Protocol › The three phases · Last reviewed 2026-05-16
The three treatment phases
Summary
The Dutch Protocol distinguishes three treatment phases: (1) a fully reversible phase with psychological evaluation and puberty suppression via GnRH agonists, (2) a partially reversible phase with cross-sex hormones, and (3) an irreversible phase with gender-affirming surgery. The classification by reversibility appears explicitly in the Delemarre / Cohen-Kettenis publication of 2006 and was taken over by the Endocrine Society and WPATH.
1. Overview
| Phase | Intervention | Age (original) | Reversibility |
|---|---|---|---|
| 1 | Psychological diagnostics + GnRHa | ~12, Tanner 2–3 | Fully reversible (as originally stated) |
| 2 | Cross-sex hormones (oestrogens / testosterone) | ~16 | Partially reversible |
| 3 | Gender-affirming surgery | ≥ 18 | Irreversible |
2. Phase 1 — Diagnostics and puberty suppression
The first phase combines extensive psychological assessment with suppression of endogenous puberty using GnRH agonists (triptorelin, leuprorelin or nafarelin). Diagnostics include clinical interviews, standardised questionnaires and — in minors — family assessment.1 Puberty suppression is started from Tanner stage 2 or 3, which typically corresponds to about 12 years in biologically female and around 13 years in biologically male adolescents.
The original rationale was that this phase creates "diagnostic space": time for reflection without secondary sex characteristics developing that are later hard to reverse. Cohen-Kettenis (1998) describes GnRHa treatment as "fully reversible" — a wording later criticised by evaluation reports (including the Cass Review 2024) as insufficiently supported.2
3. Phase 2 — Cross-sex hormone therapy
From around age 16, cross-sex hormone therapy is gradually added: oestrogens for MtF patients, testosterone for FtM patients. Effects on voice (with testosterone), breast development (with oestrogens) and fat distribution are classified as partially reversible; effects on fertility are considered largely irreversible if hormone therapy follows puberty suppression without prior gamete storage.3
4. Phase 3 — Surgery
Gender-affirming surgery was in the original design reserved for patients aged 18 or older. This includes mastectomy (FtM), genital surgery and facial feminisation (MtF). The order, indication and technique are determined by the multidisciplinary team in consultation with the patient and — for minors up to 16 — the parents.
Critical note
The three-way division reversible / partially reversible / irreversible is under pressure. (i) Known effects of GnRHa on bone mineralisation and brain development are not "neutral"; long-term data are missing (SBU 2022, Cass 2024). (ii) Reduced growth during GnRHa has lasting influence on body length and sexual function if CSH follows directly. (iii) Continuation rates from GnRHa to CSH are 96–98% — meaning the "reversible" first phase in practice turns out not to be a reflection phase, but a first step in a near-deterministic pipeline (follow-up overview).4
See also
- Original protocol description: Delemarre 2006
- Age and Tanner criteria per phase: Age criteria
- Informed consent around each phase: Informed consent
- Outcome measures per phase: Follow-up structure
- Continuation rates: Follow-up studies overview
- Systematic evaluation of the phases: Cass Review, SBU
- People register — Cohen-Kettenis, Delemarre, de Vries.
- International comparison — how other countries handle the phases.
- Timeline — protocol development chronologically.
- FAQ · Glossary · For parents.
Footnotes
- Delemarre-van de Waal HA, Cohen-Kettenis PT. Clinical management of gender identity disorder in adolescents. Eur J Endocrinol. 2006;155(S1):S131–7.
- Cass H. Independent review of gender identity services for children and young people: final report. NHS England; April 2024. p. 174–186.
- Hembree WC, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons. J Clin Endocrinol Metab. 2017;102(11):3869–903.
- van der Loos MATC, et al. Continuation of gender-affirming hormones in adolescents and young adults. Lancet Child Adolesc Health. 2022;6(12):869–75.