Good afternoon, everyone. Thank you for coming to our session today on women's sleep health. We have a great panel of speakers today. So I'm Gara Borgeli. I'm a professor of medicine at Brown. And I'll be speaking first. And I'll talk about sex and gender terminology and the appropriate use of that. Our next speaker is Dr. Carolyn D'Ambrosio, who's associate professor of medicine at Yale. And she's the program director for the Pulmonary and Critical Care Fellowship. There, our third speaker is Dr. Janet Myers. And she is associate professor for clinical medicine at John Abrams University. And she's the medical director for the Sleep Lab for Kaiser. And she's right here in Honolulu. I won't say she's lucky, but she is. And then our fourth speaker is Dr. Ashima Sani. And she's an assistant professor at University of Illinois at Chicago. And she's in the division of pulmonary and critical sleep medicine. So with that, I'm going to upload my talk. OK, good. So you heard about this. I have no relevant conflict for this talk. So I'm going to start with a little historical perspective about women's representation in science. So in 1989, the Physicians' Health Study, you probably are familiar with that, examined the use of aspirin for the primary prevention of MIs in 22,000 male physicians. And it came up with certain recommendations. And the practice at the time was that we do these studies, we study men, and then we come up with recommendations. And they should apply for everyone. But then around that time, the women's health movement started, and it had multiple branches looking into legislation of women's health, into different arms of research for women's health, how clinical care of women should be, and how we need to educate our students and trainees about medical education. And then in 2005, a similar study to that Physicians' Health Study was done in 39,000 women. And it was also looking at the same outcomes, aspirin in the primary prevention. But this study actually came up with different, it had different findings than the study in men. So aspirin was not beneficial for women that were 65 years or younger. And there was an increased risk of hemorrhagic stroke in women compared to other women that were not on the aspirin. So the Offices of Women's Health started many, I'm sorry, multiple government agencies started Offices of Women's Health. And that included the National Institutes of Health, the Department of Health and Human Services, the Center for Disease Control and Prevention, and the Food and Drug Administration. And then women's health started to encompass more than just reproductive health and sex organs. And I found this picture on the Women's Health Research at Yale, which I thought was really interesting. So they had this picture, which is a misconception that sex actually only impacts reproductive organs. But in fact, biological sex can impact any organ in the body. And that's what the reality is. And then in 2003, we know the Human Genome Project had happened and it influenced our understanding of the effect of sex on human biology and on disease. So about a decade ago or so, sex as a biological variable became something that many people were talking about. And the NIH was insistent that in preclinical research, there should be, the studies should include both male and female animals. Because for instance, if someone is going to study drug development, if you study the drug in preclinical research and in male volunteers or male patients only, and then you give it to male, male patients are gonna do fine. But then if you give it to female patients, then maybe the impact of the drug may not be the same. Maybe they're gonna have more side effects. So the way these drugs are going to work is not gonna be understood unless we include sex as a biological variable in all these early studies. And up until this date, many animal studies either still use male animals or do not report the sex of the animals. And we need to do a much better job at improving this. So what is the difference between sex and gender? We see this terminology used interchangeably and it's not the right way to do this. So it's really important, and we'll talk why, it's really important to differentiate what is actually sex and what is actually gender. So sex is a biological construct. So the Institute of Medicine defines it as the classification of living things according to their reproductive organs and functions that are assigned by a chromosomal complement. And it's the person's biological status that is determined by their DNA. Whereas gender is a social construct. So it's how a person self-represents, how they are seen by society, and what roles in society are expected of them based on this identification. And gender intersects with the bigger sphere that is the community and the society and all the expectations of that given individual, and then other determinants such as race and ethnicity. So why is the accurate determination important? It's important to know that because there are different impacts of sex and gender on incidence, on disease progression, disease presentation, diagnostic testing, adherence to therapy, you name it. And it really depends on whether a disease risk is related to sex or gender, our therapeutic targets are gonna be different. So if something is related to gender, there are things that we could do in terms of behavioral changes maybe, or environmental exposures, et cetera, that might impact disease risk. Whereas if something is related to sex as a biology, there are certain things that we can do in some cases where we can modify that risk. So I could give you an example of say lymphangioleumatosis, it is a disease that is most prevalent in women, pregnancy makes it worse. So knowing that this is a sex thing and not a gender thing, you can think about it in that way and then think about