The variation between individual migraine risk factor
profiles certainly alerts us that everybody is different
on a risk susceptibility level, but will we ever be able to
understand the mechanisms driving these differences and
relate them to individual therapeutic response?
One of the best studied examples of risk factors for
migraine is menstruation and fortunately, data on
therapeutic response are also available. As a primary
mechanism is believed to be the perimenstrual estrogen
‘withdrawal,’ an effective treatment is application of
estrogen gel to ‘bridge’ this deficiency. In a study 10 of 27
women, the authors chose to apply gel perimenstrually
for 7 days ending on day 2 of the cycle – which was
median day for lowest estrogen level (nadir) recorded
in pre-treatment cycles. However, such was the inter-
and intra-individual variation among the women that
treating until the median day was inadequate - estrogen
was consistently lowest at day 2 in only 5 of 27 women.
While estrogen treatment was indeed effective in
those five women, women with a later estrogen nadir
experienced a delayed estrogen withdrawal migraine, that
may not have occurred had the timing of treatment been
individualized.
Therefore, it seems that an important next step would
be to acknowledge the need to understand both the
degree of, and basis for, individual variation in chronic
disease. If we proceed in this manner, the journey started
last century to discover individual variation may finally
acquire a sense of urgency. And if the average approach
is limiting, or possibly even causing harm in some
individuals – something which might not be detected
through aggregate population analysis - then optimizing
individual therapeutic pathways and outcomes may be
the most effective way forward for patients with chronic
disease not adequately addressed by the aggregate
approach in modern medicine. HW
References
1 Williams RJ. Biochemical Individuality. New York: John Wiley & Sons; 1956.
2 Williams RJ. You Are Extraordinary. New York: Random House; 1967.
3
Oregon State University Libraries Special Collections. Roger J. Williams: Nutrition Scientist, The Pauling Blog.
https://paulingblog.wordpress.com/2014/06/26/roger-j-williams-nutrition-scientist/. Published June 24 2016.
Accessed Feb 13 2017.
4 Schork NJ.(2015) Time for one-person trials. Nature 520: 609
5 Vos et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic
analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–96
6
Peris et al. Towards improved migraine management: Determining potential trigger factors in individual patients.
Cephalagia 2016; DOI: 10.1177/0333102416649761
7 Wöber et al (2007) Prospective analysis of factors related to migraine attacks: the PAMINA study. Cephalalgia, 304-14.
8 Donoghue et al (2016) Identification of individual “protective factors” associated with reduced risk of migraine attacks.
In preparation
9
Simpson EH. The interpretation of interaction in contingency tables.(1951)
J R Stat Soc Series B Stat Methodol. 13: 238–241
10
26
MacGregor (2008) Current Pain and Headache Reports, 12:468
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Volume 7, Issue 1 • 2018