The Difference Between an Agonist, an Antiandrogen and an Antagonist in ADT?

Primary, or first line Hormone Therapy (ADT) can involve some different drugs. However, the constant standard includes either a GnRH agonist, such as leuprolide or an antagonist like Firmagon and an antiandrogen like Casodex. 

The GnRH agonists (e.g, Lupron and Zoladex) essentially tell the brain not to send a signal to the gonads to make testosterone. Because there is a feedback loop between the brain and the gonads, when the signal ceases the gonads immediately start to produce more testosterone (which is the underlying cause of a PSA flare) to try to get the attention on the brain and say, "Here I am. Tell me what to do." Over a period that connection breaks down and stops. When this happens, the testes do shut down and no longer produce testicular testosterone. 

The antiandrogens have a different mode of action.  They work by blocking the hormone receptor by binding to it and clogging the receptor rather than activating it like the agonists.  Since antagonists do not disrupt the feedback loop between the brain and the gonads they do not flood the body with testosterone, so there isn’t a PSA flare. 

Best practice dictates that before the use of

GnRH agonists (Lupron etc.) an antagonist (Casodex) should be used for two weeks to prevent the cancer from taking advantage of the flood of testosterone, which will come when the agonist is given.

GnRH antagonists, such as degarelix, work very differently, as they bypass that time where that surge occurs. There is no surge [in testosterone] and castration takes place within the next 24 to 48 hours.  Becoming castrate takes considerably longer with a GnRH agonist.

If you need to quickly drop the levels of testosterone to have more control of the cancer you should use an antagonist (no antiandrogen will be needed). Antagonists work much faster in getting that testosterone level down and it’s well tolerated. There is no evidence that one is superior to the other, the primary difference is the need to use an antiandrogen and the speed at which castration can be achieved.