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. 2024 Jun 11;25(1):98.
doi: 10.1186/s10194-024-01804-4.

PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study

Elisabeth Storch  1 , Lucas H Overeem  1 , Maria Terhart  1 , Mira P Fitzek  1 , Kristin S Lange  1   2 , Uwe Reuter  1   3 , Bianca Raffaelli  4   5
Affiliations

PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study

Elisabeth Storch et al. J Headache Pain. .

Erratum in

Abstract

Background: Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology.

Methods: This analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7-14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit.

Results: The study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 - 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 - 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 - 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 - 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval.

Conclusion: Systemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.

Keywords: Menstruation; Migraine; PACAP-38; Sex hormones; Women’s health.

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Conflict of interest statement

BR is a Guest Editor of the collection Gender-Specific Aspects of Headache and is a member of the Editorial Board of The Journal of Headache and Pain. BR was not involved in the journal’s peer review process of, or decisions related to, this manuscript. The rest of the authors have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Study design with participants and scheduled study visits (created with Canva Inc.) Schematic representation of hormone levels during the menstrual cycle and under treatment with a combined contraceptive, adapted from [10, 31]
Fig. 2
Fig. 2
PACAP-38 concentrations in plasma in patients with migraine (M) and healthy controls (C) with a regular menstrual cycle (RMC)
Fig. 3
Fig. 3
PACAP-38 in plasma in patients with Migraine (M) with a regular menstrual cycle (RMC) vs. with a combined oral contraceptive (COC). Visit 1 = day 2 ± 2 of menstrual cycle for M-RMC and day 4 ± 2 of HFI for M-COC; Visit 2 = day 13 ± 2 of menstrual cycle for M-RMC and days 7–14 of HI for M-COC
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