Bioethics Forum Essay
Finding the Signal in the Noise on Pediatric Gender-Affirming Care
The Cass Review of gender identity services for children and young people, a recent report in the U.K., has spurred many headlines and much debate, most of which tout the finding of “weak evidence” for gender-affirming care for children and teenagers. Advocates of such care reject the report as anti-trans, while critics hail it for finally outing such care as pseudoscience. However, much of the noise around gender-affirming care in pediatrics, and this report, is misleading and takes away from the substantive improvements needed to provide the best care for transgender youth, something noted in the report’s thoughtful foreword.
The Cass report was commissioned by the U.K.’s National Health Service to make recommendations on improving care for children and young people who are questioning their gender identity or experiencing gender dysphoria. The report made eight recommendations on treatment, two of them on medications: puberty blockers and hormones.
While gender-affirming care is not reducible to medications alone, they are the treatments most often singled out by critics. The report determined that the scientific evidence for puberty-blocking medications in youths needs improvement, expressing concern about the potential risks and questioning the benefits for most children. The report didn’t say that puberty blockers should not be prescribed to children, but it concluded that they should only be prescribed as part of a clinical trial. The report said that masculinizing or feminizing hormones could be given to people starting at age 16, but it advised “extreme caution.”
“I can’t think of any other situation where we give life-altering treatments and don’t have enough understanding about what’s happening to those young people in adulthood,” said Hillary Cass, the pediatrician who produced the report. This statement, and concerns raised in the report about lack of evidence, are misleading for two reasons.
First of all, most medications used in pediatrics lack long-term and pediatric-specific data, and so medicines for gender-affirming care are not exceptional in that regard. In fact, up to 38% of drugs used in pediatrics and 90% of those used for newborns are prescribed off-label and have had few studies performed on children. These off-label medications include antipsychotics, endocrine medications, and even some antibiotics.
Second, there is safety data on puberty blockers. They have been given to children for decades to treat conditions such as precocious puberty, in some cases for the indication of social distress related to early puberty. These drugs have been shown to be safe in prospective observational studies.
In looking for evidence Cass placed the greatest value on randomized controlled trials. In these studies, participants are randomly assigned to receive either an experimental treatment or a control treatment and then their outcomes are compared. RCTs are great when they are feasible and ethical. But they are not feasible for studying puberty blockers because the participants and researchers would know which group the participants were in when they either did or did not show pubertal changes. This knowledge could interfere with an unbiased scientific comparison of the outcomes.
Without RCTs on puberty blockers, Cass had to review other studies whose evidence she considered “weak.” But this does not mean a lack of benefit. Rather, it should prompt shared decision-making with clinicians, patients, and families discussing the proportionality of benefits and burdens.
Weighing the proportionality of benefit to burden from an intervention is a foundational calculus in ethical decision-making. It goes on every day in pediatrics without apparent controversy. Some arguments appeal to patient autonomy—the rights and interests of the patient who wants a treatment—rather than to the treatment’s ability to reduce morbidity and mortality, as was discussed in an article in the current issue of the Hastings Center Report. Other arguments focus on what is in the best interest of the patient. But for many decisions in adolescent health, it is not a matter of choosing either/or but rather considering both the patient’s autonomy and best interest that is necessary. For example, life-and-death decisions involving serious illness in adolescents require respecting the adolescent’s autonomy and considering the medical team’s and the parents’ assessments of the benefits and burdens, or beneficence and nonmaleficence, of those decisions.
Interestingly, in contrast to gender-affirming care, there seems to be relatively little public controversy over cosmetic surgery for teenagers. And yet in 2022 there were 23,527 cosmetic surgeries performed on teenagers in the U.S., including breast augmentation for both biologic cis males and females. These surgeries require the same decision-making process as other interventions for teenagers. But as far as we can tell, they receive less public scrutiny than gender-affirming care. There are no court cases against these surgeries or attempts by state governments to ban them despite legitimate questions about their benefits and burdens to adolescents and the fact that, unlike most gender-affirming interventions in youth, cosmetic surgeries are not reversible.
