Background and importance Recent studies have indicated that androgen deprivation therapy (ADT) increased the dementia risk in prostate cancer (PCa) patients. Phosphodiesterase 5 inhibitors (PDE5i) with nitric oxide mediated vasodilation can increase blood flow in the brain. However, no current studies have explored the association between PDE5i exposure and dementia in PCa patients treated with ADT.
Aim and objectives To determine the association between PDE5i exposure and incident dementia in PCa patients treated with ADT.
Material and methods We conducted a retrospective cohort study using the Chang Gung Research Database (CGRD) in Taiwan. We included PCa patients newly receiving ADT between 2009 and 2016. We conducted a three step matching and modified landmark approach to identify PDE5i users and non-users after ADT use. The landmark date was defined as 1 year following the start of ADT, and we defined PDE5i users as patients initiating PDE5i before and after the landmark date. We matched PDE5i users to non-users by (1) age, (2) prostatic specific antigen and (3) 1:4 propensity scores for comorbidity and co-medication. We followed the patients from the landmark date until the incident diagnosis of dementia, last date of clinical visit or 31 December 2019. We performed multivariate Cox proportional hazard models to compare the dementia risk between PDE5i users and non-users.
Results We included 4557 PCa patients starting ADT treatment, with a mean age of 69.5 (SD 7.0) years. After matching, we identified 161 PDE5i users and 644 non-PDE5i users. A total of 5.1 person years of PDE5i users and 4.6 person years of PDE5i non-users were included. Compared with non-users of PDE5i, PCa patients treated with ADT initiating PDE5i had a lower risk of dementia (adjusted HR=0.17, 95% CI 0.04 to 0.70) in the modified landmark analyses.
Conclusion and relevance PDE5i use in PCa patients treated with ADT was associated with a decreased risk of subsequent dementia. Future large scale studies are suggested to confirm our findings.
Conflict of interest No conflict of interest
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