My name is Jimena Lopez. I'm a pediatric endocrinologist in Dallas, Texas at the University of Texas Southwestern Medical Center. And I'm your co-moderator for this session. I'm Janet Lee. I'm a pediatric and adult endocrinologist at University of California San Francisco. And I'll pass it on. Today we have four presenters that will be talking on challenges in endocrine medical care for adolescents on the gender spectrum. We will have the presenters give their presentations first. And then we'll leave the questions till the end. For those virtual attendees, they can post their questions in their Q&A section. And we'll try to reach out to them. And for those in the audience, you can step to the microphone and introduce yourselves at the end of the four presentations. So with that, I'm going to introduce our first speaker. So one second. Caroline Mendoza. Carolina Mendoza. She obtained her medical degree of the University of Santiago de Chile. She specialized in pediatrics and pediatric endocrinology at the Pontificio Universidad Católica de Chile. She's a clinical staff and clinical researcher at the Unit of Pediatric Endocrinology in the medical school at Pontificio Universidad Católica of Chile. She has interest in transgender children and adolescents. And she's the pediatric representative of the gender group of the Chilean Endocrinology and Diabetes Society. And with that, I welcome Carolina. Good afternoon, everybody. I would like to thank the organizers and to Dr. Veronica Meric, especially. In the next short 20 minutes, I will try to review the information available about the effect of gender-affirming hormone therapy in cardiometabolic growth and bone health. My goals are to recognize the impact of gender-affirming hormone therapy in the treatment of women impact of gender-affirming hormone therapy in cardiometabolic growth and bone health in transgender adolescents. And to identify the gaps in knowledge regarding the effect of gender-affirming hormone therapy. We will start with cardiometabolic health. What is known? You know that body composition changes during puberty. And this change is due to the effect of sex steroid. So it is expected that the gender-affirming hormone therapy produce a change in body composition. This study investigated the changes in body composition and markers of cardiometabolic health in transgender adolescents and compare it with cisgender youth. And what they found is, what is the pointer? Here. They found that in trans males, they had higher values of lean mass percentage compared to cisgender female. And lower values compared to cisgender males. And regarding fat mass, they found lower values compared to cisgender female, but higher values compared to cisgender males. And in trans females, they found that they had higher percentage of lean mass compared to cisgender females. And lower percentage of lean mass compared to cisgender males. And regarding fat mass, they found that transgender female had lower values compared to cisgender female, and higher values compared to cisgender male. So they conclude that the body composition in transgender females and males is an intermediate between cisgender females and male. What happened with insulin sensitivity? You know that insulin sensitivity changes during puberty. And there is an increase in insulin resistance. And there are differences among sex, with cisgender girls having more insulin resistance compared to cisgender boys. And in this study, they found no difference between. They used the inverse concentration of fasting insulin, which is correlated with insulin sensitivity. And lower values indicate more insulin resistance. So they found that the trans male had no difference compared to cisgender females and cisgender males in this group. And in trans female, they found that there was no difference in trans female compared to cisgender females. But trans female had lower values compared to cisgender male, which indicate more insulin resistance. This is another study that evaluated the HOMA. And they found in a group that was followed up after starting GnRH analogs at 15-year-olds, and then start gender-affirmative hormone therapy at 17-years-old, and follow up to 22 years, they found that the only group that had higher HOMA was the trans woman. But are these changes in insulin sensitivity correlated with another changes? This study evaluated if the use of 17-beta estradiol in transgender girls found no difference in the hemoglobin A1C during the follow up. What about blood pressure? This study follow up patients after 24 months of treatment. And they found that trans female had no difference in systolic or diastolic blood pressure. And there are other studies where the use of spironolactone in trans females produced a decrease in systolic blood pressure compared to those that don't use spironolactone. And what about trans males? They found an increase in systolic and diastolic blood pressure. This was a significantly increase, but mildly clinically, because the values continue among the normal range. And the other important factor related to cardiovascular disease is lipid profile. In adult studies, it has been shown that there is a decrease in HDL in trans male using testosterone, and an increase in LDL, cholesterol, and triglycerides. And they found here that the HDL was lower in trans male compared to cisgender female. And in transgender female, they found that the HDL was higher compared to cisgender male, which is an expected effect of estradiol. And what do we don't know about cardiometabolic health? There is no consensus regarding which growth chart affirmed gender or birth-affirmed sex should be used when evaluating body mass index in transgender adolescents. And is body composition a better parameter to evaluate than BMI? There is no information about the long-term consequences of changes in body composition for cardiometabolic health. And the impact of testosterone and estradiol during puberty induction on present insulin resistance and future risk of type 2 diabetes in the effect of changes in lipid profile on future heart disease is unknown. This is a graph showing the rate when estradiol or testosterone is initiated and the dose of testosterone and estradiol. So talking about final height is important, and it can be complex in transgender adolescents. This study evaluated the effect of 17-beta estradiol in transgender girls. And what they found is that using increasing dose of estradiol, those girls with bone age below 15 years old had an average increase of 3.9, 2.4, and 0.5 centimeters during the first, the second, and the third year of treatment. And this was related to the bone age at the start of this treatment. And you can see here that those girls with bone age above 15-year-olds grow minimally. And another topic that is important is to know if there is a way to limit growth in transgender girls. The same study evaluated four girls receiving high dose of estrogen treatment. Two of them received 200 milligrams per day of ethinyl estradiol, and two received 6 milligrams of estradiol. And they found that just one, the red one here, had a growth of just 1.9 centimeters despite a bone age of 14 years old. There is not much information about this treatment in transgender adolescents, so we need more study to know if this is a safe and effective treatment to limit growth in transgender girls. And in the opposite way, is there a way to increase adult height in transgender boys? You know that transgender boys are, on average, 13 centimeters shorter than cisgender boys. And there is scarce information about this topic. And in this study, that is a retrospective study, they use oxandrolone to induce masculinization without the fusion of growth plate. And they use increasing doses of 2.5 to 10 milligrams per day, and they divide the group into those that received the treatment before the age of 14.6 year, and they were the early oxandrolone group, and the late oxandrolone group was that initiated treatment after 14.6 year. And what they found is that the early group reached an adult height of 169 centimeter, which is significantly taller compared to the late oxandrolone group that reached just 162 centimeters. This adult height was related to the age at the start of the treatment, and each early year of treatment produced 2.3 centimeter gains in height. Finally, they compared to cisgender male using the CDC male mean height, which is 176 centimeters, and 168 centimeter, which is one standard deviation below fifth percentile. And they found that the early oxandrolone group reached this minimum height of 168 in almost 53% of patient, and the late group reached this high in just 6%. So they conclude that the use of oxandrolone could be useful for increased adult height in transgender adolescents, but we need more studies. So what is a no? There are no clinical guidelines to support