Evidently correct

New support for brain studies; the WHO steers clear of paediatric transition

Photo by Milad Fakurian on Unsplash

A leading Swedish clinician and researcher has welcomed neuropsychologist Sallie Baxendale’s new review paper as “a strong case” for urgent studies of the effects of puberty blockers on the brain.

“This is a much-needed review of the potential impact on cognitive function, given the surge of puberty-suppressing treatment for children with gender dysphoria,” said Professor Mikael Landén, of Sweden’s Karolinska Institute and the University of Gothenburg, who was involved in Sweden’s 2021 systematic review of the evidence base for hormonal treatment of minors with gender dysphoria.

The preprint review paper of Professor Baxendale, who holds a chair in clinical neuropsychology at University College London, argues that the failure of researchers to properly investigate obvious questions about the potentially damaging effects of puberty suppression on the brain means that minors and their parents cannot be supplied with the answers they need in order to give informed consent to this treatment. (Puberty blocker drugs suppress the natural sex hormones that drive development.)

“[Professor Baxendale] reports that the literature is insufficient with respect to humans, where the scarce available evidence suggests that there might be detrimental effects on IQ,” Professor Landén told GCN this week.

“It is therefore valuable that she includes animal studies, which suggest that there are sex-specific effects on cognition with no evidence of them being reversible.

“Taken together, the paper makes a strong case for the urgency of measuring neuropsychological [outcomes] in future research of the effects of puberty suppression.”

Meanwhile, following an international outcry against what looked like a hasty, activist-driven project to create a new “gender-affirming” treatment guideline, the World Health Organisation this week issued a statement of clarification and extended the time for public comment.

Its statement also said that the transgender health guideline would not cover children and adolescents because the evidence base was too weak.

“The scope will cover adults only and not address the needs of children and adolescents, because on review, the evidence base for children and adolescents is limited and variable regarding the longer-term outcomes of gender-affirming care for children and adolescents,” the agency said this week.

The field of medicalised gender change for minors relies on relatively confident treatment guidelines and position statements from healthcare organisations including the World Professional Association for Transgender Health, the Endocrine Society and the American Academy of Pediatrics.

In 2018, the journal The Lancet celebrated the arrival of the first treatment guideline specifically for children and adolescents with gender dysphoria. A peer reviewed version of this document from the Royal Children’s Hospital Melbourne states: “The scarcity of high-quality published evidence on the topic prohibited the assessment of level (and quality) of evidence for these recommendations.”

“The problem that has to be addressed is that mentally unwell adolescents do not become well and free from social influences or wishful thinking on their 18th birthday. Young adults will be damaged by ideologically driven approaches to medical treatment as well.”—Queensland University emeritus professor of law Patrick Parkinson, tweet, 17 January 2024

Almost no data

Professor Landén told GCN that the Baxendale paper’s conclusions agreed with those of Sweden’s systematic review, which led to a more cautious treatment policy issued in 2022 by Sweden’s National Board for Health and Welfare.

In a 2023 statement by the Karolinska Institute marking publication of Sweden’s systematic review of hormonal interventions for minors with gender dysphoria, Professor Landén said—

“Against the background of almost non-existent long-term data, we conclude that [puberty blocker] treatment in children with gender dysphoria should be considered experimental treatment rather than standard procedure. This is to say that treatment should only be administered in the context of a clinical trial under informed consent.”

In an email to GCN last year, Professor Landén clarified the status of puberty blocker treatment in Sweden.

“According to official guidelines [issued in 2022 by the National Board of Health and Welfare], puberty blockers should not be considered first-line treatment but only [be prescribed] in ‘exceptional cases’ and in clinical trials,” he said.

“This is a change compared to previous guidelines.

“However, there is nothing preventing clinicians from prescribing these treatments. And it is up to the clinician to decide what constitutes an exceptional case.

“It is thus a more restrictive policy from the National Board of Health and Welfare, but it is still possible to give the treatment in Sweden.”

This week Professor Landén told GCN that he endorsed the Baxendale paper’s suggestion that multidisciplinary teams in gender clinics should be augmented with the appointment of a clinical neuropsychologist.

“Their tools to assess patients and the insights that can be drawn from the results of those tests are usually clinically very valuable when assessing people who struggle with psychological issues,” he said.

He concurred with Professor Baxendale’s view that research on the neuropsychological effects of hormone suppression was essential and urgent.

“We know that hormones have important effects on the brain, not least because there are significant differences between men and women,” he said.

“Hormones have two types of effects that are called activational and organisational. Activational just means that they have acute effects that disappear if the hormone is stopped. This is less of a worry.

“But we also know that many hormones, especially sex hormones, have organisational effects. Firstly, that means they have irreversible effects that do not disappear even if you discontinue a hormone. But most importantly, there are ‘time-windows’ when the hormones exert their effects.

“I am not an expert in this field, but the worry is that sex hormones need to exert their effects during a certain age—after which it might be too late. If you put children on hormone blockers during this time window, you might have interfered irreversibly, even if you later stop the treatment.

“[Professor Baxendale] argues that this [irreversible outcome] seems to be the case in animal studies. Whether this is the case in humans is unknown, but I would say [it is] at least plausible and important to find out.”