Speaker 1Hello, and welcome to Season 4 of Women's Health Interrupted. I'm your host, Dr. Lisa Galea, discussing menstrual cycle and mood, showing us that the brain and ovaries are in a long-term relationship, and sometimes it's complicated. Today I'm speaking with Dr. Aizen Laura Mool, Professor of Psychiatry and Behavioral Neuroscience at the University of Chicago. She's the Director of Clarifying the Endocrinology of Acute Risk, or CLEAR Lab, where her team is working to better understand how hormonal changes impact well-being. She is also a practicing clinical psychologist specializing in treatment-resistant premenstrual disorders. For many years, she also served as a volunteer chair of the Clinical Advisory Board at the non-profit International Association for Premenstrual Disorders. Her work is redefining how we understand disorders like premenstrual dysphoric disorder, also known as PMDD. Today, we'll learn why PMDD is a serious, chronic, biological disorder that sits at the intersection of mental health and hormonal change. Welcome, Tori. Thank you.
Speaker 2It's great to be here.
Speaker 1Let's start with a very, maybe easy question. What's the difference, understanding that there are terms out there already that people use like premenstrual syndrome, menstrual-related mood disorders, PMDD, premenstrual dysphoric disorder, I've heard premenstrual exacerbation. What's the deal, Tori? What are they all?
Speaker 2Yeah, so I think it's helpful to think sort of in layers, and if you think at the broadest level, premenstrual symptoms or menstrual cycle-related disorders, they're all very related symptoms, whether it's physical or emotional. That's a really broad category. In popular culture, we use terms like PMS or PMT, premenstrual tension, premenstrual syndrome. I think people will even use PMS sort of as a verb, often offensively, like she's PMSing, right, or they're PMSing. So I think we can think about that as a category that is so broad that, you know, when it comes to the medical system. Where we try to treat people or the research systems where we're trying to study these things, that label of premenstrual syndrome is so broad that it's sort of not, it's not useful for describing things when we really need to be precise about what we're talking about, right? So at the broadest level, we can talk about premenstrual symptoms, premenstrual syndrome as sort of this idea that emotional or physical symptoms can change across the menstrual cycle, and in particular. And so that is just this very broad umbrella, and that includes things like mild cramps, like mild fatigue around one's period, right? It can include really sort of mild things that, you know, we really wouldn't think of as like a mental health disorder or something that needs diagnosis and treatment, right? But then at some point, when those things get severe enough, and in particular, when I focus on is sort of the emotional side of those symptoms, the physical side of those symptoms can be really very serious and impairing as well, but that's more the remit of gynecology. But when we're thinking about emotional PMS, at some point, the symptoms can become significant enough that they are distressing, they are causing problems in your life, they're interfering with relationships, they're making your day-to-day life difficult to enjoy, right, and it's not this thing. It's this thing where, you know, there's a clear cut point. Okay, there's people who have severe enough symptoms that we need to diagnose them with a disorder, like premenstrual dysphoric disorder, which is just the severe end of emotional PMS, right? And then there's people who have none, right? You can certainly find people with no premenstrual symptoms ever. You can also find people, a lot of people that we might say have premenstrual dysphoric disorder or just severe enough PMS emotionally that they need a diagnosis and treatment. But then there's all these people in the middle, on the face of it. That's frustrating. But then if you look at other psychiatric disorders, that's true of other psychiatric disorders as well, other mental health disorders where everyone experience or most people experience significant sadness sometimes in their life that interferes with their day-to-day function once in a while, but maybe doesn't persist long enough or isn't severe enough where they're going to seek out diagnosis or they need diagnosis and treatment for something like depression. So I think you can think about it that way, that PMS is this really big umbrella. That is just this idea of emotional symptoms changing across the menstrual cycle. And then within that, there's sort of this range of severity. And a lot of what I work on and, you know, both clinically and in the research is to try to understand where is that line between normal and abnormal and how, what is it like for people who are sort of in the middle or have sort of inconsistent symptoms. When we think about emotional symptoms changing across the menstrual cycle, there's also this other element, which is, are you a person who has the. Those symptoms all the time and they just get worse, which we would call premenstrual exacerbation. Or are you a person who doesn't have those symptoms at all outside of the menstrual window? For those people, we, we would give the diagnosis of PMDD. So the diagnosis is pretty restrictive in terms of where your average level needs to be. Anyway, all of this is just to say, these names are all just ways of talking about premenstrual emotion changes in emotional symptoms, PMDD is sort of our attempt to say, not just normal. We're not trying to say, you know, this is what I'm going through and this is what I'm going through. This is what I'm going through. that is the threshold. You know, if that's the case, then we're not going to call it premenstrual dysphoric disorder.
