Are puberty blockers and cross-sex hormones for gender dysphoric minors supported by strong scientific evidence? Manhattan Institute Senior Fellow Leor Sapir and Zhenya Abbruzzese, Co-Founder of the Society for Evidence-Based Gender Medicine, examine the findings of the Utah review on hormonal treatments for minors experiencing gender dysphoria and discuss what the evidence says about pediatric gender care.

Audio Transcript

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Zhenya Abbruzzese (00:00:00): A systematic review requires a formal appraisal of what the totality of the evidence, looking all of the studies together across each outcome.

Leor Sapir (00:00:08): And they didn’t do that here.

Zhenya Abbruzzese (00:00:09): Not only did they not do that, they never even set out to do it. From the very beginning it was not proposed as a systematic review. And yet despite that consistently it was represented by the research team as a systematic review and by all those who have since referenced it, it’s been misrepresented as a systematic review.

Leor Sapir (00:00:36): Hello and welcome to a special episode of City Journal Podcast. I’m Leor Sapir, a senior fellow here at the Manhattan Institute, and I’m joined today by Zhenya Abbruzzese of the Society for Evidence-Based Gender Medicine. Zhenya, thank you for joining us here.

Zhenya Abbruzzese (00:00:49): Thanks for the invitation.

Leor Sapir (00:00:51): So we’re here today to discuss one specific report that came out of Utah recently and that claims to find that interventions for minors with gender dysphoria, specifically hormones, hormonal interventions are safe and effective and this finding runs contrary to every existing systematic review that has been published. But I also want us to talk a little bit more broadly about gender medicine, pediatric gender medicine specifically, where the field is, what are some of the main problems when it comes to understanding and accepting the state of the evidence. But I wanted maybe to start, if you could tell us a little bit about SEGM, the Society for Evidence-Based Gender Medicine, what it is and why it was established.

Zhenya Abbruzzese (00:01:34): Yes. And I think the Utah Review serves as a really good frame for this discussion because in a way everything that’s wrong with the field as it operates now is really evident in the review. So I think that’ll be an interesting conversation. But SEGM, Society for Evidence-Based Gender Medicine, was established in 2019 after operating more informally for about a year prior. And we formed with one specific purpose and that was to help the field of pediatric gender medicine operate according to the same principles that every other area of medicine operates on. And that is evidence-based medicine and part and parcel of that is medicine that adheres to standard principles of medical ethics.

Leor Sapir (00:02:28): So can you just explain to us in your understanding what is evidence-based medicine and why does it matter?

Zhenya Abbruzzese (00:02:36): Evidence-based medicine is a term that was coined relatively recently and it is an approach to medicine where treatments have to be informed by the best available evidence, but also they have to factor in other considerations, for example, patients’ values and preferences and societal values and preferences. So it’s a complex framework for making decisions, but the first and most fundamental principle of evidence-based medicine is that decisions have to be based on the awareness of the best available evidence and that is where we focus. So SEGM focuses on evidence appraisal. We do not so much tell physicians how to practice medicine and how to factor in patients’ values or societal values or laws. We are really focusing on the first and most fundamental aspect is that all decision makers in medicine, that includes doctors, that includes patients and their families, very importantly, and to some extent policymakers as well, people who regulate medicine, that everybody should be aware of what the best available evidence says about the benefits and harms in this case of pediatric gender transitions. That’s really our focus.

Leor Sapir (00:03:57): So I take SEGM to be a kind of a scientific watchdog where if exaggerated claims are made about a particular study, claims that are not supported by the study’s data, if in general claims are made about medical interventions that are not in sync with what the evidence actually shows, then it’s your job to say, “No, no, that’s not what this study shows. That’s not what this systematic review has found.” Sometimes, by the way, to the annoyance of people on the critical side of this debate, when you push back against exaggerated claims about what we know, for example, about detransition rates being very high, I’ve seen you guys be at the forefront of that saying, no, we actually don’t know, and let’s be modest about what we know and what we don’t know.

Zhenya Abbruzzese (00:04:39): Yeah, I would say SEGM actually does at least three different things. One is what you’ve described and that is being a watchdog over this area of medicine because the entities that should have been self-regulating and self-policing stop doing so for a multitude of reasons in the area of gender. Now, I know there are other areas of medicine that are also troubled, but this is so new and the changes were so dramatic and so quick to emerge that we began to analyze the research on which this area rested. And to our dismay, we discovered that the very foundational studies, just a pair of studies from the Netherlands were entirely misinterpreted, misunderstood, and misrepresented. And when just a couple of studies of a single group of patients, 70 patients, 55 patients by the end of it, launched an entire area of medicine that involved such irreversible, invasive interventions based on such poor quality research we became alarmed and we began to look at what followed, since we realized there was nothing that followed since that’s any better. In fact, studies progressively got worse since the Dutch research. And so that’s when SEGM formed. So it’s certainly a key lane for us is to evaluate existing evidence, but we also then commissioned independent systematic reviews because at the time of our formation, there were no systematic reviews of evidence, which is remarkable that an entire branch of medicine was launched without a single systematic review.

Leor Sapir (00:06:20): And we’ll talk about what systematic reviews are because it is really the foundational concept in evidence-based medicine.

Zhenya Abbruzzese (00:06:25): So that’s the second part we do is we do commission original research. We put it in the hands of experts. So our role is to conceptualize what’s needed, understand what is needed to help doctors and patients make the best decisions and then find the best experts in the field and have them do that and we step away and completely allow them to do their research independently. And the third function that we serve is we actually connect clinicians and researchers around the world who are concerned about the way medicine developed in this area and we hold annual conferences in the United States, internationally, and we facilitate exchanges between researchers, a lot of ideas about what researchers needed emerges from such collaboration. So these are loosely the three areas where SEGM operates.

Leor Sapir (00:07:16): You are a co-author along with me of the U.S. Department of Health and Human Services Review of Pediatric Gender Medicine. It was published in its peer-reviewed final version November of last year. The central thing that we do in that review is what’s known as an umbrella review, which is a systematic review of systematic reviews. And we identified 17 systematic reviews that dealt with various aspects of gender transition in kids, so hormones and surgeries and so forth. And the consistent findings from these systematic reviews has been that the quality of evidence is very low due to significant problems, methodological problems in the research and publication bias and so forth. But I think it’s important just to put that on the table because as we now turn to the Utah Review, the Utah Review is, I believe, the first in the field to be a review that calls itself a systematic review that looks specifically at pediatric gender medicine outcomes and that claims that the evidence is actually good. So on April 2nd, SEGM released a report titled “The Utah Review of Hormonal Treatments for Gender Dysphoric Minors: A Methodological Appraisal.” The subtitle of your report is “Assessing the Trustworthiness of the Analysis, Conclusions and Recommendations.” So could you tell me a little bit more about the Utah review, how it came about and why you decided to focus on it?