whether the birth assigned or affirmed gender's growth chart should be used for the assessment of growth. No published literature provides guidance on how to best predict final adult height for transgender youth receiving GNR8 or gender-affirming hormone therapy. Is there a role for the use of growth hormone, particularly in transgender males? And what is the best way to stop growth in transgender females? What is the impact of the final adult height or current height in transgender youth and its impact on gender dysphoria? Is there a high dysphoria? Finally, we will review information of bone development. You know that almost 90% of total bone mass will be acquired at the end of puberty due to the sex steroid effect. So using GNR8 analogs, it is shown to decrease bone mineral density. And they investigated the effect of these treatments, and it was related to the pubertal stage at the beginning of GNR8. And they divide the groups in the early, if they were tunnel two or three, and late, if they were tunnel four or five. And what they found is that regarding lumbar spine, there was an increase in bone mineral apparent density in all four groups, trans girls, trans boy, early and late pubertal. But if they look for the femoral neck, the increase was just in the group of the trans girls and early trans boys. And when they look for the C-scores of bone mineral apparent density in lumbar spine, there was an increase in all groups, but in the femoral neck, the increase was just in the trans girl group and just the early trans boy group. So despite these increases in bone mineral density, they found three girls with C-score on femoral neck below minus two, and three trans girls that had C-score in lumbar spine below minus two after the three years of treatment. And no non-trans boy had score below C-scores after the three years of treatment. And maybe this is related because trans girl had lower values at the beginning of the treatment. What is unknown? There are no longer follow-up studies evaluating outcomes such as fracture risk related to the changes in bone mineral density after GnR8 analogs and gender-affirming hormone therapy use. And what would be the best way to assess fracture risk in transgender individual is unknown. My take-home message. Transgender males and transgender females have a body composition intermediate between cisgender female and cisgender male. During gender-affirming hormone therapy, there are changes in markers of cardiometabolic health as insulin sensitivity, blood pressure, and lipid profile. Bone mineral apparent density C-scores increased during gender-affirming hormone therapy, but remain below zero in some trans girls. This data indicate that gender-affirming hormone therapy is safe during a short-term follow-up during adolescence. And longitudinal studies are necessary to know the impact of gender-affirming hormone therapy began during adolescence and long-term cardiometabolic growth and bone health outcomes. Finally, I would like to thank my patients and their families and Dr. Alejandro Martinez, who is my boss and friend and who has always encouraged me to keep working to improve the transgender patients. Thank you. of Dr. Moss's, or sorry, Dr. Moss Carswell. Sorry, Jeremy. All right, it's my pleasure to introduce Dr. Jeremy Moss Carswell, uses she, her pronouns, and is the director for the Gender Multispecialty Program at Boston Children's Hospital, having assumed this role in July of 2015. She attended the University of Pennsylvania as an undergraduate, and then returned closer to home for medical school and pediatric residency, both at University of Massachusetts in Worcester, Massachusetts. She completed fellowship in endocrinology at Boston Children's Hospital, where she has remained. Her early career research focused on congenital hypothyroidism, and she then took a fortuitous turn when she started working with Dr. Norman Speck at the gender, with the gender diverse population. We are excited to hear her speak about the known knowns and known unknowns in brain effects and cancer risks, as well as some other topics. All right, hi everyone. Let's see. So I would also like to thank the organizers and to you two for inviting me. Everybody awake still? Getting late in the day. All right. Too quiet? Okay, can everyone hear me? Okay. So my disclosures, since I actually wrote this, I have received some funding from the Nike Foundation, and I just dug into this a tiny bit because this sort of sounded familiar to me, and I was reminded that the known knowns and the unknown unknowns and all that stuff is actually attributed to Donald Rumsfeld. Can you believe that? Okay. So I am gonna be speaking on the effects of gender affirming hormone treatment on cancer risk, brain structure and function, and then just a taste of sports performance. This is a little bit about what we get into for counseling rather than the current issues that we face with adolescents. All right, so I'm gonna start with cancer and the known knowns, the known and the unknown unknowns. So can cancer occur in a reproductive organ after hormone deprivation or replacement? What factors influence cancer risk? What is the incidence of cancer in the trans population? How should we advise on screening? And what will we know in the future? So this is a table representing the total number of cancers that are reported in the literature. Please note, there is no time limit placed on the meta-analysis search. Breast cancer is the most prevalent followed by prostate cancer. And the cancers tend to follow the same cancers you would expect to see in cis populations. Invasive ductal is the most commonly reported. And really interestingly, eight incidences were found in people who had previously undergone top surgery. Prostate cancer was found on biopsy in eight trans women who had undergone gender-affirming hormone therapy and orchiectomy. And interestingly on biopsy, they were found to have a decreased size of the cancers, but well-preserved zonal architecture. This is another table talking about estimated incidence of these cancers. So this was from retrospective cohort studies and cross-sectional studies. And the authors review both, they gave us a low and a high estimate of these cancers. Some things to note. Transgender women have much lower rates of breast cancer compared to cis women. And that's pretty striking, 170 versus 0.09. And the reasons for this are not totally clear. Some people think there might be some under-reporting and maybe it has to do with a shorter lifetime exposure to estrogen. Transgender males also have a higher risk of breast cancer compared to cis males and trans females, but much lower than cis females. Let that soak in for a second. This is likely due to the high incidence of top surgery, but might also bring into the question if testosterone is somewhat protective against breast cancer. So here's the roundup. Oh, and I'm sorry, I forgot to talk about screening. The bottom line about screening is that nobody knows. I looked it up and truly screenings were all over the map. Some people said they should follow the same as cis. Some people said more, some people said less. So it is all over the map. So you can pick your poison there. Here's my roundup. Cancers can and do occur in reproductive organs after gender-affirming hormone treatment. The risk does not seem to be increased for any of the cancers studied. We do not have enough information to make high-quality recommendations for screening. And we will hopefully learn more as the population ages. And I have nicely color-coded these for you, for green is what we know and red is what we don't know. So moving on. Here, talking about the brain. So my questions are as follows. Are there differences between a male and female brain? If so, when do these differences emerge? Do brains of trans individuals resemble that of their birth assigned sex or their identified gender? And if so, are the differences dependent on sex hormones? What are the effects of lockers of gender-affirming hormone therapy? And what happens with the aging brain on hormones in terms of cognition and motor function? So it is accepted that the brain is sexually dimorphic and differences are listed in these boxes in relatively small script. And the differences are in several spheres. Connectivity refers to the differences in patterns of cognition, such as spatial, motor, and language. Males have more greater between-network connectivity and females within-network. Anatomical differences are notable for the amount of gray matter volume. Males have more, women have less, but they have a greater density. And males tend to have a total volume of the brain. I'm not gonna say if that makes any difference because we know there's really no difference in IQ. Task-oriented differences are also noted. On a population basis, males have better visuospatial