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#316 To Pee or Not to Pee: Combination agents for benign prostatic hypertrophy

For patients with benign prostatic hypertrophy (BPH) is combination therapy with alpha-blockers and 5-alpha reductase inhibitors (5ARI) more efficacious than alpha-blockers alone?

At best, adding 5ARIs to alpha-blockers reduces the number of men with clinical progression (5% compared to 10% on alpha-blocker alone), and the number needing BPH surgery (2% compared to 8% on alpha-blocker alone). Drug related adverse effects are increased from 19% on alpha-blockers alone to 28% on combination.

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  • Systematic review1 identified 6 RCTs, 2 with >1 year follow-up.2,3 Enrolled patients were symptomatic white males receiving additional testing (example transrectal ultrasound) and specialist care.2,3 Four-year outcomes reported below.
  • Doxazosin (1mg titrated up to 8mg), doxazosin plus finasteride (5mg), or placebo (n=3,047):2
    • Clinical progression: Composite of worsening symptoms [>4 point change on 35-point American Urological Association Score], acute retention, incontinence, or recurrent urinary tract infection (UTI). Symptom progression contributed ~80% of the composite.
      • Doxazosin 10%, combination 5%: Number needed to treat (NNT)=20 (placebo 17%).
    • BPH surgery:
      • Doxazosin 3%, combination 1%: NNT=50 (placebo 5%).
    • Adverse effects, statistics not reported:4
      • Decreased erectile function: Doxazosin 13%, combination 17% (placebo 13%).
    • Tamsulosin (0.4mg) or tamsulosin plus dutasteride (0.5mg) (n=4,844):3
      • Clinical progression: Composite of worsening symptoms [≥ 4-point change on 35-point International Prostate Symptom Score], acute retention, incontinence, recurrent UTI, urosepsis or renal insufficiency. Symptom progression contributed ~65% of the composite.
        • Tamsulosin 22%, combination: 13%: NNT=12.
      • BPH surgery:
        • Tamsulosin 8%, combination 2%: NNT=23.
      • Adverse effects:
        • Any drug related adverse effect: Tamsulosin 19%, combination 28%; number needed to harm=12.
        • Erectile dysfunction: Tamsulosin 5%, combination 9%, not statistically different.
        • Dizziness: No difference.
  • 5ARI may decrease prostate cancer incidence, but cancers found may be higher grade.5,6
    • 17-year follow-up: No difference in prostate cancer mortality.7
  • 5ARI decreases prostate serum antigen (PSA) levels by ~50%,8 which might delay prostate cancer diagnosis.9
    • If following, PSA should be multiplied by 2-2.3 for patients on 5ARI.5,6
  • Canadian guidelines recommend:10
    • Alpha-blockers: First line.
    • Combination: If prostate enlargement.

Janet Strome May 30, 2022

Good information. I find keeping these drugs straight a bit difficult.

Suliman Gardee June 13, 2022

the reccomendation is applicable to my practice – fell more confident in prescribing combination therapy if necessary

Andrea Coholic June 20, 2022

seems reasonable to try combo drug therapy reduce or delay need for surgery

Dr Jayantilal Changela June 22, 2022

excellent article teaching very relevant to Clinical evidance base of medicine.

Dr Jayantilal Changela June 22, 2022

excellent teaching need to present clinicla senario man age 75 BEG or ?Cancer Prostate igh PSA above 9 to 11 how long to try for above medicatiosn how we knwo it does work how to exclude we do not miss cancer of Prostate

Dr Jayantilal Changela June 22, 2022

excellent very infomrative

Dr Jayantilal Changela June 22, 2022


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  • Emelie Braschi MD CCFP PhD
  • Michael R Kolber MD CCFP MSc

1. Füllhase C, Chapple C, Cornu JN, et al. Eur Urol. 2013 Aug; 64(2):228-43

2. McConnell JD, Roehrborn CG, Bautista OM, et al. N Engl J Med. 2003 Dec 18; 349(25):2387-98

3. Roehrborn CG, Siami P, Barkin J, et al. Eur Urol. 2010 Jan; 57(1):123-31

4. Fwu CW, Eggers PW, Kirkali Z et al. J Urol. 2014 Jun; 191(6):1828-34.

5. Thompson IM, Goodman PJ, Tangen CM, et al. N Engl J Med. 2003 Jul 17; 349(3):215-24

6. Andriole GL, Bostwick DG, Brawley OW, et al. N Engl J Med. 2010 Apr 1; 362(13):1192-202

7. Thompson IM Jr, Goodman PJ, Tangen CM, et al. N Engl J Med. 2013 Aug 15; 369(7):603-10

8. Etzioni RD, Howlader N, Shaw PA, et al. J Urol. 2005 Sep; 174(3):877-81

9. Sarkar RR, Parsons JK, Bryant AK, et al. JAMA Intern Med. 2019 Jun 1; 179(6):812-819

10. Nickel JC, Aaron L, Barkin J et al. Can Urol Assoc J. 2018 Oct; 12(10): 303–312.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.