Speaker 1So in other words, it sounds a little bit more complicated than at first blush.
Speaker 2Oh, we haven't even gotten it. Oh, I know.
Speaker 1I can't wait. I can't wait. Before we get to complicated, what's the best guess out there in terms of prevalence or the percentage of people that might be suffering from pmdd or be vulnerable to pmdd so
Speaker 2before i give those numbers i'll just say these numbers exclude people who have a chronic disorder okay people who who you know how i was talking about you might be a person with higher baseline symptoms and then they get worse or you might be a person with lower or like no baseline symptoms of course yes they show up we're only talking about the people with nothing else really truly have no symptoms during the what we call the follicular phase, basically the end of menses through ovulation, you have no symptoms. You have this symptom-free window where you're basically completely, we would call euthymic or having no mood symptoms, right? For those people, when we say, okay, if you have any other chronic disorder where your symptoms are high all the time, we're setting you aside. But if we look at that, the prevalence of cyclical distress that is moderate or greater is about six percent if you instead do the opposite and you say we're only taking people with depression who have menstrual cycles what is the prevalence of a similar amount of change yes right that same pattern just happening up here instead of down here it's closer to 60 percent wow so it's important to note there though what i'm not saying is that not all females with depression have cyclical change. There's 40% of them where we really don't see a pattern or we don't see enough change that we would categorize it as, you know, sort of the amount of change we're looking for in PMDD. But it's high, right? It's still really high and it's higher than the general population. And so I think this is the first clue that, you know, we probably should be a little bit wary of tossing out people from the conversation who have chronic symptoms, right? Because it seems that there's some kind of association there and we could speculate right the sex difference in depression and other affective illness and suicidality also shows up at puberty right with the onset of menses that sex difference shows up there right it does suggest that the onset of and there's not it's not the only thing that changes right there's all a bunch of social factors right but those social factors do affect boys as well, maybe not the same way, but they do. And we just don't see anything like the increase that we see in girls. And so I think that there's kind of a possibility, right, that if you start ovarian cycling, you have menarche, you start having your period, you start having these cyclical hormones, and you're sensitive to them, and you have these emotional symptoms, it's sort of this stressor on the emotional system every month, right? And so it would make a lot of sense. And we don't have definitive proof of this, but I think the explanation that makes the most sense to me as a hypothesis right now is that sensitivity to the menstrual cycle emotionally actually kicks off risk for these other disorders, long-term depressive disorder, long-term anxiety, right? Because it's this stressor on the system is sort of kindles things, I think.
Speaker 1Yeah. So along with that, the people that show either PMDD or the cyclical, the 60% of people with premenstrual exacerbation.
Speaker 2Yeah. They're just the higher cyclers.
Speaker 1Yeah. Are they more likely to show mood symptoms with other perturbations other than the menstrual cycle? So I'm thinking about, you know, postpartum changes or, and, or perimenopausal.
Speaker 2There's much more speculation than work than data on this point. If you just ask people at a single time point, did you have postpartum depression? Maybe even use a structure questionnaire did you have do you have pmdd or or even follow people across the cycle and characterize when they have pmdd if you if you just ask them at one time point you see all these links between those things you see that these shared risk factors and so there's probably something happening there
Speaker 1there's some signal but
Speaker 2when you um like i said when you actually follow people across the cycle and you diagnose pmdd there's this only one study where they've done call Paris. So other, um, people who have had babies, right. You take like, we have PMDD people who don't, there's no difference in the prevalence of postpartum depression in those two groups. So the only really rigorous paper in terms of methods for diagnosing with those daily ratings shows no link, but there's all of these sort of single time point questionnaire studies showing lots of links. And so I'm, I'm hesitant to say that there's nothing going on there. I think there probably is. Um, but I think that there's more that we don't know. And the reason I'm emphasizing this is that I do hear a lot of sort of fear mongering. I don't think it's meant it's meant to be helpful, right. But I do hear a lot of sort of painting with an overly broad brush of like, Oh, if I have PMDD, I shouldn't have kids. It shouldn't be pregnant because then I will, right. You know, because then I will have lots of, and in fact, you know, there's some, uh, there's quite a bit of anecdotal evidence and speculation around sort of mid to late pregnancy reduction of hormone sensitive symptoms in people with PMDD. Um, you know, I've, I've had, I have permission to share this. I've had, I had a patient who had such relief of their PMDD symptoms during pregnancy that they actually became a surrogate.
