Drugs & Aging

, Volume 22, Issue 11, pp 901–912 | Cite as

Combination Therapy for the Pharmacological Management of Benign Prostatic Hyperplasia

Rationale and Treatment Options
Therapy In Practice


The management of symptomatic benign prostatic hyperplasia (BPH) continues to evolve, with new techniques and forms of medical management being introduced and traditional surgical techniques being used less frequently. Medical management of BPH has evolved from nonspecific α-adrenoceptor antagonists to uroselective α-adrenoceptor antagonists and 5-α reductase inhibitors. Traditionally, α-adrenoceptor antagonists have been used for relief of lower urinary tract symptoms (LUTS) as a result of BPH and are known for their quick onset of action. 5-α Reductase inhibitors have proven useful for the prevention of BPH progression as measured by prostate volume, disease progression, incidence of acute urinary retention and the need for subsequent BPH-related surgery. Recent studies have shown that the combination of an α-adrenoceptor antagonist and a 5-α reductase inhibitor has significantly better efficacy than either drug alone or placebo. Currently, α-adrenoceptor antagonists are used in the acute setting or for short-term relief of LUTS. The combination of an α-adrenoceptor antagonist and a 5-α reductase inhibitor is used for the longer term management of BPH symptoms and to prevent progression of BPH and perhaps avoid surgical intervention.



