Speaking of Psychology - How hormones and the menstrual cycle affect mental health, with Tory Eisenlohr-Moul, PhD

Episode Date: September 6, 2023

Despite the sexist jokes, the menstrual cycle doesn’t cause significant changes in mood or behavior for most people. But a small percentage do suffer severe premenstrual symptoms, or premenstrual dysphoric disorder (PMDD). Tory Eisenlohr-Moul, PhD, of the University of Illinois Chicago, talks about how hormones and the menstrual cycle interact with mental health, why premenstrual symptoms are not caused by a “hormone imbalance,” and what treatments are available for severe premenstrual symptoms. For transcripts, links and more information, please visit the Speaking of Psychology Homepage. Learn more about your ad choices. Visit megaphone.fm/adchoices

As the crispy chicken sandwich from 7-Eleven, people always call me loud. And I'm like, yeah, I know. I'm crispy. Did you expect me to whisper? If you want quiet, go eat some soup and reflect. Like, I know I'm a handful. I'm bold, I'm juicy. Throw some pickles and barbecue sauce on me, and baby, I'm a whole meal. And with seven rewards, I'm just $4.

Quiet. No. Crispy, saucy, and $4? Very. Only at 711. Valley 36-2326, participating stores only while supplies lastly out for full terms. PMS, or premenstrual syndrome, has long been the subject of tired, sexist jokes and stereotypes about moody and irrational women.

But psychologists who study hormones in the brain say that these stereotypes are wrong on several counts. First, for most people who menstruate, the menstrual cycle doesn't cause significant changes in mood or behavior. At the same time, a small percentage of people do experience severe premenstrual symptoms. Now researchers are working to better understand what those symptoms are and how the menstrual cycle interacts with mental health. In 2013, a new syndrome premenstrual dysphoric disorder was added to the diagnostic and statistical manual of mental disorders. Today we're going to talk about what that is and how common it is. What do we know about the causes of PMDD?

Who is most at risk and what treatments are available? What are scientists learning about how hormones, and mental health interact? What role does the menstrual cycle play for some people in suicidality and mental health disorders? Welcome to Speaking of Psychology, the flagship podcast of the American Psychological Association that examines the links between psychological science and everyday life. I'm Kim Mills. My guest today is Dr. Tori Eisenhower Mao, an associate professor of psychiatry and psychology at the University of Illinois at Chicago. She's a clinical psychologist, and scientists who studies the effects of the menstrual cycle on emotions, thought patterns,

and behaviors. In her lab, she and her colleagues research how hormone sensitivity interacts with problems such as emotional distress, substance use, and suicide attempts. In addition to her research, Dr. Eisenhower-Mell also treats patients with severe treatment-resistant pre-menstrual symptoms. She also chairs the Clinical Advisory Board for the International Association of Pre-Mensual disorders. Dr. Eisenhower-Mell, thank you for joining me today. Thank you so much for having me. It's wonderful to be here. Let's start by talking about premenstrual dysphoric disorder, which, as I mentioned, was added to the DSM in 2013. What is PMDD and how is it different from PMS, which I think is what most people think of when they think of premenstrual syndrome. Yeah, so premenstrual dysphoria disorder is a severe

emotional reaction to the normal hormonal changes of the menstrual cycle. roughly 6% of the menstruating population experiences premenstrual dysphoric disorder. In terms of its relationship to PMS, I like to say that PMS is a very broad umbrella term that has been used for so long that it started to lose meaning. It's so broad. It's been used in so many different contexts to talk about physical symptoms, emotional symptoms, and also to talk about symptoms of such varying severity where, Sometimes people are speaking of PMS as very, very mild symptoms that would not affect day-to-day life at all.

