Gonadotropic releasing hormone analogues (GnRHas) are a class of medications used to suppress puberty. They include nafarelin (Synarel), triptorelin (Decapeptyl), and leuprorelin (Prostap).

Usually, during unopposed puberty, the hypothalamus (part of the brain) releases GnRH. This acts on the pituitary gland (a gland situated below the brain) and stimulates it to produce follicular stimulating hormone (FSH) and luteinising hormone (LH). FSH and LH act on the gonads (testes or ovaries) and stimulate them to produce sex hormones (testosterone or oestrogen). These act on the bodily tissues to produce the changes associated with puberty.

GnRHa's work by binding to the GnRH receptors on the hypothalamus. This eventually results in the pituitary gland ceasing to produce FSH and LH, which in turn results in suppression of testosterone and oestrogen production by the gonads. Due to the lack of testosterone and oestrogen, the bodily changes associated with puberty are halted.

While GnRHa's eventually suppress testosterone and oestrogen production, some people exhibit an initial temporary rise in testosterone and oestrogen when commencing GnRHa's. This occurs because the initial binding of the GnRHa's to the pituitary gland causes some stimulation of the pituitary gland, which results in an initial surge in FSH and LH secretion. However, after this initial surge, the pituitary gland is no longer stimulated and stops producing FSH and LH, which in turn results in more prolonged testosterone and oestrogen suppression.

The initial surge in hormones upon commencing GnRHa's is not usually a problem in the context of gender affirming healthcare. As noted above, the rise in testosterone and oestrogen is brief and temporary. This is usually an insufficient amount of time for the hormones to produce any significant masculinising or feminising changes.

Nonetheless, if you are already taking an antiandrogen and are switching to a GnRHa, then there is the option of overlapping your old antiandrogen with the GnRHa for a couple of weeks to mitigate any potential effects from the initial hormone surge.

References

Brik, T., Vrouenraets, L. J. J. J., de Vries, M. C., and Hannema, S. E. (2020). "Trajectories of Adolescents Treated with Gonadotropin-Releasing Hormone Analogues for Gender Dysphoria". Archives of sexual behavior, 49 (7): 2611–2618.

Kumar, P., and Sharma, A. (2014). "Gonadotropin-releasing hormone analogs: Understanding advantages and limitations". Journal of human reproductive sciences, 7(3): 170–174.

Nos, A. L., Klein, D. A., Adirim, T. A., et al. (2022). "Association of Gonadotropin-Releasing Hormone Analogue Use With Subsequent Use of Gender-Affirming Hormones Among Transgender Adolescents". JAMA Network Open, 5 (11): e2239758.