Why is finasteride (a 5-alpha-reductase inhibitor) not used as first-line treatment for Benign Prostatic Hyperplasia (BPH)?

From the Guidelines

Finasteride is not used as a first-line treatment for benign prostatic hyperplasia (BPH) because it works more slowly than alpha-blockers and is most effective for men with larger prostates, as evidenced by the most recent guideline from 2021 1.

Reasons for Not Using Finasteride as First-Line Treatment

• Finasteride reduces prostate size by inhibiting 5-alpha reductase, which converts testosterone to dihydrotestosterone, but this process takes 3-6 months to achieve maximum benefit, whereas alpha-blockers provide rapid symptom relief within days to weeks 1.
• Finasteride is better suited for men with prostate volumes greater than 30cc on imaging, a PSA >1.5ng/mL, or palpable prostate enlargement on DRE, as recommended by the 2021 guideline 1.
• Finasteride has potential side effects including sexual dysfunction (decreased libido, erectile dysfunction) and, rarely, depression, which may impact quality of life and medication adherence 1.

Preferred Initial Therapy

• Alpha-blockers like tamsulosin (0.4 mg daily) are typically prescribed first since they provide rapid symptom relief and are effective for most patients with BPH 1.
• Combination therapy with finasteride and an alpha-blocker should be offered as a treatment option only to patients with LUTS associated with demonstrable prostatic enlargement, as judged by a prostate volume of >30cc on imaging, a PSA >1.5ng/mL, or palpable prostate enlargement on DRE 1.

Key Considerations

• The 2021 guideline recommends that clinicians should not offer the combination of low-dose daily 5mg tadalafil with alpha blockers for the treatment of LUTS/BPH as it offers no advantages in symptom improvement over either agent alone 1.
• Finasteride reduces the risk of subsequent acute urinary retention and the need for BPH-related surgery, with the absolute benefit increasing with rising prostate volume or serum PSA 1.

From the FDA Drug Label

The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 men ≥55 years of age with a normal digital rectal examination and a PSA ≤3. 0 ng/mL. Men received either finasteride 5 mg or placebo daily. Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study. The incidence of Gleason score 8 to 10 prostate cancer was higher in men treated with finasteride (1.8%) than in those treated with placebo (1. 1%) [see INDICATIONS AND USAGE (1.3) and WARNINGS AND PRECAUTIONS (5.2)].

The reason finasteride is not used as first-line treatment for Benign Prostatic Hyperplasia (BPH) is due to the increased risk of high-grade prostate cancer associated with its use, as seen in the PCPT trial 2. This increased risk may outweigh the benefits of finasteride in treating BPH, making it a less desirable first-line treatment option. Key points to consider include:

• High-grade prostate cancer risk: Finasteride increases the risk of high-grade prostate cancer, which is a significant concern.
• Alternative treatments: Other treatments, such as alpha-blockers, may be preferred as first-line options due to their more favorable safety profiles.

From the Research

Reasons for Not Using Finasteride as First-Line Treatment

• Finasteride may not be as effective as other treatments, such as terazosin, in reducing symptom scores and improving maximum urinary flow rates, as shown in a 1-year trial 3.
• The magnitude of clinical improvement seen with finasteride has been perceived to be modest, especially when compared with that associated with transurethral resection of the prostate (TURP) 4.
• Finasteride may not be suitable for patients with severe symptomatic BPH, as TURP or other invasive procedures may be more effective in these cases 4.
• The efficacy of finasteride may take at least 6 months to become apparent, which may not be suitable for patients who require immediate relief from symptoms 4.
• Finasteride has been associated with sexual side effects, such as decreased libido, ejaculation disorders, and impotence, which may be a concern for some patients 3, 4, 5.

Patient Selection for Finasteride Treatment

• Finasteride may be more effective in patients with a large prostate (> or = 40 ml) than in patients with a small prostate 3.
• Patients with moderate uncomplicated BPH may be suitable for finasteride treatment, especially if they are unable or unwilling to undergo surgery 3, 4.
• Finasteride may be an option for patients with more severe symptoms who are awaiting surgery or are unable to undergo surgery 3.