Zhenya Abbruzzese (00:08:37): It is a very lengthy document.

Leor Sapir (00:08:43): Over a thousand pages.

Zhenya Abbruzzese (00:08:44): 1,051 pages to be precise. It was immediately elevated to a position of prominence as the review of all reviews, the unsinkable proof that pediatric gender medicine is highly beneficial, comes with no risks and that any attempts to regulate it or restrict it is akin to telling pediatricians to stop prescribing antibiotics for infections. And it was such a remarkable claim because it contradicted by now over two dozen of systematic reviews in this area of medicine that of course we were very curious to dive in depth and see, so how did the researchers come up with their conclusions?

Leor Sapir (00:09:33): So talk about the sequence of events that led to the production of the report.

Zhenya Abbruzzese (00:09:36): The very beginning is actually already very, very telling. So in 2023, the lawmakers in Utah passed a moratorium on new pediatric gender transitions. So the existing transition, ongoing hormonal transitions could continue, but new ones couldn’t continue.

Leor Sapir (00:09:56): So this is SB16, Senate Bill 16.

Zhenya Abbruzzese (00:10:00): And in that same bill, a provision was introduced to say that a systematic review will be funded in order to evaluate the risks and benefits of these interventions. And if in fact the review shows that the benefits outweigh the risks, then that moratorium could be lifted. It was later it became very clear that that was a very strategic move by the side of this debate who really does not want to restrict pediatric gender transitions. A few advocacy groups, transgender advocacy groups in Utah started thinking, well, how do we navigate out of this situation with minimal conflict and maximum impact? And it appears that that is when the idea was hatched that if we just convinced the Republican lawmakers to introduce a condition for a systematic review, that is how we’re going to lift the moratorium eventually.

Leor Sapir (00:11:03): So just to be more concrete here, we know this because there’s one particular individual, his name is Brooks Keeshin,

Zhenya Abbruzzese (00:11:12): Yes, Dr. Keeshen, yeah.

Leor Sapir (00:11:13): Right. Who said in a 2024 talk at the American Academy of Child and Adolescent Psychiatry, he was talking to an audience we can only assume that was very friendly to his cause. And what exactly did he tell them?

Zhenya Abbruzzese (00:11:27): Yes. So there was both a lecture and a publication that accompanied that lecture and in it, Dr. Keeshin, who was by the way, an independent advisor to the Utah review process, but in his lecture it was clear that independence was lacking in that role. He was a very strong proponent of the gender clinic at Utah and of continuing of pediatric gender transitions in Utah. And so he described to his colleagues the plan and the plan was to, first of all, to work with the legislators to make sure that the bill is not called a ban, but instead a moratorium because a moratorium implies it could be lifted, whereas a ban sounds more permanent. And then secondly, to commission a systematic review that would demonstrate benefits and then bring that back to the Utah legislators and once faced with a report that shows benefits that the legislators would have no choice but to have to lift the moratorium. There was an expectation, a priori that the review would in fact provide the results that would support lifting of the ban. And as the rest of our analysis showed, every step of the methodology, whether consciously or unconsciously was designed to demonstrate benefits, to overlook arms and to conclude that the treatments are beneficial and risk-free. So the bill was fast in January of 2023. The project was put in the hands of the Utah Department of Health and Human Services.

Leor Sapir (00:13:05): So we’ll refer to this as DHHS just to-

Zhenya Abbruzzese (00:13:07): DHH, yes. DHHS then handed the actual assignment for the systematic review of evidence to the University of Utah and that happened about three months later. And so then the University of Utah research team took approximately four months, just under four months to produce the report. So by July 23, the evidence review is effectively ready, is a very rapid production. And then something really puzzling happens for several months at that point, nothing happens. So this report is produced and it sits and noth happens. And then in February ‘24, so if you do the math from July ‘23 to February ‘24, several months past before the review is presented to a group of advisors, once it’s seen in February 2024, it appears that a major part of the assessment is missing and that is long-term outcomes. It’s not evident how to analyze long-term outcomes because as we know, the first patient ever treated with this protocol is only 51 years old at the moment. We don’t even know how that individual’s health will unfold in the long term. And most of the people who underwent this treatment, the biggest cohort is only right now

Leor Sapir (): 20s and 30s maybe?

Zhenya Abbruzzese (00:14:56): Just starting, right? They’re in the early 20s. So it is unclear how to analyze long-term health costs.

Leor Sapir (00:14:48): Because some of the cardiovascular impacts and cancer, heightened cancer risks and so forth. They can appear in their 40s, 50s, or even 60s.

Zhenya Abbruzzese (00:14:56): Yeah. So it’s not trivial how to do long-term research. I think I understand why they didn’t attempt that. Nonetheless, that was a clear requirement and they completely just decided not to deal with it.

Leor Sapir (00:15:08): Yeah, they just ignored it.

Zhenya Abbruzzese (00:15:09): And they were called out by somebody. We don’t know by whom. But during an interim presentation, we now know that that was spotted and the research team was asked to go back to the drawing board and specifically address the long-term outcomes.

Leor Sapir (00:15:25): And we’ll talk about exactly how they did that.

Zhenya Abbruzzese (00:15:27): And so then there was a second bot of work and then at that point the Utah review as we know it today was completed. So it was completed in August 2024. Why it took another nine months to release it to the public is a very interesting question and one I do not have an answer to. After it was released to the public, that is when we as SEGM began to look at it. And I have to say it took us nearly a year to analyze. Of course, we were also working on other analyses, but easily the analysis of the UTAR review took our team, I would estimate at least 2000 hours to-

Leor Sapir (00:16:12): I mean, this just gives you this sense of the scale of the challenge here. Researchers, and we’ve seen this time and again over the recent decade really, researchers publish a study that claims to find good evidence of benefit. And if you have a carefully trained methodological eye, you can usually pick up on the problems very quickly, but to do an actual comprehensive analysis that adheres to the standards of, for example, using the ROBINS-I tool for assessing risk of bias and observational studies, that takes a long time and it’s a lot of manpower and it’s very expensive to do that kind of work too. And that’s your bread and butter as SEGM. So your work is usually bulletproof, but it just takes a long time.

