GnRH Agonists in Gender Care

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

The main article on this subject is Puberty Blockers.

Substances

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

How they work

GnRH is normally released in pulses by the hypothalamus. Continuous exposure through an agonist initially leads to a brief increase (flare-up), followed by desensitization of the pituitary gland. LH and FSH levels fall, after which the gonads produce virtually no sex hormones. The effect is reversible after discontinuation. The mechanism is explained step by step on puberteitsblokkers.nl.

Use in adolescents — puberty blockers

Under the original Dutch Protocol, young people with persistent gender dysphoria were given a GnRH agonist at the onset of puberty (Tanner stage 2–3) to pause puberty. The idea was that this would provide "time to think" and facilitate later surgical procedures by limiting the development of secondary sex characteristics.

Use in adults

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

Cass Review and international reassessment

The British Cass Review (April 2024) concluded that the evidence base for using puberty blockers in young people with gender dysphoria is weak. The systematic reviews conducted by the University of York found insufficient evidence of effects on psychological well-being in the medium and longer term. In 2024, NHS England decided to stop routinely prescribing puberty blockers for gender dysphoria and to make them available only as part of clinical research. Further information is provided in the article British judge clears the way for controversial puberty blocker trial involving 226 children.

Possible side effects

Known side effects include hot flashes, fatigue, mood changes, 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 ongoing research.