Trends in Urology and Nephrology Research

For patients with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH), α1-adrenoceptor antagonists remain the first-line treatment of choice.^1,2 For patients with residual LUTS despite taking α1-adrenoceptor antagonist, combination therapy with additional drugs with different mechanisms is recommended.^1,3 However, α1-adrenoceptor antagonists dose increase therapy (DIT) is also a good option in selected cases.^4,5

DIT is a method of treatment in which a low dose of α1-adrenoceptor antagonist is administered at the time of induction, and the dose is increased when the effect is insufficient. It is also recommended in the package inserts of prescription drugs to start at a low dose. In previous reports, induction of treatment with a low dose of α1-adrenoceptor antagonists has been shown to improve the international prostate symptom score (IPSS) in about 24-78% of the patients.^4-8 Even in patients with poor improvement at a low dose, increasing the dose has resulted in improvement. If improvement can be achieved at low doses, the risk of adverse events due to the use of maximum dose can be avoided.⁹ Since many patients with LUTS/BPH are elderly, concomitant use of other drugs could lead to polypharmacy problems. Therefore, it is better to administer as few drugs as possible.^9,10

Regarding the combination of α1-adrenoceptor antagonist and other drugs, the add-on of anticholinergics to α1-adrenoceptor antagonist is a good option for patients with persistent overactive bladder symptoms. However, judicious use of anticholinergics is recommended because there are reports of increased residual urine volume, decreased maximum urine flow rate, and increased risk of acute urinary retention after the use of anticholinergics in men with BPH.¹¹ Combination therapy with β3-adrenoceptor agonist is also indicated for patients with poor improvement of storage urinary symptoms after α1-adrenoceptor antagonist monotherapy.^12,13 Although not as common as combination therapy with anticholinergics, side effects of combination therapy with β3-adrenoceptor agonist have been reported. Some reports suggest that DIT also increases side effects,^6,8 while other reports suggest no increase of side effects.^7,14

Regarding 5α-reductase inhibitor, if there is an enlarged prostate (more than 30ml), there is a great benefit of concomitant use of α1-adrenoceptor antagonist and 5α-reductase inhibitor.^15,16 For patients with a large prostate, induction of treatment with a low dose of α1-adrenoceptor antagonist is less effective.⁹ On the other hand, if prostatic volume is less than 30-40ml, there is no recommendation for concomitant use of 5α-reductase inhibitor.¹ and a low dose of α1-adrenoceptor antagonist could provide significant benefits including symptom improvement.⁹

In conclusion, if the patient with LUTS/BPH is elderly and does not have a large prostate, a low dose of α1-adrenoceptor antagonist can be an initial treatment of choice. If voiding urinary symptoms persist after induction, increasing dose of the same α1-adrenoceptor antagonist (DIT) will be recommended.

None.

None.

None.

1. 1. Gravas S, Cornu JN, Gacci M, et al. EAU Guidelines on non-neurogenic male lower urinary tract symptoms (LUTS), incl. benigen prostatic obstruction (BOO). European Association of Urology 2021.
2. 2. Kakizaki H, Koyanagi T. Current view and status of the treatment of lower urinary tract symptoms and neurogenic lower urinary tract dysfunction. BJU Int. 2000;85(suppl.2):25–30.
3. 3. Kaplan SA, Roehrborn CG, Rovner ES, et al. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006;296:2319–2328.
4. 4. Yamaguchi S, Osanal H, Numata A, et al. α1D/A-adrenoceptor antagonist naftopidil for the male lower urinary tract symptoms associated with benign prostatic hyperplasia :efficacy of dose increase therapy. Int J Urol. 2013;20:513–519.
5. 5. Tanuma Y, Tanaka Y, Takeyama K, et al. The predictive factors of α1-D/A adrenoceptor antagonist, naftopidil, dose increase therapy for male lower urinary tract symptoms caused by benign prostatic hyperplasia: INFORM study. Urol Ann. 2017;9:261–267.
6. 6. Funahashi Y, Hattori R, Matsukawa Y, et al. Clinical efficacy of a loading dose of naftopidil for patients with benign prostatic hyperplasia. World J Urol. 2011;29:225–231.
7. 7. Mizusawa T, Hara N, Obara K, et al. Clinical feature of men who benefit from dose escalation of naftopidil for lower urinary tract symptoms: a prospective study. Adv Urol. 2011.
8. 8. Chung JW, Choi SH, Kim BS, et al. Efficacy and tolerability of tamsulosin 0.4 mg in patients with symptomatic benign prostatic hyperplasia. Korean J Urol. 2011;52:479–484.
9. 9. Watanabe M, Yamaguchi S, Kakizaki H, et al. Evaluation of Alpha 1 Adrenoceptor Antagonist Dose Increase Therapy: An Essential Strategy for Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia. Curr Urol. 2020;14(3):113–121.
10. 10. Zhang S, Meng L, Qiu F, et al. Medication-related risk factors associated with health-related quality of life among community-dwelling elderly in China. Patient Prefer Adherence. 2018;12:529–537.
11. 11. Filson CP, Hollingsworth JM, Clemens JQ, et al. The efficacy and safety of combined therapy with α-blockers and anticholinergics for men with benign prostatic hyperplasia: a meta-analysis. J Urol. 2013;190:2153–2160.
12. 12. Kakizaki H, Lee KS, Yamamoto O, et al. Mirabegron Add-on Therapy to Tamsulosin for the Treatment of Overactive Bladder in Men with Lower Urinary Tract Symptoms: A Randomized, Placebo-controlled Study (MATCH). Eur Urol Focus. 2020;15;6(4):729–737.
13. 13. Wada N, Iuchi H, Kita M, et al. Urodynamic Efficacy and Safety of Mirabegron Add-on Treatment with Tamsulosin for Japanese Male Patients with Overactive Bladder. Low Urin Tract Symptoms. 2016;8(3):171–176.
14. 14. Chapple CR, Al-Shukri SH, Gattegno B, et al. Tamsulosin oral controlled absorption system (OCAS) inpatients with lower controlled absorption system (OCAS) in patients with lower urinary tractsymptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): efficacy and tolerability in a placebo and active comparator controlled Phase 3a study. Eur Urol. Suppl. 2005;4:33–44.
15. 15. Roehrborn CG, Barkin J, Tubaro A, et al. Influence of baseline variables on changes in International Prostate Symptom Score after combined therapy with dutasteride plus tamsulosin or either monotherapy in patients with benign prostatic hyperplasia and lower urinary tract symptoms: 4-year results of the CombAT study. BJU Int. 2014;113:623–635.
16. 16. McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;18:2387–2398.