Speaker 1Wow. Yeah. Yeah. So because they're like, I just
Speaker 2need to be pregnant all the time. And that's the only way for me to stay well, which is, is wild. Right. So I think, I guess my point in highlighting that is that one, there may be differences in sort of the timing of those links, right? So someone with premenstrual dysphoric disorder may have one particular pattern of hormone sensitivities that then makes them more likely to have symptoms around delivery or, uh, early, very early in pregnancy where symptoms are, or hormones are still surging, right. There might be sort of certain timings that go together,
Speaker 1right. There's not a one-to-one.
Speaker 2It's not one-to-one. It's, it's not this, this, if you have this, you're going to have that. You're definitely going to have that. I think that there, we need so much more data and I know that there are people doing, starting to ask some of these questions. I'm not sure how much has been published yet, but I know some of my colleagues at UNC Chapel Hill are collecting some of these data and they do see what appears to be really meaningful links between some of these things. And even, you know, associations between people's reactions to a, an experimental hormone provocation and their self-reports have, prior reactions to hormonal changes. So I think that there could be something there, but I would say like the links are kind of overblown and there's a lot that we don't know. People can think about that for themselves, but I would say that, you know, I would say it's more like, you just don't know what's going to happen then. Oh yes. If you have this, you're definitely going to have that, like being mindful of having support and that this might be a thing for you is reasonable going into it, thinking that I'm definitely going to have it. Would not be warranted in my.
Speaker 1And there, of course, all of us can have strategies, right? If we know where, I don't know, maybe even going to a party where we might, you know, know that our mood might fluctuate based on people that will be at the party, right? It's good to have strategies.
Speaker 2And there's so many things about pregnancy and menopause and puberty, you know, or even the menstrual cycles that can be stressful for a lot of people that have nothing to do with hormones affecting the brain. Right. So, you know, I think. Having those skills in place, no matter what is a good idea in general.
Speaker 1Yeah, I completely agree. So how do you, and there's so many different places we can go, but how do you diagnose PMDD? Is there like a, do people just tell you they have it?
Speaker 2Yeah. So in terms of how we should be diagnosing it.
Speaker 1That's probably a better question.
Speaker 2So the studies that have been done suggest that for whatever reason, people are not very accurate in reporting their premenstrual symptoms. And there's a little bit of evidence that this might be culture bound. So we may get sort of a little bit more accurate reporting in some countries or areas than others. But in the United States and Canada, we don't see good alignment between a single time point measures, like even a structured interview for the, you know, the SCID for PMDD doesn't translate into actual cyclical changes in mood when we follow people. Over time and questionnaires that have been developed to try to sort of form a cut point and identify, you know, what is a self-report severity of premenstrual symptoms. People say, yes, it's very severe. It's only present here. And then it really goes away or goes down. Even in those cases, those questionnaires haven't been successful in finding a cut point that really differentiates well between people who have those cyclical changes when you follow them over time and people who don't. So the way that it should be diagnosed is daily. I mean, you know, I've seen really crazy ratings of mood across two menstrual cycles, maybe three, if one of them, if it's inconclusive and my lab does a lot of work trying to improve the ways that we identify patterns in those daily data and hopefully reducing the burden of that. So instead of giving people 25 items, can we figure out a way to give them five every day, right? So we're. It's not a bad area to try to streamline the process, but at the moment, the unfortunate state of affairs and research and clinical settings is that people tell us they have these symptoms. And then when we track their symptoms over time for 20 to 30% of them, we do see, we can see a pattern and they tell us it's distressing or impairing. And so we diagnose treat them, but in a bigger chunk, we don't see any patterns at all. And it's, we don't know what's going on with that. We don't know what, you know, is it, is it because of sort of all of the. Sitcoms with PMS episodes, right. Is it sort of because of culturally think about these things, you know, I don't know for whatever reason that, you know, there are certainly lots of people who can tell you that they have it and they're, you know, they actually show those patterns, but then there's a ton of people where we don't see it. And so the daily ratings is the way that it's supposed to be
Speaker 1diagnosed, um, over two to
Speaker 2three. Yeah. And I would use, I would recommend right now, the McMaster, um, PMSS, there's a Mac PMSS app. It's called the Maceo Phrase Lab and, but it covers the DSM five symptoms. And then it also just sort of lets you track, um, general mood over time as well. And I think it's a good tool for this and you can send the report to your doctor and it even helps to try to interpret it. Cause then one of the other things that we see, not only is it hard to do daily ratings of your mood across two months for the patient, it's also hard for a doctor when they get these. Right. These sort of like. Yes. The time series, you know, these big charts, it's like, how do I make sense of, is the timing right? And part of the reason that the PMDD world started excluding completely people who had chronic disorders is that it does make it harder to see. Of course the pattern. The pattern. Right. And you can see it statistically. Right. You can, if you sort of use the right tools, you can see it if you smooth, if you write, like it's there, it's just, it's messier. It's harder to see. And so, yeah.
