Section 01
What it's used for
FDA-Approved for Prostate Cancer
Approved by the FDA as Firmagon in 2008 for advanced prostate cancer. In patients, it lowered testosterone to castration level (under 50 ng/dL) in 96% of cases by day 3 — reaching that level faster than older GnRH-agonist drugs achieve.
▸Clinical wording
FDA-approved as Firmagon (2008). Achieves castrate testosterone (<50 ng/dL) in 96% of patients by Day 3 — faster than GnRH agonists.
Hormone-Sensitive Breast Cancer
Is being studied as a possible alternative to GnRH-agonist drugs for hormone-sensitive breast cancer, a form of breast cancer where blocking certain hormone signals is part of treatment. This use is not yet FDA-approved.
▸Clinical wording
Investigated for hormone-sensitive breast cancer as an alternative to GnRH agonists.
Enlarged Prostate (BPH)
Is being studied for benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate gland, and for the lower urinary tract symptoms — like frequent or difficult urination — that often come with it.
▸Clinical wording
Research for BPH and lower urinary tract symptoms.
Section 02
Mechanism of Action
Switching off the testosterone command signal
- Degarelix occupies the pituitary receptor for the hormone-release signal without the initial stimulation an agonist causes.
- In rats single injections cut two hormones dose-dependently, with larger doses holding suppression up to seven days.
- In monkeys a single dose kept both hormones fully suppressed beyond forty days.
- In men with prostate cancer about 96 percent reached very low testosterone by day three, versus none on leuprolide.
▸Clinical wording
Competitive GnRH receptor blockade at pituitary gonadotrophs
Degarelix occupies the pituitary GnRH receptor competitively, so gonadotroph output falls without the transient receptor stimulation an agonist produces. In rats, single subcutaneous doses of 0.3–10 µg/kg suppressed plasma LH and testosterone dose-dependently, and 12.5, 50 or 200 µg/kg held significant LH suppression for 1, 2 and 7 days respectively; in primates a single 2 mg/kg dose kept plasma LH and testosterone fully suppressed beyond 40 days (Broqua 2002). In men with prostate cancer the signature is speed: at day 3 testosterone was ≤0.5 ng/mL in about 96% of degarelix patients and in none of the leuprolide arm (Klotz 2008).
Why one injection lasts weeks
- The molecule carries chemical groups built to increase bonding within and between molecules.
- Across that chemical series, laboratory receptor strength did not predict how long the effect lasted.
- A single injection under the skin suppressed testosterone in intact rats for 57 days.
- In beagle dogs the injection site acts as a slow store, with an absorption half-life near eleven days.
▸Clinical wording
Sustained receptor occupancy from a subcutaneous depot
Duration of action is as much a formulation property as a receptor property. Degarelix carries p-ureido-phenylalanines at positions 5 and 6, urea and carbamoyl groups built to increase intra- and intermolecular hydrogen bonding; across that series no correlation was found between in vitro receptor potency and duration of action, and a single 2 mg/kg subcutaneous dose suppressed testosterone in intact rats for 57 days (Jiang 2001). In beagle dogs the injection site behaves as a depot with slow first-order input, an absorption half-life near 11 days, and absorbed fraction falling roughly by half as the dosing solution rose from 1.25 to 40 mg/mL (Agerso 2003).
The same receptor sits on prostate cells
- Five human prostate cell lines all carried both forms of the hormone-signal receptor.
- Degarelix lowered survival in each line and raised the activity of cell-suicide enzymes.
- Two agonist drugs left survival unchanged even at high concentrations, so the effect was antagonist-specific.
- One prostate line did not respond to degarelix at all.
▸Clinical wording
GnRH receptors in prostate epithelium and stroma
GnRH receptors are not confined to the pituitary. Human prostate lines — WPMY-1 stroma, WPE1-NA22 epithelium, BPH-1, androgen-dependent LNCaP and castration-resistant VCaP — all expressed GNRHR1 and GNRHR2, and degarelix lowered viability in each while raising caspase-3/7, caspase-9 and, in some lines, caspase-8; transcriptional profiling implicated MAPK and G-protein-coupled receptor signalling (Sakai 2015). The effect was antagonist-specific: leuprolide and goserelin up to 100 µM left viability unchanged, and PC-3 cells did not respond to degarelix at all.
