Aloha, hello everybody, welcome to Care of the Transgender Patient from Terminology to Clinics to ICUs. We will be discussing terminology trends and healthcare disparities, Dr. Turner will cover pulmonary issues in the transgender patient, Dr. Sarasgassian will discuss sleep-related issues in the transgender population, and we will close out with Dr. Cortez-Puentes discussing care of the transgender patient in the perioperative setting and ICU. I am Adam Mora from UT Southwestern, I do not have anything to disclose and I will be covering terminology, therapies, healthcare disparities, management considerations. When we look at the idea of transgender or those that traverse the gender, it is not a new concept even though it seems that it's a relatively new field at least in medicine. Going back to earlier recorded times, even dating back to 7,000 BC, there is evidence of what was called the third sex in Mediterranean Neolithic and Bronze Age drawings and figurines. There were depictions of human figures having female breasts and male genitalia and those that had no distinguishing sexual characteristics. It wasn't though however until the 1900s when the therapies really did start coming into play. In 1906, Carl M. Bayer was the first transgender person to undergo sex reassignment surgery which was well before the 1930s surgery of Lily Albee, the popularized Danish girl in the film. In 1919, a German doctor, Magnus Hirschfeld, established the Institute for Sex Research and this was a private research institute and counseling office that housed a library with thousands of books, many of which was on transgender or transgenderism and unfortunately this was destroyed by the Nazis in May of 1933. Nonetheless, in 1931, he introduced the German term transsexualismus and in 1931, Dora Reiter became the first transgender woman to undergo vaginoplasty in Berlin. In 1946, in Britain, plastic surgeon Harold Gillis performed the first female to male sex reassignment surgery on Michael Dillon. When we are dealing with our transgender population patients, it is important to understand the terminology and currently right now, the one that we are all following is the idea of gender dysphoria. It is a concept that was designated in the DSM-5, clinically significant distress or impairment related to gender incongruence is how it is described and it may include a desire to change primary and or secondary sex characteristics and it's important to note though, however, that not all gender or gender diverse people experience gender dysphoria, but it does refer to people whose gender at birth is contrary to the one they identify with and this did replace the DSM-4 diagnosis of gender identity disorder, mostly because of its negative connotation as well as the idea that most of our patients, when they are able to present themselves with the gender that they identify with, experience a gender euphoria. So in terms of gender dysphoria, it's also important to realize that it is not associated with sexual orientation and the approach is to actually engage in treatments that include supportive individual gender expression, hormone therapy, surgery, counseling or psychotherapy and that without this classification, gender affirming therapies would be classified as cosmetic treatments versus medically necessary treatments. It is important to note this because otherwise they would not be covered by insurances. As we delve deep into the relationship with patients who are on the transgender spectrum, it's important to really understand some of the terminology and the Human Rights Campaign does a really good job of giving us some ideas as to what is out there in terms of terminology. So genderqueer is a term that rejects notions of static category of gender. It embraces the fluidity of gender and often, though not always, sexual orientation. Most of these patients will see themselves as being either both male and female, neither male nor female or as falling completely outside of these categories. Intersex patients are those that are born with a variety of differences in their sex traits and reproductive anatomy and have a wide variety of differences among their intersex variations. These differences can include genitalia, chromosomes, gonads, internal sex organs, hormone production, hormone response and or secondary sex traits. Now when we go to gender binary, that is a system that we have all been used to in society as well as in medicine and that is a system in which gender is constructed into two strict categories of male or female. Gender identity is expected to align with the sex assigned at birth and gender expression and roles fit traditional expectations. As opposed to nine binary, which is patients that do not identify exclusively as a man or a woman, may identify as both a man and a woman, somewhere in between or fall completely outside of these categories. And while many identify as transgender, not all non-binary people do and they may refer to an umbrella term as either agender, bigender, genderqueer or genderfluid. Now with regard specifically to transgender patients, their gender identity and or expression is different from cultural expectations based on the sex they were assigned at birth and this does not imply any specific sexual orientation. They may identify as straight, gay, lesbian, bisexual or something else. The process includes several aspects. There are, in the transitioning process, social implications which begins with simply changing the name and pronoun that they present themselves with. If they make the choice to actually engage in medical therapy, then there is the medical component which includes hormonal therapy or gender affirming surgeries. And then there are legal ramifications as well where they go ahead and proceed to changing legal name and sex under government and identity documents. The therapies that they can employ for gender affirming care are varied depending on the protocol or institution in which they have chosen to engage in their care. But still the main cornerstones are testosterone, hormone therapy as well as estrogen or anti-androgen therapy and surgical options. So testosterone is one of the things that we look at that has both reversible and permanent side effects. The reversible side effects within the first year are oily skin, acne, cessation of the menstrual cycle, body fat distribution, vaginal atrophy and increased muscle mass. Within the first year, there is also a change in libido although this tends to vary by individual. And after that, in the next couple of years, there is a maximal change in the oil, skin and acne and in vaginal atrophy. By two to five years, their body fat distribution and increased muscle mass has reached its peak change. The permanent side effects that you will see in your patients are within the first year, clitoral enlargement at an onset of one to three centimeters, facial and body hair growth onset as well as deepening of the voice. There's also hair loss that happens within the first year. And after that, in the first one to two years of therapy, there is maximal clitoral enlargement and voice deepening and culminating at the end of three to five years