What is the mechanism of action of finasteride (5-alpha-reductase inhibitor)?

Mechanism of Action of Finasteride

Finasteride works by specifically inhibiting the enzyme 5-alpha-reductase, which converts testosterone into the more potent androgen dihydrotestosterone (DHT), thereby reducing DHT levels in target tissues including the prostate, scalp, and skin. 1

Biochemical Mechanism

Finasteride acts through the following specific mechanisms:

• Enzyme Inhibition: Finasteride is a competitive and specific inhibitor of Type II 5α-reductase, forming a stable enzyme complex with slow turnover (half-life ~30 days) 1
• DHT Reduction: Daily dosing of finasteride 5 mg/day reduces serum DHT concentration by approximately 70% 1
• Tissue Specificity: Finasteride primarily affects tissues where DHT plays a significant role, including:
  • Prostate gland
  • Scalp (hair follicles)
  • Skin
  • Liver 2, 1

Pharmacodynamic Effects

When finasteride is administered:

• A single 5-mg oral dose produces rapid reduction in serum DHT, with maximum effect observed 8 hours after the first dose 1
• Testosterone levels increase by approximately 10-20% but remain within physiologic range 1
• In prostatic tissue, DHT content is reduced by approximately 80% after 7-10 days of treatment 1
• Intraprostatic testosterone concentration may increase up to 10 times over pretreatment levels 1
• Intraprostatic PSA content is decreased 1

Isoenzyme Specificity

Finasteride demonstrates different effects on 5α-reductase isoenzymes:

• Type II 5α-reductase: Finasteride primarily inhibits this isoform, which is predominant in the prostate gland, hair follicles, and liver 2, 3
• Type I 5α-reductase: Finasteride has less effect on this isoform in humans 3

This differs from dutasteride, which inhibits both Type I and Type II isoenzymes, causing a greater and more consistent decrease in DHT 2

Clinical Implications

The mechanism of action explains finasteride's therapeutic effects in:

1. Benign Prostatic Hyperplasia (BPH):

   • Reduces prostate size by inhibiting DHT-mediated growth 2, 4
   • Improves urinary flow rate and reduces BPH symptoms 2, 4
   • Reduces risk of acute urinary retention by 67% 4
   • Reduces need for BPH-related surgery by 64% 4

2. Androgenetic Alopecia (Male Pattern Baldness):

   • Blocks DHT action at the hair follicle level 5
   • Improves hair count and appearance by reducing DHT-mediated follicular miniaturization 5

Common Pitfalls and Caveats

1. PSA Monitoring: Finasteride reduces PSA levels by approximately 50% after 12 months of therapy, which must be considered when interpreting PSA results for prostate cancer screening 2

   • A multiplier of 2 is typically used for PSA values in patients taking finasteride 2
   • No specific cut point or change in PSA has been prospectively validated in men taking finasteride 2

2. Adverse Effects: The most common side effects are related to sexual function:

   • Decreased libido
   • Erectile dysfunction
   • Decreased ejaculate volume
   • Gynecomastia 2, 5

3. Onset of Action: While DHT reduction occurs rapidly, clinical improvement in BPH symptoms may take 3-6 months to manifest 6

4. Hormonal Effects: Finasteride causes small increases in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but these typically remain within normal range 1

Finasteride's specific inhibition of 5α-reductase represents a targeted approach to conditions where DHT plays a pathological role, allowing for effective treatment with minimal systemic androgenic effects.