And other times they're talking about very severe symptoms that really reach the threshold of an emotional disorder. And that's where we would start to think about diagnosing with premenstrual dysphoric disorder. Is there a test for PMDD? How would a person know that they have it? So the DSM-5 included a set of diagnostic criteria for pre-menstrual dysphoric disorder. The symptoms must be emotional primarily, so there has to be this core sort of psychological distress as part of the disorder. It's not necessary that the symptoms necessarily impair daily life, although they usually do. The DSM, we can talk about this more later, but the DSM is very strict in its prescription of what PMDD needs to look like.

it requires at least one emotional symptoms and five total symptoms to show cyclical change across the menstrual cycle. And it's not just that the person needs to report these changes in an interview. Because we know that people have been culturally influenced to think that all females have PMS, we find that many, many patients report severe. premenstrual symptoms, but then when we track their symptoms across the cycle longitudinally, we don't actually see any notable change in their symptoms in the daily ratings. And so because of this, the work group that created the DSM-5 PMDD disorder actually requires two months of daily ratings of the symptoms of PMDD in order to make the diagnosis. And just for completeness,

I'll ticked on through some of the specific symptoms that we're looking for. The core symptoms need to be at least one of depression, anxiety, mood swings, or rejection sensitivity, or anger and irritability. So there needs to be across the longitudinal daily ratings pattern that we see. We need to see that at least one of those core emotional symptoms are showing this pattern of symptoms being present in the pre-monthsual week and then really disappearing in the week after mencies. Now, there's a common idea that premenstrual symptoms are due to a hormonal imbalance

or hormone levels that are out of whack. But that's not accurate, as I understand it. I mean, what do we know about the causes of severe premenstrual symptoms? It's a great question. And it intersects with mental health stigma, which I think is really fascinating. So when we think about a disorder where the symptoms are triggered by hormone changes, we can see how many patients will assume that this is a result of something being wrong with their reproductive system, something being wrong with their hormones. And it's an understandable assumption that patients

make. And this is fueled by a lot of sort of natural health outlets and people selling natural health products to promote hormonal balance. And if that were the case, that would be fine. But unfortunately, across the past decades, we've repeatedly looked, not me specifically, but my predecessors have repeatedly looked at estrogen, progesterone, LH, other hormones across the cycle in people with and without these severe premenstrual emotional symptoms. And there's really no consistent differences between the groups. And what this suggests, along with other experimental studies that have directly manipulated hormones in these groups is that it's not anything to do with an abnormal menstrual cycle, an abnormal hormonal profile, an abnormal trajectory of hormonal

change, an abnormal balance between the two hormones. None of that has really panned out. It really seems that the reproductive system in people with premenstrual dysphoric disorder is absolutely normal from what we can tell so far. It even seems so far that the critical hormonal metabolites that we know mediate or provoke the symptoms of PMDD, even those appear to be the same between PMDD and controls. And so this really leaves us with one most prominent possibility, which is that the brain is abnormally sensitive to normal changes in estrogen and progesterone in this disorder.

And so there have been several really elegant experimental studies in which the reproductive system in both PMDD and controls is suppressed, and then they manipulate estrogen or progesterone to understand whether there's this abnormal sensitivity. And in fact, they do see this, that when you manipulate the hormones in those with a history of PMDD in the daily ratings, you see that this provokes symptoms, patients become distressed. And in controls, you don't see this. And so this is a nice experimental demonstration that it really is an abnormal sensitivity to normal hormonal change. Now, one more thing that I'll say about this is that this is a disappointment to many patients. And I think we really have to look to mental health stigma to understand why that is,

right? Because if you believe that you have a disorder that is being caused by a reproductive problem or an endocrine hormonal problem, there's more of an in our society, unfortunately, there's more of a sense for most people of, this is not my fault, this is just my biology. The way that we think about mental health disorders, unfortunately in our society is very stigmatized. People think about anything to do with the brain as being more the fault of the patient and more heavily under the control of the patient, even when that's not the case. And so understandably, patients, when they learn that this is a psychiatric disorder, many of them feel that they're being blamed for their symptoms or that they're being called quote unquote crazy or quote unquote

hysterical. When that's really not the case, we think of it as, you know, what is happening in the brain that's creating this abnormal sensitivity. But you can understand for a patient, you know, they're not quite thinking on that level. Many of them steeped in the mental health stigma that we have in our world, in our country, really see that as threatening. And so there really is a desire on the part of many of the patients to think. of this as a hormone imbalance or something really that could be fixed through changing the hormones. And that's understandable, but it's also wrong. And I think we have to tear down the mental health stigma in order to then address the brain issue that's happening here.