abilities, such as rotation of objects in the head, and females have better perceptual speed and fine manual dexterity. Other commonly reported differences are noted in the medial temporal lobe, the amygdala, the hippocampus, and the frontal lobe, which we know is involved in executive functioning. So, what do we know about people who identify as trans or gender diverse, and what do their brains look like before and after gender-affirming hormone therapy? So, pre-hormone, most studies, and there are a few out there now, show that the brains of gender-diverse individuals align more closely with their affirmed gender in these spheres, performance, functional imaging, and neuroanatomical, which tends to be a little bit more variable. In post-gender-affirming hormone therapy, the neuroanatomic changes do occur. We know that hormones can influence gross morphology and white matter. Functional imaging has shown that activation areas, particularly during a mental rotation task, is closer to the identified gender, and cognitive performance is a little bit more variable, but tends to favor the identified or affirmed gender. So, when does all of this happen? Well, it is clear that we need more evidence, which is forthcoming, in that adolescence is a critical time for brain growth and differentiation, and there are differences observed prior to adolescence. So, there's a couple studies that were really actually very interesting. The first uses diffusion tensor imaging and MRI, and the authors in this study, out of China, were able, they imaged brains of children from newborn up to, I think it was 15 years old, and what they were able to do is they were able to identify, without knowing the gender of the child, they were able to identify whether a child was birth-assigned sex, male or female, based on these imaging findings alone, and it actually, at all ages, actually, but much more so after age four, which I thought was pretty interesting, and they actually used the DTI and MRI together, was much more predictive. And then another MRI study in eight to 30 years old, so you're also dealing with some adults, but noticed, definitely, some dysmorphism, sorry, the brains, the sexual dimorphism, so the amygdala and the thalamus have greater volumes in males, irrespective of age, and so even down to eight years old, so prepubertal, males with larger gray matter volumes on all low-bar levels, but more rapid loss of gray matter. So there are changes that happen. All right, does anybody recognize this? This is the Tower of London test. So I am often asked, all the time, if, when I'm prescribing blockers, if GnRH agonists, if the blockers will affect brain development. So there's not a ton of information out there, but this was a really cool study looking at children doing the Tower of London study with fMRI. So the task is to, the examiner will say, please arrange the balls on the pegs so that each peg has one ball only. Use as few movements as possible. And so they time people, and there's lots of these on the test, part of the IQ test battery. And what they found is that puberty suppression does not have an effect on Tower of London performance. Adolescent boys and girls show sex differences in the TOL-load-related brain activations. And then GnRH agonists treated participants with gender dysphoria show sex differences, or gender diversity show sex differences similar to their control groups, and pubertal hormones induced sex, atypical, what they say, but brain activations in adolescents consistent with their identified gender. And really interestingly, they had a lowest accuracy on the Tower of London test, and coincidentally, the lowest IQ in the suppressed birth-assigned males. But it was a relatively small study. So here's a roundup on this. The human brain displays sexual dimorphism in an anatomic and functional ways starting at likely a very young age. Adolescence is a critical time for brain growth and differentiation, but there are differences observed prior to adolescence. The brains of trend-identified individuals may more closely resemble those of their affirmed gender, though it is also likely that quote cross sex hormones or gender-affirming hormones likely contributes to some of the changes as well. And we don't have longer-term data yet to know what happens or fails to happen during pubertal blockade, and then followed by long-term growth gender-affirming hormone therapy. And lastly, I'm going to talk a little bit about sport performance. So lots of questions here. So what is the quantifiable advantage of cis males in sport performance, if any? How much and what is due to testosterone? Is there a period of time after which testosterone effect is negated? At what age do we see the divergence of sport performance? Can we quantify a performance advantage for individuals who have undergone a post-pubertal transition? Where do non-binary folks fit in? And what is fair and who decides, and how will sporting bodies adapt? I don't have the answers, I just want you to know that. So if you think you're getting them, you're not. So here's a nice kind of table just reviewing the physiological differences in cis women compared to cis men. And really the take-home point is that cis women basically have a lower cardiac output, lower VO2 max, they have less lean body mass. So what this all means is that cis-identified women, people who have gone in estrogen puberty, really do have less ability to move their blood and have less blood to move to feed the muscles. And they're also lugging around greater amounts of fat. Sorry. So does this translate into sports? Yes, it actually does. So is there a sport-specific competitive advantage? And I think this is what we're gonna see more and more recognition of. So the 100% is set to female in this graph here. So what you see is there is a male, a quote, male advantage for the sports moving across the screen. And the sports that have the greatest male advantage tend to have a lot of upper body strength. Body changes on gender-affirming hormone treatment. This was a lovely study in 179 trans females and 162 trans males in Amsterdam. And they used body comp measured by DEXA. And they used measurements at baseline, three and 12 months after gender-affirming hormone therapy. The most significant changes for trans women was the increase in the fat mass in the legs, loss of lean body mass in the arms. For trans men, there was a loss of fat in the leg and gain of fat-free mass in the arms. And it really didn't tend to make too much of a difference the type of estradiol or testosterone that was used. Is when do these changes really happen? So this is another great study looking at sports and sports performance in kids. So along the X-axis is age, and then along the Y-axis is the percent difference, males for females. So as we go along the X-axis, we see a greater divergence of sport performance in running, jumping, and swimming. And this coincides with testosterone levels increasing. And the greatest divergence is really in jumping, which is sort of interesting, right? Because I said it was upper body strength that is the most affected. But also we see this in running and swimming. Another great study in 2001, this is in cis males. And this is just showing, this is a dose response curve for using testosterone in people who had been previously suppressed with GnRH agonists. And they were given testosterone from sub-therapeutic to sub-physiologic to supra-physiologic and measured muscle mass and strength. And they each had equivalent amounts of training. So these lines basically keep going up. So the more testosterone you take, the stronger you're going to get. And this is why athletes still use performance enhancing drugs. And this has been replicated in other studies. We also know that there, so we know that testosterone gives you, okay, this monitor is going really wonky. We also know that testosterone gives you strength, but what happens when you take it away? Well, we do see the effect of that. So a similar study here. And what they did was they looked at the body composition of trans men, trans women, cis controls, and they do find that removal of testosterone does reduce the muscle mass. This is really the only study that I know of done in athletes. So there's lots of studies done in trans people, but this was in athletes. And this was done by Joanna Harper, who is a trans woman runner. And she's an exercise physiologist and a master runner. So she collected data from throughout the running world. She sort of just put out feelers out in the running world, said, hey, for those people who have transitioned, I'm really curious to know your times. And so she collected race times and over seven years to find out what happened. So, and she used something called an age gradient, which is basically age standards. Your fastest time ever run by a person that age times 