Protective association between nonsteroidal antiinflammatory drug use and measures of benign prostatic hyperplasia

In 1990-2002, the authors conducted a population-based cohort study of 2,447 Caucasian men in Olmsted County, Minnesota, to determine whether daily users of nonsteroidal antiinflammatory drugs (NSAIDs) were at lower risk than nondaily NSAID users of developing benign prostatic hyperplasia. Participants completed validated questionnaires during a home visit, including information about daily NSAID use. A random subset of 634 men also participated in a clinical evaluation including transrectal ultrasonography and assessment of serum prostate-specific antigen levels. Examinations and questionnaires were repeated biennially through 2002. Benign prostatic hyperplasia measures included development of moderate/severe urinary symptoms (American Urological Association Symptom Index score >7), low maximum urinary flow rate (<12 ml/second), prostate volume >30 ml, or prostate-specific antigen level >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), 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 prostate-specific antigen level (HR = 0.52, 95% CI: 0.40, 0.68). In age-specific analyses, inverse associations between NSAID use and urinary measures tended to be stronger in the oldest age groups, although this interaction was statistically significant for only obstructive symptoms and treatment. Results suggest that NSAID use may prevent or delay development of benign prostatic hyperplasia.     

Case-control study of use of nonsteroidal antiinflammatory drugs and glioblastoma multiforme

Evidence from epidemiologic and experimental studies suggests that use of nonsteroidal antiinflammatory drugs (NSAIDs) reduces risk of colon and breast cancer. The association between use of aspirin and other NSAIDs and risk of adult glioblastoma multiforme (GBM) was evaluated among 236 incident GBM cases and 401 population-based controls frequency-matched on age, gender, and ethnicity from the San Francisco Bay Area Adult Glioma Study. Cases (or proxies) and controls were interviewed in person between May 1997 and August 2000. Cases with self-reported GBM reported less use of at least 600 pills of all types of NSAIDs combined during the 10-year prediagnostic period than did controls (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.3, 0.8). Findings were consistent for aspirin (OR = 0.51, 95% CI: 0.3, 0.8), ibuprofen (OR = 0.41, 95% CI: 0.2, 0.8), and naproxen/other NSAIDs (OR = 0.34, 95% CI: 0.1, 0.8). GBM cases also reported less use of acetaminophen than did controls (OR = 0.51, 95% CI: 0.3, 1.0). Eliminating participants who initiated NSAID use within 2 years of diagnosis yielded similar results. These findings show an inverse association between NSAID use and GBM. Further studies are warranted to determine whether NSAIDs might be effective in the inhibition of GBM development or progression.     

The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer.

BACKGROUND: The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the risk of breast cancer is unclear. We assessed the association in a hospital-based case-control study. METHODS: The cases (n = 6558) were compared with cancer controls (n = 3296) and noncancer controls admitted for trauma or acute infection (n = 2925). Odds ratios were estimated using multivariate logistic regression models. RESULTS: For women who used NSAIDs regularly beginning at least 1 year before admission, the odds ratios (OR) were 0.8 (95% CI 0.7, 1.0) with cancer controls and 0.7 (95% CI 0.6, 0.9) with noncancer controls. With noncancer controls, there was a statistically significant decreasing trend in the odds ratios as duration of use increased, whereas with cancer controls there was not. The reduction in risk for regular use was accounted for largely by a reduced odds ratio for one study center (Boston), which contributed 9% of the cases. CONCLUSIONS: The data are compatible with a small reduction in risk associated with regular NSAID use. However, inconsistencies in the data detract from a causal interpretation.     

Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs

Use of nonsteroidal antiinflammatory drugs (NSAIDs) has been associated with a reduced risk of colorectal cancer, but limited information is available on the effect of individual nonaspirin NSAIDs. In addition, the dose-response relation of aspirin in reducing the risk of colorectal cancer has not been described. We carried out a population-based cohort study with secondary case-control analysis to determine the association between the risk of colorectal cancer and use of aspirin and individual NSAIDs, including the role of dose and duration. The General Practice Research Database in the U.K. was the source population. We traced 943,903 persons 40-79 years of age and free of cancer and colorectal adenoma between January 1994 and September 1997. A total of 2,002 incident cases of colorectal cancer were ascertained. The incidence rate of colorectal cancer per 10,000 person-years was 7.3. The risk of colorectal cancer was reduced in users of nonaspirin NSAIDs and became evident after 6 months of continuous treatment. The adjusted relative risk was 0.5 (95% confidence interval = 0.4-0.7). The reduction in risk disappeared completely 1 year after stopping NSAID treatment. The risk of developing colorectal cancer was reduced in long-term users of aspirin at doses of 300 mg daily (relative risk = 0.6; 95% confidence interval = 0.4-0.9). Daily doses of 75 and 150 mg aspirin were not associated with a reduced risk of colorectal cancer. Our data support the existence of an important protective effect of nonaspirin NSAID continuous intake against colorectal cancer and point to a similar reduction in risk for aspirin at doses of at least 300 mg daily. One-year treatment with NSAIDs would prevent one case of colorectal cancer in a population of 1,000 persons 70-79 years of age.     

Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case-Control Surveillance Study revisited

Several studies have suggested that use of nonsteroidal antiinflammatory drugs (NSAIDs) may reduce the risk of breast cancer. Reductions in risk may vary according to the hormone receptor status of the tumor or the type of NSAID used. The authors extended a previous US hospital-based case-control study (the Case-Control Surveillance Study) to include 444 additional cases, for a total of 7,006 incident breast cancer cases (1976-2002). They examined the relation between regular NSAID use and breast cancer risk using logistic regression to adjust for confounding. The odds ratio for regular use of NSAIDs was 0.78 (95% confidence interval: 0.63, 0.97), and a trend of decreasing risk with increasing duration of use was statistically significant (p for trend = 0.02). The inverse association with regular use of NSAIDs was stronger among premenopausal women (odds ratio = 0.62). The overall odds ratios for regular use of aspirin and ibuprofen were 0.86 and 0.85, respectively. The effect of NSAID use on breast cancer risk did not vary according to the hormone receptor status of the tumor. In conclusion, long-term regular use of NSAIDs was associated with decreased risk of breast cancer. The type of NSAID used or the hormone receptor status of the tumor did not modify the effect.     

Indications for and use of nonsteroidal antiinflammatory drugs and the risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial

The authors conducted a cohort study of nonsteroidal antiinflammatory drug (NSAID) use and risk of symptomatic benign prostatic hyperplasia (BPH), using data from 4,735 men without BPH at baseline in the placebo arm of the Prostate Cancer Prevention Trial (1993-2003). Incident BPH (n = 471) was defined as medical or surgical treatment or at least 2 International Prostate Symptom Score (I-PSS) values greater than or equal to 15. Proportional hazards models using time-dependent exposure for NSAID use were employed to estimate covariate-adjusted associations of NSAID-related medical conditions and NSAID use with BPH risk. Arthritis, other inflammation-related musculoskeletal conditions, and headaches were associated with increased BPH risk (hazard ratio (HR) = 1.77 (95% confidence interval (CI): 1.37, 2.29), HR = 1.57 (95% CI: 1.14, 2.17), and HR = 1.40 (95% CI: 1.09, 1.80), respectively). Use of any NSAID, use of aspirin, and use of nonaspirin NSAIDs were associated with significant increases in BPH risk (HR = 1.21 (95% CI: 1.01, 1.46), HR = 1.20 (95% CI: 1.00, 1.45), and HR = 1.34 (95% CI: 1.07, 1.69), respectively). Control for indications for NSAID use, including baseline I-PSS, attenuated the associations slightly, but all became nonsignificant. Among men with no indications for NSAID use, the hazard ratio for any NSAID use was 1.06 (95% CI: 0.82, 1.38). The modest associations of NSAID use with BPH risk in this cohort were probably due to confounding by indication, and NSAID use was not associated with BPH risk.     

Use of nonsteroidal antiinflammatory drugs and risk of colon cancer in a population-based, case-control study of African Americans and Whites

African Americans have the highest colon cancer incidence and mortality rates among all US ethnic groups. Epidemiologic studies suggest that use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a reduced risk of colon cancer, but no study to date with adequate sample size has reported on the association among African Americans. The authors examined the association between NSAID use and risk of colon cancer in a population-based, case-control study in North Carolina that enrolled 731 African-American (294 cases, 437 controls) and 960 White (349 cases, 611 controls) participants between 1996 and 2000. Odds ratios were calculated using unconditional logistic regression for categories of NSAIDs and colon cancer risk. Inverse associations between regular NSAID use and colon cancer were similar for African Americans (odds ratio = 0.41, 95% confidence interval: 0.22, 0.77) and Whites (odds ratio = 0.48, 95% confidence interval: 0.28, 0.83) but stronger for women than men. Inverse associations were slightly weaker for occasional versus regular NSAID use, but they were similar for aspirin and nonaspirin NSAID use. These results add new knowledge suggesting that the protective effect of NSAIDs against colon cancer is similar among African Americans and Whites.     

