Risk of the "Androgen Deprivation Syndrome" in Men Receiving Androgen Deprivation for Prostate Cancer

Background-Androgen deprivation therapy for prostate cancer has been associated with a spectrum of adverse effects, such as depression, memory difficulties, and fatigue, termed the androgen deprivation syndrome.Primary care physicians providing follow-up care for men with prostate cancer will be faced with managing these effects.We therefore sought to estimate the incidence of these effects and, by using a control group, ascertain whether these effects were related to androgen deprivation itself.Methods-We assessed the risk of physician diagnoses of depression, cognitive impairment, or constitutional symptoms in Medicare data following androgen deprivation using a sample of 50 613 men with incident prostate cancer and 50 476 men without cancer, from 1992 through 1997, in the linked Surveillance, Epidemiology, and End Results-Medicare database.Cox proportional hazards regression was used to adjust for confounding variables.Results-Of men surviving at least 5 years after diagnosis, 31.3% of those receiving androgen deprivation developed at least 1 depressive, cognitive, or constitutional diagnosis compared with 23.7% in those who did not (P<.001).After adjustment for variables such as comorbidity, tumor characteristics, and age, the risks associated with androgen deprivation were substantially reduced or abolished: relative risk (RR) for depression diagnosis, 1.08 (95% confidence interval [CI], 1.02-1.15);RR for cognitive impairment, 0.99 (95% CI, 0.94-1.04);and RR for constitutional symptoms, 1.17 (95% CI, 1.13-1.22). Conclusion-Depressive, cognitive, and constitutional disorders occur more commonly in patients receiving androgen deprivation, but this appears to be primarily because patients receiving androgen deprivation are older and have more comorbid conditions and more advanced cancers.Androgen deprivation has become a common treatment for prostate cancer, with nearly half of all men with the disease receiving the therapy at some point in their course of treatment.1, 2 Androgen deprivation is increasingly used for early stages of prostate cancer, exposing men to the therapy for longer periods.2,3 In light of these trends, concerns about the toxic effects of androgen deprivation have been raised.4,5 Sexual dysfunction is a well-documented adverse effect of androgen deprivation.6-8 However, there is increasing recognition of a spectrum of other less specific adverse effects such as depression, anxiety, malaise, fatigue, and memory