Speaker 1Yeah. I'm thinking about the. Uh, people that might not be used to. To like looking at data, but if you're talking about a daily symptom, just think about this, right? That's not five, but 25. I don't know how many symptoms there are across 60 days. Just say, just imagine that's what 60 times 25. I can't even do the math. It's a lot.
Speaker 2It's a massive number of observations. And, and I think that what happens is that there's this risk of cognitive bias in trying to process all of this information because it's just too much. Right. Yes. Of course. So, you know, again, my lab has really tried and we've got some new things. Brewing right now to try to detect patterns in a more flexible way. Um, cause the other thing that we haven't talked about is that there are some differences that we see in timing. So PMDD really requires when you're looking at those daily ratings, it really requires that symptoms piece the sort of classic way of saying that this is like very like academic, but ludicrously confined. Um, right. But I like, I, but I like this word confined because I think that it really does like, it's very descriptive of the, of the way PMDD was. Created as a disorder that needs, like it has to be locked in, like between ovulation and menses, that luteal phase.
Speaker 1So before we describe the temporal patterns, cause I love this, I mean, I love all of your work, but I love this part of your work because for, uh, you know, the listener it's complicated, you know, we think of it, we think of PMDD or PME as something that's very easy to describe, but actually, you know, in practice it's quite complicated. Um, so let's just do a little bit of math. Okay. Let's just do a little bit of menstrual cycle 101 because you said you have said follicular, you've said luteal, you've said ovulation, maybe just walk us through that just a tiny little bit and then, and then talk about your, the temporal patterns that you see.
Speaker 2Yeah. So there's kind of this standard hormonal timeline and my lab has done some work to try to make sure that when we're talking about differences across people and how they react to the cycle that we're sort of standardizing the timeline, but so for, but if we're really thinking about this standard timeline. There are two halves to the cycle that you really kind of need to understand, um, and, and the, the events that separate them are menstrual bleeding, um, or the fall in progesterone and then ovulation, or basically the rise in progesterone that happens after the egg is released. So between ovulation, when the, the egg is released and menses, when, when the corpus lidum stops functioning, basically there are two weeks where after ovulation, there's elevated estrogen and progesterone. Before it drops off, um, and those two weeks of surge high, and then drop off, they're that's where we see the development of symptoms in PMDD. And so we see ovulation causes this surge in estrogen and progesterone, mostly progesterone that then, you know, as, as this surge kind of comes online, you start to see with a lag of a few days, usually people with PMDD will start to have symptoms even just after ovulation a little bit and it'll sort of creep up. Um, and then it peaks right around the onset of menses. And then when estrogen and progesterone drop off and bleeding starts, PM, people with PMDD, because the luteal phase is over and their symptoms are confined to the luteal phase, suddenly their symptoms drop off. And so basically the menstrual cycle is menses to ovulation is the follicular phase where the eggs are sort of getting ready for prime time. And then after ovulation, you see like the rise in hormones and then a drop off at menses.
Speaker 1I like that. The, the eggs are ready for prime
Speaker 2time. They're getting ready. They're working, you know, and there's all these waves are happening all the time. Right. But Yeah. Basically you've got the follicular phase when hormones are lower estrogen starts to rise and peaks at the end of that, just for our regulation. And then you have the luteal phase, um, when both estrogen and progesterone are, um, more elevated and that, that luteal phase, that surge in hormones is really what we think triggers the development of PMDD symptoms across the luteal phase. Um, but again, we would, we would expect with the onset of menses, we would expect those symptoms to drop off, drop again, pretty rapidly with the way PMDD is defined. And there are many people for whom that is the case. That really is between ovulation and menses, you in the luteal phase, you get these symptoms, they get worse over time. Uh, and then they switch off often pretty rapidly.
Speaker 1So the definition of PMDD is this confined confinement, um, within the luteal phase, but are there other people that show symptoms outside of that sort of normal, normal pattern?
Speaker 2Yes. And this is where clinically I got into the menstrual cycle because I was treating patients, really complicated patients with, um, severe emotional problems, um, with a disorder called borderline personality disorder or, um, people who just had chronic suicidality or chronic substance use disorder where, um, often they're negative emotions, um, or positive emotions, but mostly negative emotions were sort of feeling really out of control and it was causing a lot of problems in their lives. Mm-hmm. Um, and these patients, um, either with chronic suicidality or, um, borderline personality disorder, in both cases, you see this sort of instability of their mood and it can be very frustrating both for the patient and the therapist or, or doctor or whatever kind of clinical setting you're in to have, to not know what you're going to get day to day in terms of mood from a patient. Right. And to, and to have just this. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. And to, and to have this kind of question mark over why today are you so irritable and not feeling like you can sort of make any sense of anything, not really willing to make, you know, any forward steps, um, and not really willing to engage in treatment. Right. Um, whereas last week you were.