It sounds a little bit like an autoimmune problem. Is there a relationship between other autoimmune situations and what happens in PMDD? There have been a few studies on immune function in PMDD versus controls, not many. So far, there don't appear, the data that I have seen, there don't appear to be massive differences in the periphery. That doesn't mean that there isn't some kind of neuroimmune mechanism at play, so there could be some kind of activity, abnormal activity of hormones interacting with the immune system in the brain. However, I think that the stronger evidence has to do with the effects of individual differences in sensitivity to these hormones at the level of some neurotransmitter systems.

There's some evidence that, you know, serotonin is differentially, more greatly impacted in folks with PMDD in the ludial phase. We know that SSRIs are very effective for a lot of people, but really at this point, it's early days, and we have a lot of work to do, both to understand the primary biology of PMDD and also maybe some of the variants around PMDD that could be triggered by slightly different mechanisms. What treatments are available for people who are suffering from severe premenstrual symptoms and where can they go for treatment and do you start, say, with your general practitioner, your physician, do you go to a psychologist or a psychiatrist, do you talk to your OBGYN? I mean, where do you start?

Yeah. So when evaluating symptoms, it's really important to track symptoms across the cycle. And I would say that if you have the time to track your symptoms across a couple of cycles even before you see a physician, if you have that luxury, I would do that because it really helps the provider, whoever you see, to understand the pattern of symptoms that you have and whether you would qualify for treatment. There's a major lag in the training of medical providers in the evidence-based treatment of pre-mensual dysphoric disorder. And so what I would say is that you should start, if you're having these symptoms, you should start with whoever you're most comfortable with and whoever you think is going to listen to you when you bring this up. I would say a primary care provider, you know, a general practitioner is fine. I would say an OB-Gyne is fine, a psychiatrist is fine, but it really should be somebody that

you're comfortable with. At the end of the day, it's still true that the majority of health care providers are not aware of this new disorder yet, and so unfortunately, the reality is that patients really are going to be doing a bit of education of their providers in many cases, that this is a real disorder, and that it does require treatment. What I often recommend is that patients print off some of the online resources about it and educate themselves about how the disorder is treated so that they can understand whether their provider is proceeding along an evidence-based science-backed path or not. So let me talk about what that looks like. So first, SSRIs are the number one treatment. They beat placebo very consistently in pre-monthrial dysphoric

disorder. They also beat placebo from what we can tell very rapidly. They seem to work after about 24 hours, which is much faster than we see them beating placebo in other disorders. And so this potentially suggests that there's a different mechanism of action for the efficacy of SSRIs in PMDD. It may be, in contrast to some of the other disorders, that there is sort of a straightforward serotonergic buffering mechanism where there's alter. We know that there's poorer serotonergic function in the ludial phase of the menstrual cycle when progesterone is high in PMDD. And so SSRIs may be pretty rapidly effective in buffering that. So we generally recommend that people start with trying one and maybe even two or three SSRIs before moving on to other things because they do very consistently

beat placebo in clinical trials. After that, there's also slightly less robust evidence, but clinical trials evidence nonetheless that drospirinone containing oral contraceptives. So historically, the first one of these was called Yaz, but there's a few others as well. This combined oral contraceptive pill contains both ethynal estradile, like most oral contraceptives, but also a new generation of progestin called Drospirinone that is derived from a different hormone that seems to provoke fewer side effects and also seems to have some other benefits like reduced bloating and some things like that. So that is usually the second line.

Often what we'll see is that people will have some relief with SSRIs and then they will add the combined oral contraceptive. I do think it's important to note that other combined oral contraceptives that contain other progestins, so not drospirinone, but some of the other ones, those have not beat placebo in clinical trials, and they have been tested. So it does seem that there may be something special about this particular oral contraceptive or family of contraceptives that contain drospirinone. We're not 100% sure why they work better, but that is the next step. And so both of those are FDA-approved for the treatment of PMDD. Often we'll see people do SSRIs and then add an oral contraceptive or switch to an oral contraceptive. If those treatments have

not worked and the symptoms are still very distressing and impairing, then we would recommend seeing usually an OB-guine to discuss the possibility of what we call chemical menopause. And it sounds very severe, but it's actually a fully temporary, reversible menopausal state. So you give usually an injection of a medication that suppresses activity of the ovaries, and it basically puts you into a month-long menopausal state. And then what we would do is we would add back stable levels of estrogen and progesterone so that we, you know, protect the patient against menopausal symptoms and also some of the risks associated with low estrogen. And so really the goal is to create a stable level of the hormones at roughly the same level

