differences between testosterone markers in men's faces. So for a woman in the luteal phase, when estrogen levels are lower and progesterone is high, they'll be like, they all look the same to me. You show that to a woman near peak fertility in the cycle, and she's like, that guy's different than that guy, that guy's different than that guy, and that one's hot and that one's not. And you get these really interesting differences in just being able to detect these fine-tuned differences.

35:22We also find this with scent. So they've done this looking at what a woman's sensory threshold is for picking up fine-tuned differences in a metabolite of testosterone that's picked up in scent. And women are more sensitive to that as well. And so it's like our brain is just primed for information. It is like, you know, wants to make good mating-related choices. And so it's really sensitive to all of these different types of cues. So the brain is primed for all of these cues because conception is possible. And so estrogen does act like miracle grow in the brain. It just makes it this really sensitive version of itself where it's very much aware of a lot of these fine-tuned differences that are important in partner choice.

36:00And it ends up making us more sensitive to the world. And this is also why the seizure threshold becomes lower right prior to ovulation, is because our brain is so sensitive to sensory stimuli that it can become overwhelmed. And that, of course, can produce migraine headaches and it can produce seizures. Yeah. Everything you just pointed out, it's so controversial. Why is it so controversial to say that women are attracted to a certain type of man, especially if they're naturally cycling versus birth control, that they can pick up on these scents. Because whenever I talk about this, whenever you talk about it, I see people punching back hard.

36:39And they're like, stop reducing women to this. And women select mates. We're way more intelligent than that. And I'm always like, at your core, you are an animal. You just are an animal that has a language that you understand, so you think you're unique. But you're an animal. Right. Yeah. No, part of that wisdom, because we do have so much wisdom. We have millions of years of inherited wisdom on our shoulders, right? We have a brain that is the result of an uninterrupted chain of successful reproduction for millions of years. That's a soundbite right there. It's so amazing. Well, it is. Think about this.

37:14If even one of your direct ancestors would have failed to be able to attract a mate, reproduce, and have a baby successfully, you would not be here. So each one of us is an evolutionary success story. And I think that's incredibly empowering. We have this brilliant brain that has managed to get genes down from generation to generation to generation for millions of years. It's brilliant. And so why do people have a problem with that? You know, I think that there's still this, you know, and I think part of it is, you know, the field of medicine in particular was created before we understood that the Cartesian mind-body split just wasn't true.

37:56You know, like where we used to think that the body was, you know, the sack of meat that followed these laws of biology and that the brain was a product of the soul and that it had its own sets of properties and that the two things shall never meet. But we know better now. We know that the brain is a body part. It is governed by the same rules that govern the rest of the body. And so the idea that our brains are influenced by our hormones is just, I mean, it's biology 101. It would be impossible for them not to. And it's like the most important body part we have is our brain. And the idea that it would somehow be immune to our hormonal influences is completely cuckoo nuts because our hormones make us better.

38:39They don't make us worse. And I think that there's also this belief out there that there's something wrong with our hormones and that our hormones make us somebody other than who we are. When it's like our hormones are who we are. I love that you eye roll in that statement. I mean, it's like they're who we are. You know, and in my first book, I have a chapter, and I wish I could write the same chapter in every book I write, but it's just you are your hormones. You know, they are part of what your brain uses to create the experience of who you are. So who you are is created by all of these gears and sprockets going on inside your brain that are influenced by, you know, neurochemicals and neuromodulators and neurotransmitters and electrical activity and hormones.

39:19and that is this version of yourself that you've created in your head and that's the version of yourself that creates behavior and makes you who you are in the world and we're so much better for it because our hormones help us adapt you know we talked about cortisol and it's like when you don't have that you're not able to adjust your behavior appropriately and evolutionarily speaking you would have died yeah you would have died as they escaped the predator not never no no yeah no you just be chilling with your friends you know when the saber-toothed tiger is coming or you'd be chilling with your friends when there's a potential romantic partner that's high quality because another domain in which cortisol just gets absolutely flooded in the body is attraction.

39:57You know, so it's like we, you know, stress is a lot of different things, right? It's just your body saying, this is important, right? This has consequences for your ability to survive or your ability to reproduce. Pay attention, mobilize all the resources, right? Pull up some of that energy that you're using to divide cells and deal with immunological challenges. And let's direct that to the brain right now because it needs to do whatever it needs to attract that mate or to get away from that saber-toothed tiger. Yeah. And I think what came up when we were talking at dinner last night and I had said to you, I think that the women who came before us, and we definitely see it's that boomer generation of gynecologists who, I know, I'm like, is boomer a bad word?

40:38I don't know, but it's the generation that it is. I don't know. You guys can tell me in the comments. I don't mean that with disrespect, but is that generation of gynecologists who were like, just suppress your hormones with birth control. There's no reason that you need them. You can be just like a man and work just like a man if you do that. Don't ever acknowledge that our hormones make us different, make us act different, make us think different, make us do anything different. That is just crazy talk. And I get that they did that because they were like, we feel like we have to tell men we're the same as them to be able to advance our careers.

41:10But I absolutely think they did tremendous harm in women's health. And I don't say that as like people, you know, in general, I'm talking about practitioners who were telling women that your hormones are something to be suppressed, ignored, and never acknowledged because they'll find a way to weaponize it and say we're weaker, which I have always said your hormones give you superpowers. And I believe very much in everything you're just saying, it really demonstrates that they absolutely do give us superpowers. And the dynamic change across the cycle is something that when you understand, you can absolutely leverage.

41:46I want to go into that because I feel like you've talked about the changes with estrogen, what's going on in the follicular phase. We've kind of alluded to the allopregnenolone, the GABA receptors, but can we just go across the menstrual cycle and kind of put it together for women what's happening with their brain? Right. Let's just talk about why we have two hormones instead of one. And as you noted, I mean, for a long time, it was assumed that there must be something wrong with having two hormones instead of one because men have one, right? They have one primary sex hormone. They have a very basic operating mode altogether.

42:20And I don't mean that with disrespect people I'm raising two boys, but like they don't have to do anything fancy, right? Because they just have to ejaculate, but we actually have to gestate. Like there's so much more going on. Yeah, no, it's like our bodies have two jobs to do for reproduction, right? There's mate attraction and sex, and then there's implantation and pregnancy. And so it's like we have two hormones because our bodies and our brains have two different jobs to do in order to pass down genes. Men have one. And the only reason that we think that that's better and superior is because men were studied first.

42:55So all of our default assumptions about what it means to be a human, like a functioning human, is based on a male typology. And that just doesn't work for women. And as you noted, it's like for a very long time, it was assumed that, yeah, there was something wrong with our way of being. That's simply not true. And, you know, we could turn that argument on its head. And, you know, just to give you an example, you know, there's this idea that, oh, women are fickle, right? Because our hormones change. And therefore, like, who are we? we could turn that on its head and say, men are overly simplistic.

43:28You know, like if you can't look at things through two different lenses, then you're completely inefficient. You know, you're inept, but we've embodied this idea of inferiority. And I think that that's what's guided this decision-making where it's like, we need to suppress the discussion of hormones and why they're important. Because women have embodied this idea of inferiority that's simply not true. You know, it's like our hormones are part of our wisdom. They're part of our bodily wisdom. When we tell women they don't matter, it makes them feel pathological. Yes. Right. And so part of this, my book is, you know, even though I think we've gotten more comfortable societally with the idea that women cycle, right, everything is focused on estrogen, right?

