associated with exacerbation of symptoms from prostate cancer. The symptoms may include bone pain, spinal cord compression, bladder outlet obstruction, cardiovascular problems, and so forth. However, there are wide discrepan- cies in reports of the frequency and severity of acute clinical progression or clinical ﬂare that might result from the tes- tosterone surge. The use of GnRH agonists for patients with metastatic prostate cancer can be associated with clinical ﬂare in approximately 10% of the patients.24 In contrast, patients with non-metastatic prostate cancer have very little risk for clinical ﬂare. Antiandrogen therapy reduces, but does not totally eliminate, clinical ﬂare in patients at high risk for this scenario.24 In the phase III trial it was voluntarily allowed to give bicalutamide for prevention of clinical ﬂare. However, only 11% patients received bicalutamide and no patient of the entire leuprolide group had documented clinical ﬂare.14 Abarelix (Plenaxis®; Praecis Pharmaceuticals, Cambridge, MA, USA) was the ﬁrst GnRH antagonist to be approved (in 2003) by the FDA for patients with advanced, symptomatic prostate cancer who cannot have or refuse other treatments for prostate cancer, such as other hormone treatments or surgery to remove the testicles.25 The reason for this restriction was that the administration of abarelix could be associated with acute systemic allergic reaction. In 15/1397 (1.1%) patients treated with abarelix this symptom was evident. In 14/15 patients the symptoms occurred within eight minutes of injection. In 2005, Praecis Pharmaceuticals voluntarily dis- continued promotional activities relating to abarelix in the US and the sale of abarelix for patients not currently on therapy.25 However, in 2005 the drug was approved in Germany but not in other European countries. Since 2008, abarelix is avail- able on the German market under the license of Speciality European Pharma.26 A systemic allergic reaction was not reported in any of the degarelix studies.14,20,21 Otherwise, in the randomized phase III trial 4% of the degarelix-treated patients reported chills versus none of the patients treated with leu- prolide.14 These chills were neither discussed nor explained by the authors. Therefore, further reports on degarelix with long-term follow-up on efﬁcacy and safety – especially con- cerning the allergic potential – are mandatory. Also, it should be realized that 40% of patients experienced injection site reactions of degarelix compared to 1% at the im injection site of leuprolide.14 Why is the application of degarelix so painful? One explanation could be that the injected volume is rather high. In fact, 2 × 3 ml are injected to apply the initial dose of 240 mg degarelix. If patients are diagnosed with prostate cancer the question today is: who needs androgen deprivation therapy? In a Clinical Interventions in Aging 2009:4 Degarelix in prostate cancer population-based cohort study of 19,271 patients older than 65 years (median age 77 years) having prostate cancer and treated with androgen deprivation therapy (7,867 patients) or conservative management (11,047 patients) were studied.27 Patients had a T1 disease in 49.8% (androgen deprivation group) compared to 64.2% (conservative management group) and the tumor was moderately and poorly differentiated in 65% and 34.2% (androgen deprivation group) compared to 83.7% and 14.2% (conservative management group). It was demonstrated that 10-year cancer-speciﬁc survival in patients receiving androgen deprivation therapy was 80.1% compared to 82.6% (Hazard ratio [HR]: 1.17, 95% conﬁdence interval [CI]: 1.03–1.33) in patients receiving conservative manage- ment (deﬁned as not receiving operative therapy, radiotherapy or androgen deprivation therapy within 180 during the ﬁrst days from diagnosis).27 Ten-year overall survival was 30.2% (androgen deprivation group) compared to 30.3% (conserva- tive management group) and median overall survival was 82 months in both groups. However, in patients with poorly differentiated prostate cancer it was shown that cancer spe- ciﬁc survival was better in patients receiving androgen depri- vation therapy (59.8% vs 54.3%, HR: 0.84, 95% CI: 0.7–1; p = 0.049). It is noteworthy that 75% of all patients received androgen deprivation therapy for a minimum of 18 months and 50% of patients for longer than 30 months.27 Not only the efﬁcacy of androgen deprivation therapy in terms of survival needs to be questioned but also pos- sible adverse events. Androgen deprivation therapy itself is potentially associated with several adverse events. These include hot ﬂashes, osteoporosis, loss of libido or impotence, psychological effects such as depression, memory difﬁculties or emotional lability, and others.28–32 Diabetes and cardiovascular disease are especially unwanted adverse events among older patients. However, there is growing evidence that androgen deprivation therapy is associated with an increased risk of cardiovascular disease and diabetes.28 In an observational study of a population- based cohort of 73,196 patients older than 65 years (mean age 74.2 years, standard deviation 5.8 years) having prostate can- cer were investigated. The endpoints incident diabetes, coro- nary heart disease, myocardial infarction, and sudden cardiac death occurred in 10.9%, 25.3%, 5.4%, and 4.5% of all cases. A total of 36.3% of patients received a GnRH agonist for a mean of 40% of time from diagnosis to censoring. This use of a GnRH agonist was associated with an increased risk of incident diabetes (adjusted HR: 1.44; P 0.001), coronary heart disease (adjusted HR: 1.16; p 0.001), myocardial infarction (adjusted HR: 1.11; p 0.03), and sudden cardiac 221