Speaker 1Fine. We were on the same team. Not fine, but.
Speaker 2Yeah. Everything was, you know, you might have been suffering, but you're sort of able to engage and it's, you're not so emotionally, um, vulnerable. Mm-hmm. Um, uh, sort of dysregulated or, you know, um. Yeah. Yeah. Emotions don't feel so out of control that you can't engage. So basically what I noticed was that a lot of those patients, uh, who I was seeing did have cyclical, you know, what we might call premenstrual exacerbation of their symptoms. Mm-hmm. First of all, what we noticed was, you know, well, these people won't meet criteria for PMDD because they have these other symptoms that are chronic. Right. So right off the bat, they're not eligible for any diagnosis. Right. Even if the pattern is the same. Wow. Right. But then for some of them, on top of that, it's not just that their overall symptom levels were too high and they weren't sort of clearing out entirely. It was also that maybe the timing of their symptoms was a little different. Mm-hmm. Um, and in particular, what we would see is that for a lot of people, their symptoms either start later, so more around the onset of menses. Mm. Or they may have the same pattern of sort of luteal phase symptoms, but the symptoms persist. Stay. Longer. Mm-hmm. Um, and so, um, I got really interested in what, what is the reason for these, for this different timing? And should we be excluding these people from diagnosis and treatment? Right. Should we? And then, you know, within that, we need to figure out, you know, is it the same biologically? Right? Right. Is it the same disorder, just sort of on a different timeline? And it's just, and that's still possible, I think, for a lot of people. Mm-hmm. Or are there maybe other hormonal triggers? Mm-hmm. So you remember I said for PMDD -- Mm-hmm. -- we see this surge in progesterone and the metabolites of progesterone -- Mm-hmm. -- that really we know sort of kicks off this two weeks -- Yes. -- of, of symptoms that then switch out with onset of menses. We've been really interested in this idea that estrogen withdrawal, or the drop-off in estrogen -- Yes. -- on the onset of menses -- Right. -- and maybe even a little bit briefly right after ovulation for some people, that this estrogen drop-off can trigger, can be a second -- Mm-hmm. -- trigger of symptoms. Mm-hmm. And it doesn't mean that, um, if you have that -- Mm-hmm. -- sensitivity to estrogen drop-off around menses, and that makes your symptoms last longer, it doesn't mean that you couldn't also have the progesterone sensitivity. Right. Right? Or the --
Speaker 1It's not all or one. It's not all or nothing. Right. Or one or nothing.
Speaker 2And you maybe could have each one a little bit, or maybe you'd have one a lot and the other not, right? Mm-hmm. You could have both of them a lot, right? And so, but the, the functional consequence of this is that there's a lot of diversity in the timing -- Mm-hmm. -- of symptoms. Right. You see patients where, you know, usually we're looking for this sort of on/off. Right? Mm-hmm. Like, premenstrually, it's on. Yeah. And then the luteal phase ends, and it's off. Right? Off. For a lot of people, it almost looks a little bit the opposite. Right? They're doing okay. Wow. You know, for -- if somebody doesn't maybe have whatever this thing is in the luteal phase that's kicking off symptoms earlier, this progesterone surge sensitivity or what have you, they don't have so much of that. They may not have symptoms so much in the luteal phase. It might be only at the very end -- Mm-hmm. -- that we start to see symptoms come up. And then they persist. They persist through menses. And maybe even for some people, they take really a while to resolve, and it's not until ovulation that they feel fully better. So there's a -- we're still working on understanding how consistent these things are within people, but we do know that there's some consistency. There's a lot to unpack. Right? But it's -- it does seem like if you have one pattern in the first cycle, you're more likely than not to have it in the second cycle.
Speaker 1I mean, I think this really understands -- I think this really underscores why it's so important to do deep dives, you know, within sex and within gender in terms of understanding whatever health outcome that you're interested in. Because it turns out, hey, there are different patterns that are psychically related, but they could -- they could look quite different from person to person. And it sort of occurred to me, does -- is that maybe why there's been some sort of a dismissiveness of PMDD? Or any kind of menstrually related mood disorders, because it's not the same. And people that have it, it's not exactly the same. So it can't be -- it can't be that.