whether it's hormones that are impacting it or not, et cetera. So about maybe five years ago now, NHLBI and the Office of Research for Women's Health gathered a group of people and NIH staff from different places to write this paper. It was a two-day workshop where everybody talked about their area and how sex and gender might impact lung health and disease. And they came up with recommendations about what is important and what do we need to do to take the field further. I just have to say that at the end of the meeting, we had one person who's a, she's like the grandmother of sex and gender medicine. And she said, you know, all these people in the room are brilliant in what they do, but I don't see a social scientist in here. Like what about the research about non-cisgendered individuals? And this is something that we're all lacking. I'm not a sex and gender medicine expert, but I know that we have a huge gap in our understanding of circumstances where sex and gender do not follow the same thing. Then there were other things. We wrote a narrative review on sex and gender differences in sleep disordered breathing. And then about maybe two years ago now or so, we got invited to write the sex and gender in lung disease and sleep disorders. You could see Dr. D'Ambrosio here as the senior author. So that was the first one. And then we were invited to write part two because there were so many diseases that were impacted by either sex or gender. So we talked about that. So this is a reading if you wanna do that and learn about the impact of it because we're not gonna cover everything and we're only focusing on a couple of sleep disorders in here. But some examples that I think would bring the concept into perspective to better understand it. So when we think about biomass fuel and its impact on COPD and we know how so many women develop COPD because of that exposure, this is a gender impact. So this is because of the societal role of these people in cooking for their families, et cetera. And if it had been in different societies where the men were the ones doing the cooking and using wood smoke, et cetera, then it would be the men that would be impacted. So this is not something that is biologically predetermined. Pulmonary hypertension, on the other hand, there's predilection in females. So this is a sex issue where it is sex hormones that actually impact disease prognosis and disease risk, et cetera. In the sleep world, pharmacokinetics of Ambien were one of the first things that we became aware of where women react to Ambien differently and we use different doses with this. But this is the tip of the iceberg because we don't study a lot of the drugs differently in men and women. So the same drug taken by a man or a woman could have a different absorption, a different metabolism, or even a different distribution system depending on each person that is studied. Sleep disruption postpartum, for instance, this is both a sex and a gender thing. So because there are sex hormones and non-sex hormones, like prolactin, for instance, increases immediately after delivery, progesterone goes down after delivery, and these things have been associated with changes in sleep architecture, for instance. This is a sex effect on sleep disruption postpartum, whereas the things that are expected of women, like waking up to feed the baby or change them or do the nocturnal chores, this is a gender effect on sleep disruption postpartum. The perception of pain, it's also a sex and gender thing where it has to do with both biology and what is expected of someone and how much pain they are expected to demonstrate or show when they suffer with it. Bone density is yet another thing where it's a sex and gender because it's related to biology, for instance, but it's also related to the roles that women play, the clothing that they wear, how much exposure to sunlight they have. So both of these things can impact the risk for osteopenia, for instance. And then we go to inclusivity and inclusive language. I think these two things are a little bit separate in my mind. So I feel like it is really important to be inclusive and to consider sex and gender minorities and definitely include males and females or men and women in any research unless it's something that is sex specific, for instance, or gender specific. So it's really important to include that and to better understand the interaction of biology and social identity and norms, but also because we need to understand the potential effects of exogenous hormones, for instance. So how do we deal with this when we're looking at disease risk? How do we deal with it when we interpret studies that we read differently, for instance, for men and women? There's a huge gap in the literature in terms of this literature. But then the inclusive language is where we could fall into a trap. And I know that some societies are making comments and statements about using inclusive language in their recommendations, in publications and everything. And I really have to caution people in terms of this because what we could do could be the same mistake that we made when we were studying only men and then applying the thing to women. Because when we start saying an individual or a pregnant person rather than a pregnant woman and then making recommendations about this, when all of our studies have been done on cisgendered individual, and then we're making these recommendations or these big statements that show that we are inclusive people, we're doing nobody any good. We actually could be causing more harm than good because we're making the assumption that what we currently know applies to everyone. So there's a lot of work that still needs to be done. And I see this when we wrote the chess document, the two papers, the literature that we were going over was using sex and gender interchangeably. And then trying