What is the mechanism of action of Finasteride (generic name)?

From the Guidelines

Finasteride works by selectively inhibiting the 5-alpha reductase type II isoenzyme, reducing dihydrotestosterone (DHT) levels in the prostate by approximately 80%, which leads to a reduction in androgenic growth and an increase in apoptosis and atrophy, shrinking the prostate gland. This mechanism of action is supported by a study published in 2021 in The Journal of Urology 1, which discusses the effectiveness of drug therapies in improving International Prostate Symptom Score (IPSS). The study highlights the importance of 5-alpha reductase inhibitors (5-ARIs) in reducing intraoperative bleeding and peri- or postoperative need for blood transfusion after transurethral resection of the prostate (TURP) or other surgical intervention for benign prostatic hyperplasia (BPH).

The reduction in DHT levels caused by finasteride leads to a decrease in prostate volume, with studies showing a reduction of 15-25% at six months 1. This decrease in prostate volume is associated with an improvement in symptoms, as measured by the IPSS. The study also notes that finasteride reduces serum PSA levels by approximately 50%, which is important to consider when screening men for prostate cancer who are on 5-ARIs.

Key points to consider when prescribing finasteride include:

• The medication should be reserved for patients with appropriately enlarged prostates, as defined by a minimum prostate volume of >30cc or PSA >1.5ng/mL 1
• Patients should be counseled on the slow onset of action of finasteride, with improvements in symptoms typically seen after 6-12 months of treatment 1
• Finasteride is typically prescribed at 5mg daily for the treatment of BPH, and results may vary depending on individual patient characteristics and response to treatment.
• The medication has a good safety profile, but potential side effects may include decreased libido, erectile dysfunction, and decreased ejaculate volume in a small percentage of users.

From the FDA Drug Label

The development and enlargement of the prostate gland is dependent on the potent androgen, 5α -dihydrotestosterone (DHT). Type II 5α-reductase metabolizes testosterone to DHT in the prostate gland, liver and skin. Finasteride is a competitive and specific inhibitor of Type II 5α-reductase with which it slowly forms a stable enzyme complex.

The mechanism of action of Finasteride is as a competitive and specific inhibitor of Type II 5α-reductase, which metabolizes testosterone to DHT. By inhibiting this enzyme, finasteride decreases the levels of DHT, a potent androgen that plays a key role in the development and enlargement of the prostate gland 2.

From the Research

Mechanism of Action of Finasteride

The mechanism of action of Finasteride involves the inhibition of the enzyme 5 alpha-reductase, which converts testosterone to dihydrotestosterone (DHT) 3, 4, 5, 6.

• Finasteride is a specific competitive inhibitor of 5 alpha-reductase, with no binding affinity for androgen receptor sites 3.
• It reduces prostatic DHT levels and prostate size, leading to improvements in peak urinary flow rate and urological symptoms in men with symptomatic benign prostatic hyperplasia (BPH) 4, 5.
• Finasteride suppresses DHT by about 70% in serum and by as much as 85%-90% in the prostate, with the remaining DHT in the prostate likely resulting from type 1 5alpha-reductase 6.

Effects on Testosterone and Dihydrotestosterone

• Finasteride's inhibition of 5 alpha-reductase leads to a decrease in DHT levels, while testosterone levels remain unaffected 3, 6.
• The reduction in DHT levels is associated with a decrease in prostate size and an improvement in symptoms of BPH 4, 5.
• The effects of finasteride on testosterone and DHT levels are dose-dependent, with higher doses leading to greater reductions in DHT levels 3, 6.

Clinical Implications

• Finasteride is indicated for the treatment of symptomatic BPH, with a recommended dosage of 5 mg once/day 3, 4, 5.
• The drug has been shown to be effective in reducing prostate size and improving symptoms of BPH, with long-term medical therapy reducing clinically significant endpoints such as acute urinary retention or surgery 4, 6.
• Finasteride may also be used to treat other DHT-mediated disorders, such as acne, facial hirsutism, frontal lobe alopecia, and prostate cancer, although its use in these conditions remains investigational 3, 7.