Quantifying observational evidence for risk of dementia following androgen deprivation therapy for prostate cancer: an updated systematic review and meta-analysis

Background Androgen deprivation therapy (ADT) administration was recently reported and might be positively associated with dementia. However, the existing studies showed controversial results. The aim of this study was to evaluate the relationship between ADT and the risk of dementia through a meta-analysis. Methods Original articles published up to March 2020 were retrieved from Embase, Pubmed, the Cochrane library, and Web of Science for studies focusing on associations between ADT for prostate cancer (PCa) and incidence of dementia. A meta-analysis was conducted using a hazard ratio (HR) and 95% confidence interval (CI) as effect measures. Heterogeneity between the studies was examined using I 2 statistics. Subgroup analyses, sensitivity analyses, and meta-regression were conducted, and publication bias was assessed by Egger’s test. Results Thirteen studies were included in this systematic review. Eleven cohort studies involving 339,400 cases and 436,851 controls were included in the main meta-analysis. ADT administration was associated with a 21% increase in dementia risk (pooled HR = 1.21, 95% CI: 1.13–1.30, P < 0.001). Subgroup analyses based on ADT types showed that luteinizing hormone-releasing hormone agonists (HR = 1.14, P < 0.001), bilateral orchiectomy (HR = 1.42, P < 0.001), oral antiandrogens (HR = 1.35, P = 0.138), and combined androgen blockade (HR = 1.22, P = 0.097) were positively related to subsequent risk of dementia, although the differences were not statistically significant with oral antiandrogens and combined androgen blockade. Conclusions The current study indicated that ADT administration, no matter with types of ADT, is associated with the risk of dementia in patients with PCa. Future studies are needed to determine whether ADT causes dementia or is merely associated with increased risk.