Issues around evidence in pediatrics are abundant, but gender-affirming care receives a disproportionate amount of public criticism. Resources are lacking for research that would provide more evidence on the safety and effectiveness of care in pediatrics, including gender-affirming care. The Cass report recognizes this problem and provides important guidance. The report does not support bans and criminalization of gender-affirming care, which has been the response by more than 20 U.S. states and is under review by the Supreme Court. On the contrary it calls for investment in and expansion of gender-affirming care: improved access, workforce education, and collaborative and coordinated services, along with infrastructure to ensure improved data collection and ongoing quality improvement to strengthen the evidence for various treatment options. While we disagree with the Cass report’s assessment of the evidence for puberty blockers and hormone treatments, its overall recommendations should be heeded by critics of gender-affirming care if the goal of their critiques is truly to provide improved and beneficial care for young people.
Ian D. Wolfe, PhD, MA, RN, HEC-C, is director of ethics at Children’s Minnesota and affiliate faculty in the University of Minnesota’s Center for Bioethics.
Justin M Penny, DO, MA, HEC-C, is an assistant professor in the Department of Family Medicine and Community Health at the University of Minnesota and a clinical ethics assistant professor in the Center for Bioethics.
Sadly,
the writers are un-even handed when they recommend “overall recommendations should be heeded by critics of gender-affirming care”. An even handed and ethically responsive recommendation would be that the Cass review’s recommendations should be heeded by critics AND ADVOCATES of gender-affirming care. We wonder if the writers will declare why they avoided this obvious even handedness?
The writers appear to misrepresent the Cass review’s inclusion of studies. The Cass website has a well articulated ‘FAQ’ that includes notes, such as
“Studies were identified for inclusion in the synthesis (conclusions) of the systematic reviews on puberty blockers and masculinising/feminising hormones on the basis of their quality. This was assessed using a standard quality assessment tool appropriate to the types of study identified. All high quality and moderate quality reviews were included in the synthesis of results. This totalled 58% of the 103 papers.”
So, Cass did not exclude consideration of studies showing benefit.
Cass emphasized ethical requirements of informed consent that the writers here appear to avoid. Assessing competence and capacity of the adolescent is essential, as is assessing any likely or possible coercive influences on the adolescent. These assessment cannot be made without involvement of parents, legal guardians, or others responsible for the best interests of the adolescent (a court, a social service agency, etc). These assessments must be ongoing and never a ‘one time signature’, as treatments are changed, or new treatments proposed. The writers do not take this up in their discussion. But these are essential ethical requirements aren’t they?
The writers oddly spend a whole paragraph about cosmetic surgery with adolescents. This was not a focus of Cass. But certainly surgical interventions with adolescents as gender care are controversial. The writers’ claim that cosmetic surgeries are not litigated is not 100% accurate: for example at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839246/ we find that hundreds of courts cases have proceeded after cosmetic surgeries. And – referring to out point above about the essential ethical requirement of informed consent – we read that “lack of informed consent of procedure complications was the most common allegation to be raised, representing 21% of total claims”.
The ‘noise’ of law and policy making about gender care has more than one ‘signal’. One of these signals is the lack of serious research and discussion about informed consent with adolescents seeking gender care. Providers appear to avoid it (are they fearful of being sued? or of reducing their income from gender care? etc?). And ethicists appear to avoid it (does that suggest a bias to support more convenient gender care? etc?).
Thank you,
Edward Strickler
active member, past chair, Ethics, American Public Health Assn
retired, School of Medicine, University of Virginia
etc
Thank you for reading and taking the time to comment. We agree that the recommendations in the Cass report should be heeded by all. And aside from the many NHS specific recommendations (which were most of them) they were similar to already existing standards of care set forward by Endocrine Society and WPATH. So these recommendations already existed. Children presenting to a gender program should receive holistic care to include psychological assessment and treatment. They should have long standing gender dysphoria diagnosed by a qualified clinician. etc etc. Certainly a clinic not doing so is out of line with guidance from those organizations. The focus of the essay is on US implications. And as such, the most pressing issue is restriction. The restrictions are taxing gender clinics around the country and making it increasingly hard to provide good process for children. So you are right that we didn’t explicitly say that advocates should heed the recommendations but this was partly because the current US noise is from critics.
