Controversial_Ideas 2023, 3(1), 10; doi:10.35995/jci03010010
Article
Politics Aside, Healthcare Considerations Motivate More Caution before Medical Intervention for Trans-Identifying Youth
Society for Evidence-Based Gender Medicine; jaycohn77@gmail.com
How to Cite: Cohn, J. Politics Aside, Healthcare Considerations Motivate more Caution before Medical Intervention for Trans-Identifying Youth. Controversial Ideas 2023, 3(1), 10; doi:10.35995/jci03010010.
Received: 23 August 2022 / Accepted: 24 April 2023 / Published: 28 April 2023
Open access
: JOURNAL OF CONTROVERSIAL IDEAS is a peer-reviewed open-access journal.Abstract
:The 2022 article “Legislation restricting gender-affirming care for transgender youth: Politics eclipse healthcare” by K. L. Kraschel et al. implies that attempts in the United States to restrict medical interventions for gender dysphoria are due to political motivations. Although there are likely some whose stance on these interventions is based upon politics, there are sound medical reasons, independent of politics, for advocating for more cautious medical intervention protocols. Neglecting mention of these reasons obscures the fact that medical intervention outcomes are difficult to predict and that serious risks and irreversible consequences are present. In other countries, following extensive evidence review, supportive alternatives to medical intervention are being prioritized instead. Here, several claims of Kraschel et al. regarding the state of medical intervention healthcare are compared to the research evidence and shown to fall short. Healthcare issues alone justify challenging current United States medical treatment protocols.
Keywords:
gender dysphoria; medical interventionIntroduction
The article “Legislation restricting gender-affirming care for transgender youth: Politics eclipse healthcare” by Kraschel et al. (2022)1 claims that attempts to restrict medical interventions for gender dysphoria in the United States are due to political motivations and have no basis in healthcare concerns. Kraschel et al.’s argument that proposing restrictions on these interventions is a political issue rests on the claims that there are “evidence-based clinical guidelines” for current US practices (with the implication that the medical interventions are well supported by evidence), that the medical interventions are not dangerous, and that these interventions have been shown to be beneficial. If all of these (including the implications) were true, then one might argue that objections to these medical treatments are in conflict with healthcare priorities. As shown below, when compared to the medical evidence, the last two assertions can be shown to be not true, and the first, regarding the evidence base, is misleading. Although politics may and likely does motivate some policies, the (state of the) research evidence behind these treatments, on its own, leads to serious healthcare concerns about these medical interventions. Some related claims2 have been rebutted3 previously.
Evidence-Based Clinical Guidelines
Kraschel et al. accurately claim that the two following guidelines set out treatment protocols:4
This statement does not mean there is reliable evidence behind the treatments. The Endocrine Society itself has rigorously evaluated the evidence behind its own recommendations, and found almost all of the supporting evidence to be low quality, very low quality, or ungraded.5 Only three of the 28 recommendations were supported by moderate quality evidence: confirm diagnosis, counsel regarding fertility preservation, and evaluate and address other medical conditions that might be exacerbated by hormonal treatment. Another six recommendations were “ungraded good practice statements,” i.e., with evidence “either unavailable or not systematically appraised.” The evidence behind the remaining 19 treatment recommendations was found to be low or very low quality GRADE,6 meaning that the true effect may be (for low quality) or is likely to be (for very low quality) substantially different from the estimate of the effect. Thus the Endocrine Society itself found the evidence base for its recommended treatments to be inadequate for estimating outcomes.A series of evidence-based clinical guidelines set out the treatment for gender dysphoria, in particular the Endocrine Society Clinical Practice Guideline for Endocrine Treatment of gender-dysphoric/gender-incongruent persons and the World Professional Association for Transgender Health [WPATH] Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People.
The inability of a low quality study to estimate outcomes in a reliable way is highlighted by the fact that the only statement the Endocrine Society Guidelines offer as evidence for the mental health benefits of puberty blockers (Gonadotrophin releasing hormone analogs, denoted as GnRH analogs or GnRHas) is “Treating GD[gender dysphoric]/gender-incongruent adolescents entering puberty with GnRH analogs has been shown to improve psychological functioning in several domains (86).” The referenced study (86),7 however, failed replication.8
The weakness of the evidence base is further reflected in the Endocrine Society guideline statement: “In the future, we need more rigorous evaluations of the effectiveness and safety of endocrine and surgical protocols. Specifically, endocrine treatment protocols for GD/gender incongruence should include the careful assessment of the following: (1) the effects of prolonged delay of puberty in adolescents on bone health, gonadal function, and the brain (including effects on cognitive, emotional, social, and sexual development); ... (4) the risks and benefits of gender-affirming hormone treatment in older transgender people.”9 These are significant uncertainties, especially given that every young person receiving treatment is expected to become one of the older people affected by (4).