100 divided by the race time. So it's like adjusted for your age and gender, basically. So what we know, the lower age adjusted, the age is lower. Most runners who started taking estrogen had very, very little change in their age grade or age adjusted score. So this is the only thing, this is looking backwards. So retrospective and sort of self-report, but still only one done. And again, this is the only one really, again, done, this is very cool, done in Air Force physical fitness tests. So, you know, military tape keeps great records. So this was 2.3 million, million, Air Force physical fitness tests performed by males under the age of 30. And so this person looked back at all of the tests that had been done and set a bar for like the average female, average male, cis, of course, and then looking at what happens when people transitioned. So this is retrospective again. So we, again, don't really have any data about what the transition looked like, what hormones, if they had suppression or not. So they looked at pushups. Interestingly, the trans men edged out the cis men, which I find really interesting, in sit-ups. So that was pushups, sorry. Sit-ups, kind of the same thing, the trans masculine folks really did better than the cis men and everybody else. And then the 1.5 mile run was the last one. And trans men, trans women, sorry, maintained an advantage. But out of these three tests, that was the only one. So here's my roundup. Testosterone has a measurable effect on strength. Different sports rely on different skill sets. Testosterone is not the only factor that is very clear. There seems to be a cis male advantage, even pre-puberty, but this is less clear. And nobody has the answers for fairness at the elite level of play, but I would argue, all children should absolutely be allowed and encouraged to participate in sport no matter their gender. And on that, I want to thank you all. And I guess we are not doing questions. Until the end. Until the end. We will have time for questions in the end. Thank you, Dr. Carswell. Our next presenter is Dr. John Strang. He's a neuropsychologist and gender and autism specialist at Children's National Hospital in Washington, D.C. The research director for Children's National Gender Development Program. Much of his clinical and research work centers on the common intersection of autism and gender diversity. He founded the Gender and Autism Program in 2017, the first subspecialty program for autistic transgender youth and their families. Thank you, Dr. Strang. Thanks for having me today. I'm the neuropsychologist here today and I love collaborating with endocrinologists. So I look forward to the questions that might come up later. It's good to be able to explore the common co-occurrence of intersecting autism and gender diversity. I have no financial relationships to disclose. I must begin by expressing my gratitude to the many transgender advocates who are autistic who have helped to guide this work both at the clinical level and also our research. Just a few of them are pictured here. This is a double marginalized group of people who are autistic and transgender and so their voices need to be part of the research. In response to the pressing questions in response to the pressing clinical need for specialized gender and autism services, we founded the Gender and Autism Program at Children's National in 2017. The Gender and Autism Program is the first subspecialty clinic dedicated to the intersection of autism and gender diversity and it is interdisciplinary, including neuropsychology, speech language, psychiatry, endocrinology, and gynecology. We offer evaluation of autism in the context of gender diversity and we also provide evaluation of gender-related needs in the context of autism. We offer consultations to help gender medicine providers, including endocrinologists, to understand how best to communicate with our autistic and more broadly neurodivergent trans patients. We have an ongoing support group and we provide speech and language services that target the social communication and self-advocacy needs of autistic youth as well as their transgender voice therapy needs. Clearly, it's too much to expect endocrinologists in gender care to also be autism experts, but we found in our program that a little bit of training about autism and more broadly neurodiversity can be very helpful in endocrinologists being able to communicate and successfully understand their patients. Autism is a form of developmental neurodiversity and in most classification systems, it's considered a disorder, yet some in the autism self-advocacy community have moved away from the language of disorder and think of autism as a disability or even an identity. So it may be helpful to ask your patients whether they prefer autism spectrum disorder or identity first language, that is that I'm an autistic person instead of a person with autism. Identity first language reconceptualizes autism as a neurodivergence or neurodiversity related identity instead of a condition. Autism includes the broadest range of intellectual and communication abilities. Of interest for our work, the over-occurrence of autism among trans youth has been identified among young people with average or above intellectual and verbal ability. That's not to say that there aren't autistic trans people with very limited language, but we do not see so many of these autistic youth in our gender clinics. And this may be because there are greater barriers to self-advocating around gender for those with verbal and intellectual disability. A series of studies have reported the over-occurrence of autism in gender diverse youth and adults, and there is a growing literature indicating a significant over-occurrence of gender diversity in autistic samples. In the largest study to date published in Nature Communications, among almost 650,000 individuals, the odds of being autistic when gender diverse were more than six times greater than the odds of being autistic when cisgender. With the publication this month of Amelia Kalatsonaki's meta-analysis of available studies, we can now say that across ages, evidence suggests that approximately 11% of gender diverse individuals are autistic. Our work has also identified an additional sizable subset of gender diverse youth who are at the margin of an autistic diagnosis. We might say almost autistic or slightly subclinical autistic. I'm often asked why is there an over-occurrence of autism and gender diversity? This is a question that comes up with parents and providers and clearly we do not know. However, in my work with autistic transgender self-advocates it has become apparent that over-focusing on this question of etiology may present a double standard. As noted by an autistic transgender self-advocate, do we expect to know the etiology of being gay in order to provide care to gay people? Yet, I've come to believe that it's important for those of us working with autistic trans youth to think about the assumptions we may hold consciously or subconsciously regarding our patients. And for that reason, I'd like to consider some of the theories that have been suggested regarding the over-occurrence of autism in gender diversity. Some have proposed that the common autistic thinking styles might drive the over-occurrence. For example, a few commentators have assumed that autistic youth may be mistaking inner cues and confused about their gender. However, from our clinical work, we do not have strong evidence to support this theory, at least for the majority of the young people that we've worked with. Other commentators have suggested that because autistic people may be less yoked to social expectations and conventions due to the social differences inherent in autism, that they might be more likely to express underlying gender diversity. And related to this theory, some have proposed that the more matter-of-fact and concrete thinking style common in autism may lead some autistic people to think in a matter-of-fact way about their gender. For example, I feel most comfortable as a girl, therefore I am a girl. Of course, there is always the possibility that both autism and gender diversity would overlap by chance, but this wouldn't explain the sizable over-occurrence. And some have wondered whether there might be a deeper biological link, perhaps driven by prenatal hormone levels, which have been shown to predict autism in longitudinal studies and could theoretically also impact gender identity development in the young brain. Finally, some have hypothesized that the experience of gender diversity itself could drive autism or autism-like presentations. Two commentators have suggested that gender minority stress might present as a kind of pseudo-autism. This theory has been considered autistic-phobic by some in the autistic community, and it is important to note that there is