Zhenya Abbruzzese (00:16:54): It does take a long time, but I think this was a unique, an exceptional case. In the case of the Utah review, the presentation of the material was so exceptionally obscured. They were significant parts of the report, completely redacted.

Leor Sapir (00:17:14): Yeah, it’s really remarkable. You look at the report, it looks like an FBI report. There’s all these redactions on studies and data that’s publicly available and medical publications. It’s very bizarre.

Zhenya Abbruzzese (00:17:26): Yes. It’s presented in such an unusual way that just understanding what is on those 1,051 pages is nearly impossible. It took a team of expert researchers to untangle and then it turned out that we needed a lot of additional materials to understand it. For example, we had to obtain the contracts that led to the production of this review because there was no research protocol ever shared by the end of the review when we were nearly done and there were so many baffling parts of the review that we just could not understand why certain decisions were made. And then when we began to analyze what we considered initially a supplementary part to the review, which is the recommendation report, that’s important to say that the review is the 1051 pages, but then there was a much shorter, much more succinct recommendation report that came from Utah’s DHHS. And then it really became clear that individuals charged with overseeing the integrity of this report, both in the DHS side and the advisors that they recruited had very serious conflicts of interest. And once we began to look into these undisclosed conflicts, the rest of the review really made sense.

Leor Sapir (00:18:49): Let’s actually dive in to the main problems in the report. So I want to start, maybe this may not be the most significant problem, but it certainly is a significant problem. We know that in a lot of the literature on pediatric gender medicine, it usually starts with a discussion of epidemiological trends in recent years. Across the West, we’ve seen a very sharp and sudden spike in referrals to gender clinics. Not coincidentally, we’ve also seen, especially in the United States, kind of a ballooning of gender clinics from the first was opened in Boston in 2007, then by 2022, there were over a hundred of them. Referrals in the UK, for example, their JIDS clinics saw a rise of, what was it, 35- to 50-fold within the span of a few years. And of course, the patient presentation was no longer pre-pubertal boys who almost certainly would grow up to be gay. Now it was mostly adolescent girls with no history of gender distress or gender confusion before puberty. Many of them are addicted to social media and most of them, as research has shown quite consistently, have coexisting and usually preexisting mental health and neurocognitive challenges.

Zhenya Abbruzzese (00:20:01): So the changes you described, the epidemiological changes in the population of people presenting with gender dysphoria are the primary reason why so many countries around 2020, 2022 began to look very closely at what is going in this area of medicine. That is one of the main reasons why public health authorities in England, Finland, Sweden all began to look at it. Now the Utah Review took up 1,051 pages. There is no section on epidemiology. What the Utah Review did instead is kind of immediately leaned into this narrative that we’ve seen primarily right from activist circles as opposed to evidence-based circles, which is this timeless nature of trans identities. And even that would be an interesting section if they went through the history of people who identify as transgender and talked about Magnus Hirschfeld and…

Leor Sapir (00:21:05): And the changing conceptions of what we mean by that term. I mean, the term itself really entered mainstream parlance in the 1990s. It used to be transsexual and it had a different connotation, had a different meaning then. And yet here they are, the authors of the Utah review saying, importantly, it’s always existed in the meaning that we use today, which strikes me as just because that’s clearly wrong.

Zhenya Abbruzzese (00:21:31): Right. So there is a very quick kind of attempt to just foreclose thinking to say always existed. What we’re seeing today is absolutely normal. There’s absolutely nothing changed and how do they justify it? Well, they justify it by referencing a Greek myth about a mythological figure.

Leor Sapir (00:21:55): Tyresius.

Zhenya Abbruzzese (00:21:57): Teresius struck snakes and was punished for that by being turned from a man to a woman and went on to live as a woman for seven years, even birth children and then finally was turned back into a man. So if anything, this individual, this mythical figure should be an example of a modern day detransitioner more than a timeless nature of transgender identities. Now that is not to say that people who are very, very uncomfortable with their sex and want and wish to live as much…

Leor Sapir (00:22:33): Or for whatever reason, wanted to be recognized by their societies as members of the opposite sex. I mean, those people have existed.

Zhenya Abbruzzese (00:22:41): It is absolutely the case that some people do not fit sex stereotypes and live socially somewhere in the border between male or female or even much more aligned with the opposite sex. That is not in dispute, but to describe the curren ... Let’s not forget the focus of the Utah Review was not adults. It was children, which is a entirely novel phenomenon starting from about early 2000s and really rapidly around 2015 to have this explosion of adolescence previously gender normative, having no concerns with being the sex that they are throughout their childhood and then around adolescence as their bodies begin developing, declaring a transgender identity, that is entirely novel.

Leor Sapir (00:23:35): Well, but just to be clear, I mean, the reason I say it’s anachronistic is because the contemporary understanding of transgender that surely the authors of the Utah Review intend is somebody who has a gender identity. Now that is a concept that comes out of 1960s psychology. We talk about this in the HHS report, right? Initially, it just meant having an awareness that you are in fact male or female. And if that’s the meaning, then yeah, we all have a gender identity because we become aware from a very early age. I became aware that I’m a boy, you became aware that you’re a girl, but now gender identity has taken on a different meaning. Now it means something like a gendered essence or a gendered soul that is completely distinguished or independent of your actual sex. So we have gender identity, which is a very new term. And then we have sex assigned at birth, right? Somebody who’s transgender is somebody whose gender identity is different from their sex assigned at birth. The whole idea that sex is assigned at birth, meaning a social construct that doctors impose on a baby on the basis of that baby’s anatomy, that idea comes from academic scholarship, mostly inspired by queer theory in the 1980s and 90s. So you could find parts of it in Michel Foucault, but it’s mostly Judith Butler and they kind of latched onto these very extreme and rare cases of disorders of sexual development, or as they call it, intersex cases, which have nothing to do necessarily with people who identify as transgender, but that’s kind of where the idea of sex being assigned at birth comes from. So to say that there have always been transgender people where what you mean by trans is that kind of the confluence of these two ideas and to project that backwards all the way back to Greek mythology, it just shows how unserious this is as an attempt to set the stage for why we’re assessing these treatments.

