(A-323) Association Between 5alpha-Reductase Inhibitors and Risk of Developing Parkinson’s Disease in Patients with Benign Prostatic Hyperplasia: Evidence from a Prospective Cohort Study

Background: With the aging of the global population, the prevalence of Parkinson’s disease (PD) and benign prostatic hyperplasia (BPH) has rapidly doubled in the past 30 yr. Preclinical studies suggest the neuroprotective effect of 5alpha-reductase inhibitors (5-ARIs, first-line treatment for BPH, e.g. finasteride) in animal models of PD, which is still underexplored in epidemiological studies.

Objectives: To determine the uncharted risk of PD in patients with BPH and further explore the potential effect of 5-ARIs on this PD risk at the population level.

Methods: The BPH cohort was assembled from the UK Biobank (2006-2022) and followed from baseline until the date of PD diagnosis, death, loss of follow-up, or October 31, 2022, excluding participants with androgen alopecia and follow-up for less than one yr. To quantify the risk of PD in BPH patients, BPH was considered as exposure, and non-BPH participants were selected as control group. Further, to clarify the association between 5-ARIs and the aforementioned PD risk, BPH patients were divided into drug exposed and non-drug control groups, according to whether they used 5-ARIs. Time-dependent Cox regression model along with inverse probability weighted propensity score was used to estimate the association between exposure and outcome. The propensity score was composed of age, ethnicity, BMI, Townsend deprivation index, smoking status, drinking status, physical activity, education level, marital status, history of type 2 diabetes, use of alpha1-blockers and 5-ARIs (only for the former analysis). Sensitivity analyses accounted for the exclusion of participants followed for less than two yr and correcting the bias of death competing risk using the competing risk model.

Results: During 13.19±2.05 yr of follow-up, 17,664 BPH patients and 81,962 non-BPH participants were included, with 1.59% and 0.86% developing PD. Compared with non-BPH participants, the risk of PD was significantly higher in patients with BPH (HR = 1.2192, 95%CI: 1.0154-1.4639, p = 0.0338). Meanwhile, there were 1,445 5-ARIs users in BPH patients (1,214 received finasteride alone). Compared with 16,219 non-users, the risk of PD decreased as the number of prescriptions for 5-ARIs increased (HR = 0.9381, 95%CI: 0.9301-0.9461, p < 0.0001), especially among those using finasteride alone (HR = 0.9342, 95%CI: 0.9259-0.9425, p < 0.0001).

Conclusions: This study first reports that BPH patients suffer from a higher risk of PD, and that this risk may gradually decrease with the increase of 5-ARIs administration. This finding echoes previous research suggesting that 5-ARIs may improve movement disorders in animal models of PD, strengthening population-level evidence, and provides a new perspective for multisystem health comorbidity network.