Degarelix

Origin and structure

Degarelix is a GnRH antagonist: a synthetic peptide that occupies the same pituitary receptor as gonadotrophin-releasing hormone (GnRH, also called gonadorelin) without switching it on. Ferring developed it under the code FE200486. Like natural GnRH it is ten amino acids long, but seven of them are unnatural amino acids, five of which are D-amino acids; its formula is C82H103ClN18O16 and its molar mass about 1632 g/mol.

What sets the medicine apart is the way it is given. Injected under the skin of the abdomen, the solution forms a gel depot from which the peptide is released slowly over weeks. After the 240 mg starting dose the US label gives a median terminal half-life of about 53 days; for the monthly 80 mg dose the EU product information gives 29 days. Because the release depends on how concentrated the solution is, both labels allow only the approved strengths: 120 mg at 40 mg/ml and 80 mg at 20 mg/ml.

Ferring sells it as Firmagon. Since 2023 the EU has also authorised a generic, Degarelix Accord. Both come as a powder with a solvent that is mixed just before the injection.

How it works

Degarelix binds the GnRH receptors in the pituitary competitively and reversibly, and blocks them. Output of LH and FSH drops at once, and with it testosterone production in the testes; dihydrotestosterone falls in step. Because the receptor is never stimulated, there is no initial surge. That is the key difference from GnRH agonists such as leuprorelin (leuprolide in the US), triptorelin and goserelin, which first drive LH and testosterone up for several days before the pituitary becomes desensitised.

The pivotal CS21 trial measured how fast this happens. One day after the starting dose, testosterone was at or below 0.5 ng/ml, the level of medical castration, in 52% of men on degarelix, after three days in 96% and at day 28 in all of them; on leuprorelin it was 0% at day 3, 18% at day 14 and 100% at day 28. None of the men on degarelix had a testosterone surge (a rise of at least 15% above baseline in the first two weeks), whereas most men on leuprorelin did, with an average rise of 65% at day 3. Testosterone showed no small surges after the monthly re-injections either.

Prostate cancer is androgen-sensitive, so removing testosterone slows its growth, but every effect of low testosterone comes with it: hot flushes, loss of libido, erectile dysfunction and, over time, bone loss and metabolic changes. The effect wears off after stopping. In a study in which men received degarelix for seven months, testosterone took a median of 112 days, counted from 28 days after the last injection, to rise above castrate level again, and 168 days to reach the lower end of the normal range.

Is degarelix approved?

Yes. Degarelix is a prescription medicine in the EU and the US, approved only for prostate cancer in men. Neither label covers women or children.

In the EU, Firmagon has a central marketing authorisation, valid in every member state. The EMA accepted the use in combination with radiotherapy without a dedicated degarelix trial: it relied on the mechanism and on the testosterone and PSA results of CS21, measured against GnRH agonists that had already proven themselves with radiotherapy, and asked for the results of the EORTC 1414 (PEGASUS) trial. Those appeared in 2025 (see below).

In the Netherlands degarelix is prescription-only. Firmagon (Ferring) and the generic Degarelix Accord are both on the market, and Zorginstituut Nederland's Medicijnkosten.nl lists both as reimbursed from basic health insurance.

We do not sell degarelix, and this article describes the licensed medicines only. Degarelix offered as a laboratory chemical has no marketing authorisation, is not made under a medicines licence and may not be used in people.

• EU: Firmagon 80 mg and 120 mg, authorised on 17 February 2009 for adult men with advanced hormone-dependent prostate cancer. On 19 October 2021 the European Commission added high-risk localised and locally advanced hormone-dependent prostate cancer, in combination with radiotherapy and as neo-adjuvant treatment before radiotherapy. Degarelix Accord, a generic with the same indications, was authorised on 29 September 2023. After a 2019 safety review, the EU product information lists rhabdomyolysis (breakdown of muscle tissue) as a rare side effect.
• US: Firmagon was approved on 24 December 2008 as a new molecular entity for advanced prostate cancer. The US label has no radiotherapy indication. In February 2020 it added a warning that degarelix can harm an unborn child, based on animal studies.