We did not discuss how she included studies necessarily, and the language in the final draft is a bit unclear here. What is notable in Cass is that they used the GRADE method. This method was also used by WPATH notably and since they came up with similar recommendations maybe critique here is moot rather its the way they represented the analysis. GRADE prioritizes RCTs has the highest evidence. Weak evidence doesn’t mean no benefit. The “noise” from the interpretation in the media was significantly problematic because what media folks used as the concept of weak is much different from the concept in GRADE.
Of course, there is not the ability to go into such nuance in an essay. I would recommend Antommaria’s piece in Perspectives in Biology and Medicine which provides a very comprehensive overview https://muse.jhu.edu/pub/1/article/929021.
We agree that parents must be involved and would certainly push against anyone saying otherwise. Our point here is that the ethics of gender affirming care in pediatrics is not novel. The frameworks already exist. And as we state its not simply about patient autonomy but a balance between current and future benefits and burdens, as well as considerations to current and future self. We disagree with a full autonomy based approach as Bester argued against in the recent HCR issue.
Informed consent is a more narrow concept and we would consider it more about informed decision making in line with shared decision making which includes clinician obligations around what is offered, not simply what is being requested. This is where we find the Cass report to really not say anything that isn’t already in practice and the misinformation that came out of the report, or the reporting of it, to be damaging. In this, no one seemed to have read it as the recommendations support existing ones and call for expansion.
Its possible you misunderstood what the purpose of bringing in appearance altering surgery. The point is to show comparison. We agree that gender affirming surgery for youth is controversial and in general should not be done though there may be cases in older adolescents where it may be reasonable. The point however was to show that gender affirming care for youth is being made controversial where most of it is assessment and therapy, with some youth receiving puberty blockers, some older adolescents hormones. Yet there are appearance altering surgeries happening on youth, some could even be considered gender affirming but for cis youth. And these are happening without any media or political attention. It makes one curious why not, or why certain gender affirming care is seemingly more controversial than others. What we were considering controversy is that there are no court cases trying to ban cosmetic surgery (maybe there should be) and no media attention to the level that the gender affirming care receives. Litigation over a bad outcome claiming lack of informed consent does not meet our conception of controversy.
Your last comment is a bit confusing as we read it. Yes, more research is always good and should be done. We would argue there is “serious” research already done. If we disagree on what constitutes serious research than certainly that is a debate. We are not sure what you mean by “more discussion about informed consent.” At least in our experience with gender affirming care, the recommendations, gender affirming care is not a one clinic visit but rather an ongoing process with many clinicians and meetings with parents etc. We are not sure what you mean by providers seem to avoid it. If providers are not engaging in shared decision making processes than that is certainly ethically problematic. We would say that this statement seems quite reductive to those clinicians who are working in these spaces. If there are clinicians and ethicists forgoing informed shared decision making processes then that is wrong. But this then is a problem of not following standards of care, not a reason to ban all care.
It is refreshing to see more bioethicists engaging in discussion of the ethics of pediatric gender medicine, especially in light of the publication of the Cass Review. I wish to make three comments in response to the essay by Wolfe and Penny and to their response to Edward Strickler above.
First, Wolfe and Penny argue that GRADE is an inappropriate tool for the evaluation and grading of evidence in the field of pediatric gender medicine. Whether this is true or not may be an important question for methodologists to answer, but it is not relevant here. This is because the systematic reviews commissioned by Cass and conducted by researchers at York did not use GRADE. As the researchers make clear in Appendix 2 of the Cass Review, “Where appropriate, the quality of studies included in the individual reviews were appraised using the most appropriate method. The tools used included the Mixed Methods Appraisal Tool (MMAT), modified versions of the Newcastle Ottawa Scale, and the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.” Therefore, the concern about GRADE setting too high a bar in the grading of evidence quality is misplaced. Had GRADE been used, it is unlikely that any of the studies would have fared as well as they did (e.g., one review, not using GRADE, found moderate quality evidence that cross-sex hormones were associated with short-term improvement for some psychological outcomes.)
Second, Wolfe and Penny argue that critics of pediatric medical transition treat these interventions differently than they do or would other relevantly similar pediatric interventions. For example, they claim that Cass was mistaken to claim, “I can’t think of any other situation where we give life-altering treatments and don’t have enough understanding about what’s happening to those young people in adulthood.” This claim, they say, is “misleading for two reasons.” The first reason is that many pediatric interventions, and not only puberty blockers or cross-sex hormones, are used off-label. The second is that “there is safety data on puberty blockers” in the form of studies on their use for the treatment of precocious puberty.
