Doehn et al in 38% and 48% of patients followed by fatigue in 16% and 23% of patients. Nasopharyngitis (11% vs 11%) and dizziness (11% vs 9%) were other adverse events. Pain at the injection site was evident in 6% and 8% of patients treated with degarelix.20 In the European and South African phase II trial including 187 patients with prostate cancer (of whom 147 patients completed the study) six different dose regimens of degarelix (200/80, 200/120, 200/160, 240/80, 240/120, and 240/160) were tested.21 Adverse events occurred in 57% to 75% of patients within these groups (Table 2). Most adverse events were mild to moderate but the exact number of mild, moderate, and severe adverse events was not given. How- ever, 11% of patients had at least one severe adverse event. Hot ﬂashes of mild to moderate intensity were documented in 33% (range 27%–47%) of cases. Fatigue occurred in 6% (range 3%–10%) of patients and weight increase in 9% (range 0%–13%) of patients. An increase of alanine aminotransferase was measured in 9% (range 3%–10%) of patients. Pain at the injection site was evident in 10% (range 0%–13%) of patients treated with degarelix.21 In the North American phase II trial, three patients (2%) died and another 11 patients (6%) died in the European and South African phase II trial. None of the reported deaths were considered to be related to degarelix.20,21 Results from a phase III trial In the randomized phase III trial adverse event were reported in 81% of 330% patients of the pooled degarelix groups and in 78% of 156% patients of the leuprolide group (Table 2).14 The intensity of all reported adverse events in the pooled degarelix group versus the leuprolide group was mild in 283 (69%) versus 138 (69%) patients, moderate in 225 (55%) versus 101 (50%) patients, and severe in 68 (17%) versus 26 (13%) patients. Serious adverse events were reported in 21 (10%) and 24 (12%) patients in the degarelix 240/80 and degarelix 240/160 groups compared to 28 (14%) patients in the leupro- lide group. The number of patients terminating the study due to adverse events was comparable in the three treatment arms: 15 (7%) in the degarelix 240/80 group, 19 (9%) in the degarelix 240/160 group, and 12 (6%) in the leuprolide group. The most frequently reported adverse events in both groups were hot ﬂashes (26% in the pooled degarelix group vs 21% in the leuprolide group). Patients treated with degarelix reported statistically signiﬁcant more injection site reactions than patients treated with leuprolide (40% in the pooled degarelix group vs 1% in the leuprolide group; p 0.001). These injection site reactions included pain, erythema, swelling, induration, and nodule. They were the reason for 220 discontinuation in ﬁve patients (1%) treated with degarelix although they occurred predominantly after the ﬁrst injection und were documented to be mild or moderate in intensity. In 18 patients (4%) treated with degarelix, chills were an adverse event compared to no such event in the leuprolide group (p 0.01). Further signiﬁcant differences between the treatment groups were arthralgia (4% in the pooled degarelix group vs 9% in the leuprolide group; p 0.05) and urinary tract infections (3% in the pooled degarelix group vs 9% leuprolide group; p 0.01). In each degarelix group, ﬁve patients (2%) died compared to nine patients (4%) in the leuprolide group. None of the death was considered to be treatment-related.14 Conclusions The administration of the GnRH antagonist degarelix is associated with a rapid, profound, and sustained suppression of testosterone in patients with prostate cancer. Results from the recently published randomized, open-label, three-arm phase III study showed that degarelix is not inferior to leup- rolide at maintaining testosterone suppression over a one-year treatment period and degarelix was able to produce a faster testosterone suppression and PSA decline than leuprolide.14 In the last ten years, degarelix has run through various phase I and II trials and dose-ﬁnding was a major goal of these trials.22 As a result from these trials an initial dose of 240 mg seems to be the best dose to achieve a clinically relevant testosterone suppression in more than 90% of patients within three days and in more than 95% of patients after one month.14,21 A maintenance dose of 80 mg and 160 mg degarelix every four weeks resulted in a profound and sustained testos- terone suppression.14,21 In December 2008, degarelix at a dose of 240 mg sc followed by 80 mg sc every month has been approved for the treatment of advanced prostate cancer by the US Food and Drug Administration (FDA) and its approval by the European Medicines Agency (EMEA) has been recom- mended.23 However, it is a clear disadvantage that degarelix is currently only available as a one-month formulation. Degarelix has an immediate onset of action with no need for clinical ﬂare protection with an antiandrogen as required in some patients treated with GnRH agonists.24 This kind of action of degarelix might offer advantages especially in patients with advanced prostate cancer and a higher risk for symptoms associated with clinical ﬂare. Testosterone surge begins two to three days after administration of GnRH agonists.24 Theoretically, the median testosterone can increase by 100%. In the phase III trial it was demonstrated that median testosterone increased by 65%.14 This may be Clinical Interventions in Aging 2009:4