that the patient would be experiencing normally, but without the fluctuations that we know trigger the symptoms. And so we recently, my laboratory recently published a really practical guide, how to guide for the use of GNRH agonis in the treatment of PMDD to generate agonists are the medications that are used to provoke this chemical menopause. So we wrote out of a very detailed explanation in the hopes

that perhaps reproductive psychiatrists would learn to do this as well because that's often where patients are going. Of course, OBGygines also use these medications for other things, but they're not typically as aware of PMDD. So we have the situation where the OB-Egyne know how to use the medication, but the psychiatrists know about the disorder.

And so, you know, there's sort of this mismatch, right? So we've been working on trying to increase the competence and awareness of psychiatrists in being able to offer this medication. If that does not provide relief, there are some other symptom management approaches that could be tried, you know, psychotherapy, particularly if there are other disorders happening. Evidence-based psychotherapy is certainly indicated, especially, especially if there's chronic suicidality, learning skills to keep oneself safe as you navigate the medical landscape is important. And there can be some other medications used to manage the symptoms, usually through a psychiatrist. But at that point, if symptom relief is not achieved and or the cycle's

not fully suppressed by the medication, some patients will make the drastic decision to actually have their ovaries removed and go into a surgical menopause, which then has a similar set of knees. You know, we need to add back the hormones in a stable state. But that for a lot of people is sort of the curative end point. It's not the, certainly not a common outcome, but it, but it, it's not a normal outcome, but it is, it happens for quite a few people. which speaks to how severe the symptoms must be for some people. Yes. For you to take that kind of a root which is very dire.

Typically in those situations, there is recurrent suicidality or recurrent hospitalization that really tracks with the menstrual cycle and is not resolving with this chemical menopause approach. What do we know about hormone sensitivity generally and suicidality? Yeah, so my laboratory has worked on this quite a bit in the past few years. For a long time, there was a sense that premenstrual dysphoric disorder, because it's limited to this one phase of the menstrual cycle, there was a sense among many physicians and scientists, and I was even one of these people a little bit, that, well, it's only happening for part of the time. How bad can it be at that point, right? You know, it's only going to be. last a little while and, you know, but then I spent more time with patients, especially patients who are treatment resistant, patients who did end up having surgery. And I learned pretty quickly from an anecdotal standpoint that suicidality is very common in PMDD. And one of the things that's scariest

about it is that they really feel like a different person. You know, it's very severe, dark depression during that time for some of these folks. And then when they come, out of it, there's almost an identity disturbance of now I feel completely normal and happy, who am I? What was that? Right. And it's very scary for them. And often they don't want to talk about how dark it gets when they're feeling fine, which is completely understandable. But all of this contributes a little bit, I think, to us not fully understanding the severity. So what we did, we did a global survey through the International Association of Pre-Mensual Disorders, where I volunteer, they did a global survey of the people who utilized their services and their information online.

And they asked people a lot of questions about whether they'd been diagnosed, how they'd been diagnosed. And so we took a sampling of people who had been diagnosed through daily ratings by some kind of health care provider. So it's not a perfect diagnostic gaining system, but it's pretty good. And so then we took those 600 people and we asked them about lifetime experiences of suicidal thoughts and behaviors. And what we found in those 600 patients with PMDD, we found that 72% reported active thoughts of suicidal ideation in their lifetime. 49% reported lifetime experiences of planning a suicide attempt. 42% reported having had intention to make a suicide attempt at some point. 40% had actually started to prepare for an attempt at some point,

and 34% had actually made a suicide attempt across their lifetime. So these are really quite striking high numbers. And when we co-varied other diagnoses that the patient had received, this did not account for their symptoms. So it really seems that pre-meltrial dysphoric disorder is associated with suicidal thoughts and behaviors. And then at the same time, my laboratory also does work recruiting general psychiatric patients with menstrual cycles who have suicidal thoughts to try to understand when we don't select for people who say that they're having these hormone-sensitive menstrual cycle symptoms. do we still see them in those with suicidal thoughts? Among just sort of a general psychiatric sample who menstruate that have suicidal thoughts, what role does the menstrual cycle play?