Immune cells inside artery plaques
- In mice with established artery plaques, nearly all receptor-carrying cells inside plaques were T immune cells.
- Four weeks of an agonist drug produced dead cores in otherwise stable plaques, with scavenger cells gathering.
- Degarelix produced neither the dead cores nor that cell build-up.
- Plaque size, collagen content and blood inflammation markers did not differ between the groups.
▸Clinical wording
GnRH receptors on plaque T lymphocytes
In ApoE-knockout mice with established atherosclerosis, almost all GnRH-receptor-positive cells inside plaques were CD3-positive T lymphocytes. Four weeks of the agonist leuprolide produced necrotic cores in otherwise stable plaques, a median 11.0% of plaque area against 0.6% in controls and 0.2% with degarelix, together with macrophage accumulation; degarelix produced neither (Knutsson 2016). Plaque size, collagen and smooth-muscle content, MMP-9 and plasma cytokines did not differ between groups, and only degarelix significantly lowered testosterone at 2 weeks.
Section 03
Biological Pathways
- Competitive GnRH receptor blockadeDegarelix competitively occupies the pituitary GnRH receptor, avoiding the transient flare an agonist causes; by day 3 testosterone fell to ≤0.5 ng/mL in about 96% of patients versus none on leuprolide.
- Sustained depot receptor occupancyStructural changes built for hydrogen bonding extend action independent of in vitro receptor potency; a single subcutaneous dose suppressed testosterone in rats for 57 days via a slow-release depot.
- GnRH receptors in prostate tumor cellsProstate epithelial, stromal and cancer cell lines directly express GnRH receptors; degarelix lowered their viability and raised caspase-3/7, caspase-9 and caspase-8, unlike leuprolide or goserelin.
- GnRH receptors on plaque T lymphocytesIn atherosclerotic mice, GnRH-receptor-positive cells within plaques were mostly CD3-positive T lymphocytes; the agonist leuprolide expanded plaque necrotic cores while degarelix, an antagonist, did not.
Section 04
Dosage Information
Ac-D-2Nal-D-4ClPhe-D-3Pal-Ser-4APhe-D-4APhe-Leu-ILys-Pro-D-Ala-NH2| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — label regimen | FDA and EMA labels, advanced prostate cancer | 240 mg to start, in two 120 mg injections, then 80 mg every 28 days — about 2.7–3.4 mg/kg once, then 0.9–1.1 mg/kg monthly at 70–90 kg | A clinician mixes fixed vials and injects into the abdomen; nothing is adjusted. The dose exists to cause castration — testosterone under 0.5 ng/mL. |
| Subcutaneous — phase 3 vs leuprolide | 12-month randomised trial, 610 men | 240 then 80 mg monthly, 240 then 160 mg, or leuprolide; testosterone 0.5 ng/mL or less from day 28 to 364 in 97.2%, 98.3%, 96.4% | Doubling the monthly dose added nothing measurable, and the trial measured a hormone level, not survival. Injection-site reactions: 35% against under 1%. |
| Subcutaneous — phase 2 dose-finding | 189 men, one year, North America | Start at 200 or 240 mg, then 80, 120 or 160 mg monthly. By day 3 testosterone was 0.5 ng/mL or less in 88% on 200 mg, 92% on 240 mg | This is where the label numbers came from: the first dose was picked for speed, 80 mg because it held suppression — neither for how a man feels. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Lyophilised powder
Supplied as a lyophilised powder and kept at 25 °C (controlled room temperature); no refrigerated storage is described for this product. It is reconstituted only with the diluent supplied in the kit.
After reconstitution
The reconstituted solution is not intended for storage: it is administered within 1 hour of mixing with the diluent. No extended stability data is given for the prepared solution, so any leftover is not kept beyond that window.
Section 07
Side Effects & Precautions
Degarelix's adverse effects range from common injection site and hormonal reactions to long-term class effects of androgen deprivation.
Injection site reactions
These are the most common and distinguishing side effect, occurring in 40% of patients as pain, swelling, or redness (erythema).
