NSAID Use May Prevent or Delay Development of Benign Prostate
Hyperplasia
News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP.
Release Date: September 6, 2006; Valid for credit through September 6, 2007
September 6, 2006 — Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent or delay development of benign prostate
hyperplasia (BPH), according to the results of a population-based cohort study reported in the September 5 issue of the American
Journal of Epidemiology.
"The biologic mechanisms leading to the development of BPH have not been completely elucidated; however, both chronic and
acute inflammation have been frequently noted in prostate biopsy sections and in tissue obtained during prostatic resection for
treatment of BPH," write Jennifer L. St. Sauver, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, and
colleagues. "Inflammation may therefore lead to the development of BPH, or, alternatively, arise as the result of BPH disease
progression. If inflammation plays an important role in the development or worsening of BPH, anti-inflammatory agents may offer
useful adjunct medical therapies for treatment of this syndrome."
To determine whether daily users of NSAIDs were at lower risk for development of BPH than were nondaily NSAID users, the
investigators conducted home visits on 2447 Caucasian men. During the visit, participants completed validated questionnaires,
including information about daily NSAID use. A random subset of 634 men also underwent a clinical evaluation including transrectal
ultrasonography and measurement of serum prostate specific antigen (PSA) levels, and examinations and questionnaires were
repeated biennially through 2002. Outcomes reflecting BPH included development of moderate-severe urinary symptoms (American
Urologic Association Symptom Index score, > 7), a low maximum urinary flow rate (< 12 mL/second), a prostate volume of more
than 30 mL, or a PSA level higher than 1.4 ng/mL.
After adjustment for age, daily NSAID use was inversely associated with onset of moderate-severe urinary symptoms (hazard ratio
[HR], 0.73; 95% confidence interval [CI], 0.64 - 0.82), a low maximum flow rate (HR, 0.51; 95% CI, 0.43 - 0.61), increased prostate
volume (HR, 0.53; 95% CI, 0.41 - 0.68), and elevated PSA level (HR, 0.52; 95% CI, 0.40 - 0.68). Age-specific analyses revealed
that inverse associations between NSAID use and urinary measures tended to be stronger in the oldest age groups. However, this
interaction was statistically significant only for obstructive symptoms and treatment.
Study limitations include limited dose data; measures of BPH varied considerably among individuals and within men over time;
inability to examine changes in NSAID use over time; inability to examine a dose-response relationship between duration of NSAID
use and development of BPH measures; and possible effects of an uncontrolled confounder.
"While further studies are necessary to determine whether NSAID use truly causes decreased development of BPH, and the
mechanisms by which this might occur, these data suggest that NSAID use may prevent, delay or retard hyperplastic and/or
inflammatory processes in the prostate, resulting in a decreased incidence of BPH," the authors write.
The Public Health Service, National Institutes of Health, supported this study.
Am J Epidemiol. 2006;164:497-504.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
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Describe the pathophysiology of BPH and the possible interaction between BPH and NSAIDs.
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Identify the effect of using NSAIDs on clinical facets of BPH.
Clinical Context
The primary pathologic marker of BPH is proliferation of cells within the prostate gland. However, multiple mechanisms beyond
prostate size may be responsible for the clinical symptoms associated with BPH, as evidenced by the fact that prostate size does
not always correlate with clinical symptoms.
Both acute and chronic inflammation are frequently present on biopsy specimens among men with BPH, and this pathologic fact has
led to speculation that anti-inflammatory medications, such as NSAIDs, may reduce the risk for BPH. NSAIDs may inhibit cellular
proliferation within the prostate and induce apoptosis of hypertrophic prostate cells. In the current study, the authors examine a
large cohort of men to determine whether NSAID use might prevent the clinical, radiologic, and laboratory findings associated with
BPH.
Study Highlights
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Participants included men between 40 and 79 years of age who resided in one county in Minnesota. Men with a history of
any significant urologic condition were excluded from study participation.
Subjects underwent an interview that assessed BPH symptoms, family history of urologic disease, and medication use.
Researchers also measured peak urinary flow rates. A subgroup of participants also underwent assessment with
transrectal ultrasonography and serum PSA levels.
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Examinations and questionnaires were repeated biennially from 1990 through 2002, and medical records were used to
confirm urologic events. The main study outcome was the relationship between daily NSAID use and the incidence of
moderate-severe symptoms of BPH, which was defined by an American Urologic Association Symptom Index score
greater than 7. Secondary outcomes included the effect of NSAID use on the incidence of reduced maximum urinary flow
rate (peak flow, < 12 mL/second), prostate volume greater than 30 mL, serum PSA level greater than 1.4 ng/mL, and the
use of treatment for BPH. These results were adjusted for age, several chronic illnesses, and the frequency of clinician
visits.
2447 men participated in the study, and data regarding PSA level and prostate volume were available for 634 men. 33%
of subjects reported daily NSAID use at study enrollment, and 80% of these men used aspirin. NSAID users were older
than nonusers, but they were less likely to report urologic symptoms at baseline. NSAID users were more likely to see
their clinicians more than once per year vs nonusers.
On age-adjusted analyses, NSAIDs reduced the incidence rates of moderate-severe urinary symptoms (HR, 0.73), low
maximum urinary flow rate (HR, 0 .51), increased prostate volume (HR, 0.53), elevated serum PSA level (HR, 0.52), and
treatment of BPH (HR, 0.79). Further adjustment for chronic illness and frequency of clinician visits strengthened the
protective effect of NSAIDs in these outcomes.
NSAID use was consistently associated with a reduced risk for urologic outcomes when the definitions of these outcomes
were defined more broadly.
The main study outcomes were virtually unchanged when examining long-term vs short-term use of NSAIDs or the use of
aspirin vs other NSAIDs.
Results suggested that only aspirin doses greater than 85 mg/day were associated with the full benefits ascribed to
NSAIDs. However, this finding may have been due to few participants using low-dose aspirin, resulting in low statistical
power for this subgroup.
NSAIDs were most effective in preventing BPH among older men. While the majority of risk reduction in patients between
40 and 59 years of age was not statistically significant, men 60 years and older experienced the full benefits of NSAID
protection.
Pearls for Practice
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While BPH is defined by cellular proliferation in the prostate gland, other mechanisms, such as inflammation, may also
contribute to the clinical presentation of BPH. Prostate size does not always correlate with the degree of BPH symptoms.
In the current study, regular NSAID use was associated with reduced risks for clinical BPH symptoms, prostate
hypertrophy on ultrasonography, and elevated PSA levels. The type of NSAID used or duration of therapy did not affect
the study's main finding, but older men