44:12And this is true in popular discussion. So when we talk about like, oh, you know, hormones matter and, you know, estrogen does this and estrogen does that and estrogen does this. And this is also true in research because men were studied first, the way that researchers decided to deal with women's hormonal cyclicity in research was to try to study women only when they're most like men. And so... I know, right? I just have to laugh when you say that because it's like, oh, thanks for including us in drug studies, but also not really including us in our entirety. No, yeah. So one thing that people aren't usually aware of is that in most biomedical research, women are only included as research participants during the first nine days of their menstrual cycle, right?

44:57And the idea is that they're trying to study women only when their hormone levels are maximally low to make them maximally similar to men. The problem with this is, of course, is that women are not in that hormonal state most of the cycle, right? They never study us when hormones are high. And so we have this whole other set of assumptions that our body is following when it's under progesterone that are never, ever studied, right? So it's like we're studied, they now include women in research, but they don't study us as women, right? Because women are cyclical. And so we have these two primary sex hormones.

45:36Estrogen, again, gets all of our gears working together for attraction and sex. And then progesterone gets all the gears working together for implantation and pregnancy. And this doesn't sound like that big of a deal. Like, okay, well, whatever. I don't care what that has to do with anything. It has a lot to do with everything. And the reason for this is that for pregnancy to occur, the female body has to absolutely change the rules of engagement for almost every system in the body. What our brain does has to differ, right? We have to become, for example, less interested in sensation seeking and wasting energy going out and chasing opportunities because our energy levels are going to be lower when we're pregnant, right?

46:19So it actually dampens our reward sensitivity to rewards in the environment, right? It also lowers our threshold for when we see something as threatening because women, when they're pregnant, are in a more vulnerable state. They're not able to get away as quickly. And so we become more sensitive to threats, both social threats and physical threats. our immune system has to change what it's doing because our very inflammatory immune system that we have during the first half of the cycle and not inflammatory in a bad way but just a very reactive immune system estrogen is it helps to prime the immune system in a lot of ways and progesterone has to tamp down the brakes on that because if you have a super active immune system and you have an embryo that's trying to implant it looks a lot like a pathogen because it has genetic material that doesn't belong to self.

47:08And that's what the immune system will go after if it's in its heightened state. And so it shifts our immune system from what we call a TH1 response to a TH2 type anti-inflammatory response. Our circulatory system has to change what it's doing because all of a sudden it has to have a lot more blood flow going to the uterine area. And this is something that happens in pregnancy, but also in pre-pregnancy in the luteal phase. Our body temperature increases, which means that our basal metabolic rate has to increase. And so we see that women's calorie needs increase by about 7 % to 10 % in the luteal phase of the cycle.

47:43Our respiration rate and our heart rate increases. Our respiratory drive increases, meaning that we feel the need to get breath more. So women feel more out of breath when they're working out heavily during the second half of the cycle. Our ability to build muscle mass decreases because our body is taking those energetic resources and is directing them toward building an endometrial layer, everything changes. And so the idea that we can take rules that were created from science conducted on men and apply that to women doesn't work. The idea that we can take research that was conducted on women in the early stages of the menstrual cycle when estrogen is the primary hormone and then apply that to progesterone, that also doesn't work, right?

48:29And so a lot of what we know about ourselves is completely guided from what is sort of normal for a woman during the estrogenic phase of the cycle, and it doesn't necessarily apply to the luteal phase. And so I talk about this book and talk about this idea that, you know, when we think about estrogen, everybody's like, oh yeah, you know, it does sort of make me want to have sex more, and you know, and I feel sexier, and it's doing all these things that promote sex, sex, sex. And then there's the luteal phase and that's just PMS. I just feel terrible. And it's like, well, no, like this is actually, there's a lot of wisdom in these psychological and physical shifts that are going on.

49:05It's just that one, they've been made to feel pathological because we've been given a one size fits all version of what it means to be human that does not fit for a female. It just doesn't fit. If you're a cycling female, that doesn't fit. you have two sizes, right? There's at least two, right, versions of what your body needs and what it does. And when we're not told about that, it feels pathological. And the other part is that our body actually creates pathology because we're following guidance that was never created for the cycle phase. You know, so for example, you know, one of the things I talk about in my book is this idea that, you know, all of us are told from nutritionists, here's the number of calories that you need to have on a given day.

49:46And here's how you need, you know, from your trainer, here's how you need to work out every day of the cycle. And that might work well and good during the first half of the cycle. But then when you shift into the luteal phase and your calorie needs go up by seven to 10%, you know, if you're somebody who usually eats about 2000 calories a day, that's between like an additional 140 and 200 calories a day. Women aren't told this, right? And instead they're like, God, you know, I'm so hungry. And then we start to tell ourselves a story. right about how we have no self-control what's wrong with me right and then because you're hungry and your body which thinks it's gearing up for a pregnancy is going to see this as an emergency right so your hunger hormones are going to be telling your brain emergency and so then your brain is going to be like oh my gosh like i you know and then you start having food cravings and the next thing you know right you're in the pantry eating peanut butter out of the jar and then you're like what like why did i do that you know like why did i do that and it's because we didn't do what our body needed.

50:44We didn't listen to it. And as women, you know, and you talked about this early on in the interview, and I really appreciated this, especially from somebody who's been in the clinical world. It's like our doctors have taught us to distrust our bodies from the time we're small, you know, and there's no better example of what happens in the luteal phase, you know, and we experience these shifts, right? We're feeling hungrier and we're telling ourselves a story like, I have no self-control. I just suck. I have no willpower. We tell ourselves these terrible stories about ourselves. We think that our body is the enemy when it's guiding us toward the things that we're actually supposed to be doing to take care of our bodies.

51:29But because that flies in the face of the bad advice that we've been given, we learn to distrust ourselves instead of distrusting our doctor or distrusting the nutritional advice that we've been given. And it's time that we start really taking these things seriously. Because even though I recognize that for a very long time, women were treated as inferior versions of men, just because we cycle, it's time that we totally shift that narrative and we embrace the fact that we cycle. Because when we don't do that, we go through these, you know, entire two weeks of our lives every single month where we feel completely out of control and pathological.

52:07And like, it's time that we really take that seriously. It's time that we understand it and then learn about ourselves during this phase in the cycle, which is what I'm trying to do with my book, The Period Brain, is really educate women about what is your body actually doing during this time? And what do we need to take care of it during this time? Hey there, it's Wayfair here, where delivery and setup are as easy as a few taps on your phone. You're relaxing in an old hammock, scrolling Wayfair's app when you spot it, a brand new patio set. Next thing you know, Wayfair delivers it right to your patio and sets it up.

52:36Oh, you need a new grill too? All right, Wayfair's got you covered. With Wayfair's room of choice delivery and fast experts set up on qualifying orders, life gets a little easier. Visit Wayfair.com or the Wayfair app. Wayfair, every style, every home. But then we also need to use this to change science for the better. Because currently the gold standard in clinical research and in biomedical research is to only study women in the first nine days of their cycle. That's the gold standard. That's considered a really well-done study, and that makes absolutely no sense whatsoever. And this is why a lot of women experience premenstrual worsening or premenstrual, and I say this because a lot of times when women experience premenstrual worsening of symptoms, it's during the last full two weeks of the cycle.

53:22And we see premenstrual worsening of things like asthma, ADHD, which of course we talked a lot about yesterday. You see premenstrual worsening of eating disorders. You see premenstrual worsening of personality disorders, of mood disorders. I mean, the list goes on and on and on and on. And women report that the drugs don't work as well during certain phases of the cycle compared to other. I mean, and that's just scratching the surface. You know, it's really, we need to be studying women under control of both of their primary sex hormones, not leaving progesterone in the ghetto. And as a result, leaving women in the health ghetto during this phase of the cycle.