no evidence to support this theory. In fact, in our program, which uses gold-standard autism assessment approaches, it is quite rare to find trans youth who have been misdiagnosed autistic. We've begun to examine the pseudo-autism theory at the level of brain functional connectivity. This is recently analyzed and yet unpublished data from my case study of autistic transgender, almost autistic transgender, and non-autistic transgender adolescents. There's an existing literature highlighting that the default mode functional connectivity network is over-connected to visual, sensory motor, and executive control networks, and that this has been a marker of difference between autistic and non-autistic people in numerous studies. So in this study, we tried to repeat this paradigm, and we investigated whether the autism versus no-autism patterns found in cisgender autistic studies were observed in transgender autistic youth. Our findings strongly support functional connectivity differences in autistic trans people, similar to those reported in autistic cisgender people. Additionally, we established the first neural evidence for the common clinical phenotype of the slightly subclinical autistic trans youth. These are the trans young people who almost meet criteria. And clinicians have been describing this subset of trans youth clinically for years. You can see that in terms of functional connectivity, the middle group, the subclinical almost autistic group in the five bar charts, falls evenly between the non-autistic and full criteria autism spectrum groups in each of the five regions of functional connectivity differences. Bringing these ideas back to our gender clinics, we propose four subsets of trans youth. Clearly, the majority of trans youth are not autistic. They may or may not experience other mental health or developmental differences, but autism is not relevant for them. We also have evidence for and clinical description of a subset of trans youth who show elevated autistic traits sometimes described by clinicians as quirkiness, but without any clear clinical relevance. Then there is the third subset of youth that I've just described who are approaching the autism diagnosis. These are the trans kids where maybe one evaluator has said barely yes to autism and another has said not quite. Our research has reported that this subset of almost autistic trans youth have similar levels of clinical challenge to those in the fourth subset who meet full criteria for autism. I think the big message here is that it is not just a yes, no for someone who is trans, whether they're autistic, but instead how much is autism related neurodivergence impacting the clinical needs of the young person regardless of whether they've gone over that line to meet full criteria for autism. This is data from our Children's National General Autism Program collected since 2013 and this manuscript is in preparation. Here in 1,620 youth diagnosed autistic, we see that cisgender girls were diagnosed slightly later than cisgender boys, but the gender diverse autistic youth on the right side are diagnosed considerably later than the cisgender youth at about 12 and a half years of age. In order to understand this, consider how social reluctance and social idiosyncrasies in gender diverse children may be attributed to unmet gender related needs or gender minority stress during childhood. Yet after gender is managed well, these kids continue to show the social and broader behavioral differences. So their referrals for autism related evaluation may be significantly delayed. The take home here is that if you are seeing social idiosyncrasies in the gender diverse child, it may be appropriate to refer for neuropsychological assessment because late diagnosis of autism is associated with significantly poorer mental health outcomes including suicidality. Okay, so here is a moment of true neuropsychology nerdiness although I'm impressed that it's the second neuropsychology test that we've seen in this talk with the Tower of London. This is the Ray Osterreith Complex Figure Test, a classic neuropsychological test of executive functioning skills. Executive function is that set of higher order organization and planning skills required for setting goals, thinking into the future and getting stuff done in life. Executive function is very much impacted in autism. It's often one of the areas of greatest challenge for autistic individuals. This Ray Osterreith Executive Functioning Test gives us something of a window into common autistic thinking styles. And my goal in sharing this with you is to learn a bit about how your autistic transgender patients may be processing information such as during their medical visits with you. In this test, the young person is asked to copy the complex and abstract figure first with the image in front of them and then immediately after from memory. Every 30 seconds, the evaluator switches the color of their pen so that we can see the young person's thinking and organizational strategy to copying the figure. The young person has started with the green pen and then 30 seconds later switched to blue, black, red, and finally orange. We'll look at a few renderings of this test all completed by transgender youth. In this one, copied by a non-autistic trans young woman, we see a very efficient gestalt approach. This non-autistic young woman started with the green pen and drew the base rectangle, the horizontal and vertical lines in the rectangle, and then the diagonal lines. And then she moved when she was switched to the blue pen to the side box and the diagonals within that box. And finally, with the black pen, filled in the ancillary details. When asked to draw this figure from memory, she gave a very organized rendering with the gestalt rectangle, diagonal lines, and so forth because she had organized the big picture of the image initially, and that helped her to hold onto the image. Now let's look at a copy of the figure by an autistic transgender young woman. Here we can see a very different approach. Clearly the figure is drawn with accuracy, but the copy order is complex in its detail-oriented focus. She's drawn each of the quadrants within the rectangle separately, which is a lot of work. She's processing information in a piecemeal fashion and missing the gestalt, that is the underlying structure. When the image is removed and she has to draw it from memory, the piecemeal way in which she has taken in this information very much impacts what she remembers. What an incredible amount of work this young person is given to copying this and trying to reconstruct these ancillary details, but she has completely missed the underlying structure, essentially the main idea of the figure. This is a visual representation of how your autistic transgender patients may be processing the information you share with them. Autistic youth may have extremely advanced vocabularies and conceptual abilities, and may be able to cite all of the studies on gender-affirming care, but they may struggle to comprehend the big picture of what you are trying to communicate to them. I'm gonna just let you look at one more set of Ray Osterreith figures, these by an autistic trans young man. This is his copy, and most of it is in orange because he spent so much time pulling out little details from the figure and that was inefficient for him. And then let's see what he takes from the memory round. Thank you. The overall profile of neurodiversity in autism involves differences in social processing and social communication, the presence of restricted or repetitive behaviors or interests, as well as sensory challenges, and as we've just seen, executive function differences and maybe difficulties. This profile is important to keep in mind as it can affect gender care. In terms of social communication, autistic youth may struggle managing open-ended conversations. They may have more difficulty self-advocating, and this may be why so many autistic transgender youth come out late in the process, because they didn't have that social impulse to communicate and self-advocate around their gender when they were younger. The sensory differences in autism may impact the ability of autistic young people to tolerate gender-related treatments. For example, in our clinic, we've seen difficulty with the placement of GnRHA implants and tolerating needles. And finally, executive function challenges may impact the autistic trans person's ability to remember appointments with you, keep track of prescriptions, and navigate complex healthcare systems. One of the big questions in this field has been whether autistic transgender youth show similar patterns of medical gender-related need over time. Pictured here is a figure showing a range of gender developmental pathways identified among trans youth who have had shifts in their medical requests over time. In