with maximal facial and body hair growth. The risk for testosterone are increased blood cell count, cholesterol and risk of diabetes as well as liver function compromise which may even culminate in fulminant liver failure. For those choosing to have pregnancy, there is a normal fetal development during pregnancy as a risk. With regard to estrogen and antiandrogen therapy, the side effects within the first three years are softening of the skin at the onset of therapy and reduction of oily skin, breast growth onset which tends to be a permanent effect as well as onset of body fat distribution, slowing of metabolism and decrease in muscle mass. There is also decrease in testicular volume at the onset of the first three to six months. And by the end of the year, there is thinning and slowing of body and facial hair growth. There is also within the first year a change in libido and lower sperm count. Again, though, this does vary per individual. This is followed by a maximal decrease in muscle mass that ends at about year two. And in the next couple of years, there is maximal breast growth, decrease in testicular volume and maximal body fat distribution and slowing of the metabolism. By three years of therapy, there is maximal thinning and slowing of body and facial hair growth. So this helps you to understand where in the journey and the transition process your patients may be. Now, the risk for estrogen and antiandrogen are hypercoagulability such that your patients may present with PEs, DVTs, myocardial infarction, stroke, and hypertension. There are many surgical options available to the patient population. There are face feminization surgeries which are listed here and will be available in your handouts. And there is a lot of surgical options to help our patients become more intimately presenting themselves in the gender that they find themselves. So it could be either, depending on the gender, a bilateral mastectomy or breast augmentation. There could be internal surgeries that can be done such as hysterectomy and tubal ligation and then, of course, a couple of surgeries that would create a penis for patients. Moving on to healthcare disparities, the World Health Organization defines healthcare disparities as the absence of avoidable, unfair, or remediable differences among groups of people whether those groups are defined socially, economically, demographically, or geographically, or by other means of stratification. Our transgender patients do experience a variety of healthcare disparities. In general, it can be from the inability to have the validation of who the patient is to also not having recognition or understanding of the transition process. And this could be as simple as when they come in for a procedure at the hospital or check into a clinic and having staff that is not able to recognize who they are as how they are presenting themselves. Tragically, another issue that we have in healthcare is that there is a lack of transgender medicine curriculum in our medical schools as well as in residency curriculum. There's also limited access to therapies and positive centers that are performing the whole entire spectrum of gender-affirming care for patients and the access to these centers is very limited geographically. There's also anchoring biases and improper screening that our patients have. For example, a transgender man who has not had any internal surgeries but presents with abdominal pain may have what you would look at a man having abdominal pain without thinking about ovarian or uterine complications. There are also anchoring biases with their screening. So if you go and you look at some of these patients, their doctors tend to be more caught up in the therapies that they're having, their transitioning process, and many of them do not have the same screening availability that their counterparts who are not on the transgender patient's pathway do. There's also a financial implication as many of the billing that they have to contend with do not have CBT codes that are in alignment with the care for transgender medicine. And so while they may have insurance, they may have rejection of many of the lab work that needs to be done while on the gender-affirming care. So they may still have to pay for labs and studies despite the fact that they have insurance coverage. Management considerations for this population are many, but the ones I will draw your attention to are obviously currently we have the political climate right now that has put the risk and well-being of this patient population at risk. This map from the Human Rights Campaign shows you where there's already banning of gender-affirming care for patients up to the age of 18, and the ones in yellow are those that are considering that. Why is it important? It's important because what we are starting to see are patients who are going on their own and seeking the therapies and getting exogenous testosterone and estrogen and are falling prey to therapies that are not being governed or supervised by a licensed professional and are placing them at risk to show with a lot of risks of what these therapies can do. Access to care is obviously important for us to know about, and in this patient population we also have to consider HIV therapies, and so when to start, stop, or continue both heart therapy as well as PrEP is important. And sadly, because this is a marginalized patient population, we also have to think about when we have the unconscious transgender patient that comes into our ICUs that are not able to provide consent for themselves and are often having to rely on perhaps a next-of-kin person who may not be in agreement with their journey or may actually take the opportunity to work against the trajectory that they have been on. And they may not have the appropriate proxies or they may not have the ability to pay for and do the paperwork to have a medical power of attorney. That does cover my section. Thank you questions will be answered at the end. Next is Dr. Turner who will do pulmonary issues in the transgender patient. So I'm going to talk a little bit about pulmonary issues in the transgender patient. My name is Grant Turner. I am at UCLA. I'm in transplant and CF. I have nothing to disclose. We're going to have some audience response questions, so if you guys want to point your phones to the QR code and hopefully it will work. So these are our overall session objectives again, and I'm specifically going to talk about categorizing pulmonary symptoms and etiologies in transgender patients and more specifically trying to identify potential issues in PFTs in transgender individuals, the chronic lung diseases that they may face, and then talk a little bit about chest wall binding and the pulmonary side effects. So here's our first question. So we have a 23-year-old transgender female, sex assigned at birth as male, who presents to your clinic with a chief complaint of shortness of breath. They note that they've been using an albuterol inhaler for years, but they're often distant to the point of having to stop while running or working out. It's gotten worse in the past few years. They've had PFTs from their PCP that demonstrated a