No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Berry SJ, Coffey DS, Walsh PC, et al. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: 474–9PubMedGoogle Scholar
  2. 2.
    Roehrborn CG, McConnell JD. Etiology, pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. In: Walsh PC, Retik AB, Vaughan ED, et al., editors. Campbell’s Urology. Philadelphia (PA): Saunders, 2002: 1297–1336Google Scholar
  3. 3.
    McConnell MD, Bruskewitz R, Walsh P, et al. 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: 557–63PubMedCrossRefGoogle Scholar
  4. 4.
    McConnell JD, Roehrborn CG, Bautista AM, 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; 349: 2385–96CrossRefGoogle Scholar
  5. 5.
    McConnell JD. Prostatic growth: new insights into hormonal regulation. Br J Urol 1995; 76Suppl. 1: 5–10PubMedGoogle Scholar
  6. 6.
    Imperato-McGinley J, Guerrero L, Gautieer T, et al. Steroid 5-alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974; 186: 1213–5PubMedCrossRefGoogle Scholar
  7. 7.
    Walsh PC, Madden JD, Harrod MJ, et al. Familial incomplete male pseudohermaphroditism type 2: decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med 1974; 291: 944–9PubMedCrossRefGoogle Scholar
  8. 8.
    Shapiro E, Hartano V, Lepor H. Quantifying the smooth muscle content of the prostate using double-immuno-enzymatic staining and color assisted image analysis. J Urol 1992; 147: 1167PubMedGoogle Scholar
  9. 9.
    Schwinn DA. Androgen receptors: unique localization in human tissues. Adv Pharmacol 1994; 31: 333–41PubMedCrossRefGoogle Scholar
  10. 10.
    Lepor H, Gup DI, Baumann M, et al. Laboratory assessment of terazosin and alpha-1 blockade in prostatic hyperplasia. Urology 1998; 32: 21–6Google Scholar
  11. 11.
    McConnell JD, Barry MJ, Bruskewitz RC, et al. Benign prostatic hyperplasia: diagnosis and treatment. Clinical practice guidelines. No. 8. AHCPR Publication: No. 94-0582. Rockville (MD): Agency for Health Care Policy and Research. Public Health Service, US Department of Health and Human Services, 1994Google Scholar
  12. 12.
    Chute CG, Panser LA, Girman CJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol 1993; 150: 85–9PubMedGoogle Scholar
  13. 13.
    Girman CJ, Panser LA, Chute CG, et al. Natural history of prostatism: urinary flow rates in a community-based study. J Urol 1993; 150: 887–92PubMedGoogle Scholar
  14. 14.
    Blute MI, Jacobsen SJ, Kaplan SA, et al. Evaluation and management of benign prostatic hyperplasia: proceedings of a thought leader conference held March 31, 2001. Urology 2001; 58: 1–4PubMedCrossRefGoogle Scholar
  15. 15.
    Jacobsen SJ, Jacobsen DJ, Girman CJ, et al. Natural history of prostatism: risk factors for acute urinary retention. J Urol 1997; 158: 481–7PubMedCrossRefGoogle Scholar
  16. 16.
    Rhodes T, Girman CJ, Jacobsen SJ, et al. Longitudinal prostate growth rates during 5 years in randomly selected men 40–79 years old. J Urol 1999; 161: 1174–9PubMedCrossRefGoogle Scholar
  17. 17.
    Roehrborn CG, Boyle P, Bergner D, et al. Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo. Urology 1999; 54: 662–9PubMedCrossRefGoogle Scholar
  18. 18.
    Hoffman RM, MacDonald R, Slaton JW, et al. Laser prostatectomy versus transurethral resection for treating benign prostatic obstruction: a systematic review. J Urol 2003; 169: 210–5PubMedCrossRefGoogle Scholar
  19. 19.
    Te AE, Malloy TR, Stein BS, et al. Photoselective vaporization of the prostate for the treatment of benign prostatic hyperplasia: 12-month results from the first United States multicenter prospective trial. J Urol 2004; 172: 1404–8PubMedCrossRefGoogle Scholar
  20. 20.
    Reich O, Bachmann A, Siebels M, et al. High power (80 W) potassium-titanyl-phosphate laser vaporization of the prostate in 66 high risk patients. J Urol 2005; 173: 158–60PubMedCrossRefGoogle Scholar
  21. 21.
    Sandhu JS, Ng C, Vanderbrink BA, et al. High-power potassium-titanyl-phosphate photoselective laser vaporization of prostate for treatment of benign prostatic hyperplasia in men with large prostates. Urology 2004; 64: 1155–9PubMedCrossRefGoogle Scholar
  22. 22.
    Tunuguntla HS, Evans CP. Minimally invasive therapies for benign prostatic hyperplasia. World J Urol 2002; 20: 197–206PubMedGoogle Scholar
  23. 23.
    Gup DI, Shapiro E, Bauman M, et al. Contractile properties of human prostate adenomas and the development of infravesical obstruction. Prostate 1989; 15: 105–14PubMedCrossRefGoogle Scholar
  24. 24.
    Lepor H, Auerbach S, Puras-Baez A, et al. A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. J Urol 1992; 148: 1467–74PubMedGoogle Scholar
  25. 25.
    Fawzy A, Braun K, Lewis GP, et al. Doxazosin in the treatment of benign prostatic hyperplasia in normotensive patients: a multicenter study. J Urol 1995; 154: 105–9PubMedCrossRefGoogle Scholar
  26. 26.
    Gillenwater JY, Conn RL, Chrysant SG, et al. Doxazosin for the treatment of benign prostatic hyperplasia in patients with mild-to-moderate essential hypertension: a double-blind, placebo controlled, dose-response multicenter study. J Urol 1995; 154: 110–5PubMedCrossRefGoogle Scholar
  27. 27.
    AUA Practice Guideline Committee. AU A guidelines on management of benign prostatic hyperplasia (2003): diagnosis and treatment recommendations. Chapter 1. J Urol 2003; 170: 530–47CrossRefGoogle Scholar
  28. 28.
    Walmsley K, Cjertsen CK, Kaplan SA. Medical management of BPH: an update. Campbell’s Urology Updates 2004; 2(2): 1–8Google Scholar
  29. 29.
    Lepor H. Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia: Tamsulosin Investigator Group. Urology 1998; 51: 892–900PubMedCrossRefGoogle Scholar
  30. 30.
    Narayan P, Evans CP, Moon T. Long-term safety and efficacy of tamsulosin for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. J Urol 2003; 170: 498–502PubMedCrossRefGoogle Scholar
  31. 31.
    Martin DJ. Preclinical pharmacology of al-adrenoreceptor antagonists. Eur Urol 1999; 36Suppl. 1: 35–41PubMedCrossRefGoogle Scholar
  32. 32.
    van Kerrebroeck P, Jardin A, Laval KU, et al. Efficacy and safety of a new prolonged release formulation of alfuzosin 10mg once daily versus alfuzosin 2.5mg thrice daily and placebo in patients with symptomatic benign prostatic hyperplasia. Eur Urol 2000; 37: 306–13PubMedCrossRefGoogle Scholar
