Dear Florida Board of Medicine,
We welcome the opportunity to comment in anticipation of the upcoming Board meeting which will address the question of regulating the practice of medicine as it relates to treatments for gender dysphoria. The optimal treatment pathway for children, adolescents, and young adults with gender dysphoria is not known. In light of the rapidly growing numbers of gender dysphoric youth, the determination of how to protect their health and wellbeing is urgent.
There are currently two competing models of care for gender dysphoria. The “gender-affirming” model, which conceptualizes young people presenting with gender dysphoria as “transgender youth” and focuses on the provision of hormones and surgery for those seeking gender transition (not all transgender-identifying youth seek to medically transition, but many do). Over the last several years, this model of care gradually supplanted the previous community standard of care, which is based on a holistic view of identity formation, recognizing that identity undergoes changes during the adolescent and young adult years. This developmentally informed view recognizes that gender dysphoria can have many causes and many paths to resolution and does not support the notion that current gender identity should be medicalized into permanence using hormones and surgery in young people. Instead, psychotherapy is considered the first line of treatment, and gender transition in youth is pursued only in rare instances, as a measure of last resort.
As the Florida Board of Medicine takes up the question of how best to care for the rapidly growing numbers of gender-dysphoric youth, it should consider the wealth of international experience. Every Western country is experiencing the same poorly understood epidemiologic shift, with rapidly growing numbers of youth declaring a transgender identity, often in the context of significant mental illness and neurocognitive difficulties such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Several countries are currently ahead of the U.S. in their evidence evaluation and evidence-based decision-making regarding treatment of youth gender dysphoria. We exhort the Florida Board of Medicine not to “do it alone” but to stand on the shoulders of the significant work conducted by public health authorities in these Western countries, carefully examining their plans, and adopting the elements that are most aligned with Florida’s public health values and goals.
Transgender health has become highly politicized. We urge the Board of Medicine to resist political pressures. All actions taken by the Board need to recognize the low quality of the evidence and the significant potential for medical harm of “gender-affirming” hormones and surgery for youth, rendering these treatments effectively experimental. However, the Board’s actions must be balanced with a compassionate approach toward those already on the “gender-affirmative” treatment path. It must be recognized that medical transition may be psychologically and/or physically irreversible for many, and there is no quality evidence to guide safe and effective medical detransition. Further, it should be recognized that while the evidence for medical transition for all age groups is of low quality, mature adults’ situations are very different due to their ability to provide valid informed consent. Florida must make the best decision possible in the current highly uncertain situation, while respecting the dignity and supporting the healthcare needs of all Floridians.
I. Background
Until the 1990s, gender transition was rare and largely reserved for mature adults. The practice of offering gender-transition services to young adolescents can be traced back to the Netherlands. Dutch researchers noted that mature transgender-identified adults’ psychological outcomes were often poor despite having undergone medical transition. This led the researchers to hypothesize that by intervening early, future psychological outcomes would be improved.1 Thus, the practice of youth gender transition emerged not because transitioning adults proved a success—but because it failed to deliver the hoped-for psychological benefits.
Effectively, the practice of pediatric gender transition, pioneered by the Dutch researchers, is best understood as an “innovative clinical practice,” i.e., a practice that has been implemented in general medical care without rigorous clinical research. Typically, such practices are ethically permissible when the condition, left untreated, is dire; when no effective treatment alternatives exist; and when the number of the affected patients is expected to be small.2 It also typically requires a clearly demonstrated ability to consent, as innovative clinical treatments often carry a higher risk of harm. Significant ethical dilemmas exist when offering such treatments to children and adolescents, absent quality clinical research that demonstrates that benefits outweigh risks. 3
There are many cultural, political, and financial factors that prompted the practice of pediatric transition to enter regular medical settings rapidly and prematurely, bypassing proper clinical research. Unfortunately, such situations are common in healthcare, as clinical innovations meant for small-scale settings rapidly spread before they are proven safe and effective. Such practices are commonly reversed once evidence reviews reveal problematic or uncertain risk/benefit ratios. There are many examples of practice reversals in medicine, ranging from changing recommendations for hormone replacement therapy for women, to the overuse of opioids for chronic pain.4,5,6 It is a sobering reminder that even practices such as thalidomide and lobotomy were once widely accepted, with no major medical society objecting to their use until the harms became evident.