potential restrictive lung disease. They're currently on estrogen therapy, and you notice that the gender listed on the PFT report says male, and the patient notes that she's upset about this. So what's the correct gender annotation for this individual? I'll give it five more seconds. Seems to be working, this is great. Okay. So the correct answer is male, because that's their sex assigned at birth. And we'll go through it, this is great. This is a great learning opportunity. So both the ATS and ERS have guidelines specifically about this. And the main reason why it would be male or their sex assigned at birth is because while we should give them the opportunity to discuss their gender identity and to have that annotated on the PFTs, it's sex assigned at birth and the hormones that they had during their pre-pubescent and pubescent phases that are most likely to affect lung height and size. And so both ATS and ERS agree that we should be using their sex assigned at birth as the annotation and using it for what is predicted. And ERS goes further, which I think is great, saying that talking about the timing of gender reassignment, what hormones they were on if they blocked puberty is something that we really need to research more and potentially could affect their PFTs. But unfortunately at this point, the only data we have suggests that we should go with their sex assigned at birth. So then the question is, does this actually matter? If someone is presenting as female, but their sex assigned at birth is male, are their PFTs going to be wrong? There's only two studies that have really looked at this. And anecdotally, you would think that it would be true. So one was done by an RT back in 2018, and they switched the sex on PFTs that already were available and found that 45% of born male and 70% of born female subjects would have had different interpretation of their PFTs. And then in a real-world cohort, one of the allergists at Brigham Women's looked at, and half the patients would have had significant changes in the evaluation of their FEV1-FEC. So the question is, should we change how we approach PFT testing then, especially as the percentage of individuals who would identify as gender diverse or in the gender minority is growing? And so there's this excellent sort of reference and diagram that is available that looks at really asking their gender identity as the first question, and then asking what their sex assigned at birth is, and then looking at if those are congruent or not. And if they're incongruent, then specifically asking them follow-up questions that revolve around if they took medications, if they're currently on hormones, if they took puberty blockers, and then making sure that the annotation on the PFTs references this. So references their sex assigned at birth, references a little bit about if we think that maybe their reference sex should be different based on if they've taken puberty blockers or not. And while this is not the official criteria from ATS or ERS, I think that this is important to think about overall. And then we'll go to the garment questions later on in the talk about chest wall binding. But I think this is an excellent opportunity also to talk to your patients because they're going to be upset that the incorrect gender, the gender, it's going to cause gender dysphoria for them because they see, just like they're seeing on their billing statements and other things that the incorrect gender is there, their sex assigned at birth. And so you want to counsel them a little bit on that as well. Moving over to chronic lung disease, the most robust data we have related to this is actually looking at transgender Medicare beneficiaries and their chronic conditions. And so this was 7,000 transgender individuals versus 39 million cisgender individuals. So the numbers are obviously very different, but very interestingly, regardless of if the individuals were entitled for Medicare based on disability or age, they had significantly increased rates of asthma and COPD compared to cisgender beneficiaries. And so the question is, why would this pattern exist? It hasn't been shown in other studies. Other studies are more difficult to find this specific data. So asthma, we wonder if there's a relation with sex hormones and for cisgender individuals, we know that there is, that if obese women have increased free testosterone and estradiol, they're less likely to have asthma, that non-obese men, if they have increased estradiol, are less likely to have asthma, and that starting a cisgender woman on hormonal therapy increases their risk of asthma. And so how would this affect transgender individuals is a great question. In COPD, there's always the question of if there's increasing use of tobacco, and I didn't have time to go through it, but there's a long standing history of targeting by the tobacco industry against LGBT individuals to get them to use their products, reduced access to healthcare for tobacco cessation, and again, is this hormonally mediated at all, that we know that women are 1.5 times more likely to develop COPD even if they're non-smokers, and that they're more likely to have chronic bronchitis. And so again, I think the overall theme is that more research is needed. So does this fit the general gender minority population? Do hormones really matter? Should we see if PFTs, if people are more likely to get asthma or COPD once we start hormone replacement therapy? And is there any chance that maybe some of these diagnoses in these Medicare beneficiaries were because their PFTs were just wrong? An area that's near and dear to my heart is CF when we talk about chronic lung diseases. It's a unique genetic systemic disease with specific pulmonary issues. Women are more likely than men to have pulmonary exacerbations and have higher morbidity and mortality, and are more likely to have pseudomonas, and hormonal therapy actually will increase the risk of pulmonary exacerbations. This is only in case reports, but seems that it's related to asthma and may have more specific targets related to IL-8 and TH17 with increased neutrophil response and probably increasing pseudomonas, specifically the mucoid phenotype, which we know can cause more exacerbations. So I think this is a really interesting case report then of a 23-year-old transgender female who was already chronically ill with ABPA, CFRD, nephrolithiasis, and coincident to starting gender-affirming hormonal therapy they started having significant decrease in their PFTs and increasing exacerbations. You can see with ciproheptidine and estrogen and having to have significant changes in their therapies afterwards. So we're coming back to that same question essentially. It's the same patient, but now they're talking about how they've been using a chest wall binder for the past three years. Often they're wearing it while working out and sleeping. They had the PFTs with male for reference formulas from their PCP that demonstrates a potential restrictive lung disease and they're on estrogen therapy. So what would be your first step in management of this patient? Last call, okay. So great, the correct answer would be to decrease the amount of