to explain that literature when we had a section about how to use the right terminology was really tricky because we know that it's being used wrong, but we don't have access to the data to be able to know who exactly had been studied. So I think there's a lot that still needs to be done in terms of improving education to standardize the correct use of sex and gender. So we need to make sure that journals and medical schools and fellowship programs and residency programs teach about what this means and what the impact of these things is on health and disease. And then journals need to mandate the inclusion of sexes and limit publications of studies that are not inclusive. So if there's a disease that is only about sleep apnea, for instance, or about insomnia, and it's only including men or women or males or females, there should be a reason why that is the case. Other than that, this should not be published because that contributes to the current problem that we have. The Office of Research for Women's Health and the Society for Women's Health Research urged scientific journals to do so more than a decade ago, but only maybe two handfuls of journals had been doing it the last time this was looked at in the major journals in the literature. So there's a lot of need for this. And then we need to enhance the knowledge about sex and gender minorities because this is a huge gap in the literature. And that's all I have to say. Thank you. So we'll take questions at the end. We'll have Dr. D'Ambrosio speak next. Wonderful. So those are my disclosures, none of them relevant for today's talk. And so what I'm going to do today is take you through the patient experience and show you the sex and gender differences with what we know so far in presenting with obstructive sleep apnea, getting screened for it, diagnosing and treatment, and then the outcomes that are affected by that. So just to start off with symptoms, that's where most people get screened, right? Initially they talk to their doctor about certain symptoms, but there's a definite difference between what males and what females say when they have obstructive sleep apnea, and you can see some of those there. We have men are more likely to have witnessed apneas, women are more likely to say they're tired and have headaches and nightmares and memory loss, and let's see, attention problems, and then nocturnal awakenings. So tiredness, headaches, nightmares, nocturnal awakenings, the average person won't necessarily think sleep apnea, right? And so that's exactly what we've seen is that women go for a long time with these complaints before somebody actually thinks about sleep and gets a sleep test. And this is from one of the chapters I wrote, and we put it together between men and women. And when I say men or women or males or females, it's because that's what the terms were used in the literature that I'm quoting. But like Dr. Borgioli said, they're often used interchangeably, and I'm very sorry about that. But here you go. Women with all these symptoms that might not even make you think about sleep apnea, whereas men have the classic ones that we've learned, snoring witness apneas, daytime sleepiness. And when they get tested, women tend to have more of their apneas and hypopneas during rapid eye movement sleep. But remember, the AHI is an index, and the denominator of which is the total sleep time. So they tend to have a lower AHI, and they have longer hypopnea events, et cetera. Their polysomnogram looks different. So the men typically have the symptoms we all learned, and then have a sleep study that looks very much consistent with sleep apnea, whereas women have these sort of vague symptoms that don't necessarily bring up sleep apnea as your cause. And then their polysomnogram, yeah, there's some apneas there, but the AHI is low. Maybe it's something else. And so that's what happens to women along the way, is it gets discounted, and they don't get the diagnosis or the treatment necessary. This is a study looking at the prevalence of sleep-disordered breathing symptoms, snoring and daytime sleepiness by age and gender between males and females. So males are in the black bar. Females are in the hatched bar. And it's broken up into different age groups, less than 35. Oops. Where am I? Oh no. I lost my red dot. There it is. Less than 35, less than 35 to less than 40, 40 to 45, et cetera. And at each age group, despite having the same, excuse me, at each age group females had less of the snoring and daytime sleepiness, right. So again, sleep doctors, somebody comes to me and they're a female and they're tired and they're waking up at night and they're having morning headaches, I'll think sleep apnea. Family medicine, GYN, primary care provider might not necessarily think that. So that's one of the problems right off the bat. They have sleep apnea. This is a group of people who later were diagnosed with sleep apnea. But these were their presenting symptoms. It doesn't look like sleep apnea so it gets misdiagnosed for a while. But even when using screening tools such as questionnaires, women are at a bit of a disadvantage. So the Upward Sleepiness Scale has shown no gender difference between it. The STOP-BANG, typically men have a higher score overall. So you're more likely to catch sleep apnea with the STOP-BANG questionnaire. If you only use STOP, you actually do better at identifying women with sleep apnea. The Berlin questionnaire is good for both genders. And STOP-BANG in Berlin is similar for both genders when the OSA is very severe. I don't know what to recommend to you. But I will just say STOP is pretty good and STOP-BANG is good. But our insurance companies where I work want the Epworth. But again, women don't necessarily say sleepiness. Remember the Epworth is very subjective, how likely are you to fall asleep in these situations. We all