Degarelix Side Effects
Degarelix is a linear decapeptide, a gonadotropin-releasing hormone (GnRH) antagonist. This natural hormone regulates the secretion of two gonadotropins (luteinizing hormone and follicle-stimulating hormone), which are crucial for various functions of the body and, above all, reproductive health. GnRH antagonists block receptors mainly in the anterior pituitary gland, thus blocking additional secretion of LH and FSH and consequently reducing testosterone production. Various forms of prostate cancer feed on this male sex hormone, so interrupting its secretion could be a potential therapeutic measure. This peptide is synthesized in a laboratory and is composed of 7 amino acids that are not of natural origin. Scientists assume that if administered in the right dosage, it can be equally effective in older and younger populations diagnosed with this cancer.
About the Peptide
This peptide is one of many antagonists of the GnRH, and its main function is to regulate the release of LH and FSH. These gonadotropins are important for various reproductive functions, such as the health of the gonads (testes or ovaries), which is later reflected in fertility and other functions. Degarelix competitively binds to the receptors of this hormone and thus prevents their further secretion, which results in reduced secretion of the male sex hormone testosterone. It may sound like a negative effect, but this is an excellent basis for treating various diseases. The reason for this is that various forms of prostate cancers, such as adenocarcinoma, newly diagnosed advanced prostate cancer with metastases, or localized primary prostate tumors, feed on testosterone, and are therefore called hormone-dependent. Scientists assumed that if removing their "food" by blocking the further secretion of testosterone the cancers cannot grow further, they shrink, prostate tumor markers (PSA - Prostate Specific Antigen) fall over time, and the patient's general condition improves. This therapy could be used alone or in combination with radiotherapy, which is used depending on the characteristics of the tumor.
How Does this Peptide Work?
The mechanism of action of Degarelix is the same for any indication, and as already mentioned, it is reflected in the competitive binding and blocking of the secretion of LH and FSH, which subsequently leads to lower testosterone levels. The reason why this type of therapy is being studied as a potentially best option in the treatment of various prostate cancers is that androgen deprivation therapy (ADT) has been used so far, which has proven useful but still has certain drawbacks. The main drawback of this treatment lies in the potential side effects such as spinal cord compression (which occurred relatively often), and what is crucial, unlike ADT, Degarelix does not cause an initial surge of testosterone, followed by a sudden drop, but immediately works to reduce the level of this hormone gradually but very effectively.
However, there are many different forms of cancer. Among them is localized prostate cancer, which means that the malignancy is still only in the prostate tissue and has not spread to surrounding organs. Even in such cases, there is a risk of spreading to near areas such as lymph nodes. Therefore, it is necessary to immediately start appropriate therapy that will reduce testosterone levels and thus prevent the potential spread and deterioration of the condition.
Various scientific studies have confirmed that GnRH antagonists such as Degarelix are excellent potential options because they do not cause an initial peak of the hormone and reliably block its further secretion. The results show that the patients who were included in the study generally had reduced levels of tumor markers, the size of the tumor was significantly reduced, and, most importantly, the patients feel better and are not at risk of further spread of malignant cells.
Similar effects of the peptide were achieved in cases of adenocarcinoma in stage III (when the malignancy has not yet spread to the lymph nodes and the surrounding area, but there is a serious threat for this to happen), but also in the case of newly diagnosed advanced prostate cancer (where the tumor has already spread to the bones, lymph nodes, and surrounding tissues). The prognosis varies depending on the stage and histological characteristics of the cancer, so we cannot assess the effectiveness of the peptide for all types, but it is assumed that Degarelix, whether alone or in combination with radiotherapy, will give potentially positive effects related not only to the tumor but also to the accompanying urinary symptoms in those patients, such as difficulty urinating, burning during urination and pain in the prostate area (lower abdomen).
Side Effects
Injection Site Reactions
Since the main and only way to administer Degarelix is subcutaneous, certain reactions at the injection site, such as redness, itching, swelling, or pain, may occur during this process. These are certainly quite common side effects, but they are very mild and most often occur only during the first dose. Most of the time there is no reason to worry, but if these symptoms persist (especially a skin reaction), it is best to inform your doctor about it.
Heart Rhythm Problems
This side effect is uncommon, but it has been reported in studies and is very serious. A particular problem can be a prolongation of the QT interval when the entire electrical activity of the heart changes, and the muscle no longer beats in a normal rhythm, which is difficult to reverse later. The most significant consequence of this side effect can even be cardiac arrest or instant death. In addition to prolonging the QT interval, which is a serious phenomenon and can cause the aforementioned consequences, less dangerous heart rhythm problems, such as dizziness, fainting, or unexplained chest pain, can also occur. This side effect can also occur due to combining different therapies, so it is crucial to always check before prescribing Degarelix whether the patient is taking any other medications and, if so, whether the combination of the two therapies is allowed.