chest wall binding you're doing and never while sleeping. So I wanted to go through quickly, we talked a lot about all of the potential gender affirming interventions, but some of the consequences that may come from them. And really important, we went through all those surgeries, but I think the data would show from 2015, the US Transgender Survey, that was the largest survey to date, that 25% of individuals have already undergone some sort of surgical intervention, but a fair amount of them may not want it. So if we look specifically at chest surgery for sex assigned at birth of female or transgender men, 10% of them don't want it, 17% aren't sure if they want it. And so for those individuals, it's more likely that they may use chest wall binding in a long-term format, and how will this affect their breathing? There are also obviously genital surgeries and facial feminizing surgeries that we talked about, as well as colloidal augmentation. So I think when we think about chest wall binding, I'm obviously gonna talk to you about it, but sometimes it's better to hear from these own individuals' words. And so I find that these two articles are really helpful to hear specifically from patients that are undergoing chest wall binding, and they're just excellent New York Times articles, so I always put these in any talk I have, because I think the headline in and of itself, it's binding or suicide, really helps sort of solidify why these individuals are wanting to bind their chest. And if you ever wanted to see what actually goes into it, this is a really helpful website aimed at people who are going to chest wall bind, but I think hopefully the visual is enough that you should not use duct tape, but the talking sort of through exactly how they can chest wall bind, I think it's helpful for those of us that will never actually do that. So chest wall binders can look like a lot of different things. All of these, for the most part, are commercial binders, and I think it's really helpful to see the difference in that bottom right, where the first is with a bra, and then the second is with a binder, so you can see how much that really does flatten out their chest, and helps with the gender dysphoria. And like I said, it's for prior to top surgery for transgender men, and really can be instrumental to their mental health, just like that New York Times article headline was saying, there was also a study that looked at their overall mood on a scale of one to five, a fair number of respondents, 1,800, where their mean mood significantly increased before and after binding. And while commercial binders exist, like all those pictures I was showing, they really can be cost prohibitive, or if they're not totally out to their loved ones, or they're in an unsafe household, then they may use alternatives, and these are all the alternatives that those individuals talked about using, and I think duct tape, homemade, and other sort of compression wear can be really dangerous, especially if they're too tight. The reason why it can be so dangerous, as I think we all know, is that it can have serious respiratory side effects. In that same study from before, 50% of individuals that were chest wall binding had some sort of respiratory outcome, with it being as minor as cough, and severe as sort of shortness of breath and respiratory infections. Unfortunately, there really isn't any data on how long you should be binding for, how many days a week, how many hours a day, but the overall thought is to wear for around eight hours a day, never while sleeping, and if possible, not while exercising as well, because of how much it decreases chest wall excursion. I think the important thing as pulmonologists, or other sort of chest physicians, or providers, is that we really should be open to having those discussions with the individuals, because gender minority individuals want to have the discussions, but they don't always feel comfortable initiating it, and so talking with them about it can be really helpful, and specifically going back to those garment questions, so this is the end of that wonderful flow diagram from before, that this can be what respiratory therapists can talk about, so if you ask them, and they say they are wearing a compressive sort of device or garment, that you give them the, you tell them that it could interfere with their results, and give them the option to remove it in a safe space, knowing that that could cause some gender dysphoria, letting them do it, though, with it on, and making sure to annotate that they were wearing some sort of item that could restrict their breathing. So I think overall conclusions is that we should make sure that we're respecting gender identity when we're doing PFTs, but that sex assigned at birth, currently, we think, as the most important part when looking at full lung capacities, and that future research really needs to be done on, do puberty blockers matter, do hormones matter overall to individuals' lung function, that they may be at increased risk for asthma and COPD, and obviously a lot more research needs to be done on that, that people with CF may be more sensitive to it, that chest wall binding is very, very important, we should think about allowing them to remove their binders, but not requiring it, and that a lot more research needs to be done there as well. So I think the one thing that you can do, leaving here today, other than all of that information, is being open and honest with your patients, and being willing to talk to them more about it. Consider wearing pronoun pins, which I think is great, that Chest added those for these, showing that you're an ally. You can sign up for this LGBTQ plus healthcare directory, so that they know that their providers are potentially, that are open to having those discussions, and that the 2022 Transgender Survey is coming out, so hopefully that will have a lot more great information. Hi, I'm Dr. Leila Sargsyan from McGovern, and I'll be speaking about the sleep issues in the transgender population today. I'm not sure if this is the same QR code, but please go to it to answer the IRS questions, so I'll give you a second. So I plan to share with you today the extent of sleep disturbances in the transgender population, and really delineate hormone therapy, and how it affects sleep, sleep disturbances, and specifically obstructive sleep apnea. So let's start with a real life case of Deanne. Deanne is a 43 year old trans woman, who comes to our clinic complaining of fatigue. She actually works two jobs, a full time day job, and a full time night job, and some of those nights and days do overlap. She needs both to pay bills. She snores and has apneas, as witnessed by her partner. However, she was not able to get diagnosed with sleep apnea, nor treated, because she thought she couldn't afford a pop device. She takes progesterone inconsistently, because her bedtime varies so much, and because the progesterone makes her sleepy, and she recently has cut down her alcohol use to only four days a week, instead of all seven. We will return to her at the end. So I'd like to start with limitations, and really it's about the sparsity of the data, and