Speaker 2Yeah. I think that we're in this place where, again, that sort of umbrella of PMS has not been differentiated in the public's minds enough from PMS that is severe enough that it really causes distress -- life distress and -- Yes. Life impairment, right? Not just, oh, I feel a little less happy today, right? But more impactful emotionally or in terms of function. I think that differentiation isn't there, right? So whereas if we think about something like -- and, you know, it's tricky because some disorders are really sort of you have it or you don't. And some aren't, right? But if we took the example, like, of breast cancer, men can have breast cancer. Yes. That's a really good argument that we're just thinking about -- Right. Right. -- about female folks here. You know, just because females are the ones with breasts or more prominent breasts generally doesn't mean that all females are going to have breast cancer, right? Yes. And the metaphor is not perfect there. But go with me a little bit, right? Yes. Yes. I'm following you. You know, so is it important to screen all people with breasts for breast cancer? Yeah. You know, does that -- is that generally women? Yeah. Right? Yeah. Yeah. But do we go into every sort of doctor's appointment with a woman with the baseline assumption that she's going to have breast cancer because she has breasts? No, we don't, right? No. And so I think that it's the same thing, right? Just because you have a menstrual cycle doesn't mean that you're going to have the symptoms. Right. But there's a lot of sort of basic neuroscience or sort of, like, population-level neuroscience that focuses on just the effects of the menstrual cycle, right? Mm-hmm. And I'm really torn about it because I think -- I think we can see important signals there. And I think it's really -- it can be really useful. But when I look at my data and I see how different -- How complex it can be. -- these patterns, when I see -- even just people who have cyclical change and don't, right? It's just -- you're going to wash out, right? You're basically -- Right. You're putting -- you're putting black and white in the same bucket. Mm-hmm. And you're going to get gray. And basically, the shade of gray that you get is going to be proportional to how many people in the sample sort of have more of those symptoms. Mm-hmm. But then if your conclusion at the end is that, well, the menstrual cycle creates these symptoms for everyone to this degree --
Speaker 1Or doesn't. Or doesn't to me.
Speaker 2anything right right and that and that again that that um that conclusion that we make as scientists over yes this exists in general no it doesn't is often if you look at the person level really just dependent on how on the proportion you happen to get with more or less of these symptoms right so it's a it's a really tricky thing and you know there's a lot of projects and i've done a lot of them sort of saying okay in adhd in borderline personality disorder in you know alcohol use disorder do we see cyclical change and you know we're still working on writing this up but i can tell you in every case the answer is for some people right and maybe even for half of people right which again is more than we would expect to see in the general population but it's not it's not going to be everybody right and so it's right we have to think about the category of people with cyclical emotional changes is not going to be women it's not going to be right female psychiatric patients or females with mental health concerns that's not going to be the category right the category really has something more to do with this biological sensitivity to hormone changes and we don't have good we don't have a blood test we don't have a questionnaire we don't you know really the only way to study this is to follow them over time so it's not very efficient yet
Speaker 1yeah and it also seems like there are going to be different signs of hormone sensitivity right people with the rise but some people with the fall of estrus right and you see that in pregnancy too right yeah i'll keep so scalpidu i always like that she made fun of me after a talk about about exactly that because i said oh look there's two subtypes and she said no there's she laughed at me and said no there's like four and now i always use that in my talks i'm like there's there's way more and i was just thinking about your breast cancer analogy i mean of course it's not just one type of breast cancer either there are many kinds of breast cancer so you know the analogy and there are different kinds of treatments that you need for the different kinds of breast cancer the same possibility exists for mentally related mood disorders as well and
Speaker 2unfortunately you know what we're up against is that breast tissue is something that you can study yes right in in and you can you know do all these really sophisticated amazing studies with human breast tissue with you know um with other uh you know species breast right there's so many different types of breast cancer and there's so many different types of breast cancer and there's so much you can do to understand the pathology and to really you know get into that tissue and understand what's going on what where's the signaling happening that matters right how can we diagnose it in a precision way and then treat it in a precision way we can't go around sampling chunks of people's brains we don't you know that and that's not to say that there aren't any inroads but it's so difficult right and so we can't just take out a chunk of a piece of the brain that we think is sensitive and and study that right and so there have been other approaches you know sort of growing neurons from regressed cells and you know i mean there's some really cool things that have been done you know peter schmidt's lab at nimh has just done some incredible work along those lines and they find some really interesting differences you know but it's not it's not the same thing right as being able to sample that tissue and really say you know is this estrogen receptor positive right breast cancer is it right i'm her
Speaker 1too positive but i'm my
Speaker 2ignorance but you know it