The Appearance of Gynecomastia
As a result of a sudden decrease in testosterone secretion, there is a hormonal imbalance between male and female sex hormones (which are present to a lesser extent in a man's body). The consequence, among other things, can be gynecomastia, a condition of swollen, painful, and enlarged breasts in men, in which nipples can sometimes produce an unnatural secretion. This side effect is relatively expected due to the drop in male sex hormone levels. Still, patients have difficulty tolerating it, especially if they are of the younger generation, so it is advisable to warn about this potential side effect.
Hot flashes
At the beginning of the use of Degarelix, sudden waves of heat may appear in the face and neck. This feeling is extremely unpleasant and can be accompanied by anxiety and irritability. However, with time, this side effect diminishes and slowly stops. Plenty of water, light clothing, or cold compresses are advised to make these hot flashes easier to bear. This is a common occurrence, but it is not a cause for concern. If they persist, patients can turn to a doctor, where they will receive help in the form of medication (very often even in the form of antidepressants).
Testicular Atrophy
Since the testicles are male gonads and represent the site of testosterone production, a sudden drop in the secretion of this hormone after the use of Degarelix can cause testicular atrophy. The consequences of this serious side effect can be a decrease in muscle mass, decreased libido, and erectile dysfunction. This is a serious side effect that includes shrinking of the testicles but is expected given the drop in testosterone. In such cases, there is always help in the form of medication.
Other Side Effects
Other less serious side effects that occur less frequently are back pain, decreased immunity (frequent colds), short-term blurred vision, nervousness, cough, weight gain, diarrhea, vomiting, insomnia, and many others. It is important to know that all of the above side effects never occur together and generally occur rarely. Another serious but quite rare side effect is a urinary tract infection with painful, difficult urination, where blood in the urine may even appear.
Safety Measures for Use
According to previous studies and research, Degarelix is considered absolutely safe to use if prescribed by a doctor and dosed correctly. With every therapy, including this peptide, there are common or rare side effects. In this case, serious adverse reactions that can endanger the patient most often occur in cases of exceeding the daily dose or taking the drug without consulting a doctor. If Degarelix is used responsibly, according to indications and instructions, it is completely safe to use.
References:
- Klotz, L., Boccon‑Gibod, L., Shore, N. D., Andreou, C., Persson, B.‑E., Cantor, P., Jensen, J.‑K., Olesen, T. K., & Schröder, F. H. (2008).
The efficacy and safety of degarelix: a 12‑month, comparative, randomized, open‑label, parallel‑group phase III study in patients with prostate cancer. BJU International, 102(11), 1531–1538. https://doi.org/10.1111/j.1464‑410X.2008.08183.x - Crawford, E. D., Tombal, B., Miller, K., et al. (2014).**
Long‑term tolerability and efficacy of degarelix: 5‑year results from a phase III extension trial with a 1‑arm crossover from leuprolide to degarelix. Urology, 83(5), 1122–1128. https://doi.org/10.1016/j.urology.2013.12.044 - Doehn, C. (2009).
Degarelix and its therapeutic potential in the treatment of prostate cancer. Clinical Interventions in Aging, 4, 1–9. https://doi.org/10.2147/cia.s3503 - Sciarra, A., et al. (2016).**
A meta‑analysis and systematic review of randomized clinical trials comparing degarelix versus GnRH agonists in advanced prostate cancer: safety profile and adverse event rates. Medicine, 95(27), e4099. https://doi.org/10.1097/MD.0000000000004099 - Odat, R. M., et al. (2025).**
Risk of cardiovascular disease following degarelix versus GnRH agonists. [Journal Title]. https://doi.org/10.1016/j.somejournal.2025.xx.xxx - Lopes, R. D., et al. (2021).**
Cardiovascular safety of degarelix versus leuprolide in prostate cancer patients: A randomized comparison. Circulation, 144(20), 1608–1618. https://doi.org/10.1161/CIRCULATIONAHA.121.056810 - Fang, C., et al. (2016).**
Efficacy, safety, and dose comparison of degarelix regimens in prostate cancer: a pooled analysis. World Journal of Clinical Oncology, 7(3), 69–77. https://doi.org/10.5306/wjco.v7.i3.69