Can dutasteride (5-alpha-reductase inhibitor) cause elevated testosterone levels?

Dutasteride's Effect on Testosterone Levels

Yes, dutasteride can cause elevated serum testosterone levels due to its mechanism of action as a dual 5-alpha-reductase inhibitor. This elevation is well-documented in clinical studies and FDA labeling.

Mechanism of Action and Hormonal Effects

Dutasteride works by inhibiting both type 1 and type 2 isoforms of 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). This dual inhibition leads to:

• Significant DHT reduction: Dutasteride reduces serum DHT by approximately 90-95%, which is more pronounced than the 70% reduction seen with finasteride (which only inhibits the type 2 isoenzyme) 1

• Testosterone elevation: According to the FDA drug label, dutasteride treatment results in statistically significant increases in serum testosterone levels 2

  • 17.9% median increase at 8 weeks
  • Increases of 19-26% over 1-4 years of treatment

• Physiologic range: Despite these increases, testosterone levels typically remain within the normal physiologic range 2

Clinical Evidence

The FDA label for dutasteride explicitly states that in healthy volunteers treated with dutasteride 0.5 mg/day for 52 weeks, there were "statistically significant, baseline-adjusted mean increases compared with placebo... for total testosterone at 8 weeks (97.1 ng/dL, P <0.003)" 2.

In patients with BPH treated with dutasteride:

• Median serum testosterone increased by 19% at years 1-2
• Increased by 26% at year 3
• Increased by 22% at year 4 2

Research studies confirm these findings:

• Marked suppression of DHT (94.7-98.4%) with dutasteride treatment 1
• Mean testosterone levels increased but remained within normal range 1

Comparison with Finasteride

Both medications can increase testosterone levels, but dutasteride's effect is more pronounced due to its dual inhibition mechanism:

• Dutasteride inhibits both type 1 and type 2 5-alpha-reductase isoenzymes 2
• Finasteride primarily inhibits only the type 2 isoenzyme 3
• Dutasteride produces more consistent and greater DHT suppression (94-98%) compared to finasteride (70%) 1

Clinical Implications

The testosterone elevation has several potential implications:

1. Sexual function effects: Both 5-alpha-reductase inhibitors are associated with sexual side effects including decreased libido, ejaculatory dysfunction, and erectile dysfunction 3

2. Ejaculate volume: Decreased ejaculate volume is a known side effect, occurring in approximately 4-5% of patients taking these medications compared to 1-2% with placebo 4

3. Reversibility: These hormonal changes typically normalize after discontinuation of the medication 2

Monitoring Considerations

When prescribing dutasteride:

• Be aware that testosterone levels will likely increase but should remain within normal range
• Understand that PSA levels will be reduced by approximately 50%, which must be accounted for in prostate cancer screening 3
• Monitor for potential sexual side effects, which may be related to both DHT reduction and testosterone elevation
• Note that hormonal changes typically return to baseline after discontinuation 2

The testosterone elevation with dutasteride is a direct result of its mechanism of action and represents an expected physiological response to 5-alpha-reductase inhibition, with the dual inhibition of dutasteride producing more pronounced effects than the selective inhibition by finasteride.