The influence of low dose finasteride, a type II 5 alpha-reductase inhibitor, on circulating neuroactive steroids

Background: Finasteride is a 5 alpha-reductase inhibitor that has received clinical approval for the treatment of human benign prostatic hyperplasia and androgenetic alopecia. The treatment is practically without side effects, although some occasional cases of depression syndrome have been reported. 5 alpha-Reductase is an enzyme responsible for the reduction of testosterone, progesterone or deoxycorticosterone to their 5 alpha-reduced derivatives possessing anticonvulsant, antidepressant, and anxiolytic activity. Therefore, the formation of GABAergic neuroactive steroids is likely to be impacted by finasteride. Objective: The objective of the study was to show how the treatment of premature androgenetic alopecia with low doses (1 mg/day) of finasteride influences the broad spectrum of steroids with potential neuroactivity. Methods: A group of 12 men with premature androgenetic alopecia participated in the present study. The steroid hormone profile was determined for all individuals. Finasteride was administered for 4 months at a daily dose of 1 mg. After the treatment, the same hormonal profile was determined again. Results: 5 alpha-Reduced steroids, e.g., 5 alpha-dihydrotestosterone, androsterone, epiandrosterone, 5 alpha-androstene-3 alpha, 17 beta-diol, allopregnanolone, isopregnaolone, and some 5-ene steroids, such as dehydroepiandrosterone and pregnenolone, decreased gradually during treatment. Conclusions: The decrease of 5 alpha-reduced steroids, especially of allopregnanediol, dihydrotestosterone, and pregnenolone, is probably one of the factors responsible for the increased occurrence of depression in men treated with finasteride, even at low doses.