Zhenya Abbruzzese (00:25:25): I would say that there is room for mythology in our understanding of humanity and those allegories often invoke something real and it could very well be that that myth in some way touched on people who actually even in ancient times defied gender norms or sex stereotypes. What is entirely unserious is that a report commissioned in order to evaluate the safety and efficacy of extremely powerful drugs, puberty blockers and cross-sex hormones, chose to not engage at all with the underlying enormous ethical and medical dilemma that the world is looking at right now is what to do with this explosion of teenagers who for the first time in adolescence begin to declare that they’re transgender and desperately wishing to undergo gender transitions, scientific reports specifically targeted at a rigorous evaluation of these treatments chose to sweep under the rug this novel presentation and sort of whitewash it with a Greek myth that this has always existed and there’s nothing to see.

Leor Sapir (00:26:45): Okay. So let’s turn then to what I think, and you probably agree, is by far the most significant problem with the Utah review. And that is that despite calling itself a systematic review, it is not a systematic review. So before you present the evidence for that, can you just tell us what is a systematic review and why do they occupy a central place within the field of evidence-based medicine?

Zhenya Abbruzzese (00:27:07): So a systematic review is an approach to evaluating the totality of the evidence in order to determine what is the best available knowledge as of today about interventions and their effects. So if you want to know whether treatment A is better than treatment or what is the effect of one treatment on the condition in question is you want to do a systematic review of evidence, not just look up individual studies. The reason for that is that individual studies are notoriously inconsistent. Study designs could be weak, two different studies could go into different directions, just enough if you ever follow the chocolate debate about 10 years ago. I did not. Well- I just eat chocolate. One day you’re supposed to chocolate because it’s extremely good for you and then a next study comes out that it’s bad for you. So there’s almost for every question, there will be studies that will have different conclusions and study designs and methodological rigor, length of follow-up…

Leor Sapir (00:28:25): So for example, if there’s no comparison group, if patients are not randomized into the control arm versus treatment arm…

Zhenya Abbruzzese (00:28:33): Right. Or if the patients were only followed for a short period of time. So any given study could be unreliable, but when you look at the totality of the evidence and really factor in both how good each study is in its rigor, but also do studies agree or disagree with one another? What effects are they reporting? Are there tiny effects or are there big effects? Statistically speaking, what are the confidence intervals? If they’re really, really tight, we’re really certain that the estimate is quite precise or they’re so wide that we really don’t know. So systematic reviews are able to factor in all of that and issue an overarching statement about what do we actually know about the effect of a treatment on each specific outcome, outcome by outcome. Does anxiety improve? Does depression lift? Does quality of life improve? They’re very, very specific.

Leor Sapir (00:29:36): So in other words, quality of life being, if these are kids, can they get up in the morning, go to school, function well?

Zhenya Abbruzzese (00:29:43): It’s mostly around functioning. We also want to know, do the bones get impacted in a positive or negative way? What about the brain development?

Leor Sapir (00:29:52): Because bone development during puberty is driven by hormones.

Zhenya Abbruzzese (00:29:55): Sex hormones. And then very important Certainly, what are the impacts on fertility?

(00:30:02): And so systematic reviews are the primary mechanism to factor in all of the studies that ever looked at this treatment, this treatment being puberty blockers by themselves, cross-sex hormones by themselves or their combination, which actually is very three different treatments in a way. And for each type of treatment, the questions are what are the range of benefits and what are the potential physical effects which are often in the area of harms? Because we know the very premise for these treatments is psychological benefits that likely come at the risk of physical harms. That’s the premise. And now the question is, what is that risk benefit ratio?

Leor Sapir (00:30:44): Right. I’m just reminded when I testified and actually testified in the hearing for SB-16 and in the state of Texas for SB-14. And I just remember that when the topic of systematic reviews came up, the medical professionals who were there testifying against these laws, meaning in favor of pediatric gender interventions, they would say some version of, “Yeah, you have these systematic reviews, but they don’t matter because look at this study and look at this study and look at it. “ It says, “These studies have found that the hormones are beneficial.” Nevermind that the systematic reviews evaluated those studies, looked at their underlying methodological quality. And so when doctors said those types of things in those hearings, they inverted the pyramid of evidence in evidence-based medicine and they put individual studies, in this case, deeply flawed studies above, meaning having more credibility than the actual systematic reviews that looked at their underlying methodological quality.

(00:31:38): I found that to be very bizarre and actually quite depressing if you think about it, because here you have medical professionals who don’t understand the basic principles of how evidence-based medicine works, or maybe they do understand and they’re just being dishonest about it. I don’t know. But this is maybe the challenge that we have faced, you and I over the last five, six years, is how to get medical bodies like American Academy of Pediatrics or state health authorities to not just to understand the area of research here, but more importantly and more fundamentally, first to just understand how evidence-based medicine works. What is a systematic review and why does it occupy such a central role in evidence-based medicine? And maybe one last thing to say about systematic reviews is that what makes them trustworthy is that they’re transparent and they’re reproducible. So in theory, you can have a very biased researcher doing a systematic review, but if they follow the protocol in a way that’s transparent and reproducible, somebody with different biases should be able to arrive at the exact same results because they apply the same methodology to the same body of evidence. But okay, so what exactly did the Utah Review authors do that makes it not a systematic reviews contrary to what they represent?

Zhenya Abbruzzese (00:32:53): So first I think it’s really important to acknowledge that the Utah lawmakers absolutely requested a systematic review.

Leor Sapir (00:33:01): Yes, in the law.

Zhenya Abbruzzese (00:33:03): There’s no question about it. And then when we evaluated the proposal that the research team put together to conduct it, the word systematic review were also present. But when they described how they plan to go about it, even at the proposal stage it was clear that the most important element of the systematic review, which is assessing the body of evidence for certainty was absent.

Leor Sapir (00:33:30): Certainty meaning quality. Certainty and quality are interchangeable terms and EV.

Zhenya Abbruzzese (00:33:34): A systematic review requires a formal appraisal of what the totality of the evidence, looking all of the studies together across each outcome.

Leor Sapir (00:33:43): And they didn’t do that here.

Zhenya Abbruzzese (00:33:44): Not only did they not do that, they never even set out to do it in their proposal. And that was already very, very clear that at the proposal stage, the hallmark of the systematic review, which is assessing that final step after you identify the studies, after you analyze each study for study quality, the final step where you look at the totality of the evidence and there is missing already at the proposal stage. So to us as researchers, the question was how did the Utah DHS department, which was responsible for overseeing the scientific process except such a proposal that was already clearly missing a key step of a systematic review, the step that makes a systematic review a systematic review.

