Treatment of Moderate to Severe BPH with 5-Alpha Reductase Inhibitors
5-alpha reductase inhibitors (5-ARIs) such as finasteride 5mg daily or dutasteride 0.5mg daily are strongly recommended for men with moderate to severe BPH symptoms who have enlarged prostates (>30cc) or PSA >1.5ng/mL to reduce prostate size, decrease risk of acute urinary retention by 67%, and reduce the need for BPH-related surgery by 64%. 1
Patient Selection for 5-ARI Therapy
5-ARIs are most effective in patients with:
- Prostate volume >30cc (confirmed by transrectal ultrasound or cross-sectional imaging)
- PSA >1.5ng/mL (as a proxy for prostate size)
- Moderate to severe symptoms (IPSS/AUA-SI score 8-35)
The larger the prostate gland, the more pronounced the effects of 5-ARIs 2, 1
Available 5-ARIs and Their Mechanisms
Finasteride
- Selectively inhibits 5-AR type II isoenzyme
- Reduces serum DHT by approximately 70%
- Reduces prostate tissue DHT by approximately 80%
- Standard dose: 5mg once daily 2, 1
Dutasteride
- Inhibits both type I and type II 5-AR isoenzymes
- Reduces serum DHT by approximately 95%
- Reduces prostate tissue DHT by approximately 94%
- Standard dose: 0.5mg once daily 2, 3
Clinical Efficacy of 5-ARIs
Symptom Improvement
- 5-ARIs provide 3-4 point improvement in IPSS/AUA-SI scores over 6-10 years of follow-up 2
- Dutasteride demonstrated a mean decrease from baseline in AUA-SI total symptom scores of -3.8 units compared to -1.7 units for placebo at 24 months 3
- Symptom improvement is more significant in men with larger prostates (≥40cc) 3
Reduction in Disease Progression
- 5-ARIs reduce the risk of acute urinary retention by 57-67% 1, 3
- 5-ARIs reduce the risk of BPH-related surgery by 48-64% 1, 3
- Prostate volume reduction of 15-25% at six months of treatment 2
Important Clinical Considerations
Onset of Action
- 5-ARIs have a slower onset of action compared to alpha blockers
- Patients should be counseled that symptom improvement may take several months 2, 1
PSA Monitoring
- 5-ARIs reduce PSA levels by approximately 50%
- After 1 year of therapy, measured PSA should be doubled to accurately assess for prostate cancer 2, 1
- Any confirmed increase in PSA while on 5-ARIs should be evaluated for possible prostate cancer 3
Side Effects
- Sexual side effects: erectile dysfunction, decreased libido, ejaculation disorders (1-2.1%)
- Gynecomastia (2.2%)
- Potential increased risk of high-grade prostate cancer 1, 3
Combination Therapy
- Combination therapy with an alpha blocker and 5-ARI is more effective than monotherapy for patients with enlarged prostates (>30cc) and moderate-to-severe symptoms 1
- The combination of doxazosin and finasteride has been most extensively studied 2
- Consider combination therapy for patients with larger prostates and more severe symptoms 2, 1
Perioperative Considerations
- 5-ARIs may be considered to reduce intraoperative bleeding and perioperative need for blood transfusion during TURP or other surgical interventions for BPH 2
Follow-up and Monitoring
- Schedule follow-up 3-6 months after initiating therapy
- Assess symptom improvement using IPSS/AUA-SI
- Monitor for medication adherence and side effects
- Consider uroflowmetry and post-void residual volume
- Monitor PSA (remember to double the value if on 5-ARI) 1
Cautions and Contraindications
- Contraindicated in pregnancy (women who are pregnant should not handle 5-ARI capsules)
- Patients should not donate blood until 6 months after their last dose of 5-ARI
- Use with caution in patients taking potent CYP3A4 inhibitors (e.g., ritonavir) 3
5-ARIs represent an important treatment option for men with moderate to severe BPH symptoms, particularly those with enlarged prostates. Their ability to alter the natural history of BPH by reducing the risk of acute urinary retention and need for surgery makes them valuable in long-term BPH management.