Role of 5α-reductase inhibitors in Parkinson's disease: Gambling or not?

Parkinson's disease (PD) is a progressive neurodegenerative disease due to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental cause of PD is not completely confirmed. However, genetic, epigenetic, and environmental factors are intricate in the progressive accumulation of mutant α-synuclein (α-Syn) in the dopaminergic neurons of the SNpc. PD is frequently linked with other age-related diseases such as benign prostatic hypertrophy, which is treated by the 5α-reductase inhibitor finasteride. Particularly, 5α-reductase, which is expressed in the prostate, is also expressed in the brain for the biosynthesis of the neuroprotective neurosteroids. Thus, 5α-reductase inhibitors such as finasteride may adversely affect the pathogenesis of PD. Nevertheless, numerous preclinical and clinical investigations highlight that finasteride may have a neuroprotective effect against the development and progression of PD. Despite this effect of finasteride, prolonged use of a 5α-reductase inhibitor is associated with the development of dementia in the initial periods after starting treatment. However, reducing the magnitude of the association over time suggested that the risk may be completely or in part due to increased dementia detection among patients with benign prostate enlargement. The fundamental mechanism by which 5α-reductase inhibitors are related to cognitive impairment is indistinct. Therefore, the possible role of finasteride in PD is not completely clarified. Consequently, the objective of the present review was to explain and discuss the precise role of finasteride in PD.