Leor Sapir (00:34:31): Yeah. And in this particular field of research, it’s that step, the formal synthesis, the evaluation of the evidence quality is what allows you to be able to look at all these individual studies that each claim to find that hormones and surgeries and so forth are good and beneficial. I’m speculating here, but you can only assume that the authors of the Utah Review knew what they were doing when they skipped over the one stage that could show you that the studies that they’re citing are actually not trustworthy. I mean, that’s speculation.

Zhenya Abbruzzese (00:34:58): It is speculation. And the DHS department, Utah DHHS described the team or University of Utah team as experts in evidence synthesis.

Leor Sapir (00:35:10): So they knew. Yeah.

Zhenya Abbruzzese (00:35:13): It’s unclear, but I will say that the proposal for this particular research project was just extension of a longstanding contract between that research team and DHHS and the overarching contract is just kind of a routine ongoing review of drugs and whether certain drugs should be covered by Medicaid or not. And it appears that these sort of systematic assessment methods weren’t part of that overarching contract either. So did they explicitly choose not to conduct that final step or is it just not part of how that team approaches evidence evaluation?

Leor Sapir (00:36:25): Yeah. I’m not sure which of those options is worse.

Zhenya Abbruzzese (00:35:13): I’m not sure either. And so we could speculate of course, but I think it’s more important to acknowledge that it’s simply from the very beginning it was not proposed as a systematic review. And yet despite that consistently it was represented by the research team as a systematic review and by all those who have since referenced it, it’s been misrepresented as a systematic review.

Leor Sapir (00:36:25): Okay. So I do want to pivot in just a second to the second and related issue of how they treated the clinical studies, the exclusion of studies and of course how they treated the question of harm. But could you just tell us what approach did SEGM or the researchers who did this on behalf of SEGM, what approach did they take? What tools did they use? And for listeners or viewers who are not into the weeds on this issue, feel free to skip forward here. It might get a little bit wonky, but this is actually very important because again, because what we have been trying to do for the last few years is say there are all these very strong claims being made about evidence and research. We have structured tools in the field called evidence-based medicine to evaluate whether these claims are true and trustworthy, let’s apply them, let’s use them. So what tools did you use to evaluate the Utah report?

Zhenya Abbruzzese (00:37:14): So we use standard approaches that are used in evidence-based medicine and we also recruited two expert methodologists to apply those tools and you don’t need all of them, but we actually applied both. One is called AMSTAR-2 and the other one is called ROBIS, and obviously it’s in the methodological weeds, but both of those tools effectively in slightly different ways, attempt to answer very common-sense questions. Did they search all of the available evidence or was the search too narrow and omitted important studies? Then once the search was conducted and the relevant studies were identified, to what extent did the researchers analyze study quality rigorously? Did they properly find mistakes in weak studies or was that analysis not conducted when the studies were just accepted at face value, which often happens. And once you assess whether they appropriately dealt with each individual study, then you get to that final question of did the researchers factor in the problems that they found in the studies and also did they look across all studies and did they observe all the studies pointing in the same direction or are they going in different directions? Once they’re reporting on specific effect sizes, for example, depression, some studies showing improved depression, some worsened depression and some mixed, or are they all in the same direction of improved depression? How big are those effect sizes? Is that tiny or are they really large? And then really, really importantly, is there evidence of publication bias and that is a really…

Leor Sapir (00:39:08): Define what that is.

Zhenya Abbruzzese (00:39:10): Speaking of Greek myths, that’s the Achilles heel of pediatric gender medicine.

Leor Sapir (00:39:37): I see what you did. Very good.

Zhenya Abbruzzese (00:39:41): But it is truly the Achilles heel of pediatric gender medicine is research teams that do not know this area of medicine and enter it just using their methodological lens and rigor, which is how most methodologists separate. They’re not really experts in any given area of medicine. They’re experts in evidence evaluation.

Leor Sapir (00:39:37): Which is a strength because they come without predispositions and biases.

Zhenya Abbruzzese (00:39:41): It’s absolutely strength and they usually need to have a couple of experts advising them, but they also really want to distance themselves from such experts.

Leor Sapir (00:39:37): You mean subject area experts?

Zhenya Abbruzzese (00:39:41): Subject area experts, yes. Yes. They’re shocked and you’re often unaware and don’t even have the ability to detect the amount of publication bias that plagues this particular area. They do have some methodological tools to determine bias. Like for example, if you create a plot of study findings and null results are missing, null results. And when the study says, “Oh, we can’t tell. There’s no effect,” then that gives you a hint that something is going on because you will always, if all the results are published, you will always find positive, negative, and neutral. And if there are enough studies, they start moving in a certain direction, and that is when you begin to conclude that actually these things are more beneficial. When you have only studies, when you have missing null results or some other signs, you could conclude there’s publication bias. In this area of medicine, the publication bias is so significant and it’s not just publication bias, it’s research bias where research originating from gender clinics notoriously is not to look in the domains of physical harms because that is where harms are expected and very disproportionately focuses on psychological domain of benefits. So that’s another important area.

Leor Sapir (00:41:17): So for example, in 2024, the New York Times reported that Johanna Olson Kennedy, one of the leading advocates and practitioners of pediatric gender medicine in the United States, that a research project, NIH funded $10 million research project that she had led looking at puberty blockers, they chose to sit on their results and not publish them because as she articulated to the Times reporter, she was worried that the unimpressive findings would be, and I think the word she used was “weaponized” by critics of these treatments, which of course is very perverse reasoning because critics of these treatments are right to criticize them if these invasive, harmful drugs don’t have benefits that outweigh the harms. And then in the U.K., the famous puberty blocker trial in the UK, which was the first to try to replicate the Dutch protocol, also ended up being very unfavorable findings. And so they sat on that research and just didn’t publish it. They just didn’t want it out and it took public records requests to get to force them to release the data. And once again, it showed that on the whole there was no improvement and some patients deterioration too. So publication bias exists. You and I know this firsthand. We’ve submitted commentaries to medical journals pointing out kind of basic and obvious methodological flaws and those commentaries or letters to the editor more often than not almost always actually get rejected, creating the impression that these studies have no scientific criticism, right?