this study, currently under review, 68 trans youth were followed over a span of several years. Ultimately, 20 of the young people showed some level of shift in their gender-related medical requests over time. Importantly for today's talk, trans autistic youth were no more likely to experience shifts in their gender-related medical requests as compared to non-autistic trans youth. This is clearly a pilot study, a first look, because of the small sample size, but it does provide some early information for providers regarding the apparent similarity of medical gender profiles between autistic and non-autistic trans young people. We'll finish with four pointers for working with autistic and almost autistic trans youth. First, international consensus guidelines on the intersection of autism and gender diversity call for providers to establish interdisciplinary teams to support these young people. We found that these teams often need to include neuropsychology, mental health, school representatives, legal guidance, particularly for youth who require special academic placements, gender medical providers, and specialists in transition to adulthood. This is a different kind of transition to adulthood than you're thinking about for your patients when you're thinking of transitioning them just to adult medical care, because shockingly, only 9% of autistic adults with average or above IQ reach full functional independence in adulthood. So this is a major concern for providers. For youth yet to be diagnosed autistic, careful assessments are required to characterize autism and other neurodevelopmental differences. It is concerning that so many autistic trans youth obtain their autism diagnoses very late. Gender diverse and cisgender female autistic youth often present a different form of autism than cisgender boys. They tend to have relatively stronger social motivation and tend to look more neurotypical because they may develop skills for masking their social differences. But the social compensation or masking is taxing on the individual and may exacerbate mental health risks, including suicidality. So as you are making referrals for autism assessment from your gender clinics, it is critical that the autism specialists be experienced in making autism diagnoses across the gender spectrum. Otherwise, autism may be missed. Clearly, it is important to accommodate the communication differences of autistic transgender youth. Learn from the neuropsychological or speech language evals how best to communicate with your patient. There's usually a part in those reports that talks about how best to interact with the young person. You can provide simple visuals in your medical consults, such as visual checklists. And don't assume that the autistic patient's vocabulary or knowledge means that they will fully process your complex language. Keep in mind those images of the Ray Ostery test when you're communicating with your autistic patients. Use concrete language and avoid metaphors. And remember that future thinking is harder for autistic youth. And this is very much in demand when you're thinking about consents regarding gender-affirming treatment. It is critical to accommodate autistic transgender youth executive functioning. Here, you may provide reminders for appointments, help the young person manage prescriptions, think of memory aids for taking medications, such as programming reminders on the iPhone, and when surgery or other medical procedures are indicated, prepare and rehearse with the young person prior to the procedure. Here's my final point. This is one of the tables from our 2021 paper highlighting the importance of supporting executive function for transgender youth. In this regression analysis, we see a range of possible predictors of suicidality in trans youth. The three significant predictors of suicidality in this study were, first, perceived stigma, and there's no surprise there. There's a huge literature on stigma relating to mental health problems in LGBTQ plus populations. The second predictor was executive function problems. So, in this case, actually measured by that Ray Osterreith complex figure score. And the strongest predictor of suicidality in this trans youth study were executive function gender barriers. Executive function gender barriers are the young person's experience of challenges moving forward with their gender-related needs due to their problems with organization, planning, and broader executive function. And so, those small accommodations that you can provide as endocrinologists working with autistic trans youth may make significant impacts in their well-being and outcomes. And with that, I will end and we'll have questions at the end. Thank you. Thank you so much, Dr. Strang. We're going to wrap up with our final speaker, Dr. Sarah Duvall. Dr. Duvall is an associate professor of pediatrics and endocrinologist at Seattle Children's Hospital at the University of Washington. She provides care at the Seattle Children's Gender Clinic, a collaborative clinic of adolescent medicine, endocrinology, psychiatry, and the autism spectrum. Dr. Duvall is an associate professor of endocrinology, psychiatry, and the autism center. Her published works and scholarly interests encompass the basic and clinical sciences of puberty, hyperandrogenism, and gender care. We're excited to hear her speak today with her talk entitled, Beyond the Binary, Hormone Replacement in the Non-Binary Patient. Okay, thank you very much. I have no financial relationship due to close, and I will be discussing off-label use of medications and hormone replacement. This is the grid I was asked to present at the beginning. I will also present at the end for questions and comments. So the outline of this talk, I will first talk about who are in the prevalence of non-binary in different populations, and discuss their mental health, and how to think about embodiment goals in discussing their gender care. We'll next discuss the affirming treatment, whether hormonal or non-hormonal, future needs, and resources at the end. And my qualifications for the study is, it's a discussion on the population and general guidelines. In discussion on therapy for persons less than 18, I am not an expert. The assumption is that the gender dysphoria diagnosis has been made according to the Endocrine Society guidelines and the DSM-V5, and the person is eligible for medical therapy due to this diagnosis. And lastly, I am learning how to best address the needs of these patients, just like you all. So the gender unicorn is a tool used to teach the concepts of gender and identity and sexuality to school-aged children. So in this talk, I'm sticking with the first line there, the gender identity, and those whose gender identity is in the other category. Other people may encompass, in this other category includes people who oscillate in their identity between male and female and people who are on the spectrum between the male and female binary gender identity. So the terms you will find used in medical literature and how people describe their non-binary identity to others is in this word cloud, and which I picked up from this reference at the right, you see at the lower right-hand corner. Note that many terms used, such as bisou, faafane, mahu, hijra, and two-spirit are from non-Western societies and non-European societies that have often centuries-old practice of having these non-binary persons present in their societies. And the terms non-binary and genderqueer are the terms most often encountered in the medical world, so I will use the term non-binary for the rest of the talk. So how many non-binary youth are there out there? So, well, it depends on the base population that is studied. The first part of the table is where the base population is in all youth, and it also depends upon how people were asked about their gender, whether a non-binary option was given, and whether there's a space provided to give an answer other than trans or cis. And here, again, I used studies only that, I reported on studies only that specifically asked whether participants had an identity other than cis or trans. This first in this study is for, I have to use the pointer, and these first are general studies in youth school age between roughly 12 and 25. And you can see the prevalence of self-reported non-binary identities is less than 10% in some countries, maybe higher, although in the Spain study, the community probed in how they recruited people was from LGBTQ2 sites, so it may be a little bit altered. I guess there is an amber alert. And for those who are online. And the second population is what is the prevalence in trans and non-binary youth present in the community? And these two studies I have are from Canada and the UK, and these are national samples of LGBTQI identified people, and the prevalence is between 40 and about 55% of non-binary, excuse