What is the mechanism of action of finasteride (5-alpha-reductase inhibitor) in treating benign prostatic hyperplasia (BPH) and androgenetic alopecia?

Mechanism of Action of Finasteride

Finasteride works by selectively inhibiting the Type II 5-alpha-reductase enzyme, which blocks the conversion of testosterone to dihydrotestosterone (DHT), reducing DHT levels by approximately 70% in serum and 80% in prostatic tissue. 1

Enzymatic Inhibition

• Finasteride is a competitive and specific inhibitor of Type II 5-alpha-reductase, forming a stable enzyme complex with extremely slow turnover (half-life approximately 30 days). 1
• The drug has no affinity for the androgen receptor itself, working exclusively through enzyme inhibition. 1
• Type II 5-alpha-reductase normally metabolizes testosterone to DHT in the prostate gland, liver, and skin. 1

Effects on Hormone Levels

• A single 5-mg oral dose produces rapid reduction in serum DHT concentration, with maximum effect observed 8 hours after the first dose, and suppression is maintained throughout the 24-hour dosing interval. 1
• Daily dosing at 5 mg/day for up to 4 years reduces serum DHT concentration by approximately 70%. 1
• Median circulating testosterone levels increase by approximately 10-20% but remain within the physiologic range. 1
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increase by about 10%, but levels remain within normal range. 1

Tissue-Specific Effects in BPH

• In prostatic tissue, finasteride reduces DHT content by approximately 80% compared to placebo, while testosterone tissue concentration increases up to 10 times over pretreatment levels. 1
• This reduction in androgenic growth leads to increased apoptosis and atrophy, shrinking the prostate by 15-25% at six months. 2
• Atrophy is most pronounced in the glandular epithelial component of the prostate, which is the source of PSA production, reducing PSA levels by approximately 50%. 2
• The reduction in prostate volume provides clinical benefits including improved urinary flow rate and decreased obstructive and irritative symptoms. 2

Comparison with Dutasteride

• Unlike finasteride, which selectively inhibits Type II 5-alpha-reductase, dutasteride inhibits both Type I and Type II isoenzymes. 2
• This difference results in finasteride reducing serum DHT by approximately 70% compared to 95% with dutasteride. 2
• However, in BPH tissue where Type II 5-alpha-reductase is far more common than Type I, the reduction of DHT in prostate tissues is approximately 80% with finasteride and 94% with dutasteride. 2

Effects in Androgenetic Alopecia

• In male pattern hair loss, DHT is implicated in the development of hairlessness in genetically predisposed men. 3
• Reduction in DHT at the 1 mg/day dose results in significant improvement in hair growth and density by preventing DHT-mediated miniaturization of hair follicles. 3, 4

Clinical Onset and Duration

• Due to the slow onset of action compared to alpha-blockers, patients should be counseled on slower symptom improvement if treated with finasteride alone for BPH. 2
• The hypothalamic-pituitary-testicular axis is not affected, as finasteride does not alter the response of LH and FSH to gonadotropin-releasing hormone. 1
• No clinically meaningful effect is observed on plasma lipid profile, bone mineral density, or circulating levels of cortisol, prolactin, thyroid-stimulating hormone, or thyroxine. 1