53:58This is so well said. And it's, as you're saying this, I'm like, you know, part of why you and I are considered so controversial in our work is because we're challenging an entire paradigm that has told women that they're inferior, but not just told them that actually profited off of that actually been able to, you know, basically put us in the corner so that other things can be advanced at our expense. As you were saying, these things that get worse before your period, I was actually surprised when I read in your book where you said that studies show that almost 70%, hard exclamation point right there, of women with major depressive disorder and bipolar disorder experience exasperation premenstrually.

54:43So for people listening, everything's getting worse leading up to your period. And in the case of PMDD, and we're going to define PMDD and PMS in a second, when you consider that this is two weeks out of every month, that is half the year. In what world would we ever tell a man it is okay for you to be debilitated and feel awful for six months out of the year? And yet it is something that has been perpetuated in women. And I'm not saying this as if men had it out for us in saying this. It is that medicine didn't care about us enough to study this. So I want to shift gears to talking about PMDD.

55:23Let's define PMS versus PMDD because you talk a lot about this in your new book. Yeah, so the difference between PMS and PMDD. So PMS describes almost everything that women experience in the luteal phase, you know, from really minor disturbances in just feeling more tired and sluggish, which is allopregnanolone actually stimulating your GABA receptors and making you try to conserve energy because the luteal phase is so metabolically expensive because of all that new cell creation in the endometrial area. Not to mention immune risky. Yes. You want to stay home more. Yeah, no, exactly. yes, yes, no, yes, brilliant, yes.

55:59And so PMS has been used to describe, again, just even minor experiences that we have during the second half of the cycle to a whole host of combination of things where you're feeling a little bit sad and you've got food cravings and you've got whatever. But PMDD is more serious. It's generally like one of the defining characteristics of PMDD that separates it from just run-of-the-mill PMS is suicidal ideation. And it's funny because it's a landmine for doctors to screen for PMDD because as soon as you ask somebody about suicidal ideation, there's a whole protocol that you have to follow that could lead to institutionalization of their patients.

56:44And most doctors don't want to do that for a good reason because the women don't want to do that. And so it can be a little bit tricky to navigate, but it's also characterized by really debilitating mood-related symptoms. The sort of crown and jewel symptomology of PMDD are these really severe debilitating mood-related symptoms, oftentimes accompanied by suicidal ideation. And so in my book, I list what the criteria are for being diagnosed with PMDD. I don't actually published because there's the DSM guides, which is the diagnostic statistical manual, which is what the APA uses to define different categories of psychological illness.

57:28I can't publish the exact questionnaire, but all of the items are in there. They're in a table about what you need to be paying attention to and how clinicians are able to actually distinguish whether you fall into the category of PMDD or not. But it's really these debilitating mood-related symptoms. And for women who have PMDD, I mean, this is like endometriosis, which was something we spent a lot of time talking about last night at our really wonderful dinner with experts. When you hang out with endometriosis surgeons. Yeah, it was so fun. Yeah, it was like there was scans being cast around the table.

58:03I was saying that. I was like, at some point, always in our dinner, here comes the imaging, and we start talking about cases and stuff. So fun. No, it was just so fun. But it usually takes women a very long time to get a PMDD diagnosis. And so this is something that I always recommend that women start tracking their symptomology early because if they can go to their doctor with evidence, and this is what your doctor is going to ask for, is like at least two months of evidence showing that your mood changes that you're getting that are so debilitating are specific to the luteal phase. And this is something that is incredibly debilitating to women.

58:40I mean, is incredibly debilitating. I mean, some women aren't able to get out of bed. They lash out at people they love. And then they've got this brain because during the luteal phase, it's really primed for social sensitivity to threats. And so they're lashing out at people and then they're really sensitive to the feedback they're getting. And I mean, it just creates these loops that are really terrible for women. It's a really heartbreaking diagnosis to get because as you noted, this is a woman feeling on the brink 50 % of the time. It's a really terrible, it's a really terrible condition. We're going to talk about treatments.

59:12I don't want to jump there yet, but so I didn't know I had PMDD as a teenager. And now I didn't know I had PMDD and I didn't know I had endometriosis and my doctors could care less because they were like, take the pill. But I remember being on the pill and being so debilitated that I would get in the shower and I would just cry and be on the floor of the shower, physically unable to get out. And I look back at that and I just remember thinking like, what's wrong with me? People telling me like, you just need to, you know, you need to try harder. You need to suck it up. And it is something that, you know, I have worked a lot.

59:44It's the work that I do that I've been able to resolve my PMDD symptoms. But I shared with my audience that, so following my miscarriage and my cycle came back and it was, I felt it. Like I can almost, I'm like getting kind of teary because, because I was, I remember I was just sitting there and I'm like, it feels like I can see how good my life is, but there is a glass panel between me and my life and I cannot touch it. And I'm stuck here in this horrible dark side. And I was like, Hell no, we are not going back there. And I think that for women listening, like the minute you start to have feelings like that, it is absolutely time to take action.

1:00:23So we're going to talk more about taking action today. But one of the things we have to start talking about, like, what are the causes of PMDD? Big floating question mark above my head right now, right? Because we just don't study the female body the way that we should. But we brought up allopregnenolone. So allopregnant alone, for some of us, is like the best thing we ever met. And we like feel so in love with our life and we sleep well. But for others of us, it is not. Can you talk about that and what is going on with the GABA receptors in the brain that may be potentially one of the contributing factors to PMDD?

1:00:59Right. Yeah. So as noted, PMDD is very poorly understood. And in the book, I talk about there's some research into looking at inflammatory processes and whether or not that might be a contributing factor. I'm looking at dysregulation in vagal tone, so your vagus nerve and its ability to be able to communicate effectively with the brain. There's research looking at the HPA axis again and whether or not that is at play. It's probably a combination of all of these things. And one of the other issues that researchers have really been looking at is this issue with allopregnanolone, as noted. And what seems to be happening is, so allopregnanolone, like, you know, if I had to, like, place a bet on what it's going to do, like, let's say I'm studying a mouse model or I'm, you know, studying a healthy human, if I had to place a bet on what it's going to do in the brain and then, like, the subjective responses were going to have to it, it would be that it's going to make you feel good.

1:01:53Because for most people, it is very calming, it's very kumbaya, and it is related to this calming neurotransmission. But for some people, for some women, and including some women who have PMDD, what you find is that you have this dysfunctional relationship with allopregnanolone. And it seems to be, again, this has to do with the GABA-A receptors in the brain not remodeling themselves appropriately in response to changing levels of aloe or alopregnanolone. And what happens during the luteal phase, if we want to just like kind of zoom out a little bit, is you get this really intense rise of progesterone.

1:02:34And then you get an intense fall of progesterone if you're not pregnant. And this requires your brain and your GABA receptors, which are receiving stimulation from this really beautiful allopregnanolone. Allopregnanolone operates and it rises and falls almost in lockstep with progesterone levels. And so when progesterone is rising, your brain is getting all this beautiful activity. And then when progesterone levels start to fall, if your brain is able to adjust to that, you can feel a little more sad. but it's not very noticeable because your brain is able to ride the wave you know it's sort of like coasting up and down a hill but if your brain isn't able to adjust quickly to the amount of stimulation it's getting on the GABA receptors because of dysfunction in the GABA receptors which we can talk about this can lead to it feeling like they're falling off a cliff right so instead of coasting up and down a hill they're climbing a mountain and then falling off a cliff because all of a sudden they're, you know, they have all of these naked GABA receptors, you know, so imagine that you're a receptor in the brain whose job it is to pull in chemicals that are soothing the brain, right?