Speaker 1of course we can't do that same way but you know maybe the hope could be for you know precision psychotherapy we might get there someday if we pay a little more attention
Speaker 2sure maybe i think the cool thing about hormone related mood disorders is that we know we know the trigger right we often know the trigger we know the the set of triggers right and we can we can provoke them we can often prevent them by manipulating those hormone triggers um and we can you know use all of the amazing biomedical infrastructure that we have to say okay we can provoke the symptoms what are the sort of cascade of you know what's the cascade of signals that sort of you know goes along with the provocation of symptoms and it's it's not perfect but there are i think there's some inroads there and there's there are so few labs
Speaker 1there are so few labs in this area
Speaker 2you know and even fewer who are doing those experimental manipulations and experiments aren't the only way to learn things about this but i do think that given that we know what the trigger is right and that we can experimentally manipulate this in in various safe ways that are thoughtful you know that seems like an inroad that we maybe don't have in something like just general depression exactly no bipolar disorder or we don't know and then we don't have this sort of singular like this is the trigger that sets off the cascade so i do think that there's hope in that yeah if we can train enough scientists that we have you know more than
Speaker 1three labs doing yeah wouldn't that be nice okay i'm um starting to run out of time with you although i could keep talking to you forever and i'm sorry brevity is
Speaker 2not my i'm i'm a rambler no no no i am too don't
Speaker 1worry about it no it's been fantastic but i want to get to suicidality because i know you have some work on that and i think it's really important i think you said and perhaps this was in the seminar you did for the cluster as well that it did you say it used to be the number two cause of mortality in reproductive aged so it
Speaker 2kind of jumps around year to year right um but but there are many years in which it is sort of number two in terms of the uh you know suicide as as the cause of death among sort of eight you know 18 to 44 you know that sort of range um and again from year to year it sort of jumps around with accidents and some other things of course but but in general you know it there's this idea that men die by suicide whereas women simply make attempts and you know it certainly is the case that females make more suicide attempts and men die by suicide more frequently but what explains that is more that men are socialized with lethal more lethal means they tend to be socialized and using guns in particular um and we know that that just increases risk of death when a suicide attempt is made by by so many um degrees so it's you know women experience more suicidality they make more suicide attempts but men by virtue of the fact that they're socialized in using these really highly lethal methods tend to to die by suicide more frequently so um anyway all this is to say there's this sort of idea that women don't die by suicide and that is just it's just wrong they absolutely do and particularly during
Speaker 1reproductive and is there a tie to the
Speaker 2menstrual cycle yes so what we see is very high rates of self-reported lifetime suicide attempt about 34 percent uh of um in a global survey of patients who said they've been diagnosed by daily ratings with pmdd about 34 percent told us they had made a lifetime suicide attempt um around 72 percent had had lifetime suicidal ideation so that even if that's a relatively severe sample it's you know it's like 600 people even if that's a relatively severe estimate um even if it's half that right it would be quite concerning yes um and then there have been more actually prospective studies that have come out just in the last five years showing that yes if you follow patients with premenstrual dysphoric disorder over time you do see fluctuations in suicidality that match their symptoms um in my case i recruit patients who have menstrual cycles and who have suicidality um who may or may not have pmdd that those hormone sensitivities and what we see is really high rates of cyclical mood change when we recruit for suicidality so we get you know again 50 to 60 percent sort of similar to the depression so it seems to be correlated right um and you know the question is what is the prevalence need to be in pmdd of that symptom in order to move it into the dsm-6 potentially as an actual criterion the way that it is for some other disorders it's i don't want to say hope and suicide in the same sentence in this way but i'm hopeful that it will be considered as a criterion because i think it's quite um i think the data are pointing very strongly in the direction of it being a common symptom it
Speaker 1seems like a very important thing to add so let's hope and one
Speaker 2of the most difficult things about you know i started out as a dialectical behavior therapy clinician treating patients with chronic suicidality and one of the most difficult things about that work for both the patient and the the clinician is that we don't know when an attempt will happen we don't know when symptoms will sort of ramp up and so if you have somebody who's had suicidal thoughts for years you know you we really don't want to overreact and sort of assume that just because they have suicidal thoughts they're going to make an attempt we need to keep them in the hospital all the time right we couldn't do that they it doesn't a lot of people have these thoughts that are sort of transient and mild and right but the menstrual cycle gives us something in many cases that lets us predict those crises in terms of when they happen and that is just such a rare thing to be able to do that so i think it's important that you know suicide as clinicians especially are aware that that might be a foothold for many patients in terms of when um not all but be curious about it because if you can predict it in terms of that timeline it really could make a big difference of sort of being on guard for a week and a half rather than the whole all the time in the same