know, we've gone through medical training, we can be very sleepy but not be likely to fall asleep because we have something to do. So it's not an ideal screening tool. If you adjust the scoring for STOP-BANG to a score of greater than or equal to 5 instead of 3, you increase the specificity for men and women. And if you increase the BMI cutoff to greater than or equal to 30 or 31, it better predicts OSA. So the screening tools are useful if you just adjust them a little bit when you're giving them out. And you might be able to detect sleep apnea in your women and female patients. Comorbidities are also different, right. So you already have symptoms for the woman who comes to the office. It's a little bit different, it's a little squirrely, not what you normally think of for sleep apnea. The questionnaires aren't quite there. They might meet mild criteria. But then you look at their comorbidities and you think, well, maybe hypertension and depression. But men have diabetes and ischemic heart disease, much scarier, much more tied to sleep apnea. And so all along the way, it doesn't look like sleep apnea for women necessarily. I'm trying to convince you that we have to rethink and we have to rebrand sleep apnea, that it's not just snoring and excessive daytime sleepiness, particularly for women. And so there's a lot of work now on phenotypes and endotypes in obstructive sleep apnea. What's the cause? And should we be treating the phenotypes and endotypes with different treatments? And just a nice little summary here, for women, they tend to have a less collapsible airway. They have lower loop gain and a lower arousal threshold. Men have increased neck fat distribution and a longer pharyngeal airway. And then for aging, women, more collapsible airway as they age. And then menopause causes more central fat distribution and decreasing upper airway tone. And so there's a couple things along the way that also, so OSA doesn't look the same in every patient for those of you who take care of these patients. And certainly the difference between men and women, it can be a very different cause of the obstructive sleep apnea. So this is a really nice figure here looking at the proportion of participants with sleep-disordered breathing symptoms, snoring and excessive daytime sleepiness at baseline who had OSA diagnosed and treated at follow-up. And the mean time to OSA diagnosis was 6.3 years. Again the males are in the black bar and the females are in the hatch bar. So we know these people have obstructive sleep apnea eventually. And then if they go back and they look at them, the OSA diagnosis, women were less likely to get diagnosed, and then less likely to be offered any treatment, less likely to be offered CPAP or surgery. Oral appliance for some unknown reason to me had equal offers to males and females. So even getting the woman to get screened for sleep apnea, get tested for sleep apnea, we still have hurdles because when they get diagnosed they still don't get offered treatment. It's really crazy. You know they have sleep apnea. Why aren't they getting treated? I don't have the answer for that. But at every step of the way, the woman or the female is at a disadvantage. And so why is that important? The important is the outcomes, right. So here is a study, it's a great study that just got published this year. 2,000 patients with acute coronary syndrome were given a home sleep apnea test while they're in the hospital. Only 15% of that 2,000 ended up being women. The prevalence of obstructive sleep apnea in this cohort was 43% women and 54% men. So quite a lot of women in that 15% actually had obstructive sleep apnea. The primary endpoint of this study was actually major adverse cardiovascular or cerebrovascular events. And that included death from cardiac disease, myocardial infarction, stroke, ischemia-driven revascularization or hospitalization for unstable angina or heart failure. So really dramatic findings. Remember these are people coming in for acute coronary syndrome, get a home sleep apnea test. We now know they have obstructive sleep apnea. So what happens to them over time? This is untreated obstructive sleep apnea, untreated. So overall the blue bar are the people without sleep apnea age and sex and other comorbidity controlled versus those who had the home sleep apnea test and had sleep apnea. So they had more adverse events, more cardiovascular and cerebrovascular events. Then if you separate out the women and the men, the women had much more compared to the men over just three to four years. Dramatic difference. Such that the authors of this paper actually ended up, here's the results of the analysis. I'll say that first. OSA was associated with a greater long-term risk of these major adverse events in women, 28.1% versus 18.8%, but not in men. So untreated sleep apnea was not associated with an increased risk according to their multivariate COX-IT analysis. So their concluding statement was, in hospitalized patients with acute coronary syndrome, obstructive sleep apnea was associated with increased risk of subsequent events, particularly among women. Female patients, here again you see they used interchangeable terms. female patients with ACS should not be neglected for OSA screening and dedicated intervention studies focusing on women with ACS and comorbid OSA should be prioritized. Dramatic paper that came out, right? We have forever thought that men had the cardiovascular disease and that the OSA really happened in women after menopause and they sort of maybe probably don't have cardiovascular, not nearly as bad as men. And Susan Redline and group had published a paper a couple of years ago that I didn't make a slide for on this showing that women with OSA had higher high sensitivity troponins than the male colleagues when their OSA wasn't treated. So starting the process and now this paper is