Other common effects
Hot flashes occur in 26% of patients. Weight gain, fatigue, and elevated liver enzymes can also occur.
Long-term effects of androgen deprivation
Long-term use is linked to bone density loss and metabolic syndrome. These are class effects of androgen deprivation, shared by the whole drug class rather than unique to degarelix.
Section 08
Regulatory Status
FDA / United States
Approved in 2008 as Firmagon
Firmagon is a GnRH antagonist indicated for androgen-deprivation therapy in advanced prostate cancer, given as a prescription-only subcutaneous injection.
EMA / Europe
Approved for the same indication
Firmagon holds EU marketing authorisation for advanced, hormone-dependent prostate cancer, administered under the same prescription-only conditions as in the US.
WADA
Not prohibited — antagonists are excluded
WADA's S2.2.1 bans GnRH and its agonist analogues because they raise testosterone in men. Degarelix is a GnRH antagonist that lowers testosterone instead — the opposite pharmacology — and it does not appear anywhere on the 2026 Prohibited List.
Regulatory status differs by country and changes over time. Oncology use under a physician's supervision is not equivalent to unsupervised or off-label use — check the current rules of your own regulator.
Section 09
Research Studies
- [1]GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6Jiang G, Stalewski J, Galyean R, et al. · Journal of Medicinal Chemistry · 2001
- [2]Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelixBroqua P, Riviere PJ, Conn PM, et al. · Journal of Pharmacology and Experimental Therapeutics · 2002
- [3]The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH antagonist, after s.c. administration to beagle dogsAgerso H, Koechling W, Knutsson M, et al. · European Journal of Pharmaceutical Sciences · 2003
- [4]The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancerKlotz L, Boccon-Gibod L, Shore ND, et al. · BJU International · 2008
- [5]In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonist degarelix on human prostate cell growthSakai M, Martinez-Arguelles DB, Patterson NH, et al. · PLoS ONE · 2015
- [6]Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE-/- miceKnutsson A, Hsiung S, Celik S, et al. · Scientific Reports · 2016
Section 10
Frequently Asked Questions
A GnRH agonist like leuprolide first stimulates the pituitary before shutting it down, causing an initial testosterone surge; degarelix blocks the GnRH receptor directly from the first dose, so there's no such flare. In a head-to-head trial, testosterone had fallen to castrate levels (≤0.5 ng/mL) in about 96% of men on degarelix by day 3, versus none of the men on leuprolide at that point — relevant because a testosterone flare can worsen tumour symptoms, spinal cord compression or urinary obstruction.
Degarelix is FDA-approved (as Firmagon, 2008) for advanced prostate cancer, where it suppresses testosterone to castrate levels. It has also been investigated, but not approved, for hormone-sensitive breast cancer and for benign prostatic hyperplasia.
The approved regimen is 240 mg to start, given as two 120 mg injections, then 80 mg every 28 days thereafter — fixed vials mixed and injected by a clinician, nothing adjusted for the individual. In the phase 3 trial that set this dose, doubling the monthly maintenance dose (160 mg vs 80 mg) produced no measurable extra benefit; the trial tracked testosterone suppression, not survival.
Injection site reactions — pain, swelling, redness — are by far the most common and distinguishing effect, reported in around 40% of patients versus under 1% on a comparator drug in one trial. Hot flashes occur in about 26%, alongside weight gain, fatigue and elevated liver enzymes; with longer use, bone density loss and metabolic changes appear, class effects of androgen deprivation generally rather than specific to degarelix.
Fast, by design: in the pivotal comparison trial, about 96% of men reached castrate testosterone levels (≤0.5 ng/mL) within 3 days of the first dose, and 88-92% did so by day 3 across the phase 2 dose-finding doses that led to the approved regimen. That speed, rather than a superior long-term suppression rate, is degarelix's main distinction from GnRH agonists.
Degarelix is supplied as a lyophilised powder kept at 25°C (controlled room temperature); no refrigerated storage is described for the unmixed product. Once reconstituted with the diluent provided in the kit, it is given within 1 hour — no extended storage data exists for the mixed solution.
No — the material reviewed lists degarelix as not prohibited by WADA, on the basis of its medical use in cancer treatment.