Zhenya Abbruzzese (00:42:46): Right. Although in a systematic review process, there is actually no mechanism for consulting published critiques and that in my view is actually an area of improvement that people who are working to improve methods should really factor in because independent researchers just diving into this area and their primary expertise being methodological as opposed to subject matter are sometimes entirely unprepared for the level of concealment of negative outcomes and exaggeration of positive outcomes that gender clinic researchers are producing.

Leor Sapir (00:43:29): So just to finish out the point of the methodology of the SEGM analysis here, there was one really interesting example that I saw in your analysis, which was how the Utah review authors used comparators to inflate the quality of certain studies. Can you say more about that?

Zhenya Abbruzzese (00:43:45): Yeah. So just to kind of finish your previous question though, you asked what tools we used. We used standard methodological tools according to both of these tools, the Utah review got the lowest possible quality rate.

Leor Sapir (00:44:00): Okay, lowest possible. Lowest possible rating. Okay. So give us an example of the shenanigans that they did with regard to comparators, because as we know, the lack of comparison groups is one of the reasons, a persistent reason why these studies are of such low quality.

Zhenya Abbruzzese (00:44:16): Yeah, that was really surprising to us. I would say it’s one of many really troubling aspects of the Utah review. I don’t even know that that’s the most egregious one, but it is a curious one. So we know that there are no randomized control trials in this area. That’s one of the problems, but we also know that even setting aside randomized controlled trials, there are other types of research that produces reliable results and the prerequisite for that is having a comparator. Comparative research has become the standard of medicine.

Leor Sapir (00:44:53): You can’t draw any causal inferences, right?

Zhenya Abbruzzese (00:45:05): Correct.

Leor Sapir (00:44:53): If you can’t control, for example, placebo effects or if these kids are getting hormones, but also psychotherapy at the same time, how do you know which of those is responsible for improvement?

Zhenya Abbruzzese (00:45:05): Right, exactly. So comparative research is really essential. There’s higher quality comparative research and lower quality comparative research, but comparative research is really essential and that’s well understood. And interestingly enough, when we looked at how the Utah University of Utah researchers assessed individual studies, they consistently rated studies higher by giving them extra points for having comparative groups. And what they did instead is essentially if the study reported separately on females transitioning to male and male to female, then they would say, “Well, females were the comparator for males and males were the comparator to females.” If the study reported on different socioeconomic status, then high income individuals were sort of treated as though they were comparative for lower income, same with race, white patients versus African-American patients. Of course, the studies themselves never claimed that they had a comparative group. In fact, some of the well-known studies in this area of medicine explicitly acknowledged we don’t have a comparator group, but the University of Utah researchers would say, “Actually, no, they did have a comparison group.” Yeah, that is quite surprising. So it was surprising and it led to the inflation of the ratings of individual studies, although it’s really problematic how the Utah review handled studies that had no comparative groups by representing them as though they had comparative groups. I think there’s several other aspects that are actually more concerning, and one of them is the decision that the Utah review research team made about how to handle studies that report on harms.

Again, I don’t want to speculate about why that decision was made, but once the research team identified a very large number of studies, there was no time and resources to rigorously analyze each study, so they had to make some choices what to focus on and they chose to not focus on studies where harms were expected, for example, and they explicitly talked about that in their methodology, which is baffling. For example, they said that because infertility is an expected outcome of treatment with puberty blockers and cross-ex hormones, it’s known, it’s expected, there’s no need to expand resources on analyzing studies that report on fertility outcomes.

Leor Sapir (00:47:47): I mean, just pause right there, I mean, because this is really just astonishing because we know that fertility impacts, including sterilization, are expected if you treat, especially biological boys from the very onset of puberty with puberty blockers followed by cross-ex hormones, that’s guaranteed sterility because their gametes never have a chance to mature. And for females, I think there’s kind of a strong expectation of at least some fertility impacts that could be long-term and we don’t really know if these girls are going to later on be able to go on it and reproduce and have children. And so the University of Utah authors, they said, “Because we know that these are known harms, we’re going to exclude them from our analysis.” And later on, they also excluded them from the risk benefit analysis is my understanding.

Zhenya Abbruzzese (00:48:37): And that is the most problematic aspect. It’s shocking that the decision on which studies to include in the analysis was based on the essentially fundamental misunderstanding of the task. The task was to assess the benefits and the harm. I do not recall any engagement with sexual function as an outcome and that takes us back to the very beginning. How did the researchers determine which outcomes are important? Well, they didn’t. They said early on that they are interested in all outcomes. And that is why they got so many studies. Again, that goes to the research process question. When you are undisciplined and unfocused, it comes at a cost. The cost is then you’re flooded with hundreds of studies that you don’t have the resources to properly analyze. And then once they were faced with this flood of studies, some very puzzling studies of questionable relevance, then they had to make choices and in the process of making those choices, it looks as though their perhaps bias came through. The Utah lawmakers explicitly requested studies related to desistance and for some puzzling reason, the researchers chose explicitly to deprioritize studies related to detransition and desistance and regret and related phenomenon. So to have a review commission specifically to look at treatments for youth, for adolescents, and to then explicitly deprioritize, remove from the consideration set the various studies that have the potential of discovering problems in these areas is very, very problematic.

Leor Sapir (00:50:32): Right. Let’s just finish with the question of conflicts of interest. Let’s call it problems of bias in general and conflicts of interest in particular. I know, for example, that the authors of the Utah Review referenced the American Academy of Pediatrics policy position or stance on pediatric gender medicine articulated in 2018 by Dr. Jason Rafferty. It’s been subject to significant scientific criticism. It’s kind of a classic example of why narrative reviews are so untrustworthy compared to systematic reviews. But what exactly do the University of Utah authors say about the American Academy of Pediatrics Review?

Zhenya Abbruzzese (00:51:10): So it’s an interesting question because in addition to the analysis of primary studies, which we’ve spent most of the hour discussing, the Utah Review also undertook the analysis of clinical guidance documents that they considered influential. And that was just another area that was remarkable in how poorly it was handled. First of all, the researchers said they’re not even going to analyze for quality. The guidelines that came from recognized medical authorities, they will automatically assume them to be evidence-based.

Leor Sapir (00:51:46): And just to be clear, WPATH is maybe the medical authority on this issue. And in 2024, we got through a lawsuit in Alabama, we got smoking gun evidence from their own mouths that they had commissioned systematic reviews of evidence and then suppressed their publication because those reviews were likely to find the WPATH’s preferred approach to pediatric gender medicine was not supported by evidence. And so these are groups that have explicitly suppressed not just systematic reviews, but also scientific discussion. And here we have the Utah review authors saying, “We’re going to defer to them because they only develop guidelines that are based on good evidence.”