1:03:41And all of a sudden you're naked, right? And you're like, oh, where's, you know, where's all that soothing stuff? Like, I need that. Like, what am I going to do? And the brain feels really alarmed and it feels really terrible. And so that is one of the factors that seems to be related to some women not responding well to allopregnanolone is that they get withdrawal syndrome or symptoms when it goes away. Other women, and this one's really interesting because it again gets at how idiosyncratic each one of us are, which is why one of the things I talk about in the book is like you absolutely need to be tracking your cycle and you need to be tracking, like I have a list of symptoms and I hate the word symptoms because they're not symptoms or experiences.

1:04:20Experiences, I like that. You need to be tracking your experiences over the cycle to understand your own personal relationship to your hormones because all of us respond differently. And just as a caveat, and then we'll jump back on it. Or a side note, there are some women who feel terrible near ovulation. There's a small handful, it's about 7 % of the population who reliably feel terrible at that time, which is crazy for those of us who feel so wonderful during that time. But with allopregnanolone, some women metabolize it too fast. And so these women are like super metabolizers. And what happens is progesterone is being broken down in the body and then L-pregnanolone is being released and their body's like pulling it all away because it's really quick at breaking it down.

1:05:02And then it's not getting that, again, that really soothing activity in the brain because their bodies are super metabolizers of the stuff. And so there's all kinds of things that can go wrong in this side of the cycle just because it is characterized by such huge inconsequential hormonal changes that when things aren't working exactly as they should, it can lead women to feel pretty awful, including things like developing PMDD. So with what you're talking about with progesterone, so we'll see this called progesterone sensitivity. There's also, we know that sometimes when we dose women with oral micronized progesterone, there's progesterone intolerance.

1:05:41So they feel, they might feel really groggy the next day and kind of bluesy. And so we have to like titrate the dose down, but other times they don't get that like, I feel really chilled out and calm. They get, I feel really anxious and amped up and like there's a problem going on in my body. And so there's a lot of focus on just getting the progesterone levels right. We even see that. There was a newer study that came out with a progesterone modulating drug and it's like, the key is keep progesterone low. Just keep it low and steady the whole time. But you talk about in your book, like, we need to not just focus on hormone levels, but the actual individual sensitivity to them.

1:06:21Can you talk more about that? Yeah. So when we look at differences in hormone levels between people who have, like, PMS, severe PMS, PMDD, and then people who really don't even notice the luteal phase very much, their hormone levels are indistinguishable from one another, right? And so in the research world, we've long abandoned the idea of looking at hormonal imbalances or whatever as the key to understanding different types of symptomology that we get. I mean, instead, most of the research focus is on what you've noted, hormonal sensitivity. And that is, you know, how sensitive are you to hormonal changes?

1:06:58And so with PMDD, for example, one of the leading hypotheses about sort of mechanistically what's going on there is that women are just super sensitive to hormonal changes. And again, for one of these different reasons that we talked about, whether it's that they aren't able to adjust their GABA-A receptors quickly enough to be able to adjust to changing levels of allopregnanolone, whether they're allopregnanolone super metabolizers and they're sort of breaking it down faster than it can be sort of received by the body, leading to this perceived shortage. any dysregulation in the HPA axis, that's like just decreasing your ability to navigate stressors of all sorts.

1:07:35I mean, it's all over the map. But so the actual cause of the sensitivity can be variable. But one thing that we do know is that, yes, it is the sensitivity that seems to be causing the symptoms. This is one of the reasons that doctors will give women, for example, birth control pills. because, and they'll usually give them the ones that go for three months without a withdrawal bleed because going for that three months of having every day be the same day hormonally for some women can be very palliative because they are sensitive to hormonal changes and keeping things constant makes them feel better.

1:08:11Even if that constant may not be as good as they would feel if they were naturally cycling. And this is also why, interestingly enough, why it is that antidepressants dosed only in the luteal phase also seem to be palliative to women who have PMDD. And what this research finds is, you know, for people who take antidepressants for depression or anxiety, you have to take them for several months before they actually start working and making you feel better. And the reason for this is that the primary mechanism by which they're believed or hypothesized to work, researchers still don't actually know how they work, by the way, in case you didn't know that.

1:08:51But the leading hypothesis is that they increase neuroplasticity in the brain. And by having all of that serotonin and the synaptic cleft, which is what you get when you take an SSRI, that this causes the brain to have to sort of change how it's doing things in ways that increase neuroplasticity that may lead to mood-stabilizing benefits. With women who have PMDD, they're able to just take antidepressants or SSRIs during the luteal phase, and it works. And so there's a lot of women who find support this way. And it works by actually increasing, it sort of smooths out the way that the body deals with GABA, or deals with allopregnanolone in ways that keep levels of allopregnanolone more constant than what you see in women who aren't using them, which is also, I think, really, really interesting.

1:09:45And it also offers, you know, I'm not a big proponent of, I'm not somebody who loves prescription drugs, but I do love when they can help people. And for women who have PMDD, there's a lot of them looking for help, however they can get it. And for some of them, hormonal birth control can be palliative. For others, taking intermittent dosing of SSRIs can be very palliative. And I like that option for women better than just taking SSRIs all the time because of course it does allow them control. And I think that that's a lot of the things that women really struggle with with SSRIs because they have terrible side effects.

1:10:19And the idea that they can just take them when they need to makes women more at least willing to try it if that's what they want to go or that's the way they want to go. There's also non-medical things that I think are always, I always think it's better to try those things first just because the side effects of the non-medical interventions tend to be so positive. So some of the ways that research supports treating PMDD and helping women really feel better, even when they have pretty tough cases of PMDD, cognitive behavioral therapy and neurofeedback therapy is found to be incredibly supportive to women who have these types of symptoms.

1:11:00And essentially what these types of therapies do is they work with women to be able to recognize the trains of thought that they get into when they're having these episodes. Because a lot of times they do tend to be characterized by periods of rumination and teaching women to recognize when they're in one of those periods and then how to talk themselves out of it. Using neurofeedback, you're able to actually see the brainwaves that are happening when you're in that terrible state. And you have to learn by watching your brainwaves and just trying all sorts of different mental gymnastics until you're able to see it calm down.

1:11:37You learn what makes your brain calm down. So I love neurofeedback because it's different for everybody what those sorts of thoughts are going to be. And then really working to get in the habit of shifting into that mindset when you're starting to recognize symptoms. And those things can be very useful to women. There's also some really great research. We're starting a project right now looking at stimulating your vagus nerve. and that as something that is a non-medication-based treatment because one of the things that we know is that many women who have PMDD, they do have low vagal tone. So the communication between their periphery, so their body outside of their brain, and their brain doesn't seem to be very adept.

1:12:22They don't have a good communication pathway. Their brain and body doesn't like to communicate well. And doing vagus nerve stimulation is a way to get your body to learn and get better at having these kinds of connections. And it seems to be really helpful with major depressive disorder. And there's even some new research showing it's helpful with endometriosis, which is fascinating. I am a big fan of vagal nerve stimulation. Yeah, so cool. We have a whole episode that we did on it with Dr. Navas. He's a friend of mine, and that's like all he talks about. But before we got more research on it, but with patients, like I would, and this is gonna sound bad, but I would even have patients gag themselves with a toothbrush because it will stimulate that like first thing in the morning.

1:13:07And people would say like, my day is actually better. And it sounds really awful to do like humming, singing, you know, different breathing patterns. There's other things you can do, but if you really want to stimulate it, you put a toothbrush back there and it really will wake up. It sounds so terrible. It sounds so terrible. But I picked that up actually from doctors who were doing a lot of work with a neurodegenerative disease. And that's something that they had patients do because they're like, when you stimulate it in that way, there's an influx of like oxygen. It helps like get, they're stimulating like we need more mitochondria here.

