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The concentration of calcitonin gene–related peptide is related to the concentrations of endogenous sex hormones in women suffering from episodic migraine

Feb 27, 2023 | Neuroscience

The researchers from Germany conducted this study to investigate possible differences in the concentration of calcitonin gene-related peptide (CGRP) during the menstrual cycle phases between women who suffer from migraines and women without migraines. The results have shown that the concentrations of CGRP in both, plasma and tear fluid, in women suffering from episodic migraine, were related to the concentrations of endogenous sex hormones. 

The etiology of migraine remains unknown, but, it is well known that the neuropeptide CGRP is involved in its pathophysiology. The CGRP is released from the trigeminal afferent nerve fibers during migraine attacks, causing vasodilation and inflammatory response.

The prevalence of migraine is three-fold higher in women than in men. According to the “estrogen withdrawal hypothesis”, the fluctuation of endogenous steroids is involved in the complex pathophysiology of migraine attacks. A decrease in plasma estrogen concentrations may trigger migraine attacks, activating the trigeminal-vascular system and releasing CGRP. The estrogen receptors are highly expressed in CGRP-positive neurons in the trigeminal-vascular system, so, fluctuations in hormonal concentrations can modulate their excitability.  Previous data have demonstrated that women suffering from migraine attacks have significantly elevated plasma concentrations of CGRP.

About the study

The research team investigated a difference in concentration of the CGRP between women with migraine and women without migraine during the phases of the menstrual cycle. They also examined whether a decrease in the concentrations of endogenous sex steroids, caused by oral contraceptives (combining estrogen and progesterone) or menopause, alters the concentration of CGRP.

The study included 180 women who were diagