What is Avodart (Dutasteride)?
Avodart (dutasteride) is a dual 5-alpha-reductase inhibitor (5-ARI) that inhibits both type 1 and type 2 isoenzymes, used primarily to treat benign prostatic hyperplasia (BPH) in men with enlarged prostates by reducing dihydrotestosterone (DHT) levels, which leads to prostate shrinkage and improved urinary symptoms. 1, 2
Mechanism of Action
- Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both type 1 and type 2 isoforms of steroid 5-alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT) 2
- By inhibiting both isoenzymes, dutasteride reduces serum DHT levels by approximately 95%, compared to finasteride's 70% reduction (which only inhibits type 2) 1
- In prostate tissue specifically, dutasteride reduces DHT by approximately 94% compared to finasteride's 80% 1
Clinical Indications
- Treatment of moderate to severe symptomatic BPH in men with an enlarged prostate 3
- Improvement of lower urinary tract symptoms (LUTS) associated with BPH 1
- Reduction of the risk of acute urinary retention (AUR) 4
- Reduction of the need for BPH-related surgery 5
Efficacy
- Dutasteride reduces prostate volume by 15-25% after 6 months of treatment 1
- Provides improvements of 3-4 points on standardized symptom scores (e.g., IPSS) maintained for up to 6-10 years of follow-up 1
- In the REDUCE trial, dutasteride reduced clinical progression (defined as increase in IPSS of 4, AUR, UTI, or BPH-related surgery) compared to placebo (21% versus 36%) 1
- Long-term studies show sustained improvement in symptoms of BPH with the dual 5-alpha-reductase inhibitor dutasteride over 4 years [1, @38@]
Important Clinical Considerations
- Dutasteride is most effective in men with demonstrable prostatic enlargement (prostate volume >30cc on imaging, PSA >1.5ng/mL, or palpable enlargement) 1, 6
- Has a slower onset of action compared to alpha blockers, with patients typically noticing improvement after 3-6 months 1, 3
- Reduces serum PSA levels by approximately 50% after 1 year of therapy - this must be considered when screening for prostate cancer 1, 2
- For accurate PSA interpretation in prostate cancer screening, the measured PSA value should be doubled after 1 year of dutasteride therapy 1, 6
Side Effects
- Sexual side effects: impotence, decreased libido, ejaculation disorders 2
- Gynecomastia (breast enlargement) 1, 5
- Potential concerns about post-finasteride syndrome (controversial constellation of symptoms that may persist after discontinuation) 1
- May affect sperm characteristics, though the effect on fertility is unknown 2
- Rare but serious allergic reactions including facial swelling and skin reactions 2
Combination Therapy
- Combination therapy with dutasteride and an alpha blocker (such as tamsulosin) is more effective than either monotherapy alone for men with moderate-to-severe LUTS and enlarged prostates 6, 7
- The CombAT study demonstrated superior outcomes with combination therapy in improving symptoms, reducing risk of AUR, and decreasing need for BPH-related surgery [1, @27@]
- Combination therapy should be reserved for patients with demonstrable prostatic enlargement, as this population benefits most from the addition of a 5-ARI 6