The Evidence Pyramid in Gender Care

In evidence-based medicine, research is organized in a pyramid.

The Evidence Pyramid

In evidence-based medicine, research is organized in a pyramid. At the top are systematic reviews and meta-analyses of randomized controlled trials (RCTs). Below them are individual RCTs, prospective cohort studies, retrospective cohort studies, case-control studies, case series, and finally expert opinion.

Gender Care Research

RCTs are almost entirely absent from transgender care; for practical and ethical reasons, randomizing people to receive or not receive hormone treatment is difficult. Most of the evidence comes from observational cohort studies (the Amsterdam Cohort of Gender Dysphoria and the ENIGI network) and from case series.

Cass Review

The systematic reviews conducted by the University of York, which underpin the Cass Review (2024), concluded that the evidence for the effectiveness of puberty blockers and cross-sex hormones in young people is predominantly of low quality. Similar conclusions were reached in the systematic reviews underpinning policy changes in Sweden, Finland, and Norway. A summary of the British NICE reviews, which likewise rated the evidence as very low quality, is available at transkompas.nl.

GRADE: How Certain Is the Evidence?

Alongside the pyramid, guideline developers use the GRADE system. It classifies the certainty of evidence into four levels: high, moderate, low, and very low. Observational research starts at the low level and can be upgraded or downgraded, for example because of a large effect or, conversely, substantial loss to follow-up. Very low certainty means that the true effect is likely to differ substantially from what the studies show.

Why Randomized Research Is Lacking

In a randomized study, chance determines who receives the treatment. This is difficult for puberty blockers and hormones. Participants and doctors automatically know who is receiving treatment, making blinding impossible. Young people assigned to the control group may seek treatment elsewhere or drop out. And those convinced of the treatment's benefits consider it unethical to withhold it. Critics counter that it is equally unethical to apply an invasive treatment broadly without having demonstrated that it works.

What This Means for Policy

Countries draw different conclusions from the same weak evidence. Finland, Sweden, and England reason that a treatment with irreversible consequences should only be widely provided when its benefits have been established, and therefore restrict it to exceptional cases or research settings. Other countries, including the Netherlands, continue existing practice and point to clinical experience. The reviews themselves are described under systematic reviews in gender care; the pitfalls of the underlying research under bias in gender research. The underlying question of what medicine owes its patients is addressed in medicine as restoration or as a wellbeing project.