Degarelix is an injectable synthetic peptide resembling human gonadotropin-releasing hormone (GnRH), which is being investigated for the treatment of endometriosis.
How degarelix works
During the normal menstrual cycle, GnRH binds to GnRH receptors on the cells of the pituitary glands in the brain and stimulates them to produce two hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). FSH drives the growth and maturation of the egg as well as the production of the female sex hormone, estrogen. LH promotes ovulation, the release of an egg from the ovaries. FSH, LH, and estrogen control the menstrual cycle, including the breakdown and shedding of the endometrium (lining of the uterus).
In endometriosis, tissue resembling the endometrium develops outside the uterus. This tissue responds to hormonal changes in the same way as the normal endometrium and starts to break down and bleed during the menstrual cycle. However, unlike the normal endometrium, it has no way out and therefore causes inflammation. This results in symptoms such as severe pain, especially in the pelvic region, infertility, and fatigue.
Degarelix is a GnRH antagonist. It blocks the binding of GnRH to its receptor on the cells of the pituitary gland. This prevents GnRH from binding and stimulating the pituitary gland cells, and therefore blocks the surge in the levels of LH and FSH that are required for estrogen production. It is hoped that in this way, degarelix could reduce the symptoms of endometriosis.
Degarelix in clinical trials
The long-term safety and efficacy of degarelix have been well-established in conditions such as prostate cancer. The treatment is now also being explored as a potential treatment for endometriosis.
A Phase 3 randomized controlled study (NCT01712763) was conducted to compare the efficacies of degarelix and the GnRH agonist goserelin in preventing the recurrence of endometriosis. The study enrolled 100 women, ages 20–45, who previously had surgery to treat endometriosis and had shown recurrence of pain symptoms. Half of the women were randomly selected and treated with 80 mg of degarelix in one administration over three months. The other half were treated with 3.75 mg of goserelin once every month for three months. The patients were then followed up for 24 months to record their disease-free time as well as any reduction in endometriosis lesions. The study was completed in March 2016, but the results have not yet been published.
A study published in the journal Fertility and Sterility reported the results of a randomized controlled clinical trial that analyzed the efficacy of degarelix in treating endometriosis recurrence compared to the GnRH agonist leuprolide. A total of 40 women who previously had surgery for endometriosis and one year of progestin treatment but whose disease recurred were enrolled in this study. Half of the patients were randomly chosen and treated with 80 mg of degarelix once a month for three months and the other half were treated with 3.75 mg per month of leuprolide for three months. The patients were followed up for six months; they were evaluated by pelvic ultrasound and levels of a protein called CA-125 in their blood, measured every three months (CA-125 is a helpful additional parameter of the presence of endometriosis). Their pain intensity was analyzed using the visual analog scale. Women treated with degarelix had a significant reduction in pelvic pain, lower levels of CA-125 protein in their blood, and a lower rate of endometriosis recurrence compared to those treated with leuprolide. These results supported the effectiveness of degarelix in treating recurrent endometriosis.
A study published in Fertility and Sterility reported the efficacy of degarelix in improving the outcomes of in vitro fertilization (IVF) in women with endometriosis compared to those treated with leuprolide. A total of 31 women assigned randomly received a single under-the-skin injection of 120 mg of degarelix, while 27 women received 3.75 mg per month of leuprolide for six months. At the end of the treatments, all 58 women underwent the IVF protocol and during this time were followed up for the time of disappearance of endometriomas and the IVF outcome. The study showed that endometriomas disappeared in a shorter period of time in women treated with degarelix compared to those treated with leuprolide. During the IVF procedure, patients treated with degarelix showed significantly higher egg implantation and pregnancy rates. They also had significantly higher numbers of mature oocytes and embryos (fertilized eggs). These results suggest that the treatment of women with ovarian endometriosis with degarelix may be beneficial in avoiding further surgery and preserving eggs or oocytes, which can improve IVF outcomes.
Other details
Degarelix was approved by the U.S. Food and Drug Administration (FDA) in 2008 for the treatment of advanced prostate cancer. It has been developed and marketed by Ferring Pharmaceuticals under the brand name Firmagon and has been shown to be safe and effective in suppressing the production of the male sex hormone testosterone, which promotes the growth of prostate cancer cells.
Last updated: Aug. 2, 2019
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