  33. 33.
    Lukacs B, Grange JC, Comet D, et al. History of 7,093 patients with lower urinary tract symptoms related to benign prostatic hyperplasia treated with alfuzosin in general practice up to 3 years. Eur Urol 2000; 37: 183–90PubMedCrossRefGoogle Scholar
  34. 34.
    Roehrborn CG, 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: 953–9PubMedCrossRefGoogle Scholar
  35. 35.
    Li X, Chen C, Singh SM, et al. The enzyme and inhibitors of 4-ene-oxosteroid 5 alpha-oxidoreductase. Steroids 1995; 60: 430–41PubMedCrossRefGoogle Scholar
  36. 36.
    Rasmusson GH, Reynolds GF, Steinberg NG, et al. Azasteroids: structure-activity relationships for inhibition of 5 alphareductase and of androgen receptor binding. J Med Chem 1986; 29: 2298–315PubMedCrossRefGoogle Scholar
  37. 37.
    Gromley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia: the Finasteride Study Group. N Engl J Med 1992; 327: 1185–91CrossRefGoogle Scholar
  38. 38.
    Beisland HO, Binkowitz B, Brekkan E, et al. Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia. Eur Urol 1992; 22: 271–7PubMedGoogle Scholar
  39. 39.
    Vaughan D, Imperato-McGinley J, McConnell J, et al. Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia. Urology 2002; 60: 1040–4PubMedCrossRefGoogle Scholar
  40. 40.
    Bruskewitz R, Girman CJ, Fowler J, et al. Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. Urology 1999; 54: 670–8PubMedCrossRefGoogle Scholar
  41. 41.
    Kaplan SA, Holtgrewe HL, Bruskewitz R, et al. Comparison of the efficacy and safety of finasteride in older versus younger men with benign prostatic hyperplasia. Urology 2001; 57: 1073–7PubMedCrossRefGoogle Scholar
  42. 42.
    Matsumoto AM, Tenover L, McClung M, et al. The long term effect of specific type II 5-alpha-reductase inhibition with finasteride on bone mineral density in men: results of a 4-year placebo controlled trial. J Urol 2002; 167: 2105–8PubMedCrossRefGoogle Scholar
  43. 43.
    Schafer W, Tammela TLJ, Barrett DM, et al. Continued improvement in pressure-flow parameters in men receiving finasteride for 2 years. Urology 1999; 54: 278–83PubMedCrossRefGoogle Scholar
  44. 44.
    Roehrborn CG, Boyle P, Nickel JC, et al. 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: 434–41PubMedCrossRefGoogle Scholar
  45. 45.
    Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215–24PubMedCrossRefGoogle Scholar
  46. 46.
    Bostwick DG, Qian J, Civantos F, et al. Does finasteride alter pathology of the prostate and cancer grading? Clin Prostate Cancer 2004; 2: 228–35PubMedCrossRefGoogle Scholar
  47. 47.
    Scardino PT. The prevention of prostate cancer: the dilemma continues. N Engl J Med 2003; 349: 297–9PubMedCrossRefGoogle Scholar
  48. 48.
    Vaughan ED. Medical management of benign prostatic hyperplasia: are two drugs better than one? N Engl J Med 2003; 349: 2449–51PubMedCrossRefGoogle Scholar
  49. 49.
    Kearney MC, Bingham JB, Bergland R, et al. Clinical predictors in the use of finasteride for control of gross hematuria due to benign prostatic hyperplasia. J Urol 2002; 167: 2489–91PubMedCrossRefGoogle Scholar
  50. 50.
    Pareek G, Shevchuk M, Armenakas NA, et al. The effect of finasteride on the expression of vascular endothelial growth factor and microvessel density: a possible mechanism for decreased prostatic bleeding in treated patients. J Urol 2003; 169: 20–3PubMedCrossRefGoogle Scholar
  51. 51.
    Hagerty JA, Ginsberg PC, Harmon JD, et al. Pretreatment with finasteride decreases perioperative bleeding associated with transurethral resection of the prostate. Urology 2000; 55: 684–9PubMedCrossRefGoogle Scholar
  52. 52.
    Donahue JF, Sharma H, Abraham R. Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of the role of finasteride for decreasing operative blood loss. J Urol 2002; 168: 2024–6CrossRefGoogle Scholar
  53. 53.
    Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. N Engl J Med 1996; 335: 533–9PubMedCrossRefGoogle Scholar
  54. 54.
    Debruyne FE, Jardin A, Colloi D, et al. Sustained-release alfuzosin, finasteride, and the combination of both in the treatment of benign prostatic hyperplasia: European ALFIN Study Group. Eur Urol 1998; 34: 169–75PubMedCrossRefGoogle Scholar
  55. 55.
    Kirby RS, Roehrborn C, Boyle P, et al. 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: 119–26PubMedCrossRefGoogle Scholar
  56. 56.
    Bautista OM, Kusek JW, Nyberg LM, et al. Study design of the Medical Therapy of Prostate Symptoms (MTOPS) trial. Control Clin Trials 2003; 24: 224–43PubMedCrossRefGoogle Scholar
  57. 57.
    Lowe FC, McConnell JD, Hudson PB, et al. Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia. Urology 2003; 61: 791–6PubMedCrossRefGoogle Scholar
  58. 58.
    Lam JS, Romas NA, Lowe FC. Long-term treatment with finasteride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up. Urology 2003; 61: 354–8PubMedCrossRefGoogle Scholar
  59. 59.
    Baldwin KC, Ginsberg PC, Roehrborn CG, et al. Discontinuation of alpha-blockade after initial treatment with finasteride and doxazosin in men with lower urinary tract symptoms and clinical evidence of benign prostatic hyperplasia. Urology 2001; 58: 203–8PubMedCrossRefGoogle Scholar
  60. 60.
    Barkin J, Guimaraes M, Jacobi G, et al. Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5-alpha-reductase inhibitor dutasteride. Eur Urol 2003; 44: 461–6PubMedCrossRefGoogle Scholar
  61. 61.
    Rossouw JE, Anderson GL, Prentice RI, et al. Risks and benefits of estrogen plus progestin in healthy post-menopausal women: principal results from the Women’s Health Initiative randomized control trial. JAMA 2002; 288: 321–33PubMedCrossRefGoogle Scholar
  62. 62.
    FDA News. FDA issue public health advisory on Vioxx as its manufacturer voluntarily withdraws the product: FDA P04-95, September 30, 2004 [online]. Available from URL: http://www.fda.gov/bbs/topics/news/2004/NEW01122.html [Accessed 2005 Sep 30]
  63. 63.
    Bambardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 1520–8CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of UrologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of UrologyYork Presbyterian Hospital, Weill Cornell Medical CenterNew York, F-913USA

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