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


CLINICAL QUESTION
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?


BOTTOM LINE
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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EVIDENCE
  • 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.
Context
  • 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.


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Author(s):

  • 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.