With respect to the first claim, Cass, an accomplished pediatrician, would of course know that many interventions are used off-label. Her worry clearly has to do with “life-altering treatments” given in the absence of good evidence of a favorable risk/benefit profile, and not with the use of off-label medications, per se. With respect to the second claim, precocious puberty and gender incongruence/gender dysphoria are not the same thing. They are clinically independent diagnoses intended for patients who differ in many ways, including age and prevalence of psychiatric comorbidity. In the former case, nearly all patients prescribed blockers go on to endogenous puberty at the typical age, while in the latter case nearly all patients go on to be prescribed cross-sex hormones. These are radically different medical courses.
Third, in their response to Strickler above, Wolfe and Penny significantly understate the dissimilarities between Cass’s recommendations and 1. clinical practice at U.S. clinics and 2. WPATH guidelines. While we do not have much data on actual clinical practice in the U.S., we know from Reuter’s 2022 investigation that some US clinics prescribe blockers or even hormones after just one visit, and that some clinicians regard mental health assessment prior to the prescription of blockers/hormones as well as the requirement that patients be seen by mental health professionals during treatment as a form of unduly pathologizing gatekeeping (I discuss this in more detail in the published paper linked to above in Wolfe and Penny’s first essay). While Wolfe and Penny believe the legal restrictions on pediatric medical transition are the “most pressing” issue, they should consider the role that a medical field unable to regulate itself has played in the cultural dynamics and political polarization within which these restrictions have taken hold.
Finally, while this is not the place to demonstrate the ways in which Cass departs substantially from WPATH, it is worth noting briefly that WPATH guidelines are currently undergoing significant scrutiny due to the recent publication of internal documents unsealed by the State of Alabama. While more documents are still set to be released and it will take time for the full story to be told, we now know that WPATH leadership blocked the publication of the systematic reviews they commissioned from researchers at Johns Hopkins University. According to emails and other documents, WPATH leadership was concerned about the results of the reviews and their legal and political repercussions. For example, the (at the time) incoming president of WPATH, Walter Bouman, urged in an email to the guideline working group that any research had to be “thoroughly scrutinised and reviewed to ensure that publication does not negatively affect the provision of transgender health care in the broadest sense.” The systematic reviews were initially intended to form the basis of WPATH’s new Standards of Care (Version 8, published in 2022). WPATH’s concern with how the language of their clinical guideline would play out before judges and politicians—a concern made explicit in their communications—raises serious questions about the scientific integrity of the document as a whole, and thus the question of how it departs from Cass’s recommendations is in one important sense moot.
Thank you for your thoughtful reply, we agree that constructive discourse is necessary. Thank you for reading and engaging. We would like to clarify a few points that we feel may not be too far of a chasm from your points.
We do not say that GRADE is inappropriate but point out that by design it values RCTs higher, AND the terminology around “weak” evidence should not be misconstrued as no benefit or no evidence. A rating of weak does not equal nonbeneficial: “The strength of recommendations are actionable: a weak recommendation indicates that engaging in a shared decision-making process is essential.” We would also point readers to the articles on this topic in the recent Hasting’s Center Report in addition to Dr. Gorin’s such as https://onlinelibrary.wiley.com/doi/10.1002/hast.1592. This nuance may lead to significant confusion and misinformation to the public. Many guidelines are developed with “weak” evidence. (I would point readers to Dr Antommaria’s more in depth paper https://muse.jhu.edu/pub/1/article/929021) Additionally it is worth noting that WPATH used the GRADE method as well for their recommendations. GRADE, like most methods, lends to subjectivity which is generally balanced with transparency. But we find it interesting that Cass made came to similar recommendations as WPATH in the end at least in terms of good process for holistic assessment. The Majority of the Cass recommendations were on NHS process aimed at unifying and expanding access.
We agree that Cass is an accomplished pediatrician. And, as clinical ethicists (one physician) we know that just because one is accomplished does not mean one is immune to hubris. I will give her the benefit of the doubt that she knows full well about off label medications and that her statement was not meant to say that all medications are studied in pediatrics, but I think it is a misleading and unhelpful statement.
