Degarelix
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GnRH antagonist decapeptide that provides immediate testosterone suppression without flare; FDA-approved for advanced prostate cancer.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Firmagon, FE200486, degarelix acetate |
| Category | GnRH Antagonist / Sexual Health |
| Sequence | Ac-D-Nal-D-Cpa-D-Pal-Ser-Aph(Hor)-D-Aph(Cbm)-Leu-ILys-Pro-D-Ala-NH2 |
| Molecular Weight | ~1631 Da |
| Molecular Formula | C82H103ClN18O16 |
| PubChem CID | 16136245 |
| Administration | SubQ (abdominal region) |
| Typical Dose Range | 240 mg loading dose (two 120 mg injections), then 80 mg monthly maintenance |
| Half-Life | ~53 days (depot formation after SubQ injection) |
| Storage | Refrigerated (2-8C); reconstitute immediately before injection |
| FDA Status | Approved (2008) — Firmagon for advanced prostate cancer |
| WADA Status | Not prohibited (FDA-approved medication) |
Mechanism of Action
Degarelix is a third-generation GnRH receptor antagonist that acts by competitive blockade of the GnRH receptor (GnRHR) on anterior pituitary gonadotroph cells. Unlike GnRH agonists (leuprolide, goserelin), degarelix does not cause initial receptor activation, thereby avoiding the testosterone "flare" phenomenon entirely.
Upon subcutaneous injection, degarelix immediately binds to and blocks pituitary GnRH receptors, producing a rapid and dose-dependent suppression of LH, FSH, and consequently testosterone. Castrate testosterone levels (<0.5 ng/mL) are achieved in 96% of patients within 3 days of the loading dose, compared to 0% with leuprolide at the same timepoint (PMID: 19035858). This eliminates the need for concomitant anti-androgen therapy to prevent flare.
The peptide forms a depot at the injection site due to its physicochemical properties, providing sustained drug release. The multiple unnatural amino acid substitutions (D-Nal, D-Cpa, D-Pal, etc.) confer high receptor binding affinity and resistance to proteolytic degradation. Degarelix also lacks the histamine-releasing properties that limited earlier GnRH antagonists (abarelix), making it better tolerated at therapeutic doses (PMID: 20952020).
Key Research Areas
- Prostate cancer — no testosterone flare — Pivotal Phase III trial demonstrated 96% castration within 3 days (vs 0% with leuprolide), establishing the key clinical advantage of GnRH antagonism (PMID: 19035858)
- Faster PSA suppression — PSA levels at days 14 and 28 were significantly lower with degarelix vs leuprolide (P<0.001), potentially reflecting faster disease control (PMID: 19035858)
- Cardiovascular safety — Phase III CV analysis showed comparable overall safety but numerically lower ischemic heart disease with degarelix (4% vs 10% leuprolide) (PMID: 20952020)
- Real-world cardiovascular outcomes — Observational data support potential CV advantage of GnRH antagonists over agonists (PMID: 39343637)
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Systematic reviews | 0 | — |
| Human RCTs | 2 | Phase III pivotal trial; CV safety analysis |
| Human observational | 1 | Real-world CV safety comparison |
| Animal in vivo | 0 | — |
| In vitro | 0 | — |
Clinical Applications
- Cancer Adjunct Therapy — First-line androgen deprivation therapy for advanced prostate cancer, especially when testosterone flare must be avoided (spinal cord compression risk, ureteral obstruction, bone pain)
- Sexual Health — Testosterone suppression for hormone-dependent conditions
Protocols Using This Peptide
- No current vault protocols use degarelix (FDA-approved prescription medication, not a research peptide)
Ageless Peps Products
- Not sold by Ageless Peps. Degarelix is an FDA-approved prescription medication (Firmagon) available only through licensed pharmacies and administered by healthcare providers.
Dosing Reference
FDA-Approved Dosing
| Indication | Dose | Route | Frequency | Duration | Source |
|---|---|---|---|---|---|
| Advanced prostate cancer (loading) | 240 mg (two 120 mg injections) | SubQ | Once | Day 1 | FDA label |
| Advanced prostate cancer (maintenance) | 80 mg | SubQ | Monthly (every 28 days) | Ongoing | FDA label |
Cycling
Not applicable. Degarelix is used continuously for prostate cancer androgen deprivation. Unlike depot GnRH agonists, degarelix's antagonist mechanism allows for faster testosterone recovery upon discontinuation, which may facilitate intermittent ADT strategies.
Contraindications & Safety
- Contraindications: Hypersensitivity to degarelix or any component; severe hepatic impairment (not specifically studied)
- Common side effects: Injection site reactions (pain, erythema, swelling — 40% of patients), hot flashes (26%), weight gain (11%), fatigue, elevated liver enzymes
- Serious adverse effects: QTc prolongation (monitor in patients with risk factors), anaphylaxis (rare), osteoporosis with long-term use
- Drug interactions: Caution with QTc-prolonging medications (Class IA and III antiarrhythmics, methadone, certain antipsychotics)
- Pregnancy/nursing: Not applicable (indicated only for male patients with prostate cancer); however, it is expected to cause fetal harm based on mechanism
- Special populations: No dose adjustment needed for mild-to-moderate renal or hepatic impairment; injection site reactions are the most distinguishing tolerability concern compared to GnRH agonists
Synergistic Combinations
- Leuprolide — Not combined; degarelix is an alternative to GnRH agonists, often used after GnRH agonist failure or when flare must be avoided
- Relugolix — Both are GnRH antagonists; relugolix offers oral convenience while degarelix provides reliable monthly depot
- Goserelin — GnRH agonist alternative; degarelix preferred when immediate castration is required
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 19035858 | Degarelix Phase III: 12-month comparative study vs leuprolide | 2008 | RCT |
| 20952020 | Degarelix cardiovascular safety: Phase III results | 2010 | RCT |
| 39343637 | Comparative cardiovascular safety of GnRH antagonists vs agonists | 2025 | Observational |
References
- PMID: 19035858 — Klotz et al., BJU Int 2008
- PMID: 20952020 — Smith et al., J Urol 2010
- PMID: 39343637 — Patel et al., Eur Urol Oncol 2025
Related
- Peptide Index
- Condition Index
- Protocol Index
- Gonadorelin
- Leuprolide
- Goserelin
- Triptorelin
- Relugolix
- Elagolix
#peptide #sexual-health #fda-approved #not-sold #subq