As of October 2022, three European countries have added “gender-affirming care” for youth to the list of practices that have been “reversed.” Finland, Sweden, and most recently, England have concluded that the risk/benefit ratio of providing youth with puberty blockers, hormones, and surgeries ranges from highly uncertain to unfavorable, and that these interventions should not be provided in general medical settings.7,8, 9, 10, 11,12 Like other practice reversals, this one came about as a result of systematic reviews of evidence, which demonstrated that the certainty of the benefits of the practice of gender-transitioning minors is very low, while the risks can be significant.13,14,15,16
Each of these European countries has adopted a unique approach to implementing new restrictions on “gender-affirming care” due to differences in their healthcare systems, but all have come to the same conclusion: public health authorities must regulate access to “gender-affirming” interventions for youth in light of the highly uncertain evidence of benefit, and the high risk of harm. Notably, England also recently determined that the practice of social gender transition is a form of active psychological intervention and it too must be regulated as a healthcare practice, and restricted to cases where the benefits of social transition are likely to outweigh the harms.11,12
This repudiation of “gender-affirming” care does not mean that all cases of pediatric transition will be banned—instead, such cases will be the exception rather than the rule and transition will only occur in research settings following extensive evaluation and trials of less invasive treatments first. To enable this change, these countries have moved away from the “gender clinic” model of care, where specialty clinics are staffed with “gender-affirming” mental health professionals who perform evaluations, and pediatric endocrinologists who provide transition services. Instead, care for gender-dysphoric youth will be provided in standard medical settings staffed with medical and mental health professionals who take a wide and holistic view of identity development. Gender-diverse youth who are not distressed will not need treatment beyond education about identity development. In cases where the feelings of gender incongruence cause distress, multidisciplinary teams comprised of experts in child development, neurodevelopmental disorders, mental health, self-harm, substance use, and complex family dynamics will evaluate the young person and provide a range of developmentally appropriate evidence-based treatments. Gender transition will be offered as a last resort treatment and provided only in research settings with proper informed consent.11,15
This model of care recognizes that some youth may eventually undergo gender transition, but for the vast majority, transition will be unnecessary and gender dysphoria will resolve without invasive treatments before adulthood, as reported by nearly a dozen studies and acknowledged by the Endocrine Society.17,18, 30 It also allows for the uncertainty of future identity development of adolescents who presented with gender dysphoria for the first time after puberty in the context of significant mental illness, ASD, or ADHD—a novel presentation that remains poorly understood and the trajectory of which is not yet known.19,20,21,58
The community standard approach to care for distressed youth enables clinicians to use evidence-based approaches aimed at reducing severe distress and improving general functioning, while allowing for the possibility of medical transition in the future, once mental health symptoms are well managed, and the individual becomes a mature adult capable of consent. The ability to consent is particularly important as many “gender-affirming” interventions are associated with significant risks to health including risks that are harder to comprehend and appreciate until one becomes a mature adult— such as the loss or impairment of fertility and/or sexual function.22,23,24,25,26
II. Benefits, Risks and Uncertainties of Gender Affirming Care
The “gender-affirming” care model assumes that early gender transition with puberty blockers, cross-sex hormones, and surgery for youth who exhibit gender dysphoria will improve their long-term outcomes. This model has been promoted by the World Professional Association for Transgender Health (WPATH), a U.S.-based professional interest group of gender clinicians and non-clinical professionals who advocate for transgender rights and broad access to “gender-affirming” medical and surgical interventions. Several prominent U.S. medical organizations have adopted WPATH’s “gender-affirming” guidelines27 and currently support this practice as well.
