What are the most common side effects of 5‑alpha‑reductase inhibitors (finasteride and dutasteride)?

Most Common Side Effects of 5-Alpha-Reductase Inhibitors

The most common side effects of 5-alpha-reductase inhibitors (finasteride and dutasteride) are sexual dysfunction—specifically erectile dysfunction (4-16%), decreased libido (3-10%), and ejaculation disorders (1.4-7%)—along with breast disorders including gynecomastia (0.5-2.3%). 1, 2, 3

Sexual Side Effects

Erectile Dysfunction

• Erectile dysfunction occurs in 4.2-15.8% of patients in mid-term studies (1-2 years), representing an excess risk of 2-4% compared to placebo 1, 4
• During the first 6 months of treatment, approximately 4.7% of patients experience erectile dysfunction, with incidence decreasing over time 2, 4
• The FDA label for dutasteride confirms impotence as one of the most common adverse reactions requiring reporting 3
• Long-term data from the PCPT trial showed 67.4% cumulative incidence over 7 years versus 61.5% with placebo (relative risk 1.10), though this older population had high baseline sexual dysfunction 1, 4

Decreased Libido

• Decreased libido affects 3-10% of patients in treatment groups, representing a 2-4% excess over placebo 1
• With dutasteride specifically, 3% of patients report decreased libido in the first 6 months, decreasing to 0.3% by 19-24 months 2
• The FDA label lists decreased libido as one of the most common adverse reactions for dutasteride 3

Ejaculation Disorders

• Reduced ejaculate volume occurs in 1.4-7.2% of patients, representing a 2.6-fold increased risk versus placebo 1
• Dutasteride causes ejaculation disorders in 1.4% of patients initially, decreasing to 0.1% by 19-24 months 2
• Combination therapy with tamsulosin significantly increases ejaculation disorders to 11% compared to 2% with dutasteride monotherapy 3

Breast-Related Side Effects

• Gynecomastia occurs in 0.5-2.2% of finasteride users versus 0.1-1.1% with placebo 1
• Dutasteride causes gynecomastia in 2.3% of patients compared to 0.74% in placebo groups (relative risk 3.11) 2
• Breast tenderness affects 0.4-0.7% of finasteride patients 1
• The FDA label confirms breast disorders (including enlargement and tenderness) as common adverse reactions 3

Clinical Magnitude and Time Course

Magnitude of Effect

• The sexual dysfunction impact is clinically modest: finasteride causes a mean difference of only 3.21 points on a 0-100 scale, compared to 1.26 points for each year of aging 1
• This translates to an effect roughly equivalent to 2.5 years of natural aging 1

Time-Dependent Patterns

• Sexual side effects decrease over time and remain statistically significant but clinically small after the first year 1
• Most sexual adverse reactions occur during the first 6 months, with decreasing incidence in subsequent periods 2, 3
• Most men experience spontaneous improvement within the first three months after stopping finasteride 1

Discontinuation Rates

• Overall discontinuation rates are approximately 15% for both 5α-reductase inhibitors and placebo groups, indicating many reported side effects may not be drug-related 1, 2
• Discontinuation specifically due to adverse events is 6-7% in both treatment and placebo groups 1, 2, 4
• The most common adverse reaction leading to discontinuation is impotence (1-1.5%) 1, 3

Laboratory and Monitoring Considerations

• PSA levels decrease by approximately 50% after 12 months of therapy with both finasteride and dutasteride 1, 2
• PSA values must be doubled after 12 months to accurately interpret prostate cancer screening, as failure to adjust may delay cancer diagnosis and lead to worse outcomes 1, 2

Important Caveats

Persistent Symptoms

• The FDA amended finasteride labels to warn about persistent symptoms after discontinuation, though this is based on anecdotal patient reports rather than prospective trials 1
• Post-finasteride syndrome remains poorly defined and controversial, with unclear data quality supporting its existence 1
• Sexual adverse reactions may persist after treatment discontinuation, though the role of dutasteride in this persistence is unknown 3

Comparison Between Agents

• Finasteride and dutasteride have essentially equivalent effects on erectile function, with no clinically meaningful difference between the two medications 1
• Choice between agents should be based on factors other than erectile function impact, such as cost or efficacy considerations 1

Population Considerations

• Baseline sexual dysfunction is common in BPH populations, with 46% of men having a history of sexual dysfunction at screening 1
• Higher rates of erectile dysfunction are consistently reported in older BPH populations compared to younger men using 1 mg finasteride for hair loss 1