Calcitonin gene–related peptide (CGRP) concentrations, instigated by hormonal fluctuations, may explain a higher susceptibility for migraine among women who menstruate, according to findings were published in Neurology.
Women (n=180) with episodic migraine were recruited for this cross-sectional, matched-cohort study at the Charité Universitätsmadizin Berlin in Germany between 2020 and 2022. On days when participants were free from migraine or acute medication use for 12 hours, blood and tear samples were collected.
Patients were stratified into 3 groups: patients with regular a menstrual cycle (RMC; n=30), receiving combined oral contraception (COC; n=30), and post-menopause (PM; n=30). Sample collection depended on menstrual cycle, in which the RMC group gave samples on days 2 and 13 of their cycle, the COC group gave samples on day 4 of the hormone-free interval and between days 7 and 14 of the hormone intake, and the PM group gave 1 sample on a random day. Matched non-migraine cohorts were used as the control group for each menstrual cohort (n=30 per group). The primary outcome of this study was to determine whether menstrual cycle affected CGRP concentrations.
The experimental and matched control RMC, COC, and PM cohorts comprised women aged median 26.00-26.50, 25.00-27.00, and 57.50-58.50 years and they weighed 59.00-63.00, 59.00-62.00, and 70.00-73.50 kg, respectively. Among the migraine groups, symptoms began at 16.75-20.50 years of age, 30.0%-43.3% had aura, they had 4.00-5.80 monthly migraine days, and numeric analogue scale (NAS) score for pain intensity was 7.0-8.0 points.
Intraindividual correlations between CGRP concentrations in plasma (r, 0.809; P <.001) and tear fluid (r, 0.635; P <.001) at both collections among the RCM group and similar plasma (r, 0.797; P <.001) and tear fluid (r, 0.615; P <.001) correlations among the COC group were observed.
Among all participants, women with migraine generally had higher CGRP levels in tear fluid (median, 0.67 vs 0.41 ng/ml; P =.013) but not plasma (median, 5.22 vs 5.95 pg/ml; P =.965) compared with controls, respectively.
The RMC group with migraine had significantly higher CGRP in tear fluid (median, 1.20 vs 0.4 ng/ml; P =.005) and blood plasma (median, 5.95 vs 4.61 pg/ml; P =.020) on day 2 of the cycle compared with controls, respectively. No differences in CGRP levels were observed on day 13 of the cycle.
Compared between migraine groups, the RCM cohort had higher levels of CGRP in tear fluid on day 2 of their cycle compared with the COC group during the hormone-free interval (P =.015) and on days 7-14 of hormone intake (P =.029).
In blood plasma, the RCM group had significantly lower CGRP concentrations on day 2 of their cycle compared with the hormone free interval of the COC group (P =.035) and the PM group (P =.015) and lower levels on day 13 of their cycle compared with the hormone free interval of the COC group (P =.030) and the PM group (P =.013).
“[O]ur data suggests hormone dependent changes in CGRP concentrations in female patients with episodic migraine. The elevated CGRP release from the trigeminovascular system following hormonal fluctuations could help to explain a higher susceptibility for migraine in female people who menstruate,” according to the study authors.
This study may have been biased by not collecting samples within 12 hours of migraine.
Raffaelli B, Storch E, Overeem LH, et al. Sex hormones and calcitonin gene–related peptide in women with migraine: a cross-sectional, matched cohort study. Neurology. 2023;10.1212/WNL.0000000000207114. doi:10.1212/WNL.0000000000207114