1:13:40Like it sends this really powerful signal. It's very interesting. So everything that you just talked about, PMDD, we see from reports that women who are autistic, roughly 90 % of them report PMDD and almost half of those with ADHD report PMDD. And there's things that you brought up that I want to connect for this community. So one, talking about the neuroplasticity and SSRIs, we know that those with ADHD specifically, I'd have to look at the research for autism, lower levels of BDNF alpha, so brain-derived neurotrophic factor. So neuroplasticity can be an issue actually generating energy in the brain.

1:14:21You talked about how HPA dysregulation and cortisol is just a very metabolically expensive event going on. How having so much estrogen priming your brain is very expensive going on. I like to say that basically people with ADHD, they're burning through rocket fuel to run through their day because they are metabolically using so much energy. And what's interesting is you talk about like, we can't be sensitive all the time. That's why we got to dial back on the luteal phase, but we know that, you know, part of the issue with autism and we can even see with ADHD brains is that there wasn't actually pruning in their brain.

1:15:02Like they should have went through developmentally. So they are more sensitive. They're taking in so much more of the environment. They tend to have different metabolic pathways. They tend to have more inflammatory issues, more immune system dysregulation. So I just wanted to like highlight all of that for people because it's something that I talk about in this community a lot of like, why do you struggle with PMDD so much more? And it is something that I see time and again, when we have issues with progesterone sensitivity, so often they are somewhere falling into the under in that neurodivergent umbrella.

1:15:37And the question is, is that was this your brain's operating system that has made you so sensitive or was your brain's operating system put you at risk for trauma in your life and experiencing that? Because you have a different brain trying to fit into a neurotypical world. You're often told things like you're lazy, you're dumb, what's wrong with you? Why are you weird? Like, and you're treated differently. And so it's a big, like, we don't know at this point. And as you said, it's likely the kitchen sink, right? It's like everything is contributing. But I do want to talk about that piece of trauma because you brought it up earlier.

1:16:13And I think it's a good thing to bring up because you noted in your book the connection between trauma, adverse childhood experiences or ACE scores, and the risk of PMDD. So can you talk about that? Hey, it's Kelly Rowland. You may not know this, but I have eczema. So I get how it can steal your time. But why let eczema take over when you can talk to your doctor about ebglis?

1:17:03reactions can occur that can be severe. Eye problems can occur. Tell your doctor if you have new or worsening eye problems. You should not receive a live vaccine when treated with EpGliss. Before starting EpGliss, tell your doctor if you have a parasitic infection. Paid partnership with Lilly. Respect your time. Ask your doctor about EpGliss and visit EpGliss.com or call 1-800-LILLY-RX or 1-800-545-5979. Yeah, no, there's definitely a link. They've done studies where they look at the risk of developing PMDD based on whether you have a trauma background or you do not have a trauma background. So looking at ACEs scores in particular, and what you find is that women who've been through traumatic events do have a greater risk of developing PMDD, and it's pretty significant.

1:17:43And again, I think that this linkage has to do with dysregulation of the HPA axis and also dysregulation of the ability to regulate inflammation because one of the things that we know about dysregulation in the HPA axis is that it also tends to be related to heightened inflammatory activity in the body. and an exaggerated inflammatory response to stress. And so one thing that people don't really recognize about their stress response is that it really is tightly tied to our immune response. And the two things work together in concert. And you do get exaggerated inflammatory activity in response to stress when you have blunted cortisol.

1:18:23And I think all of these things, in terms of, like you said, it's a big mess of spaghetti. That's a good analogy. You know, it's like, and everything is bi-directional, right? And so we know, for example, that is it that you have a brain that's made this way and then you're more, you know, susceptible to trauma and then the trauma then it like works in a sort of a forward-facing feedback loop where it's just, you know, reinforcing difficult patterns in the brain. We don't know. You know, it's messy to study. And as we know, women's health is in the ghetto and it's just not, you know, whenever you look at research in women's health, it's about everything below the belt and almost nothing at looking at the actual health of women.

1:19:03You noted the bikini medicine in your book, and I appreciate that. Could you tell people what that is, what you mean by that? Yeah. So bikini medicine is just this idea that the only thing that's different between men and women is the parts of the body that can get covered with a bikini, right? And this is used to justify the fact that most medical research is done on men, and then we apply it to women with the idea that women are going to respond in exactly the same way as men, you know, unless it has to do with the breasts or the ovaries or the uterus. And I mean, and that's completely ludicrous.

1:19:34And, you know, one of the things I note in my book is that, you know, bikini medicine is grounded in bikini science. And it's not as fun as it sounds. It's not a beach party, you guys. No, I mean, you know, scientists, and again, this gets out to the way that women's cycles were handled by research. It's like we're treated just like men, you know, and when you look at women's health research and the women's health initiative or whatever, it's always about things that have to do directly with reproduction or menopause. And it doesn't have to do with the health of women. And it's like the fact is like women, you know, our bodies are different than male bodies.

1:20:12And to study women's health, that means that you need to study things like Alzheimer's disease, cancer, heart disease, lung disease, asthma. You need to study that in women. as women. And we're not doing that. We're treating male and female bodies as indistinguishable from one another, and it's completely inappropriate. And it's one of the reasons that we are so overwhelmingly more likely to be misdiagnosed. It's one of the reasons that we're more likely to have bad side effects from medications. It's just because people aren't appreciating that sex runs through the body, and it runs through the brain.

1:20:50And yeah, and this is part of the big problem that we have. And certainly, you know, with an issue like PMDD, which is, you know, a mood-related disorder primarily, not very well studied in women, and we know very little about it. One of the things that I can say is that what research tends to support is, you know, because there's all of these different factors that are oftentimes working against a woman when she has PMDD. So oftentimes there is like sort of a neuroatypicality. So whether it's dyslexia, ADHD, autism, right? So you've got that. You've got dysregulation in the HPA axis. You've got dysregulation in the inflammatory activity in the body.

1:21:34All of these things can be improved upon if we can try to increase cellular and neuroplasticity in the body. Because anything we can do to support the health of our body is going to support the health of our brain. and it does allow us to coast through these hormonal changes in a more graceful way. And this doesn't mean that you can sort of, you know, eat healthy and exercise your way out of PMDD because for a lot of women, it's not that simple. And it's really hard to exercise when you're so sad that you don't want to leave the house. But anything that you can do, even small changes that you can make to help support the health of your body, help support the health of your brain, helps support neuroplasticity and brain plasticity, and those things are going to make it a little bit more manageable.

1:22:21And so one thing that I try to emphasize in my book is just really, you know, really taking seriously the idea that the brain is a body part. Because I think that we forget that. You know, I think that there was this quote, and I'm going to butcher it, but this was said by, I think, like an Eastern philosopher. and they said that in the West, we think about our brain and our head as this thing that just, or no, let me say that again. We think about our body as this thing that just takes our head to meetings, right? And it's just like this idea that totally separate from one another and we totally discount how important the body is.

1:22:59But our brain is a body part and we treat our body well and we do things like going out and getting sunlight and trying to regulate our sleep by setting our circadian rhythms, like getting that morning sunlight in your eyeballs is super important and super helpful for helping to regulate your circadian rhythms. That's going to help you sleep better. Better sleep also increases cellular plasticity. It's also going to give you more energy to go out and go for a walk, do something in nature. If you walk outside and get your body moving, all of that causes a cascade of hormones to get released that increase neuroplasticity, increase cellular resilience to hormonal changes.

1:23:38All of these things are going to help sort of start getting the deck loaded in your favor to help be able to tackle some of the ways that you're feeling, whether it's with cognitive behavioral therapy or if you try a medical intervention, all of these things are going to be supported by better supporting your health. And so one of the things I talk about in the book is really talking about what are some of the things that we can do that are going to help to support the health of the body that are actually doable because I think that a lot of times if you tell somebody, you know, especially when they're in the throes of PMDD, like, well, you know what you need to do?