The “gender-affirming” model of care is relatively new and was scaled into practice without rigorous clinical research. Selected outcomes associated with using the so-called “Dutch protocol” to medically transition minors were published in 2014 in a case series of 55 patients.28 Many of the authors associated with the development of the Dutch protocol for medical transition of minors also authored The Endocrine Society guidelines for hormone administration to minors in 2009;29 these guidelines were updated in 2017, lowering the age of eligibly for medical interventions.30
Several newer studies have been conducted since the publication of the 2014 Dutch study. However, both the foundational Dutch research as well as these newer studies suffer from significant limitations, which render them highly unreliable. This is evidenced by the conclusions of several recent systematic reviews of evidence, which failed to find credible evidence of psychological benefits. The systematic reviews of evidence deemed the entire body of evidence on this topic to be “very low” to “low” quality and highly unreliable, due to the short-term, uncontrolled studies subject to bias, confounding, and/or chance. 13,14,15, 31,32
While the evidence of benefits has been found to be uncertain, the risk of harm associated with the provision of “gender-affirming” hormones is substantial. Sterility is expected in 100% of young people when the current Endocrine Society guidelines are followed (puberty blockers at Tanner Stage 2, followed by cross-sex hormones).30 Other medical risks are uncertain, but include impaired development of the bones and brain as well as increased risks of cardiovascular disease and cancer. 33,34,35,36,37,38,39
There also is the psychological risk of regret from an inappropriately undertaken gender transition. Although young regretters have become more visible in the popular media and peer-reviewed medical literature,40, 41,42,43,44 the rate of regret in the population of youth currently undergoing transition is unknown. Research from the last 24 months suggests a significant rate of discontinuation of medical interventions—10-30%, within a relatively short time following initiation.45,46,47 Not all those who detransition express regret. However, this high rate of cessation of what is meant to be lifelong treatment is worrisome, because “gender-affirming” hormones result in largely irreversible effects, and “gender-affirming” surgeries are completely irreversible. In the past, the average time to regret for adults who underwent rigorous screening prior to transition was estimated to be approximately 10 years.48,49 As such, accurate treatment discontinuation and regret rates will not be known for some time.
III. The Dutch Protocol
The practice of gender transition of minors rests largely on the results of one key study, which gave rise to the practice of pediatric gender transition worldwide. 28 In 2014, Dutch clinicians reported on a carefully selected group of 55 youth who underwent gender transition. At follow-up 1.5 years post-surgery, the young adults (average age of 21) retained good psychological function. However, a comparison of pre- and post- transition improvements in psychological function found improvement was modest at best. The main clinically significant outcome was a resolution of “gender dysphoria.” However, subsequently it was demonstrated that this finding was critically compromised by improper use of the scale to measure “gender dysphoria.” The “drop” in gender dysphoria scores largely resulted from switching the scale between male and female version for the same patient, and a corresponding reversal in scoring.50
Notably, a UK study that attempted to closely follow the Dutch protocol through the puberty blocker phase, failed to identify any psychological benefits of the practice.51 No other attempt has been made to fully replicate the entire treatment protocol including cross-sex hormones and surgery in youth, using similar criteria to those utilized by the Dutch researchers. The long-term outcomes of the cohort of the 55 young patients, beyond 1.5 years post-transition, have not been published.
The 2014 “Dutch study” revealed a significant risk of harm of the gender-affirming hormones and surgery pathway.28 One patient died due to surgical complications. Three of the original 70 cases experienced new onset diabetes or clinically severe obesity. Several others refused to participate or did not return their questionnaires, adding to the uncertainty about their outcomes. In total, at least 6-7% of the treated youth had severe adverse effects associated with transition. Less severe but known risks such as risks to bone and cardiovascular health were not assessed by the 2014 Dutch study.
Minimizing Risk of Psychological Harm in the Dutch Model
The Dutch researchers were acutely aware of the risk of psychological harm from wrongly transitioning a young person whose identity is still undergoing development.52 Consequently, they developed strict inclusion criteria for youth gender transition. Those who did not meet the criteria were not allowed to medically transition as minors, and instead had to wait for the standard time to transition—upon reaching mature adulthood and meeting the adult qualification criteria. Below is a list of formal and informal criteria articulated in a range of studies by the Dutch treatment team. 53,54,55
1. Discourage early social transition. The Dutch clinicians recognized that early gender transition creates a stressful environment for children as they reach adolescence, should they wish to detransition. At the time it was widely acknowledged (and is still acknowledged by the current Endocrine Society guidelines) that most gender dysphoric children will not identify as transgender by the time they reached adulthood.30 It was also noted that even for those who would go on to transition, early social transition creates unrealistic expectations and subsequent disappointment with the natural limits of transition-related healthcare.