The other "evidence-based" guideline mentioned is the WPATH SOC7, “Standards of Care.”10 However, the WPATH SOC7 are not evidence based11 nor standards of care, but rather practice guidelines, which can be biased.12 In fact, in a formal guideline review,13 five out of six reviewers did not recommend use of WPATH SOC7 as guidelines; the last reviewer recommended use only if modified. The reviewers observed: “Some extracted statements might have been intended as recommendations or standards, but many were flexible, disconnected from evidence and could not be used by individuals or services to benchmark practice.” After the appearance of Kraschel et al.,14 WPATH released new recommendations (WPATH SOC 8),15 which also have significant shortcomings, for example, “the strength of evidence presented to justify a recommendation was ‘at odds with what their own systematic reviewers found.’”16 Although several systematic reviews were already publicly available (see below),17,18,19 WPATH SOC 8 stated that “a systematic review regarding outcomes of treatment in adolescents is not possible.”20 It has been noted with regard to WPATH SOC 8 specifically that an entity making recommendations without a systematic review would be “violating standards of trustworthy guidelines;”21 furthermore, the WPATH SOC 8 methods are prone to bias.22
It is worth mentioning that another influential set of recommendations, by the American Academy of Pediatrics (AAP), is also not evidence based.23 A peer-reviewed critique found that “remarkably, not only did the AAP statement fail to include any of the actual outcomes literature on such cases, but it also misrepresented the contents of its citations, which repeatedly said the very opposite of what AAP attributed to them.”24 A recent investigative report discusses differences between the WPATH SOC 8 and AAP recommendations and evidence-based medicine guideline requirements, as well as “serious problems” with the Endocrine Society recommendations.25
Beyond the Endocrine Society GRADEs, several different evaluations of the evidence base for providing puberty blockers, hormones, and surgeries have been done, including:
- UK National Institute for Health and Care Excellence (NICE) evidence reviews for under 18: “The critical outcomes for decision making are the impact on gender dysphoria, mental health and quality of life. The quality of evidence for these outcomes was assessed as very low certainty using modified GRADE.”26,27
- Swedish National Board of Health and Welfare (NBHW) (2022) for adolescents, finding: “The NBHW deems that the risks of puberty suppressing treatment with GnRH-analogues and gender-affirming hormonal treatment currently outweigh the possible benefits, and that the treatments should be offered only in exceptional cases.”28
- Cochrane review “found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition.”29
These findings are consistent with the low quality found by the Endocrine Society, underscoring the difficulty in estimating likely outcomes with medical intervention.
