Protocol › Changes · Last reviewed 2026-05-16

Changes over time

Summary

The Dutch Protocol has had several documented revisions: the case report of 1998, the formal codification by Delemarre & Cohen-Kettenis in 2006, the Endocrine Society guideline of 2009 (revised in 2017) and the Dutch Quality Standard of 2018. From 2020 various countries have introduced substantial departures from the original protocol after systematic evidence reviews.

Chronological overview

Year	Document / event	Change
1987–1988	First GnRHa treatment (VUmc)	Clinical introduction
1998	Cohen-Kettenis & van Goozen, case report	First publication
2006	Delemarre & Cohen-Kettenis (Eur J Endocrinol)	Formalisation: Tanner-2, age 16, age 18
2009	Endocrine Society guideline	International codification
2011	de Vries et al., 1-year follow-up	First cohort publication
2014	de Vries et al., cohort study (n=55)	Central empirical publication
2017	Endocrine Society revision	"< 16 years" hormones possible in selected cases
2018	Quality Standard Transgender Care (NL)	National guideline adopted
2022	SBU (Sweden)	Evidence base "very low certainty"
2024	Cass Review (UK)	NHS restriction GnRHa outside research

Main substantive changes

1998 → 2006: transition from case material to standardised criteria.
2006 → 2017: opening for cross-sex hormones under age 16 in selected cases (Endocrine Society; see WPATH SOC).
2017 → 2024: several countries (Sweden, Finland, UK, Norway) introduce restrictions on GnRHa outside research settings.

Critical note

Each change in this overview has stretched or relaxed the scope of the protocol (lower ages, shorter diagnostics) — without new comparative research preceding each relaxation. The Cass Review (2024) finds that a large part of contemporary clinical practice no longer rests on the original evidence base, but on successive expansions whose empirical status is unclear.¹