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Observational Study
. 2021 Jun;8(6):1251-1259.
doi: 10.1002/acn3.51360. Epub 2021 May 2.

Plasma calcitonin gene-related peptide (CGRP) in migraine and endometriosis during the menstrual cycle

Bianca Raffaelli  1   2 , Lucas Hendrik Overeem  1 , Jasper Mecklenburg  1 , Maxi Dana Hofacker  1 , Henriette Knoth  1 , Claus Peter Nowak  3 , Lars Neeb  1 , Andreas Dietmar Ebert  4 , Jalid Sehouli  5 , Sylvia Mechsner  5 , Uwe Reuter  1
Affiliations
Observational Study

Plasma calcitonin gene-related peptide (CGRP) in migraine and endometriosis during the menstrual cycle

Bianca Raffaelli et al. Ann Clin Transl Neurol. 2021 Jun.

Abstract

Objective: Migraine, endometriosis, and the comorbidity of both are frequent pain disorders of special relevance for women. The neuropeptide calcitonin gene-related peptide (CGRP) is critically involved in migraine, and circumstantial evidence suggests a role in endometriosis. We assessed CGRP levels at different times of menstrual cycle in four groups: healthy women, women with migraine or endometriosis and with the comorbidity of both.

Methods: Women with episodic migraine and women with a histologically confirmed endometriosis were recruited from specialized centers. For CGRP determination with a commercial enzyme immunoassay kit, cubital vein blood samples were collected on menstrual cycle day 2 ± 2 (during menstruation) and on day 15 ± 2 (periovulatory period). The primary endpoint of the study was the absolute difference of CGRP plasma levels between the menstrual and the periovulatory phase of all study groups. Groups were compared using nonparametric test procedures.

Results: A total of 124 women were included in the study. The change of CGRP plasma levels between menstruation and the periovulatory period was different between groups (p = 0.007). Women with comorbid migraine and endometriosis showed an increase of CGRP in the menstrual phase of +6.32 (interquartile range, IQR -3.64-13.60) compared to the periovulatory time, while healthy controls had a decrease of -10.14 (-22.54-0.91, p = 0.004). CGRP levels were different in the periovulatory phase among groups (p = 0.008), with highest values in healthy controls.

Interpretation: CGRP levels change significantly during the menstrual cycle. Different patterns in women with the comorbidity point to a deviant regulation of CGRP release.

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Conflict of interest statement

BR reports grants from Novartis, during the conduct of the study, personal fees from Novartis, Teva, and Allergan, all outside the submitted work. LHO has nothing to disclose. JM reports personal fees from Novartis, outside the submitted work. MDH has nothing to disclose. HK has nothing to disclose. CPN has nothing to disclose. LN reports personal fees from Novartis, Allergan, TEVA, BIAL, Hormosan, and Eli Lilly, all outside the submitted work. ADE has nothing to disclose. JS reports personal fees from Roche, grants and personal fees from Eli Lilly, personal fees from Johnson and Johnson, all outside the submitted work. SM has nothing to disclose. UR reports personal fees from Abbvie, Allergan, Amgen, Eli Lilly, Medscape, Novartis, StreaMedUp, and Teva; institutional fees from Amgen, Eli Lilly, Novartis, Teva, and Alder, and grants from Novartis, all outside the submitted work.

Figures

Figure 1
Figure 1
Flowchart of participant selection.
Figure 2
Figure 2
Endometriosis Health Profile‐30 (EHP‐30) scores (mean ± standard error) in five domains in women with endometriosis (dark gray bars) and women with migraine and endometriosis (light gray bars). Higher scores indicate a worse perceived endometriosis‐related health status in the respective domain.
Figure 3
Figure 3
Boxplot and jitter plot for calcitonin gene‐related peptide (CGRP) plasma concentrations at the perimenstrual (PM) and periovulatory (PO) visit for each study group. The boxes are drawn from the 25% to 75% quartiles, the horizontal line represents the median. The whiskers are drawn out to 1.5*interquartile range. The dots represent single data points. a p = 0.078 between PM and PO. *p = 0.003 between PM and PO. **p = 0.004 for the changes from PM and PO between groups.
See this image and copyright information in PMC

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