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GnRH agonists in gender care

GnRH agonists (gonadotropin-releasing hormone agonists) are synthetic peptides that stimulate the pituitary so strongly that it becomes insensitive to the body's own GnRH. The result: the production of testosterone or oestrogen by the gonads stops almost completely.

Substances

The most commonly used GnRH agonists are leuprorelin (Lupron, Lucrin), triptorelin (Decapeptyl, Pamorelin) and goserelin (Zoladex). They are usually administered as a depot injection, with intervals of one to six months.

Action

GnRH is normally released in a pulsatile manner by the hypothalamus. Continuous exposure via an agonist leads first to a short rise (flare-up) and then to desensitisation of the pituitary. LH and FSH decrease, after which the gonads produce almost no more sex hormones. The effect is reversible after stopping.

Use in adolescents — puberty blockers

Within the original Dutch Protocol, young people with persistent gender dysphoria at the start of puberty (Tanner stage 2–3) are given a GnRH agonist to pause puberty. The idea was that this provides "thinking time" and facilitates later surgical interventions due to less pronounced secondary sex characteristics.

Use in adults

In adult trans women, GnRH agonists can be an alternative to other anti-androgens such as cyproterone acetate or spironolactone, especially when testosterone suppression is insufficient. The WPATH Standards of Care version 8 and the Endocrine Society guideline mention GnRH agonists in this context.

Cass Review and international reorientation

The British Cass Review (April 2024) concluded that the evidence base for the use of puberty blockers in young people with gender dysphoria is weak. The systematic reviews carried out by the University of York found insufficient evidence for effects on psychological well-being in the medium and longer term. NHS England decided in 2024 no longer to routinely prescribe puberty blockers for gender dysphoria and to make them available only within clinical research.

Possible side effects

Known side effects include hot flashes, fatigue, mood complaints, weight gain and effects on bone density with long-term use. The impact on bone growth and final bone density in adolescents is the subject of active research.