Analgesic drug use and risk of ovarian cancer

BACKGROUND: Previous epidemiologic research suggests that analgesic use may reduce the risk of ovarian cancer, although results are not consistent. METHODS: In a population-based, case-control study, we analyzed data from 586 ovarian cancer cases and 627 matched controls in North Carolina for the relationship between analgesic use and ovarian cancer risk. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for potential confounders. RESULTS: Use of any nonsteroidal antiinflammatory drugs, including aspirin, within 5 years of diagnosis/interview was found to be associated with a reduction in the risk of ovarian cancer (adjusted OR = 0.72; 95% CI = 0.56-0.92). For use of acetaminophen, the OR was 0.78 (95% CI = 0.56-1.08). CONCLUSIONS: These data support an inverse relationship between the use of both nonsteroidal antiinflammatory drugs and acetaminophen and the risk of ovarian cancer.     

Benzodiazepine use and risk of dementia: a nested case-control study

The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case--control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patient's medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2-2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2-4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6-1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.     

Analgesic drug use and risk of epithelial ovarian cancer

Analgesic use may reduce ovarian cancer risk, possibly through antiinflammatory or antigonadotropic effects. The authors conducted a population-based, case-control study in Washington State that included 812 women aged 35-74 years who were diagnosed with epithelial ovarian cancer between 2002 and 2005 and 1,313 controls. Use of analgesics, excluding use within the previous year, was assessed via in-person interviews. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Overall, acetaminophen and aspirin were associated with weakly increased risks of ovarian cancer. These associations were stronger after more than 10 years of use (acetaminophen: odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.3, 2.6; aspirin: OR = 1.6, 95% CI: 1.1, 2.2) and were present for indications of headache, menstrual pain, and other pain/injury. Reduced risk was observed among aspirin users who began regular use within the previous 5 years (OR = 0.6, 95% CI: 0.4, 1.0) or used this drug for prevention of heart disease (OR = 0.7, 95% CI: 0.5, 1.0). These results, in the context of prior findings, do not provide compelling evidence of a true increase in risk of ovarian cancer among women who use these drugs. However, they add to the weight of evidence that, in the aggregate, provides little support for the use of analgesic drugs as chemoprevention for this disease.     

Recreational drug use and the risk of primary infertility

Recreational drug (marijuana, lysergic acid diethylamide or LSD, speed, cocaine, and "other") exposures of women with primary infertility were compared with those of a matched control group of women with proven fertility. Women who reported smoking marijuana had a slightly elevated risk for infertility due to an ovulatory abnormality (RR = 1.7, 95% CI = 1.0 to 3.0). The risk was greatest among women who had used marijuana within one year of trying to become pregnant (RR = 2.1, 95% CI = 1.1 to 4.0). No consistent frequency or duration of use effects could be demonstrated, and the risk was confined to low-frequency users. Risks associated with the use of other drugs were not elevated. The risk of infertility from a tubal abnormality associated with cocaine use was greatly increased (RR = 11.1, 95% CI = 1.7 to 70.8). Our results are consistent with animal studies suggesting that smoking marijuana may cause a transient disruption of ovulatory function. The possibility that cocaine exposure influences the development of tubal infertility needs further investigation.     

Illicit drug use and the risk of new-onset seizures

The authors studied the use of heroin, marijuana, and cocaine before the onset of a first seizure in 308 patients with seizures and 294 controls at Harlem Hospital Center, New York City, between 1981 and 1984. Heroin use, both past and present, appeared to be a risk factor for all first seizures (adjusted odds ratio = 2.80, 95% confidence interval (CI) 1.53-5.74). For unprovoked seizures, the adjusted odds ratio was 2.58 (95% CI 1.36-4.90) for ever heroin use and 4.70 (95% CI 0.86-25.78) for heroin use within 24 hours of hospitalization. For provoked seizures, respective adjusted odds ratios were 3.65 (95% CI 1.54-8.65) and 27.74 (95% CI 3.57-215.52). Marijuana use appeared to be a protective factor against first seizures in men. For men with unprovoked seizures, the adjusted odds ratio was 0.42 (95% CI 0.22-0.82) for ever marijuana use and 0.36 (95% CI 0.18-0.74) for marijuana use within 90 days of hospitalization. For men with provoked seizures, respective adjusted odds ratios were 1.03 (95% CI 0.36-2.89) and 0.18 (95% CI 0.04-0.84). Cocaine use, while common among study subjects, was not shown to be a significant risk factor either for all first seizures or for subgroups of seizures, regardless of the time of last use. The authors conclude that heroin use is a risk factor and marijuana use a protective factor for new-onset seizures.