What are alpha blocker and 5-alpha-reductase inhibitor (5-ARI) combinations?

From the Guidelines

Alpha blocker and 5-alpha-reductase inhibitor (5-ARI) combinations, such as dutasteride (0.5 mg daily) with tamsulosin (0.4 mg daily) or finasteride (5 mg daily) with doxazosin (4-8 mg daily), are the most effective treatment options for benign prostatic hyperplasia (BPH) with demonstrable prostatic enlargement, as they provide more effective symptom relief than either medication alone. These combinations are particularly beneficial for men with larger prostates (>30cc), moderate-to-severe symptoms, and higher PSA levels (>1.5ng/mL) 1. Alpha blockers, such as tamsulosin, alfuzosin, doxazosin, and terazosin, work quickly to relax smooth muscle in the prostate and bladder neck, providing rapid symptom relief by improving urine flow. The 5-ARIs, such as finasteride and dutasteride, shrink the prostate gland over 3-6 months by blocking the conversion of testosterone to dihydrotestosterone, addressing the underlying cause of prostate enlargement.

Some key points to consider when using alpha blocker and 5-ARI combinations include:

• The combination of an alpha-adrenergic receptor blocker and a 5 alpha-reductase inhibitor is an effective treatment for patients with LUTS associated with demonstrable prostatic enlargement 1
• The combination therapy is typically intended for long-term use to prevent BPH progression
• Side effects may include dizziness, orthostatic hypotension, and sexual dysfunction
• Patients should be aware that while alpha blockers provide quick relief, 5-ARIs require several months to reach maximum effectiveness

The most recent and highest quality study, published in 2021, recommends that 5-ARI in combination with an alpha blocker should be offered as a treatment option only to patients with LUTS associated with demonstrable prostatic enlargement as judged by a prostate volume of >30cc on imaging, a PSA >1.5ng/mL, or palpable prostate enlargement on DRE 1. This study provides the strongest evidence for the use of alpha blocker and 5-ARI combinations in the treatment of BPH.

From the FDA Drug Label

1.2 Combination with Alpha-adrenergic Antagonist 2.2 Combination with Alpha-adrenergic Antagonist 7.2 Alpha-adrenergic Antagonists 14.2 Combination with Alpha-blocker Therapy (CombAT)

The alpha blocker and 5-alpha-reductase inhibitor (5-ARI) combinations refer to the use of medications such as dutasteride (a 5-ARI) in combination with alpha-adrenergic antagonists (alpha blockers) for the treatment of certain conditions, such as benign prostatic hyperplasia (BPH).

• The combination of these two types of medications is intended to provide a more comprehensive treatment approach by addressing both the static and dynamic components of BPH.
• Alpha blockers work by relaxing the muscles in the prostate and bladder neck, making it easier to urinate.
• 5-alpha-reductase inhibitors (5-ARIs), such as dutasteride, work by shrinking the size of the prostate gland, which can help to improve urine flow and reduce symptoms of BPH. 2

From the Research

Alpha Blocker and 5-Alpha-Reductase Inhibitor Combinations

• Alpha blockers and 5-alpha-reductase inhibitors (5-ARIs) are two types of medications used to treat benign prostatic hyperplasia (BPH) 3.
• Alpha blockers work by relaxing the smooth muscle in the prostate and bladder neck, improving urine flow and reducing symptoms 3.
• 5-ARIs, such as finasteride and dutasteride, work by blocking the conversion of testosterone to dihydrotestosterone (DHT), which contributes to prostate growth and BPH symptoms 4.

Combination Therapy

• Combining alpha blockers and 5-ARIs may be more effective in relieving and preventing the progression of BPH symptoms than either medication alone 3, 5.
• Patients with larger prostates and higher prostate-specific antigen (PSA) values may be more likely to benefit from combination therapy 3.
• Studies have shown that combination therapy with alpha blockers and 5-ARIs can improve symptoms, reduce prostate volume, and decrease the risk of acute urinary retention and BPH-related surgery 5, 6, 7.

Specific Combinations

• The combination of doxazosin and finasteride has been shown to be effective in improving symptoms and reducing the risk of BPH progression 3, 6.
• The combination of tamsulosin and finasteride has also been studied and found to be effective in improving symptoms and reducing prostate volume 7.
• The combination of tamsulosin and dutasteride has been shown to be effective in improving symptoms and reducing the risk of BPH progression 7.

Adverse Effects

• 5-ARIs, such as finasteride, have been associated with adverse effects including ejaculation disorder, impotence, and decreased libido 6.
• Alpha blockers, such as doxazosin and terazosin, have been associated with adverse effects including dizziness, postural hypotension, and asthenia 6.
• The combination of alpha blockers and 5-ARIs may have a lower risk of adverse effects compared to monotherapy with either medication alone 6, 7.