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NICE evidence review (2020): evidence of very low certainty

Before the Cass Review came the NICE evidence review. In 2020 the UK National Institute for Health and Care Excellence examined the evidence for puberty blockers and cross-sex hormones in children and adolescents. NICE rated the quality of evidence for all critical outcomes as very low using a modified GRADE approach (source). The reviews were made to inform the Cass Review.

What NICE did

NICE — a leader in evidence-based medicine — carried out evidence reviews commissioned by NHS England to inform the Cass Review (source). Two separate reports: one on puberty blockers, one on masculinising/feminising hormones in children. Standard methodology, public, replicable.

Key conclusions — puberty blockers

• Nine observational studies, all small and uncontrolled or with limited comparison, and subject to bias and confounding.
• Quality of evidence for the critical outcomes (gender dysphoria, mental health, quality of life): very low using modified GRADE.
• De Vries et al. (2011) found no change in gender dysphoria, anxiety or anger, but lower depression scores; no evidence was found for quality of life (source).

Key conclusions — cross-sex hormones

• Ten observational studies; none compared hormones with a control group, and follow-up was relatively short.
• Five uncontrolled studies suggested that hormones may reduce gender dysphoria and may also improve depression, anxiety, quality of life, suicidality and psychosocial functioning.
• That evidence, too, was rated as very low certainty (source).

What it yielded — and what it did not yield

According to the Cass Review, the evidence from the NICE reviews was so inconclusive that NHS England could not form a policy position on these medications (para. 3.13) (source). The Cass Review built on this work in 2024 with its own systematic reviews. In March 2024 NHS England decided that puberty blockers would no longer be routinely prescribed to under-18s (source); see also hormones.

Comparison with other systematic reviews

The NICE conclusions are in line with those of SBU (Sweden 2022), which found the evidence insufficient, and with the caution advised by COHERE (Finland 2020) and Ukom (Norway 2023). See also the WPATH Files.