Pharmacodynamics
Finasteride is a 5α-reductase inhibitor.[23][4] It is specifically a selective inhibitor of the type II and III isoforms of the enzyme.[4][68][69] By inhibiting these two isozymes of 5α-reductase, finasteride reduces the formation of the potent androgen dihydrotestosterone (DHT) from its precursor testosterone in certain tissues in the body such as the prostate gland, skin, and hair follicles.[4][70] As such, finasteride is a type of antiandrogen, or more specifically, an androgen synthesis inhibitor.[71][72] However, some authors do not define finasteride as an "antiandrogen," a term which can refer more specifically to antagonists of the androgen receptor.[73]
Finasteride results in a decrease of circulating DHT levels by about 65–70% with an oral dosage of 5 mg/day and of DHT levels in the prostate gland by up to 80–90% with an oral dosage of 1 or 5 mg/day.[68][74][75] In parallel, circulating levels of testosterone increase by approximately 10%, while local concentrations of testosterone in the prostate gland increase by about 7-fold and local testosterone levels in hair follicles increase by around 27–53%.[76][77] An oral dosage of finasteride of only 0.2 mg/day has been found to achieve near-maximal suppression of DHT levels (68.6% for 0.2 mg/day relative to 72.2% for 5 mg/day).[77][78] Finasteride does not completely suppress DHT production because it lacks significant inhibitory effects on the 5α-reductase type I isoenzyme, with more than 100-fold less inhibitory potency for type I as compared to type II (
As of 2012, the tissues in which the different isozymes of 5α-reductase are expressed are not fully clear.[70] This is because different investigators have obtained varying results with different reagents, methods, and tissues examined.[70] However, the different isozymes of 5α-reductase appear to be widely expressed, with notable tissues including the prostate gland, seminal vesicles, testes, epididymides, skin, hair follicles, liver, kidneys, and brain, among others.[70]
By inhibiting 5α-reductase and thus preventing DHT production, finasteride reduces androgen signaling in tissues like the prostate gland and the scalp. In the prostate, this reduces prostate volume, which improves BPH and reduces the risk of prostate cancer. Finasteride reduces prostate volume by 20 to 30% in men with benign prostatic hyperplasia.[80] Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.[81]
Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from progesterone) activate the GABAA receptor in the brain; because finasteride prevents the formation of neurosteroids, it functions as a neurosteroidogenesis inhibitor and may contribute to a reduction of GABAA activity. Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction.[82][83][84]
In accordance with finasteride being a potent 5α-reductase inhibitor but a weak inhibitor of 5β-reductase, the medication decreases circulating levels of 5α-reduced steroids like allopregnanolone but does not reduce concentrations of 5β-reduced steroids like pregnanolone.[85][86][87] Pregnanolone acts as a potent GABAA receptor positive allosteric modulator similarly to allopregnanolone.[88]