me, non-cis and non-trans youth. And the last is the base population of people receiving care in gender clinics. And so in youth receiving care in gender clinics, the proportion goes down to about 14, 15%. And these two studies from the USA and the UK. So what is the reasons between the differences between here and here? It could be due to barriers in accessing care, or it could be to the fact that people who identify as non-binary do not feel the need to access hormonal care or transgender care. When I did the same for adults, again, the first part of the table is base population, all persons, and again, only reported on studies that specifically asked people to, had an option for non-cis, non-trans identity to identify themselves. And again, the prevalence is variable across countries, but please note that there's also a variability in when these studies were done, and it varies anywhere from 4% to about less than 1%. And in national samples of trans and non-binary adults between around 10 and 35% of people in different population study identify as non-trans. And in the base population of persons receiving gender-related care, up to 30%. And again, this was people age 18 plus identified as non-trans, so therefore non-binary. So conclusion based on that, so prevalence stats vary widely, and it can be dependent on how gender was asked in the survey. Youth identified as non-binary include less than 10 percent, maybe even less than 5 percent of the population. Again, it depends on the study. Nationswide, non-binary youth include 40 to 50 percent of those who identify other than cisgender. And within youth served by gender clinics, less than 15 percent identify as non-binary. It's important to note that these studies are cross-sectional. Longitudinal identification of youth has not been identified yet, and we know that identity may change a little bit with time. And survey responses and identity presented to medical staff, of course, may be different. And I'll expand on that later. So what about mental health? So I look specifically for reports of mental health, comparing specifically trans-identified versus non-binary identified people, and not lumping them together. So the first study on the upper left is out of the UK, who received referrals from persons aged 18 to 25, referred to their national transgender health services. The participants completed the hospital anxiety and depression scale, a self-esteem scale, and a scale of perceived social support. So persons who self-identify as non-binary, as you can see, scored highers on these scales of anxiety and depression. And in this scale, scores of 8 to 10 is suggestive anxiety, and scores of 11 or higher is probable depression or anxiety disorder. And non-binary persons also score lower on a validated scale of self-esteem. Non-binary persons scored similar to binary persons, a scale of perceived social support, and of note, a cumulative score of 84 on this scale is the highest support in all facets. And the study below that is a study conducted in the U.S. of youth aged 12 to 24 who sought services from the Trevor Project, and the Trevor Project is a national gender and sexual minority crisis prevention service. Of the 589 youth recruited to complete the questionnaire, about 281 were gender minority with roughly half of the gender minority as transgender and half as non-binary. And again, the basis, these youth are high-risk youth, about 33% of all the 328 persons reported suicide attempts. When using cisgender as the reference population and calculating odds, the non-binary and binary transgender persons had double the odds of reporting a suicide attempt compared to cisgender sexual minority youth. And they also had a higher, and in linear regression, non-binary and transgender persons scored similarly to cisgender sexual minority persons on a depression scale. They used the Center for Epidemiological Studies depression scale, but they were more likely than cisgender persons to score higher on a PTSD civilian checklist, which is a validated checklist screening for PTSD in populations. So in this study, U.S. college students accessing counseling services were questioned, again a population higher risk for anxiety and depression. Of the 300,000 college students, the researchers identified 892 in each category of cisgender men, cisgender women, transgender persons, and self-identified people who self-identified their gender, so therefore probably non-binary or questioning. Using the Counseling Center assessment of psychological symptoms, the CCAFS 34, shows that in general, persons of transgender or in the self-identified categories had double the scores on the survey of assessments of generalized anxiety, social anxiety and depression, and disordered eating. And also, additionally, transgender and non-binary persons scored higher on measures of self-injury, suicidations, and attempts there on the right. So when non-binary persons access healthcare, what are their experiences? So this is a qualitative study of young adults in the San Francisco area accessing transgender targeted health services, and there's about four themes that came out from their experiences. One thing was the provider inability to see beyond the binary, and the quote was, the standard formula is you get on hormone replacement, then you get top surgery, then you get bottom surgery, and that's the standard idea in the medical field. A second theme was lack of competence in providing non-binary care. So one quote was, they're wasting their and my time because I'm not trans, I don't need trans health stuff, I need genderqueer health stuff, I need androgynous healthcare. Is there an androgynous clinic? No, but there's trans health, trans clinics, and the last is, well, I guess the biggest barrier is that people do not understand what two-spirit is, they don't know what genderqueer femme means. I have explained myself every time. I think that stops me from being able to access services because there's no service for me, I have to make the service myself. Another theme that came out was borrowing the trans label, but you know, you gotta lie when you go into a clinic, you gotta say you're trans, and you gotta say you want hormones and surgery. They're not gonna understand genderqueer, and they're not gonna understand, but they're gonna understand trans. And do you know how much easier it is to say trans than genderqueer? I don't get second glances if I say trans. The last theme was inadequacy of gender services, and you know, just recognizing, too, that the providers might have transgender competency training and all that jazz, but at the end of the day, I'm not the kind of trans person you probably got during these trainings. I'm not a man, neither am I a woman. So, to summarize that section, non-binary youth experience depression, anxiety, and suicidality at rates higher than or comparative to the transgender-identifying individuals, and both experience rates higher than cisgendered individuals. In accessing healthcare, non-binary persons may not feel comfortable or supported, even in spaces built to welcome transgender persons. And as you know, language is important, and language is extremely important, and using desired pronouns is also important. And Dr. Strang alluded to, but minority stress theory is a framework used to build and provide therapeutic support and intervention for sexually minority and gender minority youth. So, in providing care and respect for non-binary persons, we as providers must binary our language, in addition to using the chosen names and pronouns. For instance, phrases like masculinize or feminize, which we find very useful from an endocrine standpoint, are often binary, and they're often vague and non-specific as masculinize or feminize. What that means is very different from person to person, and even from culture to culture. So in my practice, I have, and still am trying, I have an everyday trying to use body part-specific language in discussion of the effects of estrogen or testosterone, or other hormonal interventions on their body. Those of us who are pediatricians probably already do that for a younger set, but I think we should do that for all persons as well. And I'm starting to use pictures and have people draw pictures of what the body looks, would agree with their identity or their idea of themselves. And I use that both when I talk about puberty blockers, and what the child and what the adolescent thinks that is going to happen to their body parts if they have, if they move forward, if they develop without blockers, what they can and what will happen if they have blockers. And lastly, what body and what their body looks like to affirm their sense of self. I often provide, this often is helpful as I manage and manage their expectations about what puberty blockers can and cannot do, and also about what hormones