out really showing a dramatic difference in untreated sleep apnea in women having much more risk of adverse cardiovascular and cerebrovascular events. So I know I talked a little bit fast, but I wanted to get across a really good point for all of you is that at every step along the way, if you have a woman, female patient in front of you, think about sleep apnea. The symptoms are different. They say fatigue. They say insomnia. They wake up. They have nightmares. They have headaches. There's screening tools. Change your criteria. Stop BING. Get a score greater than 5. Use that. Or a BMI greater than 30. Or use Berlin questionnaire. Diagnostic testing, even if it looks like really mild OSA, it has consequences for that patient. And women are more likely to have mild OSA because the majority of their events occur during rapid eye movement sleep. Offer them treatment. I know it sounds like the silliest statement to make, but that paper was incredible that even with diagnosed OSA women were far less likely to be offered treatment and offer them the treatment that's appropriate for them. Because the outcomes are worse and the outcomes are a problem. So we have to help these patients. It's not just feeling better, sleeping better. The cardiovascular and cerebrovascular events are significant. And then we also know that all the other adverse effects of untreated OSA with car accidents, metabolic syndrome, et cetera. And so with that, I will pass it off to the next speaker. »» Good afternoon, everybody. Welcome to Hawaii. Aloha. I actually live here. So it's wonderful to have you join us today. So I'm going to be talking about women and insomnia. And I'm local. So I have nothing to disclose. So the lesson objectives for today, we're going to go over the definitions and the prevalence in the United States for insomnia in women. And then discuss the manifestations and the impact of insomnia at various stages in women's lifespan. And then finally review some treatments and some newer pharmacologic and even technologic options that are now available. So that's basically the overview. And then we'll go from adults. So young adult through to older women. So what is insomnia? So the International Classification for Sleep Disorders was recently revised. That's what the TR is. So insomnia, it's not just that you can't sleep at night, it's that it affects you during the daytime. So that's the key thing. It affects you during the daytime somehow. And it used to be in the old classification, the number three, that insomnia was thought of as more of a byproduct of some other process that was going on. But now it's got its own morbidity and deserves its own attention and its own treatment. So that's what I'm going to focus on today. So the definition for the different kinds of insomnia, there's chronic, if it's three months or longer, three days a week, or it's short-term insomnia disorder. And so what I'd like you to think about as we go on through the slides is, what can you do to keep your short-term insomniac from becoming a chronic insomniac? So kind of just keep that on the brain. I won't talk about the other insomnia disorders and other normal variants. In the United States, this is the most recent census data. There's a lot of people in our country, right? And we're all getting older. What I want to point out is, if you think that 10% of people complain of insomnia, chronic or short-term, that's 33 million people, right, with insomnia. So these are patients that we're not always picking up. So we should be asking about it. The prevalence in early studies is anywhere from 16% premenopausal to up to 60% or even more in postmenopausal women. So what are those complaints? Sometimes the complaints are somatic, pain is a common one, weakness, for example. But there's really no clear endotype for us to hang our hat on, no objective markers other than just asking, do you have insomnia? And then females are more likely to seek help. So what are the causes of these fluctuations over time? The obvious one is hormones. Hormones can affect not only your body, right, your sleep architecture. They can affect circadian rhythm as well. That's important in terms of your differential diagnosis for someone with insomnia. We talk about younger women who are still having menses. There's that premenstrual syndrome, anxiety, irritability. And then during pregnancy, your body is changing so much. There's both physiologic changes and then psychological changes that occur both during pregnancy and then afterwards, postpartum. And then natural and surgical menopause, the common thing we talk about is vasomotor symptoms like hot flashes, for example. But really, as women age, the elderly may be the most vulnerable group because they have prolonged sleep onset and lower melatonin secretion over time. When I went to go look at what is out there for young women, there's not a whole lot of studies talking about young women and insomnia. It's more focused on peripartum pregnancy and then older postmenopausal groups. But I did find this interesting study, just looking at diet as a factor in the development of insomnia in the younger group. And it could potentially be a target to help prevent insomnia down the road. But pregnancy deserves its own, it could be its own talk all by itself. Men express as much as 80% of women will complain of insomnia at some point during the pregnancy. And it's typically worse during the third trimester. That's not a surprise. But when they have it, it's associated with increased perception of labor pains, longer labor, and more likely to have an operative birth. And those daytime effects are associated with fatigue, hypersomnia, mood changes. And all those things can negatively impact not only partner relationships, but the ability for the mother to bond with the child. And then furthermore, women with insomnia may be