And what we see is that it is pretty consistently 50 to 60% of our sample that has significant cyclical changes in mood and suicidality. And so it really seems that that's a much higher number than the 6% in the general population with pretty, menstrual changes. And so it really does seem that, you know, when you recruit for PMDD, you get suicidality. When you recruit for suicidality, you get PMDD. You get those hormone sensitive cycle changes. So we're still trying to understand exactly why that is. My laboratory does clinical trials to try to probe and understand, especially in those suicidal populations, what is the role of different

hormone dynamics in provoking acute suicide risk. But we have a long way to go to really bring all of this together and understand how this develops over time and what role the hormone sensitivity plays. Let's talk for a minute about people who are assigned male at birth. Do they have the same sensitivity to hormones as people who are assigned female at birth? Is it similar? Yeah, so I'm not an expert in sex differences in the brain overall, but my understanding is that there really isn't a lot of evidence for a male brain or a female brain. And it really is a lot more complex than that. And I think that that's likely to be true in this case as well.

Unfortunately, there has been very little research on how those assigned male at birth react to similar estrogen and progesterone changes in the brain. Of course, the upshot is that those assigned male at birth generally don't have menstrual, cycles. They don't have menstrual cycles. And so they're not going to be exposed to these fluctuations on the same time scale. And so even if they did have, you know, again, if the brain is sort of similar in many ways between males and females, you would expect that there's probably a similar percentage of males who would react the same way if we were to induce sort of a menstrual cycle in them. But this is a little bit less of less public.

interest in the sense that they're not likely to experience those changes. And so it's a little bit of an artificial proof of concept, right? One thing I will say is that Peter Schmidt at NIH, the wonderful scientist, who leads the behavioral endocrinology branch, he has done, I believe, one experimental study that did provide some support that some males are sensitive to normal testosterone changes. And so there is, I think there's, there's no reason to think that males wouldn't have much of the same possible hormone sensitivity. It's just that in general, testosterone doesn't have a monthly cycle, right? It may change for other reasons, and that very well may provoke symptoms at some time points in males. But again, because of the fluctuations being

less regular, it ends up being less of less interest from a public health standpoint. I do think that one thing that would be interesting to study is that we know that the ovaries are not the only source of progesterone. The adrenals also produce progesterone, especially in response to stress. And so it does seem possible that, you know, perhaps there could be a stress-related episode of hormone sensitivity in both men and women. I think that's, been a little bit understudied. And I think that, you know, that's something that could be very interesting. Well, to wrap up, I want to go back to my introduction when I talked about the history of using the menstrual cycle to justify stereotypes of women as being emotional and irrational.

What can researchers do to study the menstrual cycle without contributing to those stereotypes? It's a fantastic question. I think it's very important to abandon the idea of studying the effects of the menstrual cycle on behavior as a general concept. We need to study individual differences in reactivity to the menstrual cycle. So if we want to understand, for example, the effects of the menstrual cycle on anxiety, we need to select a sample of people who have cyclical changes in anxiety versus people who do not. Because otherwise, if you think about it, if only 6% of the population has cyclical changes in emotional symptoms, and only some of those people have cyclical changes in anxiety,

you're really looking at a very small percentage of the population that's going to show the type of changes that you're interested in understanding. And so it really behooves us to select a hormone-sensitive sample, and usually we do this by collecting daily ratings at the beginning to try to really select people who are, showing some kind of change in the construct that we're interested in, and then diving into how those people differ from people who don't have the symptoms. So I really think that this assumption that the menstrual cycle has a standard effect on any kind of behavior probably needs to end.

Well, and on that note, I want to thank you so much for joining me today, Dr. Eisenhower-Mell. This has been very interesting. Thank you. Thank you so much for having me. You can read more about psychologists' research on hormones and mental health in the September issue of APA's magazine, Monitor on Psychology. To read it, go to www.apa.org slash monitor. You can find previous episodes of Speaking of Psychology on our website at www.w. speakingof psychology.org or on Apple, Spotify, YouTube, or wherever you get your favorite podcasts. And if you like what you've heard, please leave us a comment or a review.

If you have comments or ideas for future podcasts, you can email us at Speaking of Psychology at APA.org. Speaking of psychology is produced by Lee Winerman. Our sound editor is Chris Condihan. Thank you for listening for the American Psychological Association. I'm Kim Mills.