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Year : 2006  |  Volume : 22  |  Issue : 2  |  Page : 163-164

Are two drugs better than one?

Department of Urology, Christian Medical College, Vellore, India

Correspondence Address:
J C Singh
Department of Urology, Christian Medical College, Vellore
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How to cite this article:
Singh J C, Kekre N S. Are two drugs better than one?. Indian J Urol 2006;22:163-4

How to cite this URL:
Singh J C, Kekre N S. Are two drugs better than one?. Indian J Urol [serial online] 2006 [cited 2023 Feb 7];22:163-4. Available from:

The long-term effect of Doxazosin, Finasteride and combination therapy on the clinical progression of benign prostatic hyperplasia. McConnell JD, Roehrborn CG, Bautista OM andriole GL Jr, Dixon CM, Kusek JW, et al. N Engl J Med. 2003 Dec 18;349(25):2387-98.

The medical therapy of prostatic symptoms (MTOPS) study was designed to determine whether therapy with the alpha-blocker Doxazosin or the 5 a-reductase inhibitor Finasteride, alone or in combination, would delay or prevent clinical progression of benign prostatic hyperplasia.[1] It was a multicentric randomized prospective trial involving 17 centers. 3047 men were recruited. Men at least 50 years of age, with an American Urological Association (AUA) symptom score of 8 to 35 and a maximal urinary flow rate between 4 and 15, were included. Those who had either medical or surgical intervention, supine blood pressure of 90/70 mm Hg,and a prostate-specific antigen level more than 10 ng per milliliter, were excluded. The sample size was calculated, so that the study would have 81% power to detect a 33% reduction in the incidence of progression. Subjects were randomly assigned to receive placebo, Doxazosin, Finasteride or combination therapy. Finasteride was given at 5 mg, once daily in the night. Doxazosin was begun at 1mg and titrated up to 8 mg. Overall clinical progression was the primary outcome, manifesting as increase in AUA symptom score of at least four points, acute urinary retention, renal insufficiency, recurrent urinary tract infection or urinary incontinence. Secondary outcome measures were changed over time in AUA symptom score and the maximal urinary flow rate. Over a mean follow-up of 4.5 years in all four groups, 351 primary outcome events occurred: 128 in the placebo group, 85 in the Doxazosin group, 89 in the Finasteride group and 49 in the combination-therapy group. 78% of the occurrence of primary outcome, was in the form of 4 point worsening, in the AUA symptom score. Overall risk of progression was 4.5 per 100 years in the placebo group and it was reduced by 39% ( P <0.001), 34% ( P =0.002) and 66% ( P <0.001) in the Doxazosin, Finasteride and combination groups respectively. The risk of invasive therapy was reduced by 64 and 67%, respectively in the Finasteride group and combination group. There was no significant reduction of invasive therapy in the Doxazosin group. The number of patients that needed to be treated to prevent one instance of overall clinical progression, was 8.4 for the combination group, 13.7 for the Doxazosin group and 15.0 for Finasteride group. In a preplanned subgroup analysis of patients with larger prostates, the number needed to treat, was halved in the combination group. The combination of Doxazosin and Finasteride was safe and the overall risk of clinical progression was reduced significantly more than either drugs alone.[2] Finasteride or combination reduced the long-term risk of acute urinary retention,and the need for invasive therapy.

Combination was studied earlier in the Veterans affairs Co-operative studies benign prostatic hyperplasia study[3] -(Terazosin and Finasteride) and by the Prospective European Doxazosin and Combination Therapy Trial[4] -(Doxazosin and Finasteride), but they did not find any benefit with the combination. This may be because these studies assessed the longitudinal changes in AUA symptom score and maximal urinary flow rate, rather than the clinical progression. The duration of follow up (12 months) might have also contributed to the observations. Enthusiasm for the widespread use of dual therapy has however, been dampened by the results of the Prostate Cancer Prevention Trial[5] as Tumors of Gleason grade 7 to 10 were more common in the Finasteride group, though the overall incidence of prostate cancer was 25% less. Taken together, the encouraging results reported by McConnell and colleagues are a mandate for the development of appropriate studies, to determine the risks of Finasteride therapy. In the meantime, the prudent physician needs to counsel men carefully, before they begin combination therapy, weighing the benefit of preventing the progression of benign prostatic hyperplasia, against the potentially increased risk of high-grade prostate cancer.[6]

   References Top

1.McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW et al . The long-term effect of doxazosin, finasteride and combination therapy on the clinical progression of benign prostatic hyperplasia. N Eng J Med 2003;349:2387-98.  Back to cited text no. 1    
2.Should Combination Therapy Be Standard for Benign Prostatic Hyperplasia? John M. Fitzpatrick. (Accessed 22.12.2005 at  Back to cited text no. 2    
3.Lepor H, Williford WO, Barry MJ, Brawer MK, Dixon CM, Gormley G et al . The efficacy of terazosin, finasteride or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Eng J Med 1996;335:533-9.  Back to cited text no. 3    
4.Kirby RS, Roehrborn C, Boyle P, Bartsch G, Jardin A, Cary MM, 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;61:119-26.  Back to cited text no. 4    
5.Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al . The influence of finasteride on the development of prostate cancer. N Eng J Med 2003;349:215-24.  Back to cited text no. 5    
6.Vaughan ED Jr. Medical management of benign prostatic hyperplasia-are two drugs better than one? N Eng J Med 2003;349:2449-51.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]


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