What the research shows

The evidence comes from Ferring's phase 3 programme, in which degarelix was compared with GnRH agonists, and from later trials on radiotherapy, heart safety and breast cancer. The four main prostate-cancer trials against agonists were open-label, so patients and doctors knew which treatment was given; only PRONOUNCE had its outcome events judged by assessors who did not know the treatment. The main results:

• CS21 (BJU Int 2008): 610 men with prostate cancer of any stage received degarelix (240 mg, then 80 or 160 mg monthly) or leuprorelin 7.5 mg monthly for a year. Testosterone stayed at or below 0.5 ng/ml from day 28 to day 364 in 97.2% on the approved 240/80 mg regimen against 96.4% on leuprorelin, which showed degarelix to be non-inferior. PSA fell faster with degarelix at first (−64% after two weeks, −85% after one month), but from day 56 the groups no longer differed, and the US label notes that no evidence links the faster PSA fall to a clinical benefit.
• CS30 (Clin Oncol 2013): 244 men with intermediate- to high-risk prostate cancer due for radiotherapy received 12 weeks of degarelix or goserelin plus the anti-androgen bicalutamide. The prostate shrank by 36.0% against 35.3%, so degarelix was non-inferior. This trial underpins the EU neo-adjuvant indication.
• EORTC 1414, also called PEGASUS (Eur Urol Oncol 2025): 379 men with very high-risk prostate cancer received radiotherapy plus 18 to 36 months of degarelix or a GnRH agonist. Because recruitment was slow, the primary endpoint was switched from progression-free survival to PSA response: PSA fell below 0.1 ng/ml within six months after radiotherapy in 52% on degarelix against 60% on agonists, not a significant difference, and two-year progression-free survival was 88% in both arms.
• PRONOUNCE (Circulation 2021): the cardiovascular safety trial in men with heart disease, stopped early at 545 men. It found no significant difference in major cardiovascular events between degarelix and leuprorelin; details in the comparison below.
• Cochrane review (2021): 11 randomised trials with 3 to 14 months of follow-up. There were no data to assess overall survival. Serious side effects and quality of life may be similar to standard androgen suppression (low- and moderate-certainty evidence), while injection-site pain was about 16 times as common with degarelix (risk ratio 15.7).
• Breast cancer, TREND (J Clin Oncol 2019, not an approved use): in a phase 2 trial, 51 premenopausal women with breast cancer received letrozole before surgery plus degarelix or triptorelin to switch off the ovaries. Oestradiol reached the target level after a median of 3 days with degarelix against 14 with triptorelin. Suppression held in every cycle on degarelix, while 15.4% of women on triptorelin were insufficiently suppressed after the first cycle.

Degarelix versus GnRH agonists

The firm differences are speed and the absence of a flare. Degarelix brings testosterone to castrate levels within days and never raises it first, so no anti-androgen is needed as cover at the start; with an agonist, the EU product information for triptorelin, for example, advises considering one. The EU product information for Firmagon adds that a clinical benefit over an agonist combined with an anti-androgen in the first phase of treatment has not been shown. After a year, degarelix kept as many men at castrate levels as leuprorelin did (CS21).

The trade-offs are practical. Degarelix comes only as a monthly injection, while agonists also come as three-monthly depots, and injection-site reactions are far more common: 35% against under 1% with leuprorelin injected into the muscle in CS21.

The open question is the heart. A post hoc pooled analysis of six of Ferring's phase 3 trials (2,328 men, Eur Urol 2014) found about half as many cardiac events in the first year with degarelix among men who already had cardiovascular disease (hazard ratio 0.44), but the authors stressed that a post hoc result can only generate hypotheses. PRONOUNCE, with Ferring as sponsor, was set up to test it: men with prostate cancer and atherosclerotic cardiovascular disease were randomised to a year of degarelix or leuprorelin. With slow enrolment and fewer events than expected, it stopped at 545 of the 900 planned men. A major cardiovascular event (death, heart attack or stroke) occurred in 5.5% on degarelix against 4.1% on leuprorelin (hazard ratio 1.28, 95% CI 0.59 to 2.79), and the authors concluded that the relative cardiovascular safety of the two classes remains unresolved. In EORTC 1414, among the 41 men with heart disease at the start, one on degarelix and four on agonists had a cardiovascular event, a subgroup too small to settle the question.

Relugolix, a GnRH antagonist taken as a daily tablet, had fewer major cardiovascular events than leuprorelin in the HERO trial, which our leuprorelin article describes. For degarelix, the one trial designed for the question, PRONOUNCE, found no significant difference.

