GnRH agonists and antagonists (“Puberty blockers”)

Agonists and antagonists of GnRH (Gonadotropin Releasing Hormones) are mostly known by most people as the “puberty blockers” proposed in some countries to minors, before adding exogenous sex hormones. But blocking puberty means nothing else than to block the production of endogenous sex hormones. Consequently, GnRHa can be used as a very efficient androgen blocker for all transfem people (as well as transmasc people)

They have mostly been conceived to treat hormone-dependent cancers (breast, prostate), but also as puberty blockers for cisgender children who show signs of puberty at an age considered too early. In this respect, it is good to notice that the medication has been given to cisgender children without any protest and concerns, but it has become a public health debate at the moment it was used for trans children/teens.

In practice, they work by blocking the production of testosterone at the very early stage of the process. We make the distinction between GnRH antagonists and GnRH agonists. Both work at the same level of the production chain, but in opposite ways; but both reach the same goal, and have the same effect - nearly total shutdown of testosterone production.

Sex hormone production is controlled by the levels of FSH and LH. The production of these is itself controlled by pulsatile release of GnRH. The idea of the medication is to reduce the levels of FSH/LH and hence of testosterone; this is where the distinction between antagonists and agonists is important.

• GnRH antagonists will reduce FSH/LH by blocking the reception of GnRH by the pituitary gland, which then doesn’t get the order to produce FSH/LH. They work on the pituitary gland’s GnRH receptors the same way bicalutamide works on the body’s androgen receptors: the broken key in the lock, which can’t be opened anymore. A GnRH antagonist available in Sweden is Degarelix (Firmagon), but is nearly exclusively prescribed for cancer treatment.

• GnRH agonists work by over stimulating the pituitary gland, which, after a phase of high production of FSH/LH (and hence a peak of testosterone of about a week), will stop reacting to GnRH, and hence the whole sex hormone production will shut down. Common GnRH agonists (the most commonly prescribed because cheaper) are Triptolenin (Gonapeptyl) and Leuprorelin (Eligard, Enanton, Procren). Usual doses of 3mg/month or 11.5mg/ 3 months.

A peak of testosterone will start around the 3rd day after the first injection. It will last around a week and does not repeat afterward on the next injections. Some people use bicalutamide in order to counter the effects of testosterone during this peak phase.

They are all quite safe, with nearly no side effects, and great efficacy. Their main problem is that they are usually quite expensive, making them difficult to access if you don’t have health insurance, or just hard to get prescribed because practitioners will tend to favor cheaper alternatives. Besides, they mostly in the form of injections, given every month or every 3 months.

A nasal spray exists (Nafarelin, sold under the brand name Synarel) which can be a good alternative for people who prefer to avoid injections.