November 2, 2021

Gender-Dysphoric Adolescents and Gender Transition Regret: What We Don't Know

The Lancet debate on gender-dysphoric youth: getting the facts right

Recently, The Lancet published an editorial defending the broad availability of medical gender transition interventions for gender-dysphoric youth. The editorial was written in response to several US bills that aim to limit the use of hormones and surgery in minors. The editorial asserted that hormonal and surgical interventions for gender-dysphoric youth are proven treatments; that puberty blockers are fully reversible and prevent suicidality; and that, because regret for gender transition is below 1%, concerns about future regret in gender-transitioned youth are not justified. 

The scientific debate that ensued (with six Letters to the Editor published, three of which were critical of the Editorial's position) revealed that these assertions are not supported by the evidence. While the debate covered several topics, the final round centered on transition regret. This is not surprising. Both the supporters and critics of transitioning minors agree that transition carries numerous medical risks, and the evidence of benefit is graded as "low/very low" quality. Thus, the argument of “low future regret” is essential to the advocates of medicalizing gender-dysphoric minors. 

Below we summarize the findings that emerged from the debate on regret, as well as other key arguments that have been highlighted by the Letters to the Editor critical of The Lancet's Editorial. 

Future Regret

One of the proponents of pediatric medical transition submitted a Letter to the Editor in defense of The Lancet's position, asserting that regret in those who gender-transitioned as adolescents is nearly nonexistent. The Letter cited a recent regret study that is frequently cited to support medical gender transition of minors. However, this study suffers from significant limitations that lessen the certainty of the claim of  "low regret" in youth:

  • The currently-treated populations of adolescents are very different from the population studied. All study subjects had severe gender dysphoria that began in early childhood and had no significant mental health comorbidities, which is not true of today's adolescent patients. Further, the study only evaluated those who underwent gonadectomy (surgical removal of testes/ovaries), which is not as commonly performed today, especially among gender-dysphoric natal females.

  • The study excluded 22% of those who started on the hormonal treatment pathway but did not proceed further with surgical removal of ovaries or testes. These individuals may have higher levels of regret than the group that proceeded to complete their medical transition as outlined in the Dutch protocol. 

  • The follow-up time was less than 10 years, which is when regret typically emerges in adult studies.

  • 20% of study subjects dropped out of care / were lost to follow-up, which can mask regret.

  • Importantly, the definition of "regret" was exceedingly narrow. For example, neither Keira Bell, nor many of the regretful detransitioners from the recent research on detransition would be considered to be "regretters" by the study. 

To qualify as a "regretter," one had to revert to living in their natal sex role by starting natal-sex hormone supplementation, and do so under medical supervision of the same clinic that facilitated the original transition. However, as a recent study demonstrated, most detransitioners do not return to their medical providers to tell them about their detransition or regret. In addition, many post-gonadectomy patients who regret their gender transition find it is not feasible to revert to living in their natal sex, in part due to the irreversible nature of genital surgeries. Just as not all detransitioners regret their prior attempt at transition, not all those who continue to live in their gender-transitioned role are free from regret over their original decision to transition.

The interpretation of “regret” is further limited because patients who died from medical complications related to transition, and those who committed suicide following transition, were excluded from the study. We know very little about the medical outcomes of the adolescents treated by the Dutch, because only the psychological outcomes have been reported. However, we do know that at least one adolescent died from surgical complications. Another paper from the same Dutch clinic published in 2020 reported that four individuals referred as adolescents subsequently died by suicide.

The debate led to a subsequent correction of the Letter that had defended the Editorial's claim. While SEGM welcomes the correction, it did not adequately explain how these corrections and other limitations of the study reduce the certainty of the "low regret" claim. Specifically, the evidence of low regret of gender transition in youth comes from a study based on a protocol that has very little applicability to today’s clinical practice. It is incorrect to assert that we know future regret rates of adolescents transitioning under vastly different circumstances today.

It is also concerning that the statement, "the only relevant case of regret of which we are aware is Keira Bell" was not corrected, given the depth and complexity of the literature, spanning decades and dozens of papers. Evidence of the rising numbers of detranstioners and their accounts have been noted by many clinicians and researchers, including Expósito-Campos (2020), Vandebussche (2021); Pazos-Guerra, et al. (2020); Entwistle (2020); and Littman (2021).

(We expand on the correction and its implications in the section "The Rebuttal—and the Correction of the Rebuttal" below).

Critical Responses to The Lancet’s Editorial

In addition to the issue of regret, the scientific debate that followed The Lancet Editorial highlighted several other key areas of disagreement regarding the evidence. This debate was made possible by The Lancet publishing 3 critical Letters to the Editor (LTE).