Zhenya Abbruzzese (00:52:25): And yes, and not only that, but it is antithetical to the very premise of evidence-based medicine, which by the way, has developed special tools for assessing guidelines for quality to say we are doing an evidence-based analysis of guidelines, but we’re not going to assess them for quality. We’re going to assume that the quality. There’s not a single methodology in evidence-based medicine that takes in the reputation of the entity that issued it as a factor in guideline quality and notoriously very established medical organizations issued poor quality guidelines, which is why-

Leor Sapir (00:53:06): That’s what the Cass Review found and the leading medical association in the UK just endorsed the Cass reviews findings and...

Zhenya Abbruzzese (00:53:13): And not only in gender medicine, in other areas, medical societies can issue bad ideas. Yeah, it happens all the time. All the time, which is why they filled the evidence-based medicine, developed the tools to look not just at individual studies, but also different tools to look at the quality of guidelines. There’s a tool called AGREE2. It’s an internationally recognized tool. So the researchers from the University of Utah did not apply any of those tools. They just stated if it came from a recognized medical authority, those are evidence-based, and now we’re just going to summarize for you what they said. And so of course the WPATH guidelines were described as evidence-based and as the standard and just the recommendations were summarized, same for Endocrine Society. But what’s interesting is that the American Academy of Pediatrics position statement didn’t even rise to the level of a document that they reviewed because according to their own approaches, they only wanted to engage with documents that at least referenced, at least mentioned a systematic review, which is a very unusual requirement.

Leor Sapir (00:54:19): AAP’s statement is, it’s a policy statement, it’s not a clinical practice guideline and it cites WPATH.

Zhenya Abbruzzese (00:54:26): Right. And so because the AAP did not even reference systematic review by their own yardstick, the AAP statement didn’t even rise to the level of a credible enough document to analyze.

Leor Sapir (00:54:37): And yet here they are citing it.

Zhenya Abbruzzese (00:54:39): And yet they’re citing it throughout the review as evidence that these treatments should really be broadly available. They lean on it as early as the proposal stage saying the American Academy of Pediatrics recommend these treatments. So it’s a very interesting situation where the narrative is so heavily built around the authority of the American Academy of Pediatrics support for these treatments as evidence that these treatments are beneficial. And yet when it came to rolling up the sleeves and looking at how the American Academy of Pediatric Statement fares or what it recommends, they couldn’t even include it in their own analysis because it doesn’t reference systematic review.

Leor Sapir (00:55:24): So this is a major red flag. This is a major red flag, but let’s talk about the specific conflicts of interest among the authors of the Utah review, because I think some of those are actually quite significant.

Zhenya Abbruzzese (00:55:33): And I think that that’s really the background story here that not just for the Utah review, but for this area of medicine more generally. In fact, we only began to understand the depth of the conflicts of interest at the very end of the process. 98 percent of our time was spent in analyzing the methodology and finding these really incongruent with common sense decisions and they really made no sense to us until the very end when we actually looked at how the sausage was made, not just from the methodological perspective, but from the individuals that were overseeing the sausage making process. And so that’s when it really dawned on us what a problematic example of failures in this area of medicine that Utah Review serves as. And I now think of it as almost like the Rosetta Stone of gender medicine because you could see all the key players coming together to issue this review

(00:56:39): And it is likely repeated not just in Utah, but in other states as well. You can really see the effort, the concerted effort by different parties to maintain the veneer of the narrative that these treatments are safe and effective in order to save them from this area of medicine from scrutiny and from regulation. What we’ve discovered, and anybody can validate this independently for themselves, is that from the very beginning, the process was placed in the hands of the executive medical director of Utah DHS, who was described publicly as a huge advocate for the University of Utah Gender Clinic. So when you think that the guardian of the process is not neutral but is an advocate for the gender clinic, that already raises concerns. Then you look at how that individual, it’s Dr. Michelle Hoffman, if I recall, how she structured this process. The process was delegated under her leadership to the University of Utah research team.

Leor Sapir (00:57:45): So the same university where the gender clinic exists is now supposed to evaluate the evidence.

Zhenya Abbruzzese (00:57:50): It was housed at another hospital, but it was a sort of co-managed clinic that was affiliated with the University of Utah, staffed with the University of Utah Pediatrics.

Leor Sapir (00:58:04): But I mean, from an institutional perspective, you could say this is basically asking an institution to grade its own homework.

Zhenya Abbruzzese (00:58:10): Right. In fact, it is, which is possible if very clear conflict of interest management exists and researchers are shielded from the pressures, but because there’s no transparency and the research process was so obviously flawed, it raises serious questions about how independent the team was. So the advocate for the gender clinic at Utah DHHS oversees the process, delegates it to the University of Utah researchers. University of Utah itself has a huge reputational potentially financial interest in the clinic because it is their gender clinic. And then the set of advisors that are appointed to oversee the integrity of the process are effectively all, the majority of them are affiliated with the University of Utah and several come directly from the gender clinic, including the director of the gender clinic itself. Those are the individuals overseeing the production of the reports.

Leor Sapir (00:59:13): So we have individual researchers, medical professionals who participate in pediatric gender medicine being asked to grade their own homework, being asked to evaluate the evidence for the practices that they have already committed themselves to professionally, potentially financially, certainly intellectually. That just seems like a clear and obvious conflict of interest.

Zhenya Abbruzzese (00:59:37): It is a clear and obvious conflict of interest. When you look at the reporting of conflicts of interest in the executive summary of the review and the recommendations, all of those individuals just listed themselves as University of Utah Academics. None of them explicitly or at all stated that they were a director of the gender clinic or They’re writing the hospital that housed the gender clinic.

Leor Sapir (01:00:02): Just to go back to what Dr. Brooks Keeshin said at the ACAP meeting, he basically said, from the very beginning of this process, we put into place certain measures so that we could find ways to basically undermine the moratorium.

Zhenya Abbruzzese (01:00:17): And just to be clear, having a position is not the same as having a conflict of interest.

Leor Sapir (01:00:21): It’s an interest, right?