1:24:13You need to go exercise and you need to like eat more vegetables. And it's like, that feels like it's insurmountable. Well, I want you to know, I am definitely ugly, ugly, cried exercise. And I was like in my, I have a home gym and I was like doing bicep curls. There's like a crying. My husband's like, what's wrong? Like, what's going on? And I'm like, I'm so sad. And he's like, why are you doing this? I'm like, I don't want to be sad. And I think that I say that because I want women to know that sometimes it doesn't look like the cover of Yoga Journal. And sometimes it doesn't look like, but there are times where it's like, you just have to like do things anyways.

1:24:49And it's hard, but you're right that, well, what I want to back up and say though, and I want to get like more of like your natural approach because people, I think some people may have already left the podcast because you brought up SSRIs. And I think that they're really villainized, and I think rightly so, in some instances, because it's one of those things that a woman comes in, she has symptoms, the doctor's like, it must be in your head. Just take an SSRI, right? And that definitely happens. But you did say in your book, it's highly unlikely that PMDD is ultimately caused by a Prozac deficiency.

1:25:24But research does find that SSRIs like Prozac do help women to feel better. And what I want for people listening to understand is we are talking about someone who may take their own life. And there's the question of, do you give the SSRI and keep the person on the planet? Or do you risk them no longer being with us? And it's a hard call in some instances to know that like, you know, whether something natural is going to be enough. And so I also want people to understand that you can always take an SSRI. And what I love about the saffron research coming out, which by the way, that's my go-to. I love saffron.

1:26:00And that's what I take personally. But if you start to have the libido side effects, something like saffron can help with that. But we see other things like you can start the SSRI and then you can start exercising and then you can start doing these other things. Now you're actually able to rally and then you're able to come off the SSRI. We see sometimes the same thing with endometriosis. Sometimes we put you on the pill, we stop your period. You don't menstruate. We take you off of it for three months and you start the nutrition, you start the lifestyle because now you have the energy and capacity to do that.

1:26:30And then you come off. It's not always like your failure if you use a medication or if you use a medication, you have to be on it for life situation. Yeah, no, it's not all or nothing. You know, and that's like one of the things I really want to highlight in the book is that on the whole, I am not somebody who is an advocate for antidepressants, especially as usually dosed, particularly in teenagers. and I think that they're given to mask a lot of problems. I remember, and my mom is going to hate me for it, I love my mom, but my mom's answer to like everything in life is divorce or antidepressants.

1:27:05Oh, really? Mine is drink water, take a nap. Yeah, oh my God, that's so funny. So I remember with my second child and I was getting ready to go back to work and thankfully we have a nanny at home, which makes things better. but it was like, you know, three months, four months after he was born. And even though I have a very supportive workplace and I was able to pump and I was able to work from home a lot and still do the regular things, it's hard, right? So I was like crying. I was like crying my mom's life and I was crying every day because I was so sad about having to go back to work. And my mom was like, you know, you might, I think you might need it.

1:27:41I'm like, mom, I'm sad because this is sad. Like it is a sad event for a woman to leave her very young baby. Like this is hard for women. You know, we've been talking about like this whole hormonal transition and how your brain has to do that. What happens in pregnancy? So you have all this estriol. So E3, a different type of estrogen, you have all this progesterone, but also your cortisol response is different. And then you shift to postpartum, you lose all those hormones and your cortisol response is changing. Then again, And it is why whenever people are like, oh, six weeks is enough. And why should a woman have a vacation just because she had a baby?

1:28:14And I'm like, her brain literally has to remodel over the next six months and change everything. That's just the brain. Not to mention, can we talk about what happens to our vaginas? Yeah, no kidding. They go through the ringer there. It's so crazy. Yeah, so I'm not a big advocate of antidepressants. I think that they're a sort of a last ditch, you know, piece of medication that a person can use. But I want like so many women when they're suffering with PMDD do get into a place where they can't do anything. And they are thinking about taking their own lives. And I'm so thankful that we have this medication that's out there for these women, even if they're only on it short term.

1:28:52And I think that it's great if they're only on it short term, because the fact is, if you're able to get your body working back with itself instead of against itself, a lot of women are able to feel a lot better without medication. And so I think that, you know, just letting people know about what's available. And again, yeah, as I note in the book, it's like PMDD is not the result of a Prozac deficiency, right? It's like, that's obviously not the problem, right? But for some women, they can find it really helpful for a month or two while they're able to feel more light and more stabilized. And then they're able to do things like go out for the morning walk and then even maybe be able to begin to exercise more vigorously, making sure that they're getting enough sleep, creating those types of social connections, because all these things that support the cycle and that support mental health as we transition between different hormonal states do require some ability to go out into the world.

1:29:49And some of these women really get into a really bad place before they're able to get the help that they need. For a woman who's recognizing what's going on early on, then I think that it makes sense to first try the behavioral techniques, right? So for example, cognitive behavioral therapy has been, as I noted, neurofeedback therapy. These have been found to be effective. Changing diet and exercise. Exercise, and I'll say this here and I'll say it a million times, and then people say, send the papers. So we can put some in the show notes. But exercise is at least as effective as antidepressants in treating depression, right?

1:30:26And this is depression of all sorts, whether it's stemming from hormones or whether it's stemming from other issues that are not hormonally related. It is as effective as antidepressants, at least as effective as antidepressants. And it can feel really hard to get to the gym when you aren't accustomed to going to the gym and when you're in a hole. And so I make some recommendations in the book for ways that women can have it stack to try to get themselves to a place where they're actually getting a therapeutic dose of exercise. And even if it means for the first day, you just go outside and you walk for five minutes, you go back home, you sit down, the next day you're going to walk at least five minutes and see if you can push yourself a little bit further.

1:31:08And then you just keep building from there. But I mean, there's a starting place for everybody. And even if you are somebody who's never exercised and it seems like totally foreign, if you build it into existing routines, it's going to make it a lot easier. You know, so like for me, I just recently picked up the habit of getting more morning sunlight right on my eyeballs to set my circadian rhythm so that way I'm able to sleep better, which is part of the reason I was so tired at dinner last night. This poor woman got up at four o 'clock in the morning. Yeah, I was like four o 'clock Texas time and I was like, oh my gosh.

1:31:41But it's because I am in the morning, I would sit outside and have my coffee in the morning anyway. And so it's like, okay, I'll sit outside in the sun and make sure I'm getting sunlight. And then it gradually changed into a morning walk with my coffee. So it's like I started just sitting outside with my coffee. Then I moved sitting with my coffee outside in the sun, getting sunlight into my eyes. Next, it was taking a little walk with my coffee outside. And now it's turned into every morning I walk at least an hour without my coffee. So doing my coffee beforehand. But it's like I gradually built up to that by habit stacking.

1:32:12So I started with an existing habit and then I made a minor modification for that until my brain felt safe and happy. And then I made another change. Because the thing is, when people try to make too many lifestyle changes at one time, it feels foreign in their brain, your amygdala actually gets activated. And people don't realize that. Your amygdala is like, shut it down. It's like, oh my gosh, what is this? It's different. I don't know what this is. And it's scary. And I don't like it. And so taking these little tiny steps where you can have it stack and take existing routines and just make a minor modification with them, be patient with yourself, make small changes, get used to the small change.