Side effects and warnings

Injection-site reactions are what set degarelix apart. In CS21, 35% of men on the approved regimen had pain, redness, swelling, hardening or a lump at the site, against under 1% on leuprorelin; across the trial, pain was reported by 28% and redness by 17%. They occur mainly after the starting dose: during maintenance the EU product information counts 3 cases of pain per 100 injections. Most were mild to moderate and passed, and fewer than 1% of men stopped because of them. Very rarely the site became infected, formed an abscess or showed tissue death that could need surgical treatment.

The other common effects come from low testosterone. In CS21, hot flushes affected 26% on degarelix and 21% on leuprorelin, and weight gain 9% and 12%; fatigue, sweating, loss of libido, erectile dysfunction, breast enlargement and testicular shrinkage are also listed. Liver enzymes rose in 10% against 5%, mostly mildly and reversibly. The EU product information reports chills (3%), fever (2%) and flu-like illness (1%) in the hours after an injection.

Androgen deprivation can prolong the QT interval on the ECG. In CS21 about 20% of men in both groups had a QTc above 450 ms, and 3 of 409 on degarelix against 4 of 201 on leuprorelin reached 500 ms or more; a dedicated study in 80 healthy volunteers found no direct effect of degarelix itself on the QT interval. The labels ask for the benefit to be weighed in men with risk factors for a long QT interval or on other QT-prolonging drugs. The US label warns of severe allergic reactions, including anaphylaxis, reported after marketing. The EU product information also warns of reduced glucose tolerance and diabetes, of cardiovascular disease linked to androgen deprivation, and of loss of bone density with long use, which it notes was never measured with degarelix. Rare side effects include heart attack, heart failure and rhabdomyolysis.

Antibodies against degarelix developed in 10% of men after a year and 29% after up to 5.5 years, without any sign that they changed its effect or safety. Degarelix can impair male fertility for as long as testosterone is suppressed. It is not for women: in animal studies it caused pregnancy loss, and the US label warns that it can harm an unborn child.

Frequently asked questions

What is the difference between degarelix and leuprorelin?

Both bring testosterone down to castrate levels, but in opposite ways. Leuprorelin is a GnRH agonist: it first stimulates the pituitary, so testosterone rises for several days before it falls. Degarelix blocks the receptor, so testosterone falls within days without a surge. After a year both kept about the same share of men at castrate levels (97.2% against 96.4% in CS21). Degarelix causes more injection-site reactions and comes only as a monthly injection, whereas agonists also come as three-monthly depots.

Is degarelix (Firmagon) available in the Netherlands, and is it reimbursed?

Yes, on prescription. Firmagon (Ferring) and the generic Degarelix Accord are both on the Dutch market for prostate cancer, and Zorginstituut Nederland's Medicijnkosten.nl lists both as reimbursed from basic health insurance. We do not sell degarelix. Degarelix offered as a laboratory chemical is not a medicine and may not be used in people.

Why is no anti-androgen needed when starting degarelix?

Because there is no testosterone surge to block. GnRH agonists first raise testosterone, which can briefly worsen prostate cancer, so the product information of agonists such as triptorelin advises considering an anti-androgen at the start. Degarelix blocks the GnRH receptor from the first dose: in CS21 none of the men on degarelix had a surge, and 96% were at castrate level after three days. The EU product information adds that a clinical benefit over an agonist plus an anti-androgen has not been shown.

Is degarelix safer for the heart than GnRH agonists?

That has not been shown. A post hoc pooled analysis of Ferring's phase 3 trials found about half as many cardiac events in the first year with degarelix in men who already had heart disease. PRONOUNCE, the randomised trial set up to test this in men with atherosclerotic heart disease, stopped early with 545 of 900 planned men and found no significant difference: major cardiovascular events in 5.5% on degarelix against 4.1% on leuprorelin. Its authors called the question unresolved.

Is degarelix banned in sport?

No. The WADA Prohibited List 2026 bans, for men only and at all times, GnRH and its agonist analogues, such as goserelin, leuprorelin and triptorelin, in class S2.2.1, testosterone-stimulating peptides in males. GnRH antagonists such as degarelix, which lower testosterone, are not named anywhere on the list. The Dutch translation of the list by the Dopingautoriteit carries the same wording.

Why does a degarelix injection leave a lump?

Because it is meant to form a depot. At the approved concentration the solution turns into a gel under the skin, from which degarelix is released over weeks. In CS21, 28% of men reported pain at the injection site and 17% redness, with swelling, hardening or a lump less often. Most reactions followed the starting dose, were mild to moderate and passed, and fewer than 1% of men stopped because of them.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

Related peptides