Natural Experimentation Is a Challenging Method for Identifying Headache Triggers


  • Conflict of Interest: None.

Address all correspondence to T. Houle, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, email:



In this study, we set out to determine whether individual headache sufferers can learn about the potency of their headache triggers (causes) using only natural experimentation.


Headache patients naturally use the covariation of the presence-absence of triggers with headache attacks to assess the potency of triggers. The validity of this natural experimentation has never been investigated. A companion study has proposed 3 assumptions that are important for assigning causal status to triggers. This manuscript examines one of these assumptions, constancy in trigger presentation, using real-world conditions.


The similarity of day-to-day weather conditions over 4 years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in 9 regularly cycling headache sufferers, was examined using several available time series. An arbitrary threshold of 90% similarity using Gower's index identified similar days for comparison.


The day-to-day variability in just these 3 headache triggers is substantial enough that finding 2 naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine vs not drinking wine) will only infrequently occur. Fluctuations in weather patterns resulted in a median of 2.3 days each year that were similar (range 0-27.4). Considering fluctuations in stress patterns and ovarian hormones, only 1.5 days/month (95% confidence interval 1.2-2.9) and 2.0 days/month (95% confidence interval 1.9-2.2), respectively, met our threshold for similarity.


Although assessing the personal causes of headache is an age-old endeavor, the great many candidate triggers exhibit variability that may prevent sound conclusions without assistance from formal experimentation or statistical balancing.