at increased risk of mortality, cardiovascular disease, diabetes, and obesity. And chronic sleep loss can be associated with numerous outcomes, but particularly adverse fetal outcomes, postpartum anxiety, depression. And so it's important to screen and treat insomnia so you can prevent these things down the road. There's a couple of studies that I just want to highlight. One is ongoing studies. But one is the study of women's health across the nation, the SWAN study, just looking at a data set of multi-ethnic women across 10 years. And they found in this group that anywhere between 31% and 42% of patients complained or commented, described insomnia at some point in their lives. And then if you look at this data, your risk goes steadily up over the timeframe of 10 years. So it's 1.3 times a woman in the late stage of menopause versus earlier. But I want to point out in this slide, well, you can read here, the most prevalent symptom was wake after sleep onset. But there's also prolonged sleep onset latency and early morning awakenings. I wonder if it has something to do with REM, too, those early morning awakenings. We hear sometimes about this concept of the 3P model, predisposing patients to developing insomnia, not just insomnia, but chronic insomnia. So we think about someone who has predisposing factors, obsessive traits, for example, or previous history of depression. Looking at patients who might be at increased risk, precipitating factors like the hormone changes associated with menopause, for example, or pregnancy. And then there's the perpetuating factors. Those are the things that have to do with cognition, how you deal with these problems that allows someone to continue on to chronic insomnia. So just a way to think about insomnia. And I just want to mention this Women's Health Initiative, which many of you might have already heard about. But it takes a look at a lot of different problems in women. It's an enormous database of women at over 40 centers. And out of this, what I found is there's a lot of research about insomnia. It's one of the things they looked at. And specifically, there was an insomnia rating scale that was validated for this Women's Health Initiative cohort. And I just want to take a look at it. It's very similar to the Insomnia Severity Index, but it's also very simple. So in some of the earlier studies, it looked at things like hormone therapy and effect on insomnia. Hormone therapy basically during menopause improved with treatment with hormones. And then also there's other things that have been looked at, including cardiovascular disease, rates of cognitive decline, osteoporosis, development of metabolic syndrome. And I'm flying through these because I want to make sure we have time for all our speakers. But one of the more recent ones that focus on the cardiovascular issues is this incident atrial fibrillation. So stressful life events and insomnia were associated with development of atrial fibrillation. So you can see how insomnia can impact so many different things in a woman's life. So what do we do? What are our treatment strategies? Here's the obvious ones that are not, they may be obvious, but they're difficult to do. You can tell someone about, wake up and go to bed at the same time, get your light exposure during the day, not at night, including not with your iPhone or your tablet. Keep your environment cool, relaxing, limit your exposures to caffeine, alcohol, et cetera, and try to stay active. But we know people like to take medicines. In one study of NCHS data, women over the age of 18, you find every year women take more medicines than men for insomnia. And it increases markedly by the time you're in your older age group. We know, I'm going to back up to how to treat in the different stages in pregnancy, we try not to give medicines, right? So cognitive behavioral therapy, massage, exercise are all preferred. But women, it's a hard thing to suffer through insomnia, so a lot of women do want medication. So what are you going to do? Many women use melatonin, trazodone and diphenhydramine have been studied, but there are not great studies on the effects of medications on pregnancy outcomes on the fetus, and also on lactation. So I would encourage you to think about those other factors, not just getting your patient to fall asleep. In one study I found, which was kind of neat, all of us have this problem not having enough cognitive behavioral therapy in our practices. But there are digital options, and Sleepio is one of them, I'm sure many of you have heard of that, but it was actually studied in pregnant women, it was found to be beneficial over 10 weeks of pregnancy. What about pharmacotherapy? Dr. Bergerli and her group have this wonderful article, I would refer you to it, and what I want to highlight in here is that it's not about the FDA group ABC anymore, it's much more nuanced than that. So I would encourage you to take a look at what the effects are on fertility, lactation, and on teratogenicity. So that's an important article I want to highlight. Okay, let's talk a bit about postpartum. There are some new drugs on the horizon here, and postpartum patients, there's this medication, it's like a GABA type of neuroactive steroid, it's called Xeranolone, and it used to be that in postpartum depression, which is associated with insomnia, that these women would have to come in the hospital for a 60-hour infusion and be hospitalized, but as of, I think, within the past year, this drug has been studied and approved for use as an oral medication for postpartum. Okay, almost through here, okay. And then moving on to insomnia and menopause, I'm going to point you to another lovely article, Dr. Carlos Prosperio does a nice review on the mechanisms and treatments for insomnia and menopause, and I'll just highlight cognitive behavioral therapy, hormone