Does Stress Cause Ulcers? Round II

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This question has been posed for decades and although psychologcial stress was long believed to be a potential cause of peptic ulcer disease, the theory has been largely displaced by the discovery of the role of Helicobacter pylori in ulcer formation and with the known association between nonsteroidal anti-inflammatory drugs and gastric erosion. Several authorities on this topic actually concluded that “ulcers are not caused by stress.”¹ The findings from a recent study by Levenstein and colleagues argue otherwise.²

The cohort examined included a random sample of more than 3000 Danish adults who were participating in a World Health Organization study of cardiovascular diseases. All subjects who had ulcers or a positive H pylori serology at baseline were excluded from the study. Participants were interviewed and completed a 12-item questionnaire regarding their stress levels at baseline, at 5 years, and at 10 years. Questions asked for information on employment status, number of hours worked per week, sleep duration per night, alcohol and tobacco consumption, use of tranquilizers, leisure time, and exercise habits. A score from 0 to 10 points was assigned to each survey.

At the end of the study, 76 participants had developed ulcers confirmed via endoscopy, barium study, or surgery. Among the subjects who developed an ulcer, stress level was higher based on the results of the survey. Specifically, those who scored in the highest tertile of stress scores had more than double the risk of developing gastric or duodenal ulcers than those in the lowest tertile (3.5% vs 1.6%, respectivley). For every one point increase in the survey stress score, the risk of ulcer increased by 12%. After adjusting for NSAID use and H pylori status, stress remained a significant predictor of peptic ulcer disease. Socioeconomic status and smoking were also independent predictors. Stress increased risk for both gastric ulcers (OR = 1.19; 95% CI, 1.03-1.37) and duodenal ulcers (OR = 1.11; 95% CI, 0.98-1.27).

Despite examining a historical cohort and using an unvalidated questionnaire for stress, this study has several strengths. It had sufficient power to control for known causes of peptic ulcer disease, namely NSAID use and H pylori status. The authors confirmed all causes of ulcers and did not rely on patient self-report. Importantly, the researchers were able to follow the same cohort longitudinally for more than a decade, and all participants answered the same questions at 3 different time points. The results reintroduce the question of what role stress may play in the etiology of peptic ulcer disease. Further studies are needed to validate these findings.

References:

1. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. http://digestive.niddk.nih.gov/. Accessed May 1, 2015.

2. Levenstein S, Rosenstock S, Jacobsen RK, Jorgensen T. Psychological stress increases risk for peptic ulcer, regardless of Helicobacter pylori infection or use of nonsteroidal anti-inflammatory drugs. Clin Gastroenterol Hepatol. 2015;13:498-506.