What are the indications, dosing regimens, contraindications, common adverse effects, and monitoring guidelines for the 5‑alpha‑reductase inhibitor finasteride?

Finasteride: Comprehensive Clinical Overview

Mechanism of Action

Finasteride is a synthetic 4-azasteroid that specifically inhibits type 2 5α-reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT) in the prostate and scalp. 1, 2 Unlike dutasteride, finasteride does not inhibit the type 1 isoenzyme. 3 The drug has no binding affinity for androgen receptors and possesses no intrinsic androgenic or antiandrogenic properties. 2

FDA-Approved Indications

Benign Prostatic Hyperplasia (BPH)

• Treatment of symptomatic BPH in men with enlarged prostates 3, 1
• Reduces prostate volume by approximately 24-28% after 24 weeks of treatment 4
• Decreases risk of acute urinary retention by one-third (absolute rates: 4.2% vs 6.3% placebo) 3
• Reduces need for transurethral resection of prostate (1.0% vs 1.9% placebo) 3
• Finasteride is NOT appropriate for men with lower urinary tract symptoms who lack prostatic enlargement 3

Male Androgenetic Alopecia

• Treatment of male pattern baldness at 1 mg daily dose 3, 5

Off-Label Consideration

• Finasteride is NOT FDA-approved for prostate cancer prevention, despite reducing overall cancer detection by 25% 3, 6

Dosing Regimens

BPH Treatment

• 5 mg orally once daily 1, 2
• Therapy must continue for at least 6 months before evaluating clinical response 1
• Effects on prostate volume are rapid and predictable within 12-24 weeks 4

Male Pattern Baldness

• 1 mg orally once daily 3
• The 1 mg dose produces similar PSA suppression (50% decrease at 1 year) as the 5 mg dose in men over 50 years 3

Duration for Cancer Prevention (if pursued off-label)

• 7 years of continuous therapy based on the Prostate Cancer Prevention Trial design 3

Pharmacokinetics

• Absolute bioavailability: 63% (range 34-108%) 2
• Time to peak concentration: 1-2 hours 1, 2
• Plasma protein binding: approximately 90% 1, 2
• Elimination half-life: 6-8 hours 2
• Extensively metabolized by the liver to five metabolites, two of which retain <20% of finasteride's activity 2

Absolute Contraindications

Pregnancy (FDA Black Box)

• Finasteride is absolutely contraindicated in women who are or may become pregnant 7
• Can cause abnormalities of external genitalia in male fetuses 7
• Pregnant women must not handle crushed or broken tablets due to risk of transdermal absorption 7
• If contact occurs, wash the area immediately with soap and water 7

Hypersensitivity

• Any component of the medication 7

Common Adverse Effects

Sexual Dysfunction (Most Common)

Erectile Dysfunction:

• Absolute incidence: 4.2-15.8% in mid-term studies (1-2 years) 3, 8
• Excess risk vs placebo: 2-4% 3, 8
• Long-term cumulative incidence: 67.4% over 7 years vs 61.5% placebo (in older men with baseline dysfunction) 3, 8
• Mean decrease of 3.21 points on 0-100 sexual function scale, equivalent to approximately 2.5 years of natural aging 8

Decreased Libido:

• Absolute incidence: 3.4-10% in treatment groups 3, 8
• Excess risk vs placebo: 2-4% 3, 8
• Relative risk: 1.83 compared to placebo 3

Ejaculatory Dysfunction:

• Decreased ejaculate volume: 1.5-7.2% of patients 3, 8
• 2.6-fold increased risk versus placebo 3
• Does not appear to interfere with normal sexual function 3, 7

Critical Context:

• Sexual side effects decrease over time and remain statistically significant but clinically small after the first year 8
• Discontinuation rates due to adverse events are 6-7% in BOTH finasteride and placebo groups, suggesting many reported effects may not be drug-related 8
• Most sexual dysfunction resolves within 3 months of discontinuation 8

