Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with erectile dysfunction (ED), according to the results of a prospective cohort study reported online February 21 and in the April print issue of the Journal of Urology.
"This study is a great example of how we work to understand the safety and effectiveness of what we recommend for our patients," said senior author Steven J. Jacobsen, MD, PhD, an epidemiologist and director of research for Kaiser Permanente Southern California in San Diego, in a news release.
"We went into this study thinking we would find the opposite effect: that NSAIDs would have a protective effect because they protect against heart disease, which is also linked to ED. The next step is to dive a bit deeper to understand the underlying physiology of what might be happening with these drugs."
Beginning in 2002, the California Men's Health Study enrolled a large, ethnically diverse cohort of male members of the Kaiser Permanente managed care plans who were 45 to 69 years old. A questionnaire evaluated ED, and automated pharmacy data and self-reported use allowed evaluation of NSAID exposure.
NSAID use was present in 47.4% of the 80,966 participants, and moderate or severe ED was reported in 29.3%. NSAID use and ED correlated strongly with age. Regular NSAID use increased from 34.5% in men aged 45 to 49 years to 54.7% in men aged 60 to 69 years, and ED increased from 13% to 42% in these age groups.
Without adjustment for potentially confounding variables, the odds ratio (OR) for the association of NSAIDs and ED was 2.40 (95% confidence interval [CI], 2.27 - 2.53). A positive association persisted after adjustment for age, race/ethnicity, smoking status, diabetes mellitus, hypertension, hyperlipidemia, peripheral vascular disease, coronary artery disease, and body mass index (adjusted OR, 1.38). A positive association also was evident when a stricter definition of NSAID exposure was used.
"There are many proven benefits of non steroidals in preventing heart disease and for other conditions," Dr. Jacobsen said. "People shouldn't stop taking them based on this observational study. However, if a man is taking this class of drugs and has ED, it's worth a discussion with his doctor."
Limitations of this study include cross-sectional design, potential participation bias, and low original participation rate.
"These data suggest that regular NSAID use is associated with ED even after extensive adjustment for age and potentially confounding factors or comorbidities," the study authors write.
"While this raises the question of the role of inflammation and COX [cyclooxygenase] pathways in ED etiology, we cannot exclude alternative explanations. However, if this is a direct relationship, the current strategy of using NSAIDs for cardiovascular disease protection as well as other common uses of NSAIDs should be weighed against the potential side effects of ED. Studies are needed to elucidate this association in more detail."
The California Cancer Research Program and Kaiser Foundation Community Benefit Program supported this study. Some of the study authors have disclosed various financial and/or other relationships with Takada, GlaxoSmithKline, Kaiser Permanente, and/or Merck.
J Urology. Published online February 21, 2011. Abstract
Theoretically, NSAIDs may improve erectile function in men through positive effects on endothelial function. However, a study by Shiri and colleagues suggests the opposite. They found that use of NSAIDs led to an approximate 2-fold increase in the risk for ED. This was true after adjustment for multiple demographic and medical factors and was valid regardless of the presence of arthritis. However, men with arthritis who did not use NSAIDs did not have a significant increase in the risk for ED.
The current study seeks to build on these data by examining a large cohort of men for the risk for ED associated with NSAIDs.
- Study participants were drawn from the California Men's Health Study, and all of these men belonged to the same managed care organization. Participants were between the ages of 45 and 69 years and completed health questionnaires between 2002 and 2003. Men with a history of prostate cancer were excluded from analysis.
- The investigators identified ED by using a validated survey tool. NSAID exposure was determined from pharmacy records as well as from the health questionnaire. For the purposes of this study, men had to have regular NSAID use (a total of more than 100 days' supply of NSAIDs or NSAID use at least 5 days per week) to be considered exposed to NSAIDs.
- The main study outcome was the effect of NSAID exposure on the rate of ED. This result was adjusted to account for numerous confounding variables, including age, race, smoking status, and multiple cardiovascular risk factors.
- 80,966 men participated in the study. The overall prevalence of ED was 29.3%, and ED became more prevalent with older age. The prevalence of ED was 13% among men younger than 50 years but increased to 42% among men older than 60 years.
- Of the 80,966 men, 47.4% had significant exposure to NSAIDs. NSAID exposure also corresponded positively with age.
- The overall prevalence rates of ED among men exposed and not exposed to NSAIDs were 35.2% and 24%, respectively.
- The adjusted OR for ED associated with the use of NSAIDs was 1.22 (95% CI, 1.18 - 1.27).
- The higher risk for ED associated with NSAIDs persisted in all age groups, although it was strongest among older men.
- NSAIDs appeared to promote severe ED to a greater degree than moderate ED. The adjusted ORs for moderate and severe ED associated with NSAID use were 1.09 and 1.38, respectively.
- A previous study found that the use of NSAIDs led to an approximate 2-fold increase in the risk for ED on adjusted analyses, regardless of the presence of arthritis. However, the presence of arthritis not treated with NSAIDs did not raise the risk for ED.
- The current study suggests that NSAIDs can independently increase the risk for ED, particularly among older men.