2. No medical interventions before age 12. For prepubertal and early-puberty children <12 years, the Dutch standard of care was watchful waiting, careful observation, and psychotherapy if needed.
3. Severe gender dysphoria from early childhood that worsens in adolescence. Only children with severe early-onset gender dysphoria were considered for medical gender transition. Those whose gender dysphoria first appeared around the time of puberty or later were disqualified from transition as minors. The requirement that gender dysphoria worsen during puberty was a critical diagnostic criterion.
4. No significant mental health problems. Youth with ongoing mental health issues, aside from mild depressive feelings, were excluded from transition as adolescents. Those who presented with neurocognitive difficulties such as ASD or ADHD were treated with extreme caution, since the ability to understand and adhere to gender stereotypes is frequently impaired in youth with ASD and ADHD.
5. Binary identity. An explicit cross-sex identity was a requirement. The Dutch protocol explicitly disqualified young people with non-binary identities from eligibility for medical interventions. Such cases were treated with therapy only.
6. A strong family and social support mechanism. Family support was viewed as essential for successful transition. Challenging family environments (including estrangement from parents, guardians, and significant family conflicts) led to a delay in transition, pending stabilization of intrafamilial bonds.
7. Strong understanding of biological reality. The Dutch researchers cautioned that a young child affirmed as the opposite sex may not grasp biological reality, risking future success of transition. They required young people to demonstrate an understanding of the limitations of transition and the need for lifelong hormones and maintenance.
8. Extensive psychological evaluation with ongoing treatment and support. All young people the Dutch clinicians transitioned were reported to have received psychological treatment and support prior to and during transition. This was necessary to address gender dysphoria, distress, and manage social difficulties resulting from non-normative gender expressions.
9. Assessment of the ability to consent and understand risks. The Dutch researchers emphasized the need for young people to be able to provide meaningful consent, since the intervention is associated with known adverse effects such sterility, infertility, and a range of anticipated health risks from lifelong administration of cross-sex hormones.
10. Minimum age limits for interventions with potential or demonstrated irreversibility. In addition to the minimum age for puberty blockade of 12, there was the minimum age of eligibility for cross-sex hormones at 16, and surgery at 18. Interestingly, examination of the actual Dutch study outcomes revealed even older actual average ages: puberty blockers at 15, cross-sex hormones at 17, and surgery at 19.28
It should also be noted that the Dutch studies have poor applicability to currently presenting cases of youth gender dysphoria. To be eligible for medical transition, patients had to have persistent gender dysphoria “from toddlerhood onwards”56 with clear cross-sex identification.57, 54 Currently, most gender dysphoric youth are gender-normative until their teen years and present with a high burden of comorbid mental health conditions present before the onset gender dysphoria.58 These two factors would have rendered most of the youth seeking to transition today ineligible for transition using the Dutch protocol criteria. Therefore, it can be argued that the Dutch research should never have been used as justification for scaling the practice of pediatric gender transition widely.
The next section briefly outlines changes in the epidemiology of gender dysphoria that render the Dutch research largely inapplicable to the current clinical dilemmas.
