Abstract
To review key trials of monotherapy and combination therapy of α1-adrenergic receptor antagonists (α1-ARAs), 5α-reductase inhibitors (5αRIs) and anti-muscarinic agents in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). To assess the safety and efficacy of combination therapies for LUTS associated with BPH, a search of the MEDLINE and Cochrane databases (1976–2008) was conducted for relevant trials and reviews using the terms benign prostatic hyperplasia, lower urinary tract symptoms, α1-adrenergic receptor antagonists, 5α-reductase inhibitors, anti-muscarinics, anticholinergics, combination therapy, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, tolterodine, flavoxate, propiverine, oxybutynin, erectile dysfunction, sildenafil, vardenafil and tadalafil. Data from the Medical Therapy of Prostatic Symptoms (MTOPS) study indicated a role for long-term use of α1-ARAs and 5αRIs in combination. In the MTOPS study, combination therapy with the α1-ARA doxazosin and the 5αRI finasteride was significantly more effective than either component alone in reducing symptoms (P=0.006 vs doxazosin monotherapy; P<0.001 vs finasteride monotherapy) and in lowering the rate of clinical progression (P<0.001 vs either monotherapy). These findings were confirmed by the 2-year preliminary results of the Combination of Avodart and Tamsulosin study. In this study, combination therapy of the α1-ARA tamsulosin and the 5αRI dutasteride resulted in a significantly greater decrease in International Prostate Symptom Score (IPSS) when compared with either monotherapy. Several recent trials have studied the efficacy of combining α1-ARAs and anti-muscarinic agents in the treatment of BPH. These studies have found this combination to result in statistically significant benefits in quality of life scores, patient satisfaction, urinary frequency, storage symptoms and IPSS scores. Studies have not shown an increased risk of urinary retention associated with the use of anti-muscarinics in a highly select cohort of men with BPH. The available data suggest that combination therapy can be beneficial in the treatment of BPH and associated LUTS. The greatest efficacy for the α1-ARA and 5αRI combination was shown in patients with larger prostate size and more severe symptoms. The combination of α1-ARAs and 5αRIs appears to prevent disease progression in these patients. The combination of α1-ARAs with anti-muscarinic agents is useful for relieving symptoms of bladder outlet obstruction and detrusor overactivity. Theoretic concerns regarding the risk of acute urinary retention have been refuted in several recent clinical trials; however, it must be noted that the patients in these trials were a highly select cohort of men. Men with overactive bladder and BPH who are not receiving adequate alleviation of symptoms from the first-line α1-ARAs may benefit from the addition of an anti-muscarinic agent.
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References
American Urological Association. Guideline on the Management of Benign Prostatic Hyperplasia (BPH). www.auanet.org/guidelines/bph.cfm (updated 2006).
Welch G, Weinger K, Barry MJ . Quality-of-life impact of lower urinary tract symptom severity: results from the health professionals follow-up study. Urology 2002; 59: 245–250.
Sung JC, Curtis LH, Schulman KA, Albala DM . Geographic variations in the use of medical and surgical therapies for benign prostatic hyperplasia. J Urol 2006; 175: 1023–1027.
McVary KT . A review of combination therapy in patients with benign prostatic hyperplasia. Clin Ther 2007; 29: 387–398.
Berry SJ, Coffey DS, Walsh PC, Ewing LL . The development of human prostatic hyperplasia with age. J Urol 1984; 132: 474–479.
Kaplan SA, Walmsley K, Te AE . Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 2005; 174: 2273–2276.
McVary KT, Rademaker A, Lloyd GL, Gann P . Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005; 174: 1327–1433.
Wilt TJ, N’Dow J . Benign prostatic hyperplasia. Part 1— diagnosis. BMJ 2008; 336: 146–149.
Meigs JB, Barry MJ, Giovannucci E, Rimm EB, Stampfer MJ, Kawachi I . Incidence rates and risk factors for acute urinary retention: the health professionals follow-up study. J Urol 1999; 162: 376–382.
Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Rhodes T, Guess HA et al. Natural history or prostatism; risk factors for acute urinary retention. J Urol 1997; 158: 481–487.
Brown CT, O’Rynn E, van der Meulen J, Newman S, Mundy AR, Emberton M . The fear of prostate cancer in men with lower urinary tract symptoms: should symptomatic men be screened? BJU Int 2003; 91: 30–32.
Barry MJ, Fowler Jr FJ, O’Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 1992; 148: 1549–1557.
Lepor H . Natural history, evaluation, and nonsurgical management of benign prostatic hyperplasia. In: Walsh PC, Retik AB, Vaughan Jr ED and Wein AJ (eds). Campbell's Urology. W.B. Saunders Company: Philadelphia, PA, 1998, chapter 47 pp 1453–1477.
Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM, Henderson WG . A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med 1995; 332: 75–79.
Gallegos PJ, Frazee LA . Anticholinergic therapy for lower urinary tract symptoms associated with benign prostatic hyperplasia. Pharmacotherapy 2008; 28: 356–365.
Caine M, Raz S, Zeigler M . Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck. Br J Urol 1975; 47: 193.
Marshall I, Burt RP, Chapple CR . Noradrenaline contractions of human prostate mediated by alpha 1-A(alpha 1c-) adrenoreceptor subtype. Br J Pharmacol 1995; 115: 781.
