Hypothesis: Higher prenatal testosterone predisposes ALS patients to improved athletic performance and manual professions

Our objective was to propose a testable hypothesis arising from the recent finding of a low index-to-ring finger ratio (2D:4D ratio) in ALS. The 2D:4D ratio finding suggests that prenatal testosterone exposure may play a role in the development of the disease. Research from other fields is presented to suggest that healthy individuals with low 2D:4D ratio have enhanced sporting prowess, particularly with regard to activities requiring endurance and dependent upon slow-twitch muscles. Although studies are of varying quality, some epidemiological findings in ALS also suggest enhanced sporting prowess, as well as a higher risk of developing the disease among members of certain physically active professions. If the 2D:4D finding survives replication then this might explain the reported elevated risk of ALS among professional athletes, the military, and manual professions. Such a relationship might also explain why ALS patients were more likely to have been elite sportspeople in younger life. This hypothesis may serve as a starting point for debate and discussion over the nature of ALS risk factors, as well as generating a number of specific testable hypotheses that may yield insight into the genesis of the disease.