1:32:48And then once you're really comfortable with it, then make another small change. And you can do this over time and eventually, you know, and it doesn't need to take 10 years, you know, it can take a relatively short period of time before you develop new habits that are going to help support your health and eating whole foods. So avoiding processed foods, because that's another one where it's like the amount of inflammatory activity that goes on from lacking diversity in our microbiome and having the rise and fall of blood glucose constantly is just really, really hard on the body. And it erodes our plasticity and our ability to be resilient to hormonal changes.

1:33:24So again, making small changes. And I talk about how I have adopted, because I'm like you, I work a lot. And I know that you work a lot too. We were all talking about that at the table last night. like what is an entire like table full of people that are like workaholics like but we love what we do yeah that's it's so hard when it's like the work-life balance thing is just like when you're like but this is the thing i love like this is what brings me joy yeah no and it's just like trying to i talk about ways that i've i've learned to because i always in my refrigerator keep storage like glass storage containers full of chopped up vegetables that i can grab hand handfuls of and, you know, little things like that and how to prioritize getting those things done so that way you have those things in your refrigerator and ready for you.

1:34:08But just anything, you know, it's like the health of the body is so simple in some ways that people almost don't want to listen to it because it just seems too airy-fairy because it's not a sledgehammer approach. But it really is like when you improve the health of your body, it is amazing what it will do for you in return. And just to give another example of this, and this has to do with hormones. One thing that most people don't recognize that I think is so cool, it's like one of the cooler things I've learned about hormones last year, or I guess it was two years ago now when I was starting to research the book, was about testosterone and anxiety.

1:34:45And it's like when your testosterone is low, a lot of times you develop anxiety. And the reason that testosterone and anxiety are linked is because testosterone is, I mean, among other things that it measures, is it measures your sort of formidability, right? So it's like your ability to deal with threats. And when you're really weak and sick, your testosterone is lower because your body's essentially telling you, if somebody comes after you, retreat, right? Because you are not in good, you know, you are not in good condition. And part of that submissive sort of milieu or like part of that submissive syndrome, we can call it, is anxiety.

1:35:22Because anxiety is nothing more than our brain lowering its threshold for what it's considering a threat. And when testosterone is low, which again is an internal cue that your body isn't in very good condition right now, whether it's that it's sick or you don't have enough strength, your smoke detector is going to be super tuned to threats and that creates anxiety. And so one way that we can support ourselves and increase our ability to self-manage anxiety and not experience it at all is by lifting weights in building muscle mass because building muscle mass is something that can increase testosterone levels.

1:35:58And when we have higher levels of testosterone, that supports our mental health by decreasing anxiety. And it's like nobody, you know, it's like your doctor's not going to tell you that at the doctor's office. They're not going to say go and do a little resistance training to decrease your anxiety. Instead, they just give you medication and say take two of these and call me in the morning. But there are so many ways that by supporting the health of our physical body that it really all works together to help promote mental health and help to smooth the transitions between different hormonal states.

1:36:30You know, as you were talking about testosterone, when testosterone is low, we see women have a hard time with boundaries. They have a lot of people pleasing going on. And it's interesting when you put it in the context of like, because you are not strong enough to defend yourself that even in the modern world that we've adopted to slightly, We've been totally adopted, but it's that we're going to people-please. Like we are, we can't set a boundary because we're not, we don't have the mental and physical fortitude to actually reinforce that. And as you're bringing up exercise, I've been nerding out on the research on lactate or lactic acid because forever we were like, this is just a metabolic waste byproduct.

1:37:07And now we're like, it's jump-starting like neuroplasticity, like it's giving your brain fuel. And so when you say like exercise is rivaling an SSRI and the mechanism of action of the SSRI, maybe neuroplasticity, well, exercise is doing that for you. Not to mention like your SSRI isn't going to be pumping your blood flow the way like a cardio class or weightlifting is going to be doing. So I think that's a really good thing to underscore of like how necessary and important exercise is. I want to ask you perimenopause and PMDD. Often women are told things like your PCOS, your endometriosis, your PMDD.

1:37:47They're all going to get better when you go into perimenopause, menopause. What is the, I know, right? I like someone with endometriosis, I'm just like, yeah, no, no. But this is what doctors say, right? It's just a myth that someone probably said, you know, at a grand rounds one time and it just got passed around the campfire, like, you know, a little game of telephone. So what does the research really say about PMDD and perimenopause? Perimenopause is a time when most women get worsening of everything. And the reason for this is the first thing that happens when we're going through perimenopause is as ovulation becomes sporadic and weak.

1:38:24So meaning that your body is actually developing egg follicles and you're getting a dominant follicle, but then it's not really going anywhere. You don't release progesterone. And so you'll get, you know, estrogen being released as your body is starting to stimulate egg follicles because that's what's responsible for the production of the big estrogen bump that we get prior to ovulation. And so you get this going on. So estrogen is being produced, but if we have a non-robust egg or it doesn't develop correctly, it'll just get reabsorbed in the body, never gets released. There's no corpus luteum.

1:38:56There's no progesterone. And when we're going through this state of constant estrogen, which is again, very stimulatory and no progesterone, which really counterbalances that rise in estrogen. It makes women feel on edge. They're not getting that GABAergic activity in the brain that's really calming and kind of kumbaya. They're also getting overproliferation of the uterine lining, which is why you get the worsening of endometriosis. I mean, it can just really be a terrible time for women. And the idea, you know, when many doctors are reluctant to give women biologically identical hormones, and if they do, they just give them estrogen.

1:39:34For a lot of these women, for a couple of years, at least, they would do just fine just taking progesterone because that's where a lot of the issues are popping up. And this is in part what's responsible for the worsening of premenstrual symptoms that happen perimenopausally. And so while those things may resolve and feel better once you're in full menopause, during that 10 to 15-year period, when you're in this state of hormonal transition, things can get a whole lot worse. And for a lot of women, they really are. Yeah. And not to mention, as we were talking about the HPA dysregulation, that takes effect in that time as well.

1:40:13And I completely agree with you. So I've been prescribing hormone replacement therapy, treating menopause, perimenopausal women for over a dozen years. And the number of doctors, so I generally start with progesterone because if I'm seeing you early enough, it's progesterone that we're starting with because why should you have to suffer? Then I would start women on estrogen before they were officially in menopause. So everybody like, you don't have a period, 12 months to the day, that's your birthday, you're menopause, next day, you're post-menopause. But doctors were very much, the majority consensus was like, no, not until she's there.

1:40:50But most of the symptoms, and feeling like hell is happening before then. But it's so interesting because it's only now, I would say only now in 2025, starting to turn the corner. So whether you had a uterus or not, I didn't care. I was also going to give you progesterone if I was giving you estrogen because I knew you would sleep better. You would feel better. Progesterone is doing so much more than just protecting the uterine lining. That's so frustrating. And still today, there are doctors who will tell me, Like there's no reason that you're giving her progesterone and that's not the guidelines and you shouldn't do it.

1:41:25And I'm like, but sometimes we got to go off script because the guidelines were not updated fast enough. We're not like this woman. Sometimes I'm with a patient and she's looking at 20, 25 years left of her life. Why am I going to say, you know what? I know you feel bad, but the guidelines tell me that it doesn't matter. Like you don't have a uterus. Therefore, I'm just going to give you estrogen. I also have gotten pushback because women with endometriosis, they have a hysterectomy. I still give progesterone. Why? Because I don't know where those other lesions are. Are we certain there's not a lesion somewhere else in your body?

1:41:57And if I give you just estrogen, we're going to stimulate that. I mean, you're telling me this. So let me just say that I'm late to the party of understanding that doctors were only giving micronized progesterone to women if they had a uterus. You're crazy, right? They're still doing it. No, I just learned this like a month ago. And I was like, and I'm like, wait a minute, hold on. Can you repeat that? And then I heard the sort of status quo in hormone treatment and that they're only giving it when there's a uterus. And that, again, and I loved your what happens in Vegas stays in Vegas thing, but that's based on this idea of uterus island, right?

