Degarelix
Degarelix is a GnRH receptor antagonist for advanced prostate cancer. Unlike GnRH agonists it blocks the receptor directly, suppressing testosterone within days and without the initial hormonal flare, avoiding the need for anti-androgen cover.
01 Overview
Degarelix is a synthetic decapeptide that competitively blocks pituitary GnRH receptors. Because it does not first stimulate the receptor, testosterone falls to castrate levels within ~3 days rather than weeks, and there is no flare-related symptom worsening.
It is given as a subcutaneous depot that forms a gel at the injection site for slow release. It is used chiefly in hormone-sensitive prostate cancer, including patients where flare is especially dangerous (spinal metastases, bladder outlet obstruction).
02 Mechanism
Direct competitive antagonism of pituitary GnRH receptors immediately halts LH/FSH release, dropping testosterone without an agonist flare.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Loading dose | 240 mg | SubQ | 240 mg as two 120 mg SC injections on day 1 |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Rapid testosterone suppressionFaster castration than agonists with no testosterone flare. | castrate levels by ~day 3 | Clinical | |
| No flare phenomenonAvoids the tumour-symptom worsening seen with agonist initiation, useful in high-risk metastatic disease. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Injection-site reactionsPain, erythema, swelling, and nodule formation at the depot site, especially with the loading dose. | Moderate | Very common | Clinical | |
| Hypogonadal symptomsHot flushes, weight gain, fatigue, and bone loss from androgen deprivation. | Moderate | Most users | Clinical |