Finasteride treatment and neuroactive steroid formation

Finasteride is the 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostate hyperplasia and androgenetic alopecia. The 5alpha-reductase is enzyme responsible for the reduction of testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and deoxycorticosterone to dihydrodeoxycorticosterone, steroids modulating the action of gamma-aminobutyric acid on GABA receptors. These neuroactive steroids possess anticonvulsant, antidepressant and anxiolytic effects. The objective of the study was to determine the effect of finasteride therapy on a broad steroid spectrum in men with benign prostate hyperplasia. A group of 20 men with benign prostate hyperplasia was involved in the present study. Finasteride in the daily dose of 5 mg/day was administrated for 4 months. In all individuals, their hormonal profile of steroid hormones was determined before and after 4 months lasting finasteride treatment. Finasteride treatment resulted in a significant decrease all alpha-reduced and increase of most 5beta-reduced metabolites of testosterone and progesterone as well as in an increase of 7alpha-hydoxyderivatives, which are known as neuroactive steroids acting by modulation of GABAA and NMAD receptors in the brain. In the course of finasteride treatment the decrease of the concentration of circulating steroids with known inhibitory activity on GABA-ergic excitation in the brain is very probably an important factors contributing to the development of the symptoms of depression seen in some isolated cases of finasteride administration.