Analysis of WHI Data Links Strenuous Exercise to ALS

elderly woman running
elderly woman running
Data from the Women's Health Initiative suggest a relationship between strenuous exercise and amyotrophic lateral sclerosis.

Analysis of data from the Women’s Health Initiative (WHI) suggests a link between strenuous physical activity and amyotrophic lateral sclerosis (ALS), which may provide clues to the etiology of the debilitating and ultimately fatal disease.

According to the findings published in JAMA Neurology, the cause of ALS is unknown, with 5% to 10% of cases indicating a familial inheritance and the remaining are sporadic. Sporadic cases of ALS have been linked to environmental and occupational exposure, cigarette smoking, and even strenuous physical activity.

Yvonne Eaglehouse, PhD, MPH, of the Division of Cancer Prevention and Population Science at the University of Pittsburgh, and colleagues used WHI data to assess the relationship between ALS and strenous physical activity. The cohort included 161,809 postmenopausal women between the ages of 50 and 79 years with an average of 9.6 years of follow-up.  In total, the investigators identified 165 women who died from ALS and found they were more likely to be older (P<.001), not have diabetes (P=.03), and have a lower body mass index (BMI) (P=.04).

Within the cohort, 70.8% of the women reported no strenuous physical activity whereas 12.6% of the women reported 3 or more days per week of strenuous physical activity. As the frequency of strenuous physical activity increased, the number of deaths from ALS increased (0.09% for none to 0.16% for 4 days per week, P=.06 for trend). Likewise, women who reported no strenuous activity had an age-adjusted mortality rate from ALS of 7.4 per 100,000 person-years (95% confidence interval [CI], 5.5-9.9) vs 10.6 per 100,000 person-years (95% CI, 5.6-20.0) in those reporting strenuous physical activity 3 or more days per week (P=.07). Further, women with an ALS-related death reported more minutes of strenuous activity (39.1 vs 29.3 min/wk, P=.04 age adjusted) and more energy expenditure from strenuous activity (4.6 vs 3.4 MET-hours per week, P=.03 age adjusted). When looking at 50-year-old women who reported engaging in strenuous physical activity 3 or more days weekly, the investigators found a hazard ratio of 1.58 (95% CI, 1.16-2.15) compared with those reporting no strenuous activity.

Post- hoc analysis found an association between ALS death and engaging in strenuous activity 3 or more days per week in former smokers (age-adjusted HR, 2.34; 95% CI, 1.30-4.18) and those without diabetes (age-adjusted HR, 1.46; 95% CI, 0.96-2.21).  Finally, after adjusting for age and BMI, they found an odds ratio of 1.56 (95% CI, 1.02-2.37; P=.04) for ALS-related death in those reporting engaging in 3 or more days of strenuous physical activity vs none.

The authors further note that these results should be taken into context with the understood benefits of physical activity. They write, “Previous studies of PA and health outcomes in the WHI reported that higher PA levels were associated with a reduced risk of breast cancer, ovarian cancer, cardiovascular disease, and improved survival in women with incident breast cancer.”

The WHI is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. The authors report no disclosures.


  1. Eaglehouse YL, Talbott EO, Chang Y. Participation in physical activity and risk for amyotrophic lateral sclerosis mortality among postmenopausal women. JAMA Neurol. 2017; Jan 19. doi:10.1001/jamaneurol.2015.4487. [Epub ahead of print]