Over-the-counter NSAIDs include acetylsalicylic acid (Aspirin), ibuprofen (Advil) and naproxen (Aleve).
In a large healthcare system, the rate of erectile dysfunction was 35.2 percent among middle-age men who regularly took NSAIDs and 24 percent among those who did not (P<0.001), according to Dr. Steven Jacobsen, director of research at Kaiser Permanente Southern California in Los Angeles, and colleagues.
After adjustment for age, race, ethnicity, smoking, body mass index, and various comorbidities, that worked out to a 1.22-fold greater likelihood of erectile dysfunction in NSAID users, the researchers reported online in the Journal of Urology.
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"While this raises the question of the role of inflammation and COX pathways in erectile dysfunction etiology, we cannot exclude alternative explanations," they wrote.
Those alternatives included confounding by factors not captured in the study, like subclinical disease and the severity of various comorbid conditions, and the possibility that NSAID use was itself an indicator of other conditions causing erectile dysfunction.
"If it's a true association then I think that it needs to enter into discussions about the risks and benefits of using NSAIDs -- whether for prevention or treatment," Jacobsen told MedPage Today.
"But I think probably the more important thing is that [by] bringing this to men's attention, that it may actually stimulate some conversation with their care provider about, first, erectile dysfunction, and, second, about some of the other risk factors for erectile dysfunction," he said.
Jacobsen stressed that the study does not prove a cause-and-effect relationship between NSAIDs and erectile dysfunction.
"People should not stop taking these if it's been recommended by their provider," he said, "and if they are concerned about it, they really should have a discussion with their provider about those risks and benefits."
NSAID Use Linked to Erectile Dysfunction
Because previous studies had suggested a possible relationship between inflammation and erectile dysfunction, the researchers thought the use of NSAIDs might lower the chances of developing the condition.
To explore the issue, Jacobsen and his colleagues turned to the California Men's Health Study, which included an ethnically diverse group of men ages 45 to 69 who were enrolled in Kaiser Permanente managed care plans.
The presence of erectile dysfunction was self-reported. Those who said they were sometimes or never able to achieve and maintain an erection were classified as having either moderate or severe dysfunction.
NSAID use was assessed using both electronic pharmacy data and self-report. Regular NSAID users were defined as men who received more than a 100-day supply of at least one NSAID, had any prescription for three or more NSAID doses per day, or reported using the drugs at least five days a week.
Of the 80,966 men included in the analysis, 47.4 percent used NSAIDs regularly and 29.3 percent reported some level of erectile dysfunction. Both rates were lowest in the youngest men and increased with age.
Even after adjustment for demographics, lifestyle, and several comorbidities -- including diabetes, hypertension, hyperlipidemia, peripheral vascular disease, and coronary artery disease -- regular NSAID use was associated with greater odds of both moderate and severe erectile dysfunction.
The findings were consistent with a small, observational Finnish study.
Jacobsen and his colleagues acknowledged some limitations of their study, including the inability to establish the temporal relationship between NSAID exposure and the development of erectile dysfunction using a cross-sectional analysis, potential participation bias, and a low participation rate.