IV. Changes in the Epidemiology of Gender Dysphoria in Youth
The epidemiology of gender dysphoria markedly changed since the publication of the Dutch protocol and its outcomes. Previously, gender dysphoria in youth was rare and primarily affected prepubescent boys. For reasons that are not yet understood, there has been a several-thousand-fold increase in gender dysphoric youth in the West, with up to 2-9% of youth asserting a transgender identity.59,60 The majority of current clinical referrals are adolescent females whose gender dysphoria arose in the context of previously diagnosed mental illness or neurocognitive problems such as ASD and ADHD.58,61,62,63
The graphs below from the UK and Sweden display the marked increase in the prevalence of gender dysphoria in youth that occurred in the past several years. A recent analysis of U.S. data by Reuters found that there were over 42,000 new diagnosis of gender dysphoria in 2021 alone in youth under 18.64 Considering that these data did not include 15 million college youth in the U.S., 4%-7% of whom identify as transgender or gender diverse (males and females, respectively)65—the total number of new gender dysphoria diagnoses likely exceeds the number of new diagnoses for conditions such as Type I diabetes.66
Worldwide, the number of new diagnoses of gender dysphoria continues to grow rapidly. In the UK, the rate of pediatric “gender” referrals doubled in 2021-22 compared to the prior year (see graph below). In the U.S., the number of new diagnoses of gender dysphoria for youth under 18 increased by 70% between 2020 and 2021.64
This novel presentation of gender dysphoria in youth is rapidly evolving. For example, a nonbinary identity used to be rare, but has become common, and by some estimates, even the predominant presentation.67,68 It is likely that the extreme sex ratio skewing toward adolescent females will become less extreme in the near future. Indeed, reports of growing numbers of adolescent gender-dysphoric males following COVID-19 lockdowns have surfaced but have not yet been reported in the scientific literature, which can lag by months or even years.
V. Diagnostic Uncertainty
It should be noted that there is no valid diagnostic tool to assess the permanence of gender dysphoria in young people. While the DSM diagnosis of “gender dysphoria” can accurately determine who currently suffers from gender dysphoria (concurrent validity), it cannot predict who will persist in suffering from gender dysphoria in the future absent any interventions (predictive validity).69, 70 The assertion that trans-identified adolescents are unlikely to desist and will go on to live out their lives as transgender adults is baseless. That most childhood-onset gender dysphoria cases resolve before adulthood (provided the child is not gender-transitioned) is well-established and recognized by the Endocrine Society.30 And while it is true that the Dutch clinicians hypothesized that adolescents with childhood-onset gender dysphoria who still identify as transgender in their teen years are unlikely to desist, this assumption has never been tested. The presumption of permanence of transgender identity in teens is entirely erroneous when it comes to youth who only began to identify as transgender around puberty—the presentation that affects most of youth cases of gender dysphoria today. Little is known about this novel presentation or its future trajectory.
A study from the Netherlands that dates back to 2001 serves as a case in point.71 According to this study, 27 minors with gender dysphoria were disqualified from medical transition due to a number of psychological and life circumstances. The reasons for exclusion described by the study bear a marked resembles to the currently presenting cases of gender dysphoric youth. Upon follow-up 1-7 years later, only 20% of the rejected subjects (n=6) chose to undergo gender reassignment as adults; 80% refrained from it. Among those who refrained and participated in follow-up research (n=14), 80% “did not feel any regrets about having refrained from SR [sex reassignment] or being rejected….” Only 1 study subject expressed strong regret, however the patient chose a significantly less invasive intervention as an adult compared to what would have been provided under the Dutch adolescent transition protocol.
These data must be interpreted with caution due to the small sample size and high risk of bias in the study. Nor are these cases a perfect “match” for the currently presenting cases. However, these results challenge the notion that adolescents diagnosed with gender dysphoria will invariably grow up to be transgender-identifying adults and that harm will ensue from a delay in the initiation of medical interventions. The results also suggest potential benefits not only for those who will eventually desist from their wish to medicalize their gender identity, but also for those who will pursue medical transition in the future, by creating an opportunity to clarify their gender transition goals as adults.
It should also be noted that the recently released ICD-11 diagnosis of “gender incongruence,” which took effect worldwide in 2022 (but will take some time to implement), has added to the diagnostic uncertainty by removing the “distress” criterion that is central to the DSM “gender dysphoria” diagnosis.72 WPATH’s updated guidelines specifically state that the ICD-11 “gender incongruence,” rather than the DSM “gender dysphoria” diagnosis, should be used in the determination of the medical necessity of “gender-affirming” interventions for adolescents.27 The ICD-11 diagnosis has no clear clinical parameters to target, as the diagnosis is based solely on a subjective experience of incongruence between biological sex and gender identity. This adds to the risk that a temporary form of gender identity will be prematurely medicalized into permanence. This concern applies not only to gender dysphoric youth who may cease to identify as transgender, but also to individuals whose transgender identity and desired physical presentation to match the identity may undergo further evolution, such as a change from a “transwoman” or “transman” to a non-binary identity.