specifically sparsity of inequality data. Most of what I'll show you is based on large survey results, but also survey results put together, and a lot of retrospective data with very few RCTs. And most of it is consistent, although there are some conflicts in it. So even among the gender and sexual minority patients, transgender patients do experience the most amount of sleep disturbances, and here are some of those studies I alluded to that I'll go through really quickly. This one is based on large survey data, both out of United States and South Korea and China, that shows that 70% of adults and adolescents and young adults have shorter sleep duration and worse sleep quality when compared with non-minority patients. And this is relatively astounding at how high this percentage is. A study from 2017 of 154 transgender individuals showed that sleep was the only independent predictor of quality of life, and that sleep disturbance was present in 4 5ths of both trans men and trans women. And again, these numbers are very, very high compared to non-minority patients. This last one is a narrative study out of New York City based on a lot of in-depth one-on-one interviewing, and more than a third of these patients specifically attributed their sleep disturbances to being transgender and all the dysphoria that that led to, and the discrimination and anxiety, and many of them used medications for sleep. This particular study was done on trans women of color, and it's one of its kind. The study's aim was actually to look at rates of HIV and PrEP use in these women. However, a subgroup analysis showed that even though people at New York don't really sleep a lot, if you're a trans woman of color, you sleep much less and much shorter. So again, a significant difference. This one is almost a quarter of a million of North American college students. This is actually a compilation of a bunch of surveys, and it showed that transgender college students, when compared to other sexual and gender minority students, had significantly higher rates of various sleep disturbances, as you can see, and various diagnoses, and even more disturbingly, a lot of rates of depression, anxiety, and they were four times more likely to attempt suicide than their cisgender and non-minority college counterparts. I'd like to introduce the term allostatic load. Allostatic load is a multi-system construct that quantifies stress-induced biologic risk. It's basically the physiologic wear and tear on our body caused by chronic stress. It is a number, and it's comprised of 12 or so variables that are both biochemical but also anthropomorphic, so blood pressure, cortisol levels, insulin levels, sex hormone levels, various inflammatory cytokines, et cetera, and it's been shown that disturbed sleep, and really any sleep diagnosis, even if it's just snoring, but of course also insomnia and sleep apnea, those things raise the allostatic load in any individual. Minority stress model is a term that hasn't specifically been started to be used for transgender patients. It was initially coined for racial minority patients and people, but of course, it mirrors and goes hand-in-hand with allostatic load, and it is the postulate that minority stress specifically stigma, both external and internalized, victimization, discrimination, health disparities lead to worse physiologic, and of course, cognitive and emotional states and poor outcomes, including higher mortality. And so we know that chronic sleep disturbances increase allostatic load, which then in turn leads to sleep and circadian disturbances, and I think we can intuitively all understand and believe this, and this turns into a vicious cycle. And moreover, what else goes into this cycle if I were to expand it? So if we look at all the environmental social factors leading to recurrent chronic stress, poor short quality of sleep, then we have the biochemical consequences as noted there, and if a person happens to also have sleep disordered breathing and all the physiologic stress that that brings on to somebody at night, then this is compounded, and the levels of allostatic load are even higher, which has been shown to lead to chronic fatigue, other diagnoses, lower thresholds for pain, but also decreased cognition, all of this leading to sleep and circadian disturbances, patients coming to our clinics complaining of these things and us not fully understanding the full context of it, leading to worse health outcomes, and again, we have this cycle, and somewhere in here we have a chance to intervene. So I don't have to tell you all that sleep, yes, it really does matter. It's been shown over and over to affect all of the things that are listed on the screen, cardiovascular disease, metabolic issues, poor quality of life, and also increased mortality. The data is limited on how these vulnerable populations, what sort of sleep disturbances they have, as I've shown, but what we do know is that transgender persons compared with their cisgender counterparts do have higher rates of health disparities, mental health issues, STIs, cancer, cardiovascular disease, and premature mortality, and their utilization of healthcare is significantly lower, and therefore, they present later with these diseases, and of course, Dr. Turner alluded to tobacco use. There's also higher rates of tobacco use among transgender patients, and so what is the association between gender minority patients and the sleep problems, and who's really at risk? And it turns out that those who live where there's low support for LGBT marriage rights, who have poor parental and social relationships, low socioeconomic status, those who spend their time in school worrying about bullying and gender dysphoria issues instead of learning and studying, and of course, when we add on other causes for sleep disturbance, such as voluntary sleep deprivation from escapism behaviors, gaming is a big one, a lot of social media use, and shift work, because otherwise, they can't find jobs, and they can't keep them down, and then higher rates of depression and anxiety, then we're not surprised to find that these consequences that take these patients to our clinics, and you can see them, but I'd like to point out the misuse of meds. Progesterone has a soporific effect, and it's often misused as a sleep aid, and that's really not its intention, and so again, we find our patients in these situations. So inconsistent, unstandardized, and incomplete scales for studying the patient populations and just persons out there in real life is what leads to sparse, poor-quality data, so there's a lot of potential for us to further our knowledge and provide better care. Okay, this is not one of the ARS questions, but who'd like to tell me what these molecules are? I'm just kidding, so we're gonna shift gear and go towards hormonal therapy, and we have estradiol on the left and testosterone on the right, and we're ready for our first question. So estrogen likely has the following characteristic when compared with testosterone. It increases both the hypercapnic and hypoxic ventilatory response. It decreases the hypercapnic, but increases the hypoxic respiratory response. It decreases