Breast-Related Effects

• Gynecomastia: 4.1% vs 2.4% placebo (2.13-fold increased risk) 3
• Breast tenderness: 0.4-0.7% 8
• Patients must promptly report breast lumps, pain, or nipple discharge 7

Post-Finasteride Syndrome Controversy

• The FDA amended labels to warn about persistent symptoms after discontinuation, based on anecdotal reports rather than prospective trials 8
• Post-finasteride syndrome remains poorly defined and controversial with unclear data quality 8

Prostate Cancer Detection Paradox

High-Grade Cancer Concern

• Finasteride increases detection of high-grade prostate cancers (Gleason 7-10) on biopsy, but this is likely an artifact of enhanced detection rather than true tumor induction 3
• The 25% prostate volume reduction improves biopsy sampling accuracy, reducing sampling error 3
• Men diagnosed with cancer while on finasteride have smaller tumor burden, fewer positive cores, and less bilateral involvement—suggesting less aggressive disease despite higher Gleason scores 3
• No mortality difference exists between finasteride-treated and untreated men after long-term follow-up 6

Patient Counseling Requirements

• Men with PSA ≤3.0 undergoing regular PSA screening should be informed about the 25% reduction in overall cancer detection and the theoretical (but likely artifactual) increase in high-grade cancers 3
• Men taking finasteride for BPH or alopecia must be counseled about this detection paradox 3, 7

Critical Monitoring Guidelines

PSA Monitoring (Essential)

• PSA levels must be doubled after 12 months of finasteride therapy to accurately interpret prostate cancer screening 3
• Finasteride lowers PSA by 50% after 12 months 3
• At 3 years, PSA decline may exceed 50%, requiring a multiplier of 2.3 3
• Failure to adjust PSA values can delay cancer diagnosis and worsen outcomes 8
• Any PSA increase while on finasteride should prompt immediate evaluation for prostate cancer 6

Baseline and Follow-Up Assessment

• Document baseline prostate size (finasteride ineffective without enlargement) 3
• Assess baseline sexual function (46% of BPH patients have pre-existing dysfunction) 8
• Monitor for breast changes at each visit 7
• Evaluate symptom improvement using AUA Symptom Index/IPSS after 6 months 3, 1

Laboratory Monitoring

• PSA at baseline, then annually with 2× multiplier after 12 months 3, 8
• No other routine laboratory monitoring required 8

Common Clinical Pitfalls

Pitfall 1: Using Finasteride Without Prostatic Enlargement

• Finasteride is ineffective for LUTS in men without enlarged prostates 3
• Always confirm prostatic enlargement before initiating therapy 3

Pitfall 2: Failing to Adjust PSA Values

• The most dangerous error is interpreting PSA without doubling the value after 12 months 3, 8
• This can result in delayed cancer diagnosis with worse outcomes 8

Pitfall 3: Premature Discontinuation

• Patients must continue therapy for at least 6 months before evaluating efficacy 1
• Prostate volume returns to baseline within 12 weeks of discontinuation 4

Pitfall 4: Inadequate Sexual Dysfunction Counseling

• Inform patients that sexual side effects are modest (equivalent to 2.5 years of aging), decrease over time, and resolve in most men within 3 months of stopping 8
• Emphasize that discontinuation rates are identical in finasteride and placebo groups 8

Pitfall 5: Female Exposure Risk

• Ensure male patients understand that pregnant women cannot handle crushed or broken tablets 7
• Intact coated tablets are safe for normal handling 7

Drug Interactions

• Minimal clinically relevant drug interactions reported 2
• No dose adjustments required for concurrent medications 2

Quality of Life Considerations

• Mean AUA Symptom Index improvement: 3 points, which patients perceive as clinically meaningful 3
• Symptom improvement is not substantially greater in men with very large vs moderately enlarged prostates 3
• However, men with larger glands or higher PSA face progressively higher risk of complications, enhancing the benefit-to-risk ratio over time 3