replacement, antidepressants have been used also, melatonin comes in a long-acting form, often thought of as a first line for your older patients, GABApend has been used, but it's also associated with fluid retention and motor incoordination. And then there's this whole question of, you might give it for a short period of time, but what can you use for longer terms, you know, more than a year? So for your more chronic insomnia, what can you do? That paper has this nice little algorithm, I would refer you to it, and talking about, you know, does your patient have these or those are symptoms, are they depressed, what algorithm can you go through, what medications are available? As an option also, think about diet, what are your patients eating, do they have a high glucose, high glycemic index diet, can you change that? Will that affect their insomnia down the road? So dietary interventions I think are on the rise, people are looking at that now too, and specifically for women, we're thinking about phytoestrogens and tryptophan to replace the lowering levels of estrogen and melatonin with age. The data's sparse, but it's coming. And so on the horizon, I want to point you to the dual orexin receptor antagonist, the Adoras. Currently, there are three on the market, Bilsomra, you might hear them as Bilsomra, DeVigo, and Covivic. But the one that I've had actually luck with, which, you know, I have this one patient who's had insomnia, she says since she was born, but for a long time, I put her on this medicine, she said it was like taking Halcyon, and you know, finally having someone actually have some success with these medications is very, it's just wonderful, right? And then this is a drug I was mentioning, it has a tendency to be, you know, have a positive effects. Okay, two minutes. You know it, everyone's thinking it, right? Your patients ask you all the time, can I take my cannabis gummies with my melatonin, right? It's out there, and your patients are taking this medication, so you really ought to know about it and have something to be able to tell them. It's here in Hawaii, you can go into any store and buy the gummies, or find THC for medicinal purposes. And I will just tell you that even though the products are out there, it may work in the short term, but there's just not data to say that it's something that you ought to be using long term. So I encourage your patients if they, you know, try to be accepting, it's out there, don't use it continuously, because when you do, and you try to come off of it, it can be a really bad, some really bad reaction. So in trying to avoid that, I would encourage you to tell them not to make it a long term thing. So in summary, insomnia is common, prevalence increases with age, think about your pregnant women, think about the baby, think about lactation. Insomnia is associated with a lot of different disorders, and traditional insomnia treatments are effective, like CBTI, sleep hygiene, but newer technologic and pharmacologic options are evolving. This is the other side of the island. This is Kailua. If you get a chance, this is sunrise like two days ago. If you get a chance, go over to the other side. Welcome to Hawaii. It's been great talking with you today. So thank you so much. Aloha, everyone. Thank you for staying with us for this long. I'll be talking about RLS in women. I'm from Chicago, so I'm still jet lagged, trying to cope up. So the lessons and objectives for today's talk is to talk about the recent advances in management of RLS in pregnancy, and understand RLS in menopause, and just review the diagnostics of RLS, especially specific to women. I just want to tell you the diagnostic criteria didn't really change much with the revision, so it's still the same diagnostic criteria you've been using for RLS. So talking about the gender differences in general, when you're looking at sleep studies, comparing men versus women, you will see that the two things highlighted, there is an increased percentage of N1 sleep in men versus women, and the PLM index was higher in women as compared to men. So this is a striking thing that just stands out when you're looking at just regular sleep studies in men versus women. In this one, you're looking at non-pregnant premenopausal women, and I just want to highlight four important things that came out of this study. The age. So RLS tends to happen in older women. The BMI, the higher the BMI, the more likelihood of RLS, and then vitamin D deficiency and diabetes has been associated, especially in non-pregnant premenopausal women. During the same time, RLS is considered a chronic disease, endometriosis is considered a chronic disease. There have been studies that have supported that history of endometriosis, whether it was surgically corrected or not, has been related to RLS. Now what will be the pathophysiology? Is it related to hormones or not? That's still out there. The jury is still out there on that one. In this study, this was a cross-sectional observational study. It was comparing RLS to gender and hypertension, and the thing that really stood out is highlighted down here is hypertension. So women versus men had more risk of hypertension, and they did a bunch of statistical analysis and that continued to stand out. So women were more likely to have hypertension with RLS, so the association was pretty strong. So changing gears, talking about pregnancy and RLS. As we all know, no surprise, this was a big meta-analysis that got published in 2021, so there is a very high incidence of RLS in pregnancy. I'll be talking about two cohorts just to highlight what other things could be associated, especially in gestational RLS. So this is a Turkish cohort. You can see the first part over here is RLS positive and RLS negative. So obviously as pregnancy progresses, the incidence of RLS increases. You tend to have more RLS prevalence in