Degarelix

Degarelix (Firmagon) is a GnRH (gonadotropin-releasing hormone) receptor antagonist — a synthetic decapeptide that directly blocks the GnRH receptor on anterior pituitary gonadotroph cells. FDA-approved for advanced prostate cancer, it produces immediate and profound suppression of testosterone to castrate levels without the initial testosterone flare seen with GnRH agonists (leuprolide, goserelin). Unlike GnRH agonists which initially stimulate LH/FSH release before causing receptor desensitization, degarelix competitively blocks GnRH-R from the first dose, achieving castrate testosterone levels within 3 days. This is clinically important in advanced prostate cancer where testosterone flare can cause tumor flare, spinal cord compression, or urinary obstruction.

Degarelix competitively binds to GnRH receptors on pituitary gonadotroph cells, preventing endogenous GnRH from stimulating LH and FSH release. This produces immediate, dose-dependent suppression of LH, FSH, and consequently testosterone (in males) or estrogen (in females). The antagonist mechanism avoids the initial agonist phase (and associated hormone flare) characteristic of GnRH agonists.

Advanced Prostate Cancer (Approved) FDA-approved as Firmagon (2008). Achieves castrate testosterone (<50 ng/dL) in 96% of patients by Day 3 — faster than GnRH agonists. Breast Cancer Investigated for hormone-sensitive breast cancer as an alternative to GnRH agonists. Benign Prostatic Hyperplasia Research for BPH and lower urinary tract symptoms.

GnRH-R competitive blockade. Immediate LH/FSH suppression. Downstream testosterone/estrogen reduction. Androgen receptor signaling suppression in prostate cancer cells.

Injection site reactions (40% — pain, swelling, erythema) are the most common and distinguishing adverse effect. Hot flashes (26%), weight gain, fatigue, elevated liver enzymes. Long-term: bone density loss, metabolic syndrome (class effects of androgen deprivation).

Supplied as lyophilized powder for subcutaneous injection. Store at 25°C (controlled room temperature). Reconstitute with provided diluent. Must be administered within 1 hour of reconstitution.

FDA-approved (2008) as Firmagon for advanced prostate cancer. EMA-approved. Prescription medication. Not WADA-prohibited (medical use for cancer treatment).