1:42:31And as you said, what happens there doesn't stay there. It doesn't just stay there. There are progesterone receptors throughout the body. That is absolute insanity. And honestly, it represents a complete misunderstanding of the way that hormones work. And so anybody who says, I'm not going to give you progesterone because you don't have a uterus and that's the only thing that it influences, doesn't know anything. They need to retake human physiology because that's, I mean, it's madness. And even just to give a simple, I mean, it modulates the immune system. And in fact, one of the reasons that it's been hypothesized that autoimmune disease is so high in women now is because progesterone is potently anti-inflammatory.

1:43:13And the female immune system is way more powerful than the male immune system. So left unbridled without progesterone to help modulate the immune system, so just under the influence of estrogen, the female immune system will go absolutely bonkers over anything that it encounters. And the reason for this is that we evolved for most of our history, spending a long span of our adulthood, either in the luteal phase or pregnant. And so our bodies are adapted to progesterone. And so taking that away is one of the hypothesized reasons that women have such high rates of autoimmunity is because we are no longer exposed regularly to high doses of progesterone because we spend much less time pregnant, and that this leads our very overactive immune system to auto-react.

1:44:01And so the idea that But progesterone only matters for that when it also helps remodel bone tissue. It remodels breast tissue, leading cells from a proliferation state into a differentiation state, which reduces the risk of breast cancer. It causes all kinds of changes throughout the body outside of the uterus. And so the idea of not giving this because you don't have a uterus, like when I first heard it, I literally thought I misheard what the person was saying because it was so nuts. And it's like, I just couldn't get over it. I'm like, you do understand that that's not the only place where there's receptors for this hormone.

1:44:38But this goes back to bikini medicine, right? Well, no, totally. The only reason to ever treat you is because it's got something to do with your uterus or something to do with your breast. I know. It's based on a fundamental misunderstanding and misrepresentation of what sex differentiation means. You know, like men and women are biologically different from one another because our bodies have to be biologically different from one another because of the different demands of each sex for the act of reproduction. And that has led to the evolution of sex differences in systems ranging from our cardiovascular system and immune system to our brain and our reproductive systems.

1:45:15I mean, it's all over the place in the body, and we need to move away from bikini science and bikini medicine if we want to actually promote the health of women. Because women's health is not just about the health of the breasts and the uterus. Women's health is about the health of women, which means women from head to toe. Yeah. And, you know, as you brought up before, men have testosterone, which they have estrogen to. They have these other hormones, but that's their primary hormone. Women have two primary hormones. So why? If we know that. if a man didn't have enough testosterone, we replace it.

1:45:48We do that. Why, if a woman doesn't have enough progesterone, do we just act like, ah, game over? Yeah, it's like estrogen is seen as like the female hormone. And I think that part of it is just birth order, right? Estrogen was discovered first, and then progesterone was discovered later. And so I think that it was like, oh, look, it's estrogen. Like men have one hormone, women have one hormone. And then they're like, oh, no, look, there's two. And then it was just kind of ignored. And I think that it's because it was inconvenient, you know, because it is inconvenient. Like our cycles as a scientist, and I still work in the research lab and run studies, it's hard, you know, studying women and having to make sure that you get them at the right point in the cycle and then making sure that you get them in one phase and then you get them in the other phase.

1:46:30It is harder. It doesn't fit in the male model of research that we've created. And science was created with the idea of men in mind who have a one-size-fits-all primary sex hormone that's pretty much the same day in and day out, and we require something different. And I think that the inconvenience just led researchers to say, ah, you know, it only matters for the breasts and the uterus anyway. We'll just, you know, ignore it and just study women in this other phase. But yeah, it's completely nuts that we are only giving women estrogen when we have two primary sex hormones and calling it hormone therapy is ludicrous.

1:47:02And in fact, so I read an article in The Atlantic, which I love. So Atlantic, don't get mad at me. I love you. I love The Atlantic. And the writer is actually somebody I also really like. She's somebody whose articles I really enjoy, but there was a headline where it said something to the effect of hormone therapy is finally starting to change to actually account for the hormones that women have. And I'm like, oh my gosh, this is great. It's finally talking about progesterone. And I'm reading it, and it was about estrogen and testosterone. And it never mentioned progesterone a couple of places in there, but not as something that needs to be added into hormone therapy.

1:47:38And I was like, this is madness. I mean, it's complete madness that we're not, it's been an absolute, and it's an unsung hero in terms of promoting brain health, promoting mental health, promoting anti-inflammatory activities in the body from head to toe. I mean, it's like a really beautiful hormone. And it's just been absolutely, you know, cast aside, you know, and nobody pays any attention to it. And so I wrote the period brain because like, we need to pay attention to this. It's like, this is a hormone, you know, in which a cycling woman spends at least half of her adult life, you know, under the primary control of.

1:48:17It plays such an important role in creating the experiences of who we are. It can play such an important role in creating hormone therapy that actually makes women feel better. It plays, I mean, it's part of who we are. And the idea that we've just totally left it out of the conversation until now, totally inappropriate when we are a female body that cycles. I want to ask you one last thing. I get pushed content all the time. People are like telling on gynecologists. So I get all this content all the time. gynecologists saying ovulation is optional. It's not necessary. There's no research to show that we actually need to ovulate or there's any problem with that.

1:48:54And gynecologists who say, I'm a fan of menstrual suppression. Therefore, I recommend it to all my patients. I take issue with bias of like, just because you like something doesn't mean you push it on everybody. Why do you think it is that modern gynecology sees ovulation is optional and progesterone's not necessary. You know, I think that this all goes back to bikini medicine, bikini science. And I think that it's like the only thing that our reproductive hormones and reproductive organs are seen as doing is making babies. And our reproductive organs, by cycling and by ovulating, that's the primary way by which the female body produces sex hormones, right?

1:49:34In our body, we spent our long evolutionary history as a species in being bathed regularly in these sex hormones, whether it's estrogen, whether it's progesterone, both estrogen and progesterone, both of those things during pregnancy, during cycling. I mean, it would be like taking away oxygen and then saying, we don't really need this, right? Because if you're able to survive, then not die, which you can't do with oxygen, obviously. So it's a terrible metaphor. but um but it's like taking something like gravity right and then being surprised when the body falls apart when you don't have gravity on it it's like gravity was a constant throughout our evolutionary history and when you put people in space their bones their bones fall apart if they don't have them doing different types of exercise because that was an that was a constant we needed that in order to be healthy the female body produces sex hormones and it's part of what our body needs to be functioning optimally.

1:50:27And so the idea that we can just shut that down and that we don't need that is absolutely insane to me. I mean, it just doesn't make any sense at all. And so, you know, and I also hear this with when women are talking about like low dose birth control pills, we're like, oh, it's more natural because these are the levels of synthetics are really low. And it's like, there's nothing natural about being in a low hormonal state as a reproductively aged woman. I mean, it's like what our body is accustomed to is high and fluctuating levels of hormones. That's like what our bodies are designed to operate optimally under.

1:51:02And suppressing that generally makes people feel terrible. And we're only starting to understand what the consequences of that are, both in mental health and in physical health. Well, thank you so much for taking the time to chat with us today. I could seriously, well, you know, we talked forever last night. I could talk to you forever. But I think if people enjoy this conversation and they do want to hear more, they definitely need to grab a copy of your new book, The Period Brain. Thank you so much. No, I'm really, this was so much fun and I'm so excited to, you and I have gotten to have a lot of digital interactions and it's been so nice to have face-to-face.