Puberty Blocker Safety
Kraschel et al. (2022) state:
Although the authors wish to carry over results from treatment of a different population for a different condition, the Interim Cass report cautions that “it is important that it is not assumed that outcomes for, and side effects in, children treated for precocious puberty will necessarily be the same in children or young people with gender dysphoria.”34 For fertility in particular, when puberty blockers are followed by hormones, “GnRHa therapy prevents maturation of primary oocytes and spermatogonia and may preclude gamete maturation, and currently there are no proven methods to preserve fertility in early pubertal transgender adolescents."35GnRHas have been used in the treatment of central precocious puberty dating back to the 1970s, providing longitudinal safety data for their use in the pediatric population. ... However, there is some concern that going directly from pubertal suppression to gender-affirming hormones like estrogen or testosterone may impair fertility. For that reason, existing guidelines recommend fertility counseling prior to adolescent patients pursuing such care, so that they may consider fertility-preservation options.”33
There are other risks of puberty blockers. They can significantly decrease bone mineral density,36,37 cause depression38 and have been seen to decrease sexual desire in adult men.39 Their effects on brain development are not understood; there is a concern that “rather than buying time to make a decision, puberty blockers may disrupt that decision-making process.”40
More importantly, the medical interventions under discussion do not only involve puberty blockers, but also hormones and surgeries. Medical risks are consequential: estrogen and testosterone for gender-affirming care degrade sexual organs,41 which can also cause, e.g., significant pain from vaginal and uterine atrophy42 and/or sexual dysfunction. Also observed are associated changes in the brain,43,44,45,46 increases relative to birth sex of adverse cardiovascular events such as blood clots (venous thromboembolism; more than a factor of 4 for male to female), strokes (factors of more than 1.6 for both sexes) and heart attacks (more than a factor of 4 for female to male)47,48, as well as harmful changes to the endocrine system,49 immune system (e.g., an increase in multiple sclerosis by a factor of 5 for male to female50), and life span.51,52 Surgeries are also of concern for adolescents, and include double mastectomies at ages as young as 1353 and vaginoplasties for minors.54,55
Benefits of Gender-Affirming Care
Kraschel et al. state:
The authors then reference Turban et al. (2022)57 and van der Miesen et al. (2020).58 Five of the six studies referenced by the former were rigorously evaluated in the NICE evidence reviews mentioned above, where they had their "overall quality assessed as poor." More detailed critiques of each can be found in these two NICE evidence reviews.59,60 For puberty blockers, NICE states: "Studies that found differences in outcomes could represent changes that are either of questionable clinical value, or the studies themselves are not reliable and changes could be due to confounding, bias or chance.”61A substantial body of literature exists documenting the benefits of gender-affirming medical interventions, where indicated, for adolescents with gender dysphoria. Over a dozen studies have collectively linked such care to improvements in depression, anxiety, and suicidality.”56
Not covered by the NICE evidence reviews are the sixth Turban et al. reference,62 de Vries et al. (2014),63 Turban et al.64 itself, and van der Miesen et al.65 De Vries et al.66 is a small well-known study that reports short term (1–2 year) mental health and gender dysphoria outcomes of 55 young people after undergoing surgery, finding small psychological improvement. They reported large gender dysphoria improvement, but this appears to have been confounded by changing the measurement instrument before and after surgery,67,68 and in addition, preliminary reports of some of these patients’ long-term outcomes are concerning, including reproductive regret in more than a quarter of the patients, one or more identity changes after treatment completion for a sizable percentage, and for male-to-female transitioners, apparent sexual difficulties for more than two-thirds.69 Furthermore, two of the criteria for inclusion in this study were lifelong extreme gender dysphoria and psychological stability,70 neither of which are part of the readiness requirements for medical interventions for young people as set out in the Endocrine Society or either set of WPATH guidelines, so the study’s outcomes would not be expected to be relevant. The cross-sectional design of Turban et al.71 limits determination of cause and effect (an association or correlation does not indicate whether the intervention led to the symptom or vice versa, or whether something else caused both) and these same (non-representative72) data also show an association between greater suicidality and taking estrogen.73 The last reference provided in support, van der Miesen et al., explicitly says: “The present study can, therefore, not provide evidence about the direct benefits of puberty suppression over time and long-term mental health outcomes.”74 That is, it cannot show benefits due to medical intervention either. Benefits, when seen, have not been demonstrated to be due to medical intervention in either these or other research studies, and the risks are significant.
These facts also undermine the claim by the authors that these interventions are "medically necessary care." The WPATH SOC7 guidelines do say medical intervention is "medically necessary," but qualify it with the phrase "for many people."75 WPATH SOC7 does not provide a clinical test to identify the “many people" and no test has been established since. Identifying and excluding transient gender dysphoria from medical intervention is desirable (one WPATH SOC 8 requirement for hormones and surgery is that “Other possible causes of apparent gender incongruence have been identified and excluded”76) but the requisite relevant and reliable long-term studies are absent and there is no agreement among experts as to how to determine how a given individual’s gender dysphoria will develop, with or without medical intervention.77,78,79,80 (This significant lack of professional agreement about treatment protocols is also a challenge for the WPATH SOC 8 definition of “medical necessity,” which relies upon “generally accepted standards of medical practice” based upon “credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community”:81 the variation between expert protocols is so large that it appears difficult to establish any of them as “generally accepted.”)