Tamsulosin [package insert]. Boehringer Ingelheim: Ridgefield, Conn, 2002.
Van Moorselaar RJ, Hartung R, Emberton M, Harving N, Mazkin H, Elhilali M et al. Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction. BJU Int 2005; 95: 603–608.
McVary KT . Sexual function and α-blockers. Rev Urol 2005; 7: S3–S11.
Elhilali MM, Ramsey EW, Barkin J, Casey RW, Boake RC, Beland G et al. A multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of terazosin in the treatment of benign prostatic hyperplasia. Urology 1996; 47: 335–342.
Roehrborn CG, Siegel RL . Safety and efficacy of doxazosin in benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. Urology 1996; 48: 406–415.
Roehrborn CG, for the ALFUS Study Group. Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial. Urology 2001; 58: 953–959.
Lepor H, for the Tamsulosin Investigator Group. Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Urology 1998; 51: 892–900.
Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med 1992; 327: 1185–1191.
Marberger MJ, for the PROWESS Study Group. Long-term effects of finasteride in patients with benign prostatic hyperplasia: L a double-blind, placebo-controlled, multicenter study. Urology 1998; 51: 677–686.
McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al., for the Finasteride Long-Term Efficacy and Safety Study Group. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med 1998; 338: 557–563.
The Finasteride Study Group. Finasteride (MK-906) in the treatment of benign prostatic hyperplasia. Prostate 1993; 22: 291–299.
Boyle P, Gould AL, Roehrborn CG . Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48: 398–405.
Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G, for the ARIA3001, ARIA3002, and ARIA3003 Study Investigators. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434–441.
Blake-James BT, Rashidian A, Ikeda Y, Emberton M . The role of anticholinergics in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a systematic review and meta-analysis. BJU Int 2006; 99: 85–96.
Ruggieri MR, Braverman AS, Pontari MA . Combined use of α-adrenergic and muscarinic antagonists for the treatment of voiding dysfunction. J Urol 2005; 174: 1743–1748.
Abrams P, Kaplan S, De Koning Gans HJ, Millard R . Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. J Urol 2006; 175: 999–1004.
Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A, for the Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of overactive bladder. Urology 2001; 57: 414–421.
Cardozo L, Lisec M, Millard R, Van Vierssen Trip O, Kuzmin I, Drogendijk TE et al. Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J Urol 2004; 172: 1919–1924.
Galee BJ, Galee MA . Phosphodiesterase-5 inhibitors for lower urinary tract symptoms in men. Ann Pharmacother 2008; 42: 111–115.
McVary KT, Monnig W, Camps Jr JL, Young JM, Tseng LJ, van den Ende G . Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. J Urol 2007; 177: 1071–1077.
Stief CG, Porst H, Neuser D, Beneke M, Ulbrich E . A randomized placebo controlled study to assess the efficacy of twice daily Vardenafil in the treatment of LUTS secondary to BPH. Eur Urol 2008; 53: 1236–1244.
McVary KT, Roehrborn CG, Kaminetsky JC, Auerbach SM, Wachs B, Young JM et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2007; 177: 1401–1407.
Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L . Tadalafil administered once a day in the treatment of men with LUTS secondary to BPH; a dose-finding study. J Urol 2008; 180: 1228–1234.
McConnell JD, Roehrborn CG, Bautista OM, Andriole Jr GL, Dixon CM, Kusek JW, et al., for the Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349: 2387–2398.
Barkin J, Guimaraes M, Jacobi G, Pushkar D, Taylor S, van Vierssen Trip OB et al. Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol 2003; 44: 461–466.
Kirby RS, Roehrborn C, Boyle P, Bartsch G, Jardin A, Cary MM, et al., for the Prospective European Doxazosin and Combination Therapy Study Investigators. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003; 61: 119–126.
Lepor H, Williford WO, Barry MJ, Brawer MK, Dixon CM, Gormley G et al. for the Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. NEJM 1996; 335: 533–539.
Roehrborn CG, Siami P, Barkin J, Damiao R, Major-Walker K, Morrill B, et al., for the Combination of Avodart and Tamsulosin (CombAT) Study Group. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol 2008; 179: 616–621.
Athanasopoulos A, Gyftopoulos K, Giannitsas K, Fisfis J, Perimenis P, Barbalias G . Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized controlled trial. J Urol 2003; 169: 2253–2256.
Lee KS, Choo MS, Kim DY, Kim JC, Min KS, Lee JB et al. Combination treatment with propiverine hydrochloride plus doxazosin controlled release gastrointestinal therapeutic system formulation for overactive bladder and coexisting benign prostatic obstruction: a prospective, randomized, controlled multicenter study. J Urol 2005; 174: 1334–1338.
Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guam Z . Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA 2006; 296: 2319–2328.
Yang Y, Zhao XF, Li HZ, Wang W, Zhang Y, Xiao H et al. Efficacy and safety of combined therapy with terazosin and tolterodine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study. Chin Med J (Engl) 2007; 120: 370–374.
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Greco, K., McVary, K. The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res 20 (Suppl 3), S33–S43 (2008). https://doi.org/10.1038/ijir.2008.51
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