ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no known cause. Case studies primarily of athletes and several case-control studies have suggested that high levels of strenuous physical activity (PA) may increase the risk for ALS. This relationship has yet to be evaluated among women in population-based cohort studies.To evaluate the relationship between PA and risk for ALS mortality in a large cohort of postmenopausal women.The Women's Health Initiative (WHI) enrolled 161 809 postmenopausal women, aged 50 to 79 years (mean [SD] age, 63.6 [7.24] years), between 1993 and 1998 into either a clinical trial or an observational study at 40 clinical research centers across the United States. We conducted a cohort study from November 2014 to September 2015 using baseline and mortality data during an average of 9.6 years of follow-up from the entire WHI cohort, through September 1, 2013 (with 1.1% lost to follow-up), to address whether there is a relationship between PA and ALS mortality.The WHI assessed frequency and duration of mild, moderate, and strenuous PA at baseline via self-administered questionnaire.Underlying cause of death from ALS collected from death certificates.The WHI enrolled 161 809 women, of whom 165 died of ALS; women who died of ALS were older (median age, 66 years; interquartile range, 61-69 years) compared with the total WHI study population (median age, 63 years; interquartile range, 57-69 years). Age-adjusted ALS mortality rates varied from 7.4 (95% CI, 5.5-9.9)/100 000 person-years for no strenuous PA to 10.6 (95% CI, 5.6-20.0)/100 000 person-years for strenuous PA 3 or more days per week (P = .07). Adjusted for age and body mass index (calculated as weight in kilograms divided by height in meters squared), the odds ratio for death from ALS for participants with strenuous PA 3 or more days per week compared with no reported strenuous PA was 1.56 (95% CI, 1.02-2.37; P = .04).To our knowledge, this is the first cohort study to report an increased risk for ALS mortality associated with strenuous PA in postmenopausal women. The association between strenuous PA and ALS risk observed does not compromise the overall benefit of strenuous PA for total mortality, coronary heart disease, and breast cancer reported in other WHI investigations, but it may provide an important clue to the etiology of ALS, if replicated by other studies.
