GnRH antagonist · prostate cancer
Degarelix is a synthetic ten-amino-acid peptide, built with several unnatural amino acids, that blocks the gonadotropin-releasing hormone (GnRH) receptor in the pituitary gland. It is injected under the skin to lower testosterone quickly in men with advanced prostate cancer, a form of androgen-deprivation therapy3.
GnRH from the hypothalamus signals the pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and LH drives testosterone production in the testes. Degarelix binds reversibly to pituitary GnRH receptors and blocks that signal, so gonadotropin release falls and testosterone follows3. GnRH agonists such as leuprolide reach the same end by a different route and can cause a temporary testosterone flare at the start, often covered with an added antiandrogen. Degarelix blocks the receptor from the outset, so it acts faster and needs no antiandrogen to prevent a flare1. Lowering testosterone is the aim of androgen-deprivation therapy for advanced prostate cancer1.
In the pivotal 12-month randomized human trial of 610 men with prostate cancer, degarelix kept testosterone at castrate levels as reliably as leuprolide (about 97 to 98% versus 96% of men)1. Three days after starting, about 96% of men on degarelix had castrate testosterone versus none on leuprolide, and PSA fell faster in the first month1. Injection-site reactions were far more common with degarelix (40% versus under 1%)1. Whether antagonists and agonists differ in heart risk has been debated. The PRONOUNCE trial randomized 545 men with prostate cancer and atherosclerotic cardiovascular disease to degarelix or leuprolide; major cardiovascular events at one year were 5.5% versus 4.1%, not significantly different, but the trial stopped early and left the question unresolved2.
FDA-approved in 2008 as Firmagon for the treatment of advanced prostate cancer3.
The most common label effects are injection-site reactions (pain, redness, swelling or hardening), hot flashes and raised liver enzymes; weight gain, erectile dysfunction, testicular shrinkage and breast enlargement were also reported, and long periods of medical castration are expected to lower bone density. Like other androgen-deprivation therapy, it can prolong the QT interval. Serious allergic reactions, including anaphylaxis, have been reported, and it may impair fertility3.
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