both hypercapnic and hypoxic ventilatory response, or it has no effect on either one. Yeah, I was thinking we should have Jeopardy music here. Okay, ready? So estradiol estrogen increases both the hypercapnic and hypoxic ventilatory response and we'll address this in a second. But before we do, I would like to point out that there's a lot of bias and stereotyping in every part of the patient experience for women undergoing their journey through being diagnosed with OSA. So from the moment that women present to screening, questionnaires, diagnostic studying, but also treatment, there is bias and stereotyping. And you can see some of those aspects there. Women tend to present with milder OSA, more REM predominant. They have non-classic presentation, up to 40% of the time a woman will only present with fatigue and insomnia and really have underlying OSA. And men also don't notice their partner's poor sleep and they don't accompany women as frequently, excuse me, some do, they accompany women less frequently to appointments and notice less. And so there's some bias in recognizing that there is a problem in the first place. And in my opinion, if there's so much bias in diagnosing women, of course moreover, we may think that there's even more bias diagnosing, treating, and screening the transgender population. So what are the sex differences between men and women? And there's several, including anatomic differences, the larger soft palate, the longer airway that causes higher prevalence of OSA in men, different fat distribution, but most importantly, the respiratory stability that estrogen and progesterone promote. So this is a large part of the reason why prevalence of OSA is so much lower in pre-menopausal women because they are protective of OSA and, of course, we see the severity and the prevalence of OSA skyrocket after menopause in women. So the question is does gender-affirming hormone therapy worsen or cause OSA? This is a case series of just three quick patients, a trans woman with severe OSA upon initiation of estradiol, had the OSA resolved and you see how severe it was, and two trans men without OSA who upon initiation of testosterone therapy developed OSA. And, of course, this is just a case series, but it raises significant questions of can we cause harm and how do we prevent that? And so the questions are does testosterone replacement cause or worsen it, does OSA cause low testosterone levels? And so some of the potential mechanisms are the top two, neuromuscular control of the upper airway that changes with testosterone therapy and increased oxygen consumption, need, and hypoxia exacerbating OSA. Those two are thought to be less significant and really it's the third one, the decrease in the ventral to response to hypoxia and hypercapnia I've already spoken of causing decreased respiratory stability that is the likeliest mechanism by which testosterone may worsen OSA. And so I'd like to illustrate here the association and kind of the tri-directional path we have between OSA obesity and low testosterone. First of all, testosterone level rises through the night and it is very closely tied with the very first REM period. And so you know sleep disordered breathing disrupts and decreases REM sleep and therefore the peak concentrations of testosterone as well as the early morning level, that's supposed to be the highest in the 24-hour cycle are strongly affected by OSA. And so OSA causes low testosterone levels and then obesity in turn also through hormonal mechanisms contributes to low testosterone levels. And then in turn, low testosterone will worsen obesity, again through the mechanisms you see in the left upper and also cause poor sleep which of course may also contribute to sleep disordered breathing through decreasing the threshold for arousals, et cetera. And here we have this complex relationship that we're trying to target. So do we really have answers? Can I give you an answer of what to do? And that's complicated. The first good RCT that's worth mentioning was in 2012 which was an 18-week double-blind placebo controlled study. This is the one that people reference when they say testosterone worsens OSA. And 67 obese men with severe OSA who were started on testosterone therapy versus placebo were studied. And a PSU was repeated at 7 weeks and at 18 weeks. And you can see that at 7 weeks there was a small but significant worsening in the oxygen desaturation index as well as the total time spent with an SpO2 of below 90%. However, this difference resolved or was no longer significant by the 18-week polysomnogram. And so this concludes that the testosterone therapy in obese men with severe OSA may worsen sleep disordered breathing, however, possibly just in the short term. And of course notice that these men also underwent a weight loss program as part of the treatment. And so that is in my mind a confounder. And the next study was retrospective in 2018 and a much larger population. These men were on testosterone therapy for hypogonadism rather than hormone potentiation of their secondary sex characteristics that they wanted. However, this study had a lot of problems. But at the 2-year mark it did show a little bit higher rates of OSA prevalence. So again, it is possible that testosterone may worsen risks of risk for OSA in men using it. So you see the association between OSA and lower testosterone levels. And of course we understand there's a difference between giving someone testosterone for hormone replacement as opposed to giving it for gender affirming hormone therapy. But this is all the data we have that we can extrapolate from at this time. It's also important to remember that progesterone should always be given with estrogen as an adjunct treatment. And however, people need to be sure they're using it correctly and female sex hormones are protective of OSA. So what's happened to Deanne? We suspect that she has OSA and what are we going to do? And I propose the plan be that we order her a sleep study and we do a lot of counseling and help with resources with further counseling on alcohol use, financial counseling, helping with the timing of her progesterone, education of course, and help with a shift work disorder. And she's really under a lot of stress and screening for mental health issues is paramount. So sleep health among the transgender population is an unmet health need and a health disparity. And the things that we can do today in our clinics are ask about gender minority status, assess for sleep disturbance risk in anyone, but especially closely in those who tell us that they are transgender and other minority population. Assess for mental health issues, screen closely, refer to psychiatry when necessary. As far as testosterone OSA, we should screen for OSA in those who are beginning gender affirming hormone therapy. If we find severe OSA, and I would postulate moderate also, we should begin treatment and we should restudy these patients to make sure that we are not missing a secondary disease, but also just we're treating their OSA appropriately. And then finally, I would encourage all of us to find the community of providers and clinics and places where this patient population