Medical intervention has certainly not been shown to be medically necessary in general. The etiology and development of gender dysphoria is not yet well understood: it appears that there are many different pathways into and out of gender dysphoria.82 In particular, care for gender dysphoria is not synonymous with medical intervention. Some with gender dysphoria have had it resolve83,84,85 with mental health support such as psychotherapy86,87 and others have medically transitioned and found that it did not alleviate their distress or gender dysphoria;88,89 in particular, some have been badly harmed.90 (The number who detransition, regret, and/or have been harmed is unknown due to the lack of adequate long-term outcome studies.91,92,93,94) It has also long been observed in studies that in the absence of medicalization and social transition, the majority with childhood onset gender dysphoria have it resolve with time.95,96 For all who recovered with either time and/or mental health support, medical intervention was not necessary. For those who were instead harmed by medical intervention, this is even more true; in fact, some detransitioners report wishing they had been offered exploratory therapy instead of medical intervention which they now regret.97
Discussion
No studies have shown how to identify, in a reliable way, young people for whom the medical intervention benefits may outweigh the significant long-term risks. Nor is there sufficient clinical knowledge to predict for whom gender dysphoria will resolve with time or exploratory psychotherapy, or will not resolve with medical transition after the initial honeymoon phase is over, or will turn out to have other root causes after medicalization has commenced.98,99 These concerns, backed by the numerous systematic evidence reviews described earlier, have led many countries to restrict medical intervention for young people, often alongside prioritizing psychotherapy, in order to provide them with support more in line with the low-quality evidence for medical intervention. For example, the French National Academy of Medicine has stated that “since there is no test to distinguish a ‘structural’ gender dysphoria from transient dysphoria in adolescence” it is “therefore advisable to extend as much as possible the psychological support phase.”100 As noted above, Sweden provides medical interventions only in exceptional cases.101 Finland provides medical intervention on a case by case basis,102 Norway is revisiting its guidelines, now calling these interventions “treatment under trial”103 and the UK is closing its main pediatric gender clinic as it is not safe or viable long term104,105 and will now aim to provide more holistic106 treatment. Including supportive exploration and counseling allows gender dysphoria to be put into the context of the full situation of the young person, and addressed as part of other challenges they might be facing (many young people with gender dysphoria currently present with significant comorbidities107).
Many current US treatment protocols are based upon the affirmative model espoused by the AAP,108,109 but rejected by several other countries.110,111 Casting objections to these protocols as solely political obscures the serious outcome uncertainties, risks of medical intervention, and the significant disagreements between experts in this field.112,113 (Nor are the medical concerns elaborated upon here “science-denialist”114 as some have claimed.) Such accusations can mislead clinicians, patients, and their families, and impede efforts to determine the best way to help these young people. It is important that they all have access to accurate information about these treatments, their uncertain outcomes, their risks and their alternatives, and the professional disagreements: serious healthcare issues are involved.
Given the low-quality evidence and the lack of understanding around the different ways gender dysphoria can arise and resolve, substantive questions remain. For instance, long-term follow-up of all currently medicalized patients in a controlled research setting would provide crucial and desperately needed information to guide care of this vulnerable population, as knowledge of outcomes to improve their care is greatly needed. Similarly, more studies to better understand and improve mental health support approaches are also needed, as well as improved support for the growing (but as yet uncounted) ranks of detransitioners. It is tragic that many young people are misinformed as to the effectiveness and necessity of risky and irreversible medical intervention for gender dysphoria and believe that their happiness depends upon getting it; in order to decrease the risk of iatrogenic harm, it is crucial to better inform clinicians and the wider community of these serious concerns, of alternatives such as ethical explorative psychotherapy, and of the need for further research. No politics is required. Just prioritization of evidence-based healthcare.
Acknowledgments
I thank the peer reviewers and other clinicians and researchers for their helpful criticisms and suggestions.
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| 32 | Emphasis in the original. |
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| 56 | Kraschel, op. cit., pp. 3–4. |
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| 59 | National Institute for Health and Care Excellence. (2020). Evidence review: Gender-affirming hormones for children and adolescents with gender dysphoria, op. cit. |
| 60 | National Institute for Health and Care Excellence. Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria, op. cit. |
| 61 | Ibid., p. 13. |
| 62 | Turban et al., op. cit. |
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| 64 | Turban et al., op. cit. |
| 65 | Van der Miesen et al., op. cit. |
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