What are the 5-alpha-reductase inhibitors (5-ARIs) used to treat Benign Prostatic Hyperplasia (BPH) and androgenetic alopecia?

5-Alpha-Reductase Inhibitors (5-ARIs)

The two primary 5-alpha-reductase inhibitors (5-ARIs) used clinically are finasteride and dutasteride, which are FDA-approved for treating benign prostatic hyperplasia (BPH) with enlarged prostate and androgenetic alopecia (male pattern baldness). 1

Mechanism of Action

• 5-ARIs inhibit the conversion of testosterone to dihydrotestosterone (DHT) by blocking the 5-alpha-reductase enzyme 2
• Finasteride primarily inhibits the type II isoform of 5-alpha-reductase, which predominates in the prostate and hair follicles 2
• Dutasteride inhibits both type I and type II isoforms of 5-alpha-reductase, causing a greater and more consistent decrease in DHT 3

FDA-Approved Indications

Finasteride

• Treatment of symptomatic BPH in men with enlarged prostate (5 mg dose) 3
• Treatment of androgenetic alopecia (male pattern baldness) (1 mg dose) 4

Dutasteride

• Treatment of symptomatic BPH in men with enlarged prostate (0.5 mg dose) 1
• Combination therapy with tamsulosin (alpha-blocker) for symptomatic BPH 1

Clinical Benefits in BPH

• Reduction in risk of acute urinary retention (from 5.6% to 3.3%; absolute risk difference of 2.3%) 3
• Reduction in need for surgical intervention (from 3.3% to 1.7%; absolute risk difference of 1.6%) 3
• Improvement in urinary symptoms with an average 3-point improvement in AUA Symptom Index 3
• Reduction in prostate volume (approximately 25-28% reduction with dutasteride) 1
• Most effective in men with larger prostates (baseline PSA >4 ng/mL) 3

Effects on PSA

• 5-ARIs lower PSA by approximately 50% after 12 months of therapy 3
• For men taking finasteride, PSA values should be multiplied by 2 for appropriate interpretation 3
• Dutasteride may cause a greater and more consistent decrease in DHT and PSA, though long-term data is limited 3
• Even the 1 mg dose of finasteride used for male pattern baldness has a similar effect on PSA (50% decrease) in men over 50 years old 3

Adverse Effects

• Sexual dysfunction:
  • Erectile dysfunction (1.6% higher than placebo) 5
  • Decreased libido (1.5% higher than placebo) 5
  • Ejaculatory dysfunction (3.4% higher than placebo) 5
• Gynecomastia (1.3% higher than placebo) 5
• Mood disorders (depression and anxiety) with statistically significant but clinically minimal differences compared to placebo 5
• Potential impact on fertility with decreased sperm count in some men 6
• Sexual side effects may decrease over time but remain statistically significant 3

Important Considerations and Precautions

• 5-ARIs are not appropriate for men with LUTS who do not have evidence of prostatic enlargement 3
• Women who are pregnant or may become pregnant should not handle these medications due to potential risk to male fetuses 1
• Men taking 5-ARIs should not donate blood for at least 6 months following their last dose 1
• Concerns about increased risk of high-grade prostate cancer have been raised, though this may be due to enhanced detection rather than true biological effect 3

Clinical Application

• For BPH treatment, 5-ARIs are less effective than alpha blockers for immediate symptom relief but provide long-term benefits in reducing disease progression 3
• 5-ARIs may be used as monotherapy or in combination with alpha blockers for enhanced symptom relief 3, 1
• The benefits of 5-ARIs must be weighed against potential adverse effects, particularly sexual side effects 3, 7
• Discontinuation rates due to adverse events are approximately 6-7% in clinical trials, similar to placebo 3