Bianca Raffaelli (Berlin/ DE), Elisabeth Storch (Berlin/ DE), Lucas Hendrik Overeem (Berlin/ DE), Maria Terhart (Berlin/ DE), Mira Fitzek (Berlin/ DE), Kristin Sophie Lange (Berlin/ DE), Uwe Reuter (Berlin/ DE; Greifswald/ DE)
Abstract text (incl. figure legends and references)
Objective: Sex hormones may have an influence on CGRP release in the trigeminovascular system. We aimed to assess CGRP concentrations in tear fluid and plasma in three groups of women with episodic migraine: A. With a regular menstrual cycle, B. Under combined oral contraception (COC), C. In the postmenopause. For control, we studied three respective groups of age-matched healthy women.
Methods: The study protocol for women with a regular menstrual cycle consisted of two visits on menstrual cycle day 2 ± 2 (during menstruation) and 13 ± 2 (periovulatory period). Participants with COC were examined at day 4 ± 2 of the hormone-free interval (HFI) and between days 7-14 of hormone intake (HI). Postmenopausal women were assessed once at a variable time point. All women were migraine-free and free of pain medication for more than 12 hours. We collected tear fluid and plasma samples at each visit and measured CGRP levels with an enzyme-linked immunosorbent assay (ELISA, Cusabio Biotech, Wuhan). Data within and among groups were compared using nonparametric procedures.
Results: A total of 180 women (n=30 per group) completed study protocol. In general, CGRP concentrations in tear fluid were 80.5x higher than in plasma (IQR 27.8 – 260.7). During menstruation, women with migraine showed significantly higher CGRP concentrations in both tear fluid and plasma compared to healthy controls [tear fluid: 1.2 ng/ml (IQR 0.4 – 2.5) vs. 0.2 ng/ml (IQR 0.1 – 1.2), p=0.005; plasma: 5.9 pg/ml (IQR 4.4 – 10.8) vs. 4.6 pg/ml (IQR 2.8 – 6.9), p=0.020]. In migraine patients without hormonal contraception, tear fluid CGRP concentrations during menstruation were significantly higher compared to patients under COC (p=0.015 vs. HFI and p=0.029 vs. HI). CGRP levels did not differ between migraine and control groups under COC and during postmenopause.
Conclusion: Sex hormone fluctuations across the female lifespan have an influence on CGRP concentrations in women with migraine.