is welcome and will be treated appropriately to find not only general providers, but subspecialists, especially endocrinologists, and to educate other physicians around us and in our communities, as well as empower our patients that they deserve and should be getting and seeking the care that they really need. Thank you. And next will be Dr. Cortes Puentes. Great. Well, it's really an honor for me to be part of this panel. Thank you very much. Wonderful presentations, everyone. And to have this opportunity to share with you some thoughts about the care of the transgender patient in the preoperative setting and in the ICU. I am Gustavo Cortes Puentes, and I'm a consultant in the Division of Pulmonary and Critical Care Medicine at Mayo Clinic, and I have nothing to disclose. This is, again, the barcode for everybody in case it's different. And I think I would like to change the pace slightly here, and I think I would like to start saying that there is really a growing body of evidence that really support the very beneficial effects of gender-affirming hormonal therapy on mental health outcomes of transgender and gender-diverse patients. And in those lines, I would like to invite you, during the next few minutes, to keep in mind that we should just all meet together in one spot, and it is really trying as hard as we can to optimize the delivery of care for the transgender and gender-diverse individuals in every clinical scenario we can. And to be able to do that, I think we need to change the scenario slightly. And instead of thinking of how gender-affirming hormonal therapy changed the, quote, unquote, normal physiology of the patients, and speak too much about the consequences of gender-affirming hormonal therapy, it's better to start thinking about, you know, the physiology of adaptation to gender-affirming hormonal therapy. And also, instead of thinking, how is this going to change the standard of care in my practice if I am facing the care of a transgender individual, just start thinking about how am I going to adopt a personalized approach to delivery of care in this patient population. If we all keep that in mind, regardless of our background or affiliations, I think we can actually provide a better service to this patient population. And I would like to start for the perioperative assessment with this case. So we have a 64-year-old patient, designated male at birth, who arrived to our clinic for a candidacy assessment of lung volume reduction surgery. This patient had a past medical history of COPD and has been experiencing worsening dyspnea over the last two years. And really, there's no changes in the clinical presentation of COPD exacerbations or cough or chest pain. It's just basically shortness of breath. So here we have a chest X-ray and also a correspondent CT scan image. And just to give you an idea of the degree of dyspnea and symptoms, just to give you an idea of the MMRC of the patient, three. Here we have the pulmonary function test. As you can see, it's consistent with obstruction, which is also consistent with the underlying diagnosis of COPD, but it's not really consistent with the degree of air trapping that we were seeing on the chest imaging of this patient. So when we evolve more in understanding the clinical picture of this patient, we have to underscore that this patient was receiving gender-affirming hormonal therapy over the last three years, specifically estrogen and androgen suppression therapy with espironolactone and finasteride. And again, I want to take this opportunity to underscore the importance of gender-affirming hormonal therapy and the positive health care, mental health outcomes in this patient population. So in the absence of any other explanation for the worsening dyspnea, and this include the absence of chronic thromboembolic pulmonary disease or changes in the lung parenchyma when comparing to previous images, we start to wonder how does gender-affirming hormonal therapy influence not only the interpretation of pulmonary function, but also the symptoms of the patient. And specifically with the estrogen-based therapy, there is a decrease in muscular strength, lean body mass, and muscle area. And all of this are going to directly affect the force inspiratory lung volume, expiratory flow rates, and resting lung volumes of the patient. Even though there are no changes to the central airways, there are extra pulmonary factors that may affect the performance of pulmonary function in PFTs in this patient population. So we see here not only the development of breast tissue, but also the reduction in chest wall musculature in this particular case. And we have certainly make a lot of progress when we try to explore the effect of race in pulmonary function and the calculation of normative predictive values. But certainly, issues with representation in clinical prediction models is largely under-recognized for sex and gender. And truly, when we are interpreting pulmonary function tests based on the ATS and ERS criteria nowadays, we are assuming that sex is a variable that is a sign of birth and really doesn't change throughout the lifespan of the patient. But truly, the changes in body composition that are associated with gender-affirming hormonal therapy may actually challenge that approach, and it's important that we look into this more deeply. So in this particular case, when we analyze the PFTs of the patient using the gender identity normative values, in this particular case, we'll start to see not only a more congruent pulmonary symptom, chest imaging axis, but also we open the door for other therapeutic options. For example, endobronchial valve, lung volume reduction procedures instead of surgical lung volume reduction. And very likely, the identification of this adequate normative predictive values in this patient population could translate into a more timely process to actually monitor the pulmonary symptoms and pulmonary function changes over time. So the first question that I have for you is about the sex differences in pulmonary system morphology. A, luminal area of central conducting airways. B, lung size or total lung capacity. C, the shape of the chest wall and lungs. D, the ratio between functional residual capacity and TLC. Oops. All right. Both early and both often, as they say in Chicago. Very good. So the correct answer is D, the ratio between functional residual capacity and TLC. So there are very specific pulmonary system morphology differences between sex. And individuals who are assigned male at birth are going to have a much larger luminal area from the trachea to the third generation of bronchi. Also, these individuals assigned male at birth are going to have a much larger lung size or total lung capacity. And the shape of their lungs is going to be more pyramidal compared to a more prismatic shape that we often see in patients who are assigned female at birth. All of this is established, these differences are established approximately at the age of 14 years old. And you're going to start to imagine that, you know, these sex differences are going to be influenced, for example, by the effect of pubertal blockers, especially if they are