Zhenya Abbruzzese (01:00:24): Right. The question is whether your position can unduly impact interpretation of the evidence or the recommendations that you make. And in that regard, having a financial investment in an area of medicine is widely recognized as an egregious conflict of interest and often entirely disqualifies an individual from participating in making the recommendations. In the case of the Utah review, the director of the gender clinic who openly opposed the Utah legislators who during the moratorium actively talked and gave interviews about how she’s connecting her patients to neighboring states to receive gender transitions and who was represented by Dr. Keeshin is a really prominent advocate and cheerleader and keeping everybody’s spirits up that the moratorium will eventually will be lifted. They just need to hang in there. When that individual is a core advisor overseeing the process, that there is no denial that there is just no argument about whether or not that was a very serious conflict of interest. The majority of advisors have easily identifiable conflicts of interest just by searching their professional interests, yet none were disclosed. That is really problematic. The non-disclosure is very, very problematic. And if there’s any doubt as to whether or not the director of the gender clinic had enormous interest in steering the review in a particular direction, you should only look at what happened after the Utah governor finally signed the permanent ban on new transitions. She left her 20 plus year job at the University of Utah and opened her own private clinic, which at least on the LinkedIn profile and that was again, came about when we were just researching individual conflicts of interest, that clinic is described on her LinkedIn profile as providing among other services, gender care, targeting patients age 10 plus, which is kind of an interesting cutoff.

Leor Sapir (01:02:42): Puberty blocker range.

Zhenya Abbruzzese (01:02:42): And again, I’m not saying she’s doing anything illegal. I’m sure she’s complying with laws, but there are neighboring states that she’s been openly advocating for sending the patients to not accepting insurance, accepting only cash payments and building into those cash payments, routine testing for estrogen and testosterone.

Leor Sapir (01:03:03): So I want to bring this full circle and end, but you may be aware, but in February of this year, there was a letter sent by 106 Democratic members of Congress. I think it was the Equality Caucus. They sent a letter to Secretary Kennedy of the Department of Health and Human Services criticizing HHS’s efforts to impose restrictions, funding cutoffs for healthcare systems that perform these procedures on minors. And the letter from the Democrats claimed that puberty blockers and cross-sex hormones are “medically necessary, evidence-based care and supported by numerous studies and systematic reviews that have confirmed their safety, efficacy and benefits.” The only citation they provide is the Utah Review. So you can see how these kind of very highly flawed, activist-driven documents that have a scientific gloss to them very quickly enter the bloodstream of policymaking in a way that can shape healthcare policy for millions of kids around the country. So I want to end, but just by asking, because SEGM does not advocate for policies, that’s never been your mission. You’ve tried very clearly to stay away from that. You comment on the science. What is SEGM’s message if you have one to policymakers on both sides of the aisle, not just on the issue of the Utah review, but in general?

Zhenya Abbruzzese (01:04:23): Well, first, I’m personally dismayed that there is an ongoing effort to represent the Utah review as a high-quality document that effectively diffused the evidence produced by the Cass Review, the HHS Review, or actually at this point, two dozen systematic reviews. The fact that the review continues to be positioned as a credible document is actually deeply problematic. When politicians say that, it sounds like a political move and this area has really struggled from being politicized, but I’ve also come across a letter of, and we referenced it in our analysis from a group of deans of public health schools and other professors in public health who signed a very similar letter making very similar claims. And so when professionals responsible for public health that arguably do have training in evidence-based medicine and systematic reviews makes nearly identical claims to politicians, then we really are in trouble.

Leor Sapir (01:05:36): No, I think that’s right. And this speaks to something that we’ve been calling the broken chain of trust in medicine because I think it’s safe to assume, or we should assume that these medical school deans are acting in good faith, that they trust that their colleagues are not pulling one over them and that they trust that if there’s a report that’s over a thousand pages long, that’s called a systematic review and done by credible researchers at an academic institution, that it’s going to be a trustworthy review, that it’s going to try as much as possible to adhere to the scientific method. And so they place their trust in colleagues and it’s only later when the flaws and the biases are shown all of a sudden these public health authorities or medical school deans who have endorsed the report, now what? Now they’re going to say, “sorry, we got it wrong.” “We were trusting people who misled us.” It’s very unlikely that they’re going to do that given the reputational cost to themselves. And so there’s a kind of an asymmetry. Once this kind of medical misinformation gets out there and gets endorsed by figures of authority, it’s very, very difficult to get those same people to reexamine what they actually endure, sometimes even read it, because I doubt those medical deans read any of this report. They probably look at the top line conclusion, said done.

Zhenya Abbruzzese (01:06:47): At best. Or probably just co-signed a letter.

Leor Sapir (01:06:49): Was written by activists

Zhenya Abbruzzese (01:06:52): But came through a trusted colleague. Exactly. And so I think that more generally what our society, I think at this point needs to clearly recognize is that this area of medicine represents one of the biggest medical scandals we have in our lifetime. And it’s not the only one, but because the group of patients that’s negatively affected is vulnerable children, it’s probably one of the worst medical scandals of our time. There is no longer any credible debate about the state of the evidence. We know that this area of medicine was launched on a pair of studies that was misrepresented. There is no longer any credible debate about the quality of the evidence and what the evidence shows.

Leor Sapir (01:07:38): So your message, just to be clear, your message to policymakers on both sides, because we have seen also Republican policymakers say things that are not in accordance with the state of the evidence overstate the case and so forth, your message is before you ask the question, what should we do about this from a policy perspective, the bare minimum that politicians need to do is familiarize themselves with the state of the evidence, understand how evidence-based medicine works and not make claims that are scientifically false.

Zhenya Abbruzzese (01:08:03): Right.

Leor Sapir (01:08:03): That’s the bare minimum.

Zhenya Abbruzzese (01:08:04): Well, that is the starting point for our societal solutions. Now it’s also really important to acknowledge that we as a society and as the medical professionals have put tens of thousands of young people on a pathway toward medical transition. Some are so far into this process that they don’t even remember their lives as the members of their sex. They have socially integrated into the opposite sex. They visually pass as members of the opposite sex and some of them are just waiting, biting their time to begin these treatments after living with the idea that they want to live as members of the opposite sex. And we will need societal solutions that are empathetic and thoughtful for that segment of the population and it is unclear how to help them and we need to develop solutions that honor them and protect them and protect their long-term health and short-term health. And what it is, I don’t think we’ve even begun to conceptualize.

Leor Sapir (01:09:07): Yeah. Agreed. It’s not a happy thought to end the conversation on, but it is a very important one. Jenia, thank you so much for joining us. Hopefully we can do this again. Thank you.