third trimester. But again, the older the patient, the higher the BMI, there was more chances of having RLS. Interestingly, exercise, the less exercise was related to increased incidence of RLS. And then it says magnesium use over here, so indirectly you can see if the patient was not taking magnesium supplement, it was related to higher RLS symptoms. This was a Saudi cohort, and again, they just wanted to highlight the fact that the patients who had RLS during pregnancy were related to increased suffering from insomnia and increased waking up during the sleep. This was a study that looked at pregnant women, and they took the blood samples, looking at vitamin D levels and folate levels. So they saw that patients who had RLS tend to have pretty low vitamin D levels and folate levels, and then patients who persisted to have RLS post-pregnancy in postpartum stages continued to persistently have low vitamin D and folate. So the specific thing that really stood out to me was the vitamin D levels were as low as below 10, and that was related to the risk factor of persistence of your RLS symptoms, and the severity was significantly elevated. In gestational RLS, so the other thing that really stood out was low selenium levels were related to RLS, and the pathophysiology behind that could be related to the animal models, which I tried to specify here. So you can see that selenium partially reverses the depletion of dopamine, and it kind of enhanced. So if you look at selenium, you can, for me, it seems like a dopamine agonist. It enhances its actions. So if you have selenium deficiency, you could consider that related to a risk factor of increased RLS. The other important things that were seen is low zinc levels and low magnesium levels during pregnancy were related to RLS. And also in the same study, this showed that when the patient had RLS, it was related to higher anxiety scores as well. And obviously, we cannot forget iron. So this has been shown over and over again that iron deficiency is related to RLS, and it's no surprise that it will be there in pregnancy as well. So overall, when you have gestational RLS, how does that impact the pregnancy? So there is increased prevalence, as we had discussed, as the gestational weeks increase. It was also related to increased working time during pregnancy, increased weight gain. So it was directly proportionate to that in the study. And then whatever the pre-pregnancy BMI, if it was higher to begin with, there was increased incidence of RLS that was noted. There are other important things that came out. You can see the table up here with the p-values. But the physical health scores, the physical functioning scores, pain scores, and emotional role difficulty scores, everything was elevated. So any patient with gestational RLS indirectly had poor quality of life. So that is something we should be aware of, and we should try to look at the levels, do the supplementation, give them the iron or whatever, do the adequate counseling to help with this especially. Now changing gears, talking about menopause and RLS. So I'm just highlighting the important parts over here. So as you can highlight over here, the economic status ironically is related to increased incidence of RLS post-menopause. And the other important things that were highlighted was increased caffeine consumption, and then hypertension and diabetes. So this is all post-menopausal data for RLS. Breast cancer and aromatase therapy. This was an interesting one. So there was increased incidence, especially when the aromatase inhibitors were started for breast cancer treatment by third month. There was increased RLS symptoms that were present in these patients. I'm not clear why that will happen. The insomnia severity index did not go up in these patients. The other things did not really impact, but this was the one thing that the rating scale had been shown to go up. As far as the treatment updates are concerned, there wasn't much of a significant difference they found between clonazepam and nortriptyline in patients for RLS management, though intuitively you would think that nortriptyline being a TCA should not help with RLS. But indirectly it could be that it had a sedative effect and the patient just slept through the symptoms because of which they didn't really see much of a significant difference in this. Well, none of the talks could be complete without COVID mentioned. So COVID and RLS, the important thing I wanted to highlight in this slide was that if the patients had long COVID, long-haul COVID, the incidence of RLS was increased. And here we are at the conclusion. So the take-home points, the RLS prevalence increases in pregnancy, obviously, as the just third trimester is supposed to have the highest level. And it is associated with low iron, zinc, magnesium, folate, and vitamin D levels. The thing that I was trying to find out, I'm like, why is vitamin D so important? So the thing that I looked at the literature and it seemed like because vitamin D is considered anti-inflammatory, so when the levels were low, it was pro-inflammatory and it was related to increase inflammatory markers, which could be related to increased RLS. And the way they looked at folate deficiency was that folate is important for iron metabolism. So if you had lower folate levels, it was related to basically impacting the iron metabolism and that's how it was related to increased RLS incidence. So these were some important factors that came across me. That's all I have. I have five minutes to spare for the session and questions. Thank you so much for your attention.

women's sleep health

sex and gender terminology

representation of women in science

pregnancy and menopause

insomnia in women

hormones and insomnia

diagnosing and treating insomnia in women

pharmacotherapy for insomnia

cognitive behavioral therapy for insomnia