Puberty Blockers in Children Were Always an Unregulated Live Experiment Based on No Evidence

Five years ago, we reviewed gender-affirming hormones in children and adolescents.

To find the evidence, we searched PubMed Clinical Queries for systematic reviews (the original search strategy is available here).

Our conclusions stated:

There are significant problems with how the evidence for gender-affirming cross-sex hormones has been collected and analysed that prevent definitive conclusions from being drawn. …

The development of these interventions should, therefore, occur in the context of research, and treatments for under 18 gender dysphoric children and adolescents remain largely experimental. There are a large number of unanswered questions that include the age at the start, reversibility, adverse events, long-term effects on mental health, quality of life, bone mineral density, osteoporosis in later life and cognition. We wonder whether off-label use is appropriate and justified for drugs such as spironolactone, which can cause substantial harm and even death. We are also ignorant of the long-term safety profiles of the different [gender-affirming hormone] regimens. The current evidence base does not support informed decision-making and safe practice in children.

The review formed part of an independent analysis for the BBC’s Panorama programme, in which we said transgender teen care “needs urgent regulation”. Also, Carl wrote an article in the Times saying it was time to end the experiment on children.

In the intervening years, we’ve been labelled as transphobes, subject to three different complaints at the University of Newcastle, where Tom was a visiting professor, the University of Oxford and the BMJ, where we posted the original review.

All of these were dismissed – it’s hard to argue that reviewing the evidence should be subject to complaints. But it did have a chilling effect to shut down our BMJ Evidence-Based Medicine posts.

Now, five years after we published our review, NHS England says children will no longer routinely be prescribed puberty blockers at gender identity clinics. Its review found that there was “not enough evidence” that they were safe or effective. A 2022 review by Dr. Hilary Cass reported “gaps in evidence”.

At Trust the Evidence, we do not have any vested interest in the outcome of treatments when we review the evidence.

Yet, consistently, we have found that an evidence-based approach has proved controversial. People tend to hold strong beliefs and convictions about various treatments, which is precisely why an impartial, evidence-based approach is crucial. When the pharmaceutical industry’s competing interests and financial gains are considered, having an evidence-based approach is essential for reviewing the evidence and informing decisions.

For all those following an evidence-based approach, it’s essential to be ready for the onslaught of complaints, insinuations and abuse that comes with the territory. However, keeping to an evidence-based approach is critical to informing decisions—in the end, the evidence will win out — and the question is how many are harmed before we get there.

We’ve posted the review in full on Trust the Evidence.

Prof. Carl Heneghan is the Oxford Professor of Evidence Based Medicine and Dr. Tom Jefferson is an epidemiologist based in Rome who works with Professor Heneghan on the Cochrane Collaboration. This article was first published on their Substack, Trust The Evidence, which you can subscribe to here.

Stop Press: A Google search for puberty blockers in the U.K. brings up as the first result a pro-trans American web page from the Mayo Clinic that lists five “benefits” of puberty blockers at the top including “improve mental well-being” while side-effects are buried near the bottom. The NHS page stating that puberty blockers “are not available to children and young people for gender incongruence or gender dysphoria because there is not enough evidence of safety and clinical effectiveness” is the third result down – and barely visible without scrolling.