Psychological stress increases risk for peptic ulcer, regardless of Helicobacter pylori infection or use of nonsteroidal anti-inflammatory drugs

Clin Gastroenterol Hepatol. 2015 Mar;13(3):498-506.e1. doi: 10.1016/j.cgh.2014.07.052. Epub 2014 Aug 9.


Background & aims: There is controversy over whether psychological stress contributes to development of peptic ulcers. We collected data on features of life stress and ulcer risk factors from a defined population in Denmark and compared these with findings of confirmed ulcers during the next 11-12 years.

Methods: We collected blood samples and psychological, social, behavioral, and medical data in 1982-1983 from a population-based sample of 3379 Danish adults without a history of ulcer participating in the World Health Organization's MONICA study. A 0- to 10-point stress index scale was used to measure stress on the basis of concrete life stressors and perceived distress. Surviving eligible participants were reinterviewed in 1987-1988 (n = 2809) and 1993-1994 (n = 2410). Ulcer was diagnosed only for patients with a distinct breach in the mucosa. All diagnoses were confirmed by review of radiologic and endoscopic reports. Additional cases of ulcer were detected in a search of all 3379 subjects in the Danish National Patient Register.

Results: Seventy-six subjects were diagnosed with ulcer. On the basis of the stress index scale, ulcer incidence was significantly higher among subjects in the highest tertile of stress scores (3.5%) than the lowest tertile (1.6%) (adjusted odds ratio, 2.2; 95% confidence interval [CI], 1.2-3.9; P < .01). The per-point odds ratio for the stress index (1.19; 95% CI, 1.09-1.31; P < .001) was unaffected after adjusting for the presence of immunoglobulin G antibodies against Helicobacter pylori in stored sera, alcohol consumption, or sleep duration but lower after adjusting for socioeconomic status (1.17; 95% CI, 1.07-1.29; P < .001) and still lower after further adjustments for smoking, use of nonsteroidal anti-inflammatory drugs, and lack of exercise (1.11; 95% CI, 1.01-1.23; P = .04). The risk for ulcer related to stress was similar among subjects who were H pylori seropositive, those who were H pylori seronegative, and those exposed to neither H pylori nor nonsteroidal anti-inflammatory drugs. On multivariable analysis, stress, socioeconomic status, smoking, H pylori infection, and use of nonsteroidal anti-inflammatory drugs were independent predictors of ulcer.

Conclusions: In a prospective study of a population-based Danish cohort, psychological stress increased the incidence of peptic ulcer, in part by influencing health risk behaviors. Stress had similar effects on ulcers associated with H pylori infection and those unrelated to either H pylori or use of nonsteroidal anti-inflammatory drugs.

Keywords: Duodenal; Epidemiology; Gastric; Psychosocial Factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Denmark / epidemiology
  • Female
  • Helicobacter Infections / complications
  • Humans
  • Incidence
  • Interviews as Topic
  • Male
  • Middle Aged
  • Peptic Ulcer / epidemiology*
  • Prospective Studies
  • Risk Assessment
  • Stress, Psychological / complications*


  • Anti-Inflammatory Agents, Non-Steroidal