Speaker 1way yeah i i love that be curious be curious um all right i want to ask you um because you've served as a volunteer for the clinical advisory board at the non-profit international association for premenstrual disorders as we mentioned in the intro so can you just tell us a little bit about that work
Speaker 2yeah so the international association for premenstrual disorders is a patient-led non-profit focused on improving the lives of people with premenstrual disorders which they define as pmdd and premenstrual exacerbation so they understand that many of the patients who they're serving have these elevated baselines and have developed additional symptoms um that are there all the time so but they exist to serve that population to raise awareness um about these disorders and they're often pretty severe impact in people's lives um to make to educate clinicians um um you know science-backed um diagnosis and treatment so we know just very briefly ssris do work a little differently and faster um so selective serotonin reuptake inhibitors typically thought of as antidepressants but if we were going to rebrand them now i would say they work better and faster and more consistently for pmdd than they do for some of these other disorders that they're known for so ssris don't you know don't knock it till you've tried it really effective for a lot of people oh great and then um there's a specific um oral contraceptive uh drosperinone containing oral contraceptives that also there's some clinical trials evidence that it beats placebo for for some people not as well as that so anyway but they exist to to spread this information right about um about the disorder educate clinicians raise awareness um and you know hopefully promote research so that we understand yes these things better researches are compass and
Speaker 1map that's what i always keep trying to tell people we need the research it's not just about i mean education is a big part of it but we also need the research so that we know what to educate
Speaker 2people yeah but i would say like as a clinician and scientist you know i was fresh off of my training yeah in premenstrual dysphoric disorder and of course i was interested in pme and all of this but i think you know really after talking to these patient advocates a lot of them who weren't responding to standard treatments did have some of these different patterns where you they could show in the daily ratings like it's clearly happening here it's clearly menstrual cycle related but there's no diagnosis for me and there's no treatment right so you know it was really impactful for me to hear about what wasn't working you know as i mean we want to tell people about the things that we think will work because we have a chance to work for them but we also need to hear about i love
Speaker 1this but like again you listening to people like listening is kind of not kind of it's really important it's kind of it's
Speaker 2crucial yeah right it is crucial yeah yeah and i think it's really easy to hear this this problem that i was talking about before of people can't self-report very well when they have cyclical changes it's very easy to hear that as you know people don't know anything about their experience and that's just not the case you know there is this there is this problem but once you get into a clinical setting and you've confirmed that people have it or have these cyclical changes right they can tell you you know this group of people can tell you about their symptoms
Speaker 1okay i have two more questions they're pretty quick yeah so the first question is what gets you up in the morning tori and what puts you to sleep at night those are my
Speaker 2last two questions fan fiction yes that's fine that's i've been i'm reading something right now um well that but no uh what gets me up in the morning in terms of this work it doesn't have
Speaker 1to be in terms of work it could be
Speaker 2the sun yeah no i i'm somebody who finds the complexity of this very interesting i find it comforting that it's not simple yeah because that matches my experience growing up seeing you know hearing about this as a girl you know it matches my experience as a clinician seeing the complexity of these things it matches my experience sort of philosophically where you know i sit in rooms with people who are really upset that this disorder exists because they think just the idea of it is sexist i get that you know i'm sympathetic to some of these things right like i find all of that complexity really interesting and i want to figure it out and i'm not going to figure it out but i am gonna hopefully a pretty good job frame up some of it and push it forward and hopefully train you know more people to to think about the complexity and not be afraid of it and to have tools to to tackle the complexity you know that's a lot of what we're going to be talking about in the next couple of weeks my lab is doing these days is trying to figure out how can we identify these differences in really scientific like numbers based measurement ways so i think like tackling the complexity and sort of being a person who you know isn't afraid of that complexity like i think that is that's what excites me and that what makes that's what i feel proud of as a scientist
Speaker 1you should feel proud and what gets you to sleep at night oh also fan fiction um
Speaker 2what gets me to sleep at night i feel especially as i age i think i feel this very midwestern sort of i i did what i could today and i'm i'm at peace with that you know i think as the world gets more and more unfair and scary you know and and divisive yes you know i think i we can't all do everything but you know if we uh you know i feel like i i show up in my life as best i can and and put my skills to use where where i'm able and that makes me feel settled yeah great
Speaker 1um well thank you so much tori this has been a really terrific conversation um and i i really want to talk to you more but you know we're way over time now um so thank you so much and thanks to our audience for listening if you enjoyed the episode please follow the show leave a rating and share it with colleagues and friends we'll be back soon with another episode of women's health interrupted Thank you.
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