• Gabriele S Merki-Feld, Nina Caveng, Gina Speiermann, and E Anne MacGregor.
• Department of Reproductive Endocrinology, University Hospital Zürich, Frauenklinikstrasse 10, CH - 8091, Zürich, Switzerland. gabriele.merki@usz.ch.
• J Headache Pain. 2020 Jun 24; 21 (1): 81.

BackgroundMany studies have described the features of menstrually-related migraines (MRM) in the natural cycle and the efficacy of prevention. MRM in combined hormonal contraceptive (CHC) users has scarcely been researched. Estrogen and progestin withdrawal in CHC users are both more abrupt and from higher hormone levels compared with the natural cycle. An advantage for prevention of MRM in CHC users is that the hormone withdrawal is predictable. It is unknown, whether the attacks during the hormone-free interval are associated with the hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention.MethodsFor this prospective diary-based trial we collected migraine and bleeding data from CHC users with MRM in at least two of three cycles. We analyzed frequency of migraines over the whole CHC cycle. During the hormone-free phase the relation between onset of migraine and onset of bleeding was studied. We compared pain intensity and identified prolonged-migraine attacks during hormone use and the hormone-free phase.ResultsDuring the hormone-free interval the number of migraine days and the pain score/migraine day were significantly higher in comparison with the mean during hormone use. The prevalence of migraine attacks was fourfold on hormone-free days 3-6. Migraine typically started on days 1-4. Migraine in relation to bleeding mostly occurred on days - 1 to + 4. In 78% of the cycles the first migraine day occurred during bleeding days 1 ± 2 and 48% started on days - 1 and day 1. The predictability of the first bleeding day was very high.ConclusionThe day of hormone-withdrawal migraine and the first bleeding day are highly predictable in CHC users. Migraine onset is mostly day - 1 and 1 of the bleeding and on days 1-4 of the hormone-free interval. Migraine attacks of CHC users in the hormone-free interval are severe and long lasting. Further trials are necessary to investigate if this knowledge can be used to optimise prevention.

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