What’s best for your patient with BPH?

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Applied Evidence

What’s best for your patient with BPH?

J Fam Pract. 2009 May;58(5):241-247

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References

1. American Urological Association. AUA guideline on the management of benign prostatic hyperplasia: diagnosis and treatment recommendations. 2003/updated 2006. Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinicalguidelines.cfm?sub=bph. Accessed April 2, 2009.

2. Oesterling JE. Benign prostatic hyperplasia: medical and minimally invasive treatment options. N Engl J Med. 1995;332:99-109.

3. McConnell JD. Clinical practice guideline no. 8: Benign prostatic hyperplasia: diagnosis and treatment. Benign Prostatic Hyperplasia Guideline Panel. Rockville, Md: US Dept of Health and Human Services, Agency for Health Care Policy and Research; 1994. AHCPR publication 94-0582.

4. Austin O, Ricer RE. (1996). Prostate cancer screening: an appraisal of the PSA test. Fam Pract Recert. 1996;18:81-91.

5. Barry MJ, Fowler FJ, O’Leary MP, 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.

6. Denis LJ. Diagnosing benign prostatic hyperplasia versus prostate cancer. Br J Urol. 1995;76(suppl 1):S17-S23.

7. Andriole GL, Crawford ED, Grubb RL, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319.

8. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328.

9. American Cancer Society Guidelines for the Early Detection of Cancer. Revised March 5, 2008. Available at: http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.asp. Accessed April 6, 2009.

10. US Preventive Services Task Force. Screening for prostate cancer: recommendation statement. Available at http://www.ahrq.gov/clinic/uspstf08/prostate/prostaters.htm. Accessed April 3, 2009.

11. American Cancer Society. Cancer Facts & Figures. Atlanta, Ga: 2008. Available at http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf. Accessed on April 3, 2009.

12. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin. 2006;56:11-25.

13. Ilic D, O’Connor D, Green S, et al. Screening for prostate cancer. Cochrane Database Syst Rev. 2006;(3):CD004720.-

14. Barry MJ. Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia. Urology. 2001;58(suppl 1):S25-S32.

15. Polascik TJ, Oesterling JE, Partin AW. Prostate specific antigen: a decade of discovery—what we have learned and where we are going. J Urol. 1999;162:293-306.

16. Wilt T, Howe RW, Rutks I, et al. Terazosin for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;(4):CD003851.-

17. McConnell JD, Roehrborn CG, Bautista OM, 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;349:2387-2398.

18. Wilt T, MacDonald R, Rutks I. Tamsulosin for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2003;(1):CD002081.-

19. Guess HA, Gormley GJ, Stoner E, et al. The effect of finasteride on prostate specific antigen: review of available data. J Urol. 1996;155:3-9.

20. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215-224.

21. Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet. 1991;338:469-471.

22. Lepor HL, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. N Engl J Med. 1996;335:533-540.

23. Bent S, Kane C, Shinohara K, et al. Saw palmetto for benign prostatic hyperplasia. N Engl J Med. 2006;354:557-566.

24. Wilt T, Ishani A, MacDonald R. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 1999;(1):CD001423.-

25. Ishani A, MacDonald R, Nelson D, et al. Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis. Am J Med. 2000;109:654-664.

26. Wilt T, Ishani A, MacDonald R, et al. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;(1):CD001044.-

27. Wilt T, Ishani A, MacDonald R, et al. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev. 1999;(4):CD001043.-

28. Wilt T, MacDonald R, Ishani A, et al. Cernilton for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2000;(2):CD001042.-

29. Johnstone PA, Bloom TL, Niemtzow RC, et al. A prospective, randomized pilot trial of acupuncture of the kidney-bladder distinct meridian for lower urinary tract symptoms. J Urol. 2003;169:1037-1039.

30. Keister DM, Neal R. Managing BPH: when to consider surgery. Am Fam Physician. 2008;77:1391-1392.

31. Finnish Medical Society Duodecim. Benign prostatic hyperplasia. In: EBM Guidelines. Evidence-Based Medicine [CD-ROM]. Helsinki, Finland: Duodecim Medical Publications Ltd; 2005.

Combining an α-adrenergic blocker and 5-α reductase inhibitor. Combination therapy is appropriate and effective for patients with LUTS associated with demonstrable prostate enlargement for whom monotherapy has failed.⁹ Taken together, a 5-α reductase inhibitor and a nonselective α-1_A-adrenergic blocker alleviate symptoms more effectively than either drug can do alone.^21,22 The incidence of most adverse drug reactions with the combination is similar to the baseline risk for each drug. However, ejaculatory abnormalities are reported in 7% of patients in the combination therapy group vs 2% or less in the monotherapy groups. Discontinuation rates for combination therapy are comparable to those in the nonselective α-adrenergic blocker group.²² The adverse effect profile of combining selective α-adrenergic blockers with 5-α reductase inhibitors has not been reported; however, the combination is often used in practice.

For patients to make an informed decision about treatment, discuss with them the common adverse reactions from these agents (TABLE 2) and the need for long-term daily therapy. Also give the patient a reasonable estimate of the risk of his retention symptoms progressing.