VI. Suicidality and Suicide
The argument that transgender-identified youth are at high risk of suicide when not allowed to medically transition as soon as they wish for it is not supported by evidence. Suicide among trans-identified youth is indeed significantly higher compared to the general population of youth.73,74 However, the “transition or die” narrative is both inaccurate and ethically fraught.50 A recent analysis from the gender clinic in the UK found the rate of completed youth suicides to be 0.03% over a 10-year period, which translates into an annual rate of 13 per 100,000. The analysis found no difference between youth on the waitlist and those in treatment (however the sample size was small since suicides were rare). 73 Another study combining data from several gender clinics in Europe and North America concluded that the rate of suicidality (self-harm that did not result in suicide), while significantly elevated compared to the general population of teens, was similar to the rate of suicidality in other adolescents referred to mental health clinicians for psychological problems that were unrelated to gender identity.74
The notion that trans-identified youth are at alarmingly high risk of suicide usually stems from biased online samples that rely on self-report and frequently conflate suicidal thoughts and non-suicidal self-harm with serious suicide attempts and completed suicides. Suicide risk in all patients is a multifactorial phenomenon.75 Gender transition is not an evidence-based approach for treating a young suicidal person, as no long-term, quality study to date has demonstrated that either hormonal or surgical transition reduces suicide rates or serious suicide attempts.76,77 Trans-identified youth who are suicidal should be treated with evidence-based suicide prevention protocols.74
Conclusion
The science on how to best care for the rapidly growing numbers of youth with gender dysphoria is far from settled. Having originated as an “innovative clinical practice,” the practice of youth gender transition spread into general medical settings bypassing rigorous research. Unfortunately, the foundational Dutch research that gave rise to pediatric gender transition suffers from significant deficiencies which have not been corrected by more recent research.50
Systematic reviews of evidence consistently find that the existing studies suffer from significant risk of bias due to small sample sizes, lack of control groups, comingling of multiple interventions, and other methodological problems. 13,14 The U.S. National Institute of Health (NIH) recognized this limitation in the evidence base and has commissioned research into the health effects of puberty blockers and cross-sex hormones administered for the purpose of gender transition.38, 78 Until such research is completed, the results analyzed, and the risk-benefit ratio is found to be favorable, the practice of pediatric gender transition is experimental.
As the Board debates how to proceed, it should not lose sight of several important facts. First, three European countries have now deemed “gender-affirming” interventions for youth effectively experimental, only allowing pediatric transitions as measures of last resort in rigorously controlled research settings. Second, there is no quality evidence to guide gender detransition. As the Board contemplates their approach, careful consideration should be granted to individuals who have already undergone gender transition, many of whom rely on ongoing hormonal treatments.
Third, the Board should recognize that persons aged 18-25, while legally adults, represent a vulnerable group. There is a precedent in the U.S. healthcare system for treating this group differently from mature adults in a range of contexts, from health insurance coverage eligibility79 to mental health treatments.80 At the very least, an enhanced informed consent process should be implemented for young adults wishing to undergo gender transition to ensure their thorough understanding of the risks and uncertainties.50 Fourth, the approach to transition of mature adults should be evaluated separately, as adults are able to provide valid informed consent.
Fifth, the Board should consider that the European countries that no longer medicalize youth gender dysphoria with hormones and surgery are treating it instead with psychological and psychiatric care. The Board should make a strong and unambiguous statement that psychotherapy for gender-related distress is the community standard and should not be stigmatized or conflated with conversion therapy.
The Board should consider collaborating with the health authorities in Finland, Sweden, and the UK to learn about emerging best practices regarding clinical management of the rapidly growing numbers of gender dysphoric youth. The approach described in the recently released draft NHS England guidelines serves as a strong example of a compassionate approach care, and the core principles articulated by the model are widely applicable.11
We urge the Florida Board of Medicine to undertake a thorough and thoughtful process, consulting a range of stakeholders with divergent perspectives. It is critical that the model adopted serves to protect the long-term health of the rapidly growing numbers of gender dysphoric youth, while safeguarding the health and dignity of all Floridians.