Study: Nonsteroidal anti-inflammatory drug users at greater risk of developing erectile dysfunction

Key Points

Los Angeles-Men who regularly use nonsteroidal anti-inflammatory drugs (NSAIDs) have an increased risk of erectile dysfunction, according to analyses of data collected in the California Men's Health Study (CMHS).

The study, which was recently published in the Journal of Urology (2011; 185:1388-93), included an ethnically diverse cohort of about 80,000 male members of the Kaiser Permanente managed care system participating in the CMHS. The men ranged from 45 to 69 years of age, and those with a history of prostate cancer were excluded from the analysis. Information on over-the-counter and prescription NSAID use was obtained from automated outpatient pharmacy data and self-reports. ED presence and severity, as well as information about multiple variables that could affect ED risk, were identified from CMHS questionnaires.

Nearly half of the men (47.4%) were considered NSAID users based on having received more than a 100-day supply of one or more NSAIDs prescribed three or more times per day or self-reporting of NSAID use at least 5 days per week, and 29.3% were considered to have moderate-to-severe ED. The prevalence of both ED and NSAID use increased with age.

"Previously, Finnish investigators reported an association between NSAID use and an increased incidence of ED," said first author Joseph M. Gleason, MD, a urology resident at Kaiser Permanente Los Angeles Medical Center. "However, their study was relatively small, and there have been questions raised about potential confounding from selection bias. We thought that the combination of the very large CMHS database and the Kaiser Permanente integrated electronic health and pharmacy records provided an excellent resource to better investigate the issue.

"Our research also has limitations, as it is a cross-sectional study relying in part on survey information with its inherent recall bias. Therefore, it does not provide conclusive evidence that NSAIDs increase the risk of ED. However, we think physicians should be aware of this potential association and consider it when prescribing NSAIDs for chronic use or when taking a history in men who present with ED," said Dr. Gleason, who worked on the study with Steven J. Jacobsen, MD, PhD, and colleagues.

Study raises some questions

"The data were not obtained in a prospective longitudinal manner, and so there is no information on temporality between NSAID use and development of ED, and although the analyses adjusted for many potential confounding variables, there are many unknowns. For example, while data were available about the presence of medical diagnoses associated with ED, such as diabetes and coronary artery disease, there was no adjustment for severity of those conditions," said Dr. Chien, who was not involved with the study.

Additional analyses were performed with men stratified by age (45-49, 50-59, and 60-69 years). They showed that NSAID use was associated with an approximately 22% increased risk of ED regardless of age (p<.001 for all subgroups). Another analysis found a dose-response in the association between NSAID use and ED severity, with the increased risk being greater for severe (38%) versus moderate (9%) ED and remaining consistent regardless of age. However, because much of the data on NSAID exposure were obtained via survey, it was not possible to determine whether NSAID dose was related to ED risk, Dr. Gleason noted.

He added that the CMHS protocol includes a follow-up questionnaire, and those longitudinal data could be analyzed to investigate a temporal association between NSAID use and new-onset ED.

Since vascular inflammation has been suggested as a common factor in the link between ED and cardiovascular disease, and considering that NSAIDs protect against cardiovascular disease, the finding that ED risk increases with chronic NSAID use may be considered a surprise. The investigators postulated that NSAID use might contribute to ED by inhibiting synthesis of prostaglandins necessary for penile erection, but they also recognized that NSAID use may simply be a surrogate for other conditions underlying the development of ED.