TABLE 2
BPH medications: How they compare

AUA RECOMMENDATION FOR USE WITH LUTS SECONDARY TO BPH¹	DRUG	DOSE	MOST COMMON SIDE EFFECTS (%)	COSTS
Nonselective α-adrenergic blockers
Useful as first-line therapy due to efficacy and low cost α-Aadrenergic blockers can be used with other therapies as needed	Doxazosin (Cardura, generics)	Start at 1 mg; titrate by doubling dose every 1-2 wk. Goal: 4-8 mg. Maximum dose, 8 mg	Dizziness (16), headache (10), fatigue (8), edema (3), dyspnea (3), orthostatic hypotension (2), abdominal pain (2)*	$4 for 30-day supply for both generic agents^†
	Terazosin (Hytrin, generics)	Start at 1 mg at bedtime, increase PRN over 4-6 wk; most patients require 10 mg. If no response at 10 mg, may increase to 20 mg	Dizziness (9), fatigue (7), headache (5), orthostatic hypotension (4), somnolence (4), nasal congestion (2), ED (2)^‡	$4 for 30-day supply for both generic agents^†
Selective α-adrenergic blockers
All believed to be equal in clinical effectiveness	Alfuzosin (Uroxatral or Xatral)	10 mg/d with the same meal	Dizziness (6), headache (3), upper respiratory infection (3), fatigue (3)^§	$112 for 30-day supply^//
All believed to be equal in clinical effectiveness	Tamsulosin (Flomax)	0.4 mg/d (30 min after same meal); may increase after 2-4 wk to 0.8 mg/d if no response	Headache (19), dizziness (15), rhinitis (13), infection (9), fatigue (8), abnormal ejaculation (8)^¶	$110 for 30-day supply^//
5-α Reductase inhibitors
All believed to be appropriate and effective treatments for patients with demonstrable prostate enlargement	Finasteride (Proscar)	5 mg/d	ED (8), decreased libido (6), decreased volume of ejaculate (4)^#	$70 for 30-day generic supply^//
	Dutasteride (Avodart)	0.5 mg/d	ED (5), decreased libido (3), ejaculation disorder (1), gynecomastia (1)**	$20-$30 for 30-day generic supply^††
AUA, American Urological Association; BPH, benign prostatic hypertrophy; ED, erectile dysfunction; LUTS, lower urinary tract symptoms.
* http://www.fda.gov/medwatch/SAFETY/2006/Feb_PI/Cardura_PI.pdf.
^† Prices listed on Walmart.com as of April 6, 2009.
^‡http://www.fda.gov/medwatch/SAFETY/2006/Feb_PI/Hytrin%20Caps_PI.pdf.
^§http://www.fda.gov/medwatch/safety/2008/Sep_PI/Uroxatral_PI.pdf.
^// Prices listed on Drugstore.com as of April 6, 2009.
^¶http://www.fda.gov/medwatch/SAFETY/2008/Apr_PI/Flomax_PI.pdf.
^#http://www.fda.gov/medwatch/SAFETY/2004/apr_PI/Proscar_PI.pdf.
** http://www.fda.gov/medwatch/SAFETY/2004/sep_PI/Avodart_PI.pdf.
^†† Prices listed on Pharmacychecker.com as of April 6, 2009.

Complementary medicine: Information is still limited

Herbal or complementary medicines are used worldwide to treat BPH. These products are not regulated by the US Food and Drug Administration (FDA), and therefore no standardized formulation or dosing exists. Although a few substances appear to have some positive effects, high-quality clinical trials on clinical outcomes are lacking.

The AUA guideline does not recommend the use of phytotherapy.¹ Despite this, many patients—and any number of physicians—turn to phytotherapy to treat LUTS associated with BPH.

FAST TRACK

If monotherapy fails to relieve symptoms, consider combining a 5-α reductase inhibitor and an α-adrenergic blocker.

Some patients turn to phytotherapy without their physician’s knowledge, so it’s important to ask whether they are using any herbal preparations. Agents currently used include saw palmetto, African plum, South African star grass, and Cernilton.

Saw palmetto (Serenoa repens) has been used by more than 2 million men in the United States. In 2006, Bent et al conducted a rigorously designed double-blinded trial in which 225 men older than 49 years with moderate-to-severe symptoms of BPH were treated for 1 year with saw palmetto extract (160 mg twice a day) or placebo.²³ Saw palmetto did not ameliorate the symptoms of BPH. In contrast, a Cochrane systematic review last updated in 2002 asserted that this substance caused mild-to-moderate reductions in urologic symptoms and flow measures when given to men with symptomatic BPH.²⁴ Long-term efficacy and safety of this product are unknown. Given the efficacy of saw palmetto, it is a reasonable option for men who prefer a nonprescription product to treat symptoms of BPH.

FAST TRACK

Saw palmetto is a reasonable option for men who prefer a nonprescription product to treat their BPH symptoms.

African plum (Pygeum africanum) is more effective than placebo in reducing symptoms of BPH and has few side effects, based on poorly designed small studies.^25,26 Comparative data with finasteride or the α-adrenergic blockers are lacking.