can and cannot do for them. And this is, I also do that in discussion about surgery, is surgery in your future? And this is, I do this for trans persons as well, trans identified persons as well. I'm also getting very specific about function and body part functions down to conversations about not only menses, but conversations about fertility, of course, and also conversations about erections and libido. So what are the affirming therapy options? Of course, there's non-hormonal options, which people use all the time to express themselves and express their gender to the rest of the world, including the hair, makeup, and shaving. And of course, people can use chest binders and tuck or pack their genitalia to present to the outside world a certain gender self that they would like to present. And again, there is voice training. Surgical options are also non-hormonal options that some non-binary persons may seek and may feel that best affirms their identity and sense of self. And they may pursue these with or without hormonal therapies. And again, assuming the age of majority in pursuit of these interventions. So lastly, what are the affirming therapy options? Of course, there's estradiol and testosterone. The Endocrine Society guidelines, I'm not going to rehash them about how to provide and how to replace hormones in persons who are trans. In persons who are non-binary, there is forums on genderqueer websites and forums about using micro-dosing specifically of, for instance, 20 milligrams of testosterone sub-Q weekly or half a patch or less of estradiol weekly or intermittent dosing. Obviously, I do not have proven effects and proven studies to tell patients that you're going to have this effect if you're going to have this dose because we all know that there is highly individual variability and even within individual person tissue variability of how they'll respond to certain hormone levels and even at a proven serum hormone serum level, you know, what their tissue response is going to be. Okay, thank you. So oftentimes I do frequent check-ins about body changes and gender dysphoria as we proceed through therapy and check in about, we've started this therapy, what is your, how are you feeling? So I'm going to go through. And this leads us to, you know, what about the situation in which Jean or Agnes were started in early puberty to treat the gender dysphoria and now an older adolescent does not want, doesn't feel that estradiol or testosterone would affirm their gender. We all know the long risks of estrogen deficiency on bone health. So Ken Pang et al. explored the ethics and the unknowns of the situation in two thoughtful articles. The first article explored the issue of a person over 18, the age of majority in most countries and the second article explored and asked co-authors to provide opinion on what they would do in this situation on a person less than 18 or less than the age of majority. The thoughts varied from recommending selective estrogen receptor modulars, CIRMs, to promote health with lesser chance of breast development or possibly only provide care in the context of a research program and a prospective research. And last, state that with the information we have right now, avoiding or not having sex hormone replacement in some form is not an option and just work with the patient to provide an acceptable therapeutic plan that lowers bone health risk and minimizes body changes. So Dr. Lantos in conclusion stated that these comments illustrate the complexity of providing medical care in absence of strong scientific evidence base for making choices. Experts must make recommendations on the basis of speculation and extrapolation. Furthermore, the nature of treatment options in cases like this are such that randomized trials are likely infeasible. We can hope for cautious clinical judgments, shared decision making, and careful evaluation reporting of outcomes after different choices are made. What about CIRMs? What are they? CIRMs are the Selective Endocrine Receptor Modulators. They bind the estrogen receptor alpha and beta with different affinities and do have anti-estrogen effect in certain tissues, notably the breast. The three available CIRMs are tamoxifen, raloxifen, and lasofoxifen. Lasofoxifen is not available in the U.S. The relative effects on breast tissue, bone health, and fat distribution and DVT risk are in this table, again, thanks to Ken Pang and colleagues. As you can see, there's negative effects on breast tissue, but there is positive effects on bone, with raloxifen and lasofoxifen having greater positive effects on bone than tamoxifen. However, there is some DVT risk you see on the right. Note that all this data is gathered from persons treated for breast cancer or postmenopausal osteoporosis. And so, the higher DVT risk may be reflective of that base population, and there is no known trial of using CIRMs in the gender minority population. Okay. You're good. I'm on my future needs, which will be obvious, and I will skip. And here's a list of resources, and thanks to all patients and families. Thank you, Dr. Duval. We only have, like, two minutes for questions, but if the speakers can come up, and if there's anybody from the audience that wants to come up and ask any questions, please do, and introduce yourselves. Go ahead. Diaz from Miami. Dr. Strang, our fear as clinicians is the transition, patients, the transitioning. And the question is, are they more likely, is higher the possibility of someone who has autism to transition males or trans females or trans males than the general population? We don't have that published evidence yet, but I will say that there are two clinics that have been following autistic transgender youth now for, in one case, 15 years, and then in our clinic for, in some cases, seven to eight years. And we've only looked at the data in a qualitative way because we don't have enough of it to really do statistical tests. These are small populations. And what I will say is that the profiles seem to be complex, that there is not apparent evidence that the autistic youth are de-transitioning more. But what is interesting is that some of those early gender signals in the autistic youth might seem very mild, and for some of those kids by adulthood, they become very intense. And the reverse pattern is also seen where some of the autistic youth who are so focused on gender affirmation and transition in adolescence, later that seems to fade a bit. So I'm sorry that we don't have data yet, but those are just some clinical observations based on what we've looked at in our data. Thank you. Sorry, this is Rich Hawkins from the University of Michigan. Last speaker, I'm sorry I've forgotten your name already, but the original two-spirited, that came from the indigenous Americans, right? They had people that, and of course they didn't receive any hormone therapy. Correct. But they were accepted by their community for what they were and the role that they provided. And so many times, I mean, these people might just be seeking validation of their feelings. How often do you find that that's the case, that once they have the validation of their gender identity with a professional, that a lot of these problems then don't require any intervention? Well, I think that from the tables, it showed that the prevalence of non-binary in the gender and sexual minority population in the, was 30 to 40%, but yet in seen in the transgender clinics was, went down to 10 to 15%. So I think that these persons are self-selecting themselves out. And in our clinic, since we work so closely with our mental health providers, we work really hard to provide the support and the need to suss that out. Just looking at some of the online questions, one of them I think Dr. Strang did already address. Does hormone therapy affect autistic features? I think you answered that question some, but if you had anything else to add, we can answer that. And then the other question we had is for Dr. Duvall. In affirming therapies for non-binary, the number of non-binary people in the clinic The non-binary slide, it was mentioned combo testosterone and estrogen. Can you please elaborate? Yes. So in, this would be the situation in, for instance, would be possible in somebody who an adolescent, whom early in puberty had started on agonist to pause puberty and in thinking about how to complete their puberty and being a, give them affirming therapy to affirm their sense of self and who they are. A combination may be possible. Okay. Yeah. We would like to thank all of our speakers and all of you all for participating and asking great questions. And that concludes our session.

endocrine medical care

adolescents

gender spectrum

hormone therapy

cardiometabolic growth

bone health

cancer risk

brain structure

sports performance

autism

gender diversity

transgender youth

non-binary youth