Thread by @SEGMtweets

Have hormones been proven safe & effective for gender dysphoric (GD) youth? Is transition regret so rare that it is negligible? When a recent editorial by @TheLancet made these claims, scientific debate ensued, revealing that the science is not settled./1
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While the debate covered several topics, the final round centered on transition regret. This is not surprising. Both the supporters & critics of transitioning minors agree that transition carries medical risks, and the evidence of benefit is graded as "low/very low quality."/2

Thus, the argument of “low future regret” becomes essential to the advocates of medicalizing gender-dysphoric minors. If future regret rates aren't low, then administering poorly-evidenced interventions with known risks to minors is even more ethically fraught. /3

The Lancet debate exposed key deficiencies in the argument of “low regret”: adult regret studies don't apply to youth, and the cited youth regret study suffers from so many limitations as to be largely irrelevant to today's transitioning youth. /4
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Per the criteria of the often-cited study claiming low regret in those transitioning as minors, neither Kiera Bell, nor the young detransitioners from the recently published detransition studies would be counted as "regretters."/5
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In this series of tweets, we outline the key flaws in the “low regret” study frequently quoted by the advocates of medically transitioning minors. We also highlight three critical Letters to the Editor published by The Lancet, and the arguments they raise. /6

1. The "youth regret" study only evaluated patients with a severe childhood onset GD, and who were treated with gonadectomy (removal of ovaries/testes). This cohort is markedly different from GD youth today, both in the presentation & treatments. /7
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2. Regret was defined as starting natal-sex hormones at the same clinic that provided transition. For many, genital surgery makes it impossible to resume life in one's natal sex. Further, 3/4 of detranstioners do not return to their gender clinician. /8
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3. The study excluded 22% of those who started hormones but did not proceed further with surgical removal of ovaries/testes, as was required by the Dutch protocol. They may have higher levels of regret than the group that proceeded to complete their medical transition. /9

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

5. Finally, there are outstanding questions about what happened to the 20% of the post-gonadectomy patients who stopped getting care at the clinic, since these patients have life-long medical needs. High rates of loss to follow up frequently mask regret. /11

It is clear that the frequently cited study showing "0% regret" has very limited applicability to the currently treated populations of GD youth. It is incorrect to assert that we know future regret rates of adolescents transitioning today. /12

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 @TheLancet publishing 3 critical Letters to the Editor (LTE). /13

SEGM's LTE, “Puberty Blockers for Gender Dysphoria: the Science is Far From Settled” noted that teenagers in the Dutch studies, which serve as the foundation for affirmative care, come from a markedly different population than those presenting today. /14 thelancet.com/journals/lanch…

The Dutch studied youth with childhood-onset gender dysphoria who had no significant co-occurring mental health problems. Teens presenting to gender clinics today are much more likely to have had gender-normative childhoods, and to suffer from significant mental health issues./15

SEGM also noted that in the Dutch studies, the post-treatment change in mental health (e.g. anxiety, depression) is very small. We asked: do such small gains justify the risks to bone health, fertility, and other as yet unknown long-term effects of interrupting puberty? /16

Another published LTE (by Richard Armitage) argued that the purportedly low regret rate in adult transition populations cannot be extrapolated to youth whose capacity to make a truly informed decision is considerably different from that of adults. thelancet.com/journals/lanch…

The letter also took issue with the claim that puberty blockers reduced suicidality. That claim came from a single study on suicidality, and considered adults not children. That study and its sample had been extensively critiqued/18 link.springer.com/10.1007/s10508…
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The third published LTE (submitted by @stellaomalley3 and a group of psychotherapists) 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./19
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The LTE also 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. /20
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In response, an Australian pediatrician submitted an LTE claiming that low regret has been proven not only for adults but also for those gender-transitioning as adolescents. However, the LTE contained several errors, which The Lancet has now corrected./21
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The correction fixed the errors in the quoted sample size (much smaller than originally claimed) and treatments received (all subjects had gonadectomy). However, we would have liked to see a narrative explaining how these limitations challenge the certainty of "low regret."/22

We would've also liked to see a correction to the LTE's statement, "the only relevant case of regret of which we are aware is Keira Bell," as evidence of detransition is growing. /23
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Despite the more limited corrections than what SEGM would have liked to see, we thank @TheLancet editors for platforming this debate, and for giving balanced coverage to the LTEs that agreed with the Editorial, and those who challenged its assertions. /24

Peer-reviewed journals play a critical role in helping clinicians navigate areas of medicine where evidence is uncertain and scientific debate is unsettled. We hope that other top-ranked journals will soon follow suit, bringing nuance & balance to the gender medicine debate. /25