established before the age of 14. But outside these differences, there are external factors, such as lean body mass, total musculature strength, the distribution of fat and hemoglobin levels, which could potentially also affect the performance of pulmonary function. So it's not just the intrinsic characteristics of the pulmonary system, but also those extra pulmonary factors that may influence lung function. So there is a lot of questions about this. And, you know, there is a lot of information that we still need to gather and questions that need answered. And we're really trying to prospectively actually assess this. We're trying to identify after how many months of gender-affirming hormonal therapy are we actually going to see a clinical significant change in pulmonary function? And if we do, what is the magnitude of that change? And is that magnitude of a change correlate with a specific level of either testosterone or estrogen in this patient population? And, of course, a different compartment will be comparing those individuals that started pubertal blockers before the age of 14 and those that started gender-affirming hormonal therapy without pubertal blockers. So there is a lot of physiology to unpack to eventually be able to arrive to a personalized approach to pulmonary function interpretation. So, however, the data that is available today still allow us to make some recommendations. And it's very important to understand that the monitoring of muscle strength in this particular patient population is very important over time and is a cornerstone of actually efficient and optimal delivery of care for the transgender population, especially those who have chronic pulmonary diseases. And while we gather more data and we really have enough information to challenge the current standard of care of utilizing sex assigned at birth instead of gender identity to calculate normative predictive values, whenever we see discrepancies like in the case we just discussed between the clinical presentation and the test results that we are seeing, we might be better equipped by looking at both the analysis based on the sex assigned at birth and the gender identity of the patient and see which one of those actually follows both the clinical presentation, imaging, and pulmonary symptoms over time. And most importantly, all of this underscores the important task that we all have not only in understanding the physiology of adaptation to gender-affirming hormonal therapy but also to develop a personalized approach to BFT interpretation. And this translates into many other organs, the physiology of adaptation concept that are very crucial when taking care of transgender patients in the ICU. But perhaps the most important aspect is getting to know your patient when they land in your ICU. And the first best step is to always use the preferred name of the patient and the identified pronouns. This is a little picture courtesy of Dr. Cassie Kennedy who is a colleague and mentor at the Mayo Clinic. So it really doesn't matter what someone's name used to be. If they don't use it, we're done. So always, preferred name and identified pronouns since the beginning in every patient-provider interaction. And then ask permission to discuss all of these questions with the patient. It's very important to provide efficient care in the ICU. We need to know if they are on gender-affirming hormonal therapy for how long they have been on it. And it's very important with any other patient in the ICU to have a clear idea of what the anatomy inventory is. Do they have gender-affirming surgical procedures before? How long ago? Where do they receive gender-affirming hormonal therapy care? And also ask permission to discuss menstrual cycle periods. And very important, very early on, and again, perhaps not different than any other ICU patient, discuss who is going to be entitled to receive privileged information about their status in the ICU. And very quickly, provide the resources to either identify a power of attorney or to generate an advanced directive very early in their care. But there are many other considerations that are important in terms of the physiology of adaptation to gender-affirming hormonal therapy. And this includes medication dosage in the ICU. And the recommendation currently is that if patients are on gender-affirming hormonal therapy more than six months, we should dose medications based on creatinine clearance and ideal body weight calculations using the gender identity of the patient if they have been, again, on gender-affirming hormonal therapy more than six months. And the reason of this is because of the changes in renal function that occur in both transgender women and transgender men after approximately six months of therapy. So as you can see here, approximately six months after initiation of estradiol and, actually, approximately six months after initiation of estradiol and after achieving an estradiol goal, we have a change of approximately 0.1 drop in the creatinine in transgender women. And in transgender men, we see, actually, an increase in creatinine of approximately 0.2 after six months of exogenous testosterone administration. So it seems to be more appropriate to use a new baseline GFR that is based on the creatinine level at six months and using the identified gender of the patient to calculate this GFR and dose medications. Other important aspects to consider in the ICU is whether or not we should continue the use of pre-exposure prophylaxis and whether or not we should continue gender-affirming hormonal therapy in the setting of critical illness. And I think the answer for both questions is an individualized clinical decision. So I think patient preference is always very important. But the reality is that the clinical signs of, you know, deep venous thrombosis or any thromboembolic pulmonary disease is going to be no different than the patients that are without gender-affirming hormonal therapy. So the risk has to be individualized, and it depends on many factors, the mobility of the patient, et cetera. If there are no contraindications, the recommendation is to continue therapy. In fact, if there are issues with routes of administration, it's recommended to actually look for alternative routes of administration in order to provide that desire of the patient to continue gender-affirming therapy. And lastly, and perhaps the most robust data we have on physiology of adaptation to gender-affirming care are the hemoglobin levels and hematocrit normal ranges in these patients. And really, these are going to be almost 100% congruent with their gender identity at approximately six months of therapy. So it's important to keep that in mind when we look at hematologic emergencies or oncologic emergencies. So lastly, thank you very much to everybody for being here. I think it's great to see the interest in this topic, especially this late in the afternoon. And we're very happy to answer any questions. Thank you very much. Thank you.

transgender patients

terminology

therapies

healthcare disparities

gender dysphoria

gender affirming therapies

pulmonary issues

sleep disturbances

perioperative care

personalized care