What are the indications and potential adverse effects of finasteride (5-alpha-reductase inhibitor) in adult males?

Finasteride: Indications and Adverse Effects

Primary Indications

Finasteride is FDA-approved for two specific conditions: symptomatic benign prostatic hyperplasia (BPH) with documented prostatic enlargement at 5 mg daily, and male androgenetic alopecia (male pattern baldness) at 1 mg daily. 1, 2

Benign Prostatic Hyperplasia (BPH)

• Finasteride is only appropriate for men with LUTS who have documented prostatic enlargement - it is ineffective and should not be used in men without enlarged prostates 1
• Greatest benefit occurs in men with baseline PSA >4 ng/mL (indicating larger prostates) 1
• Reduces prostate volume by approximately 15-25% 1, 3
• Provides a 3-point improvement on the AUA Symptom Index on average 1
• Reduces acute urinary retention risk from 6.3% to 4.2% (absolute risk reduction 2.3%) 1
• Decreases need for BPH-related surgery from 3.3% to 1.7% (absolute risk reduction 1.6%) 1
• Reduces hematuria in some patients 1
• Less effective than alpha-blockers for symptom relief alone, but combination therapy may be superior for long-term progression prevention 1
• Requires at least 6 months of therapy before clinical response can be adequately evaluated 4

Male Androgenetic Alopecia

• Approved at 1 mg daily dose for male pattern hair loss 5, 6
• Works by inhibiting conversion of testosterone to dihydrotestosterone (DHT), which drives hair loss 6
• Produces similar PSA suppression (50% decrease) as the 5 mg dose in men over 50 years 1

Adverse Effects

Sexual Dysfunction (Most Common)

Sexual side effects occur in an additional 2-4% of patients compared to placebo, are generally reversible, and decrease over time after the first year. 1, 7

• Erectile dysfunction: 2-4% absolute increase over placebo, with rates of 4.2-15.8% depending on study population and duration 1, 7
• Decreased libido: 2-4% absolute increase, affecting 3.4-10% of treatment groups 1, 7
• Decreased ejaculate volume: 1.5-7.2% of patients, representing 2.6-fold increased risk versus placebo 1, 7
• Clinical magnitude is modest: On a 0-100 scale, finasteride causes a mean difference of only 3.21 points compared to 1.26 points for each year of aging 1, 7
• Sexual dysfunction decreases over time and remains statistically significant but clinically small after the first year 1, 7

Endocrine Effects

• Gynecomastia: 0.5-2.2% versus 0.1-1.1% with placebo 1, 7
• Breast tenderness: 0.4-0.7% of patients 1, 7
• Patients should promptly report breast lumps, pain, or nipple discharge 2

Discontinuation Rates

• Overall discontinuation approximately 15% for both finasteride and placebo groups 1, 7
• Discontinuation specifically due to adverse events: 6-7% in both treatment and placebo groups 1, 7

Post-Finasteride Syndrome Controversy

• The FDA amended labels to warn about persistent symptoms after discontinuation, though this is based on anecdotal reports rather than prospective trials 7
• Post-finasteride syndrome remains poorly defined and controversial with unclear data quality 7
• Most sexual side effects are reversible after discontinuation 3

Critical Laboratory Considerations

PSA levels must be doubled after 12 months of finasteride therapy to accurately interpret prostate cancer screening - failure to adjust can delay cancer diagnosis and worsen outcomes. 1, 7

• Finasteride lowers PSA by 50% after 12 months of therapy 1
• At 3 years, PSA decline may exceed 50%, requiring a multiplier of 2.3 instead of 2.0 1
• Effects on PSA before 12 months are variable 1

Prostate Cancer Considerations

• An observed increase in high-grade prostate cancers occurred in finasteride-treated men in the PCPT trial, though this is likely due to enhanced detection artifact rather than actual tumor transformation 1
• Men taking finasteride had smaller, less aggressive tumors with fewer positive cores and less bilateral involvement compared to placebo 1
• The increase in high-grade tumors is nearly completely explained by reduced prostate volume leading to better sampling, not increased cancer aggressiveness 1
• Patients taking finasteride for BPH or alopecia should be counseled about this finding, though reassurance can be provided that it likely represents detection bias 1, 2

Contraindications and Warnings

Pregnant women or women who may become pregnant must not handle crushed or broken finasteride tablets due to risk of male fetal abnormalities. 2

• Intact coated tablets are safe to handle 2
• If contact with crushed tablets occurs, wash immediately with soap and water 2

Common Pitfalls to Avoid

• Do not prescribe finasteride for LUTS without documented prostatic enlargement - it is ineffective in this population 1
• Do not forget to double PSA values after 12 months of therapy when screening for prostate cancer 1, 7
• Do not expect rapid symptom improvement - continue therapy for at least 6 months before evaluating response 4
• Do not confuse increased urinary frequency from returning obstruction with increased urine output if therapy is discontinued 3
• Benefits are lost when therapy is withdrawn, necessitating long-term treatment for sustained control 3