Degarelix is a synthetic GnRH antagonist (MW ~1632.3 g/mol) and the first injectable GnRH receptor blocker approved for advanced prostate cancer. FDA-approved in 2008 (Firmagon), it produces immediate suppression of LH, FSH, and testosterone without the initial hormonal flare seen with GnRH agonists. This is clinically significant in patients where testosterone flare could cause complications such as spinal cord compression, urinary obstruction, or bone pain exacerbation. Degarelix is administered as a monthly subcutaneous injection.
Category: Reproductive / Hormonal. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Firmagon for advanced prostate cancer, December 2008)
Degarelix is a synthetic decapeptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors without activating them, immediately blocking the release of LH and FSH. Unlike GnRH agonists, antagonists do not cause an initial surge of gonadotropins or sex steroids (no "flare"…
Safety considerations: Injection site reactions: pain, erythema, swelling, and induration at injection site (40% with loading dose; most mild to moderate and resolve within 3 days); Hot flashes (26%); Weight gain (11%).
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~1632.3 g/mol |
|---|---|
| CAS number | 214766-78-6 |
| Half-life | ~43-53 days (due to subcutaneous depot release) |
| Production method | synthetic |
| Anti-doping status | Prohibited in sport (WADA) |
| US regulatory status | FDA-approved (Firmagon, December 2008) for advanced prostate cancer. 240 mg loading dose, then 80 mg monthly maintenance. |
Related peptides: Kisspeptin, Gonadorelin, Oxytocin.
Degarelix provides immediate testosterone suppression without the flare seen with GnRH agonists. This is particularly important for patients with impending spinal cord compression, severe urinary obstruction, or widespread bone metastases where a testosterone surge could cause dangerous complications. It also eliminates the need for anti-androgen cover during treatment initiation.
Injection site reactions are the most common side effect, occurring in about 40% of patients with the loading dose. They typically manifest as pain, redness, swelling, or hardness at the injection site. Most reactions are mild to moderate and resolve within 3 days. The maintenance dose causes fewer injection site reactions.
Yes, relugolix (Orgovyx) is an oral GnRH antagonist FDA-approved in 2020 for advanced prostate cancer, offering an oral alternative to injectable degarelix. The HERO trial showed relugolix was superior to leuprolide for sustained castration rates, with lower cardiovascular event rates.