The LTE “Puberty Blockers for Gender Dysphoria: the Science is Far From Settled,” submitted by SEGM, noted that the evidence for the use of puberty blockers and cross-sex hormones in teenagers comes from the Dutch studies that considered a population distinctly different from the one presenting today: specifically, youth whose gender dysphoria began in early childhood, and who had no significant co-occurring mental health problems. The critique questioned whether earlier findings could be generalized to the novel population of young people whose gender distress and transgender identification emerged for the first time after puberty. Many of these young people have no history of childhood gender dysphoria and frequently suffer from significant mental health problems.

SEGM also noted that the magnitude of the post-treatment improvements in mental health in the original Dutch study on puberty blockers was of marginal clinical significance. The depression (Beck Depression Inventory) scores improved by around 3 out of 63 points, and the global function (Children's Global Assessment Scale) scores improved by around 4 out of 100 points, and other measures of psychological health had similar improvements of marginal clinical significance—or no improvement at all. SEGM raised the question whether such small gains justify the risks to bone health, fertility, and other as yet unknown long-term effects of interrupting puberty. 

An LTE from Richard Armitage highlighted the fact that the low purported prevalence of regret among adults cannot be extrapolated to youth whose capacity to make a truly informed decision is considerably different from that of adults. Armitage also took issue with the claim that puberty blockers reduced suicidality, pointing out that the review cited to support this claim only contained a single study on suicidality, and that study considered adults not children. (More comprehensive critiques of the suicidality study and the sample the study used were published in Archives of Sexual Behavior).

Another LTE, from a group of psychotherapists submitted by Stella O’Malley (a SEGM advisor), also took issue with the 1% regret rate, noting that this number comes from an era when more stringent guidelines determined who received medical interventions. O’Malley et al. recounted the changing practices in Sweden, Finland, and the UK, where the need for much more caution when considering pediatric medical transitions has been recently recognized.

The Rebuttal—and the Correction of the Rebuttal

In response to these letters, Ken Pang, a leading pediatrician from Melbourne’s Royal Children’s Hospital gender clinic, defended the editorial’s claim of low rates of transition regret, asserting that the regret rate is extremely low not just among those who transitioned as adults, but also among adolescents. To support their claim, they cited another Dutch study (Wiepjes et al. 2018): “Wiepjes and colleagues observed that of 812 adolescents who presented to their gender clinic since the late 1980s, 635 (78·2%) received gender-affirming hormones and surgery, and none regretted their treatment in follow-up to 2015.”

However, this summary of the Wiepjes study indicating a 0% regret rate for adolescents receiving hormonal and surgical treatments contained several factual errors and misrepresentations, which were subsequently corrected.  The relevant section of the Letter to the Editor now reads, “Wiepjes and colleagues observed that of 812 adolescents who presented to their gender clinic since the late 1980s, 309 received gender-affirming hormones and gonadectomy and, of the 80% who continued to attend the clinic up to 2015, none regretted their treatment.”

This seemingly minor correction reveals a major misstatement. Specifically: 

  • While the correction does not make it explicit, the additional data it contains make it clear that only 247 adolescents were evaluated for regret (80% of 309). This is less than 40% of the sample size originally claimed by Pang et al.

  • The correction also reveals that 20% of the treated adolescents were lost to follow-up as of 2015. It is unclear under what conditions the youth who depend on hormonal supplementation for life would be lost to follow-up in a country with centralized gender services. It is possible that those who dropped out of gender services care may have higher rates of regret.

  • Finally, the correction specifies that gonadectomy (surgical removal of testes/ovaries) was a key study eligibility requirement. This excluded 22% of the eligible participants who could have received gonadectomy but did not. The population that opted to undergo gonadectomy may have different levels of regret from the population that opted out of, or was disqualified from, completing their surgical transition, as called for by the Dutch protocol.

Concluding Thoughts

Frontline clinicians caring for the growing numbers of gender-dysphoric youths rely on scientific journals to present unbiased, objective and reliable information. By platforming both sides of scientific debates, peer-reviewed journals play a critical role in helping clinicians navigate areas of medicine where evidence is uncertain and the science is not settled. While The Lancet corrections were much more limited in scope than we had hoped, we thank the journal for platforming this important debate, and we hope that other top-ranked journals will soon follow suit, bringing nuance and balance to the gender medicine debate.

 

 

Note: The original Editorial, the 3 critical responses, the rebuttal by Pang et al., and the subsequent correction of the rebuttal are available on The Lancet site free of charge following a simple registration process.