Approximately 20 to 50 percent of skiers and mountaineers report headache at altitudes of 3,000 to 5,000 m (10,000 to 16,500 ft). Burtscher and colleagues conducted a double-blind study to evaluate the ability of aspirin to prevent altitude-related headache in volunteers traveling to high altitudes.

Twenty-nine volunteers with a history of altitude-related headache were randomly assigned to receive 320 mg of aspirin or an identical placebo every four hours, starting one hour before arrival at high altitude and continuing for 12 hours. Headache (measured on a four-point scale), heart rate, blood pressure and arterial oxygen saturation were measured one hour before and three, seven, 10 and 19 hours after arrival at high altitude. Gas exchange, heart rate and oxygen saturation were also assessed at low altitude and within five hours of arrival at high altitude, using a two-minute step-exercise program.

Only one of the volunteers who received aspirin developed headache at high altitude. Headache occurred in seven of the volunteers in the placebo group. This difference was statistically significant. The mean oxygen saturation did not differ between the treated and placebo groups, but individual values were predictive of the development of headache. Patients who received aspirin developed headache at lower oxygen saturations than did those who received placebo.

The authors conclude that aspirin prevents high-altitude headache without improving oxygenation. Aspirin appeared to raise the threshold for headache by improving the person's tolerance to lower oxygen saturation. They suggest that aspirin may enhance adaptation to high altitude by reducing sympathetic activity mediated by prostaglandins.