We would argue that there are many life altering drugs used off label (antidepressants, antipsychotics, various hormones for many conditions). It seems illogical to say that puberty suppression for precocious puberty is not life altering but puberty suppression for GAC is. While many attempt to make the argument that the use of puberty blockers in GAC solidifies a life course, this has not been proven. While precocious puberty and gender incongruence are not the same, there is an indication for puberty suppression in precocious puberty due to social distress. And so there is a need to answer the question on why they can be safe and beneficial for one and not the other. And where there is criticism around safety data, it surely exists independent of the diagnosis. One would be left arguing that the long term burdens of undergoing GAC directly caused by puberty suppression are the reason it is different, yet this argument has not yet been settled, or at least there is evidence that the benefits are significantly higher.
This is not to say that there are not those who undergo treatment and then have regret. These are important stories that need to be understood. We should want a high specificity. But regret is low, and even lower than other procedures. And studies on regret focus on surgical interventions which are not a part of pediatric GAC, except very rare exceptions for youth at the cusp of adulthood, and even then only certain interventions. On another note, there is also some hypocrisy around the issue of non medically necessary surgical intervention for intersex infants as well as cis gender appearance altering interventions for adolescents to include plastic surgery. The same ethical considerations seem to apply here with the caveat that for GAC the issue isn’t surgery (as these should be done in adulthood) but medications that are largely reversible. We do think these comparisons are important to consider.
As we argue, there is a need to balance benefits and harms to the current and future patient, there is uncertainty, there is also a complexity to our understanding about regret, desistence, reidentification. There is a potential harm in doing nothing if a high degree of mental distress is caused by gender dysphoria. There is risk in being wrong later. There is more acceptance of gender exploration in youth and so not all children who express a different gender at one point in time have gender dysphoria. Not all patients who go on to cease hormone therapy have detransitioned. And we have happy healthy trans adults who have achieved this through GAC in adolescence.
We need to understand this more. Given the complex factors, our argument is that the question isn’t “should youth receive GAC or not”, but “which youth, when, and what interventions”. To this we agree, and we believe good ethical analysis concludes that good process is of utmost importance. And for this reason bans actually make things worse because it significantly delays this, or it reduces expertise, or overwhelms expert centers. We agree with Cass that those identifying with potential gender dysphoria should have good access as soon as possible. We agree with Cass that a holistic developmental and psychologic assessment is important, and we note that this is a recommendation in WPATH.
WPATH notes the issue of inequities, and given the fractured system in the US it would be important to differentiate a patient who shows up and receives medication on the first visit with no assessment vs a patient who has had an ongoing relationship with a mental health professional for years not related to the clinic. The NHS has the structure to build a good and coordinated process, we in the US do not. But, good process for the child should weigh out.
The reasons above are why we see restrictions as pressing. In addition to the vitriol they add to society, and the real harms that they have caused. This is where we believe the wrong questions are being asked. In addition, as above, restrictions actually cause more harm given the impacts on clinics not restricted, families having to uproot, and the way they distract from the valid discussion and arguments. The Cass recommendations argue for expansion, more education, and coordinated data tracking.
The US medical field is unable to regulate itself partly because we lack any sort of unified structure. US healthcare is a web of loosely associated private entities, with some, mostly in adult, government programs. Ideally, we would have some structure that sets forward a care model (Cass presents a robust one, and we think WPATH recommendations line up well with it). We would note, there was a recent study in JAMA Pediatrics, and recently commentaries on it. Of note, the authors response discusses care model in conjunction with WPATH. Further Considerations on Gender-Affirming Care—Reply | JAMA Pediatrics | JAMA Network
We don’t feel there is that much departure of Cass from WPATH. And we think the Cass recommendations are an ideal. But overall what we wanted to convey, and maybe we did not do well in this format, was that the Cass report was being significantly misrepresented. There are areas of it that were unhelpful such as speculation on causation and exploration of nurture theory of gender. Our opinion is that bans are a pressing issue but also that the ethical analysis given all the considerations, leads towards good process and not an unregulated autonomy or complete restriction. Like many decisions in pediatrics it is a balance where many ethical considerations change by a matter of degrees as the child ages. In this, we feel that ethics of GAC for pediatrics are not novel or unique, rather the politicization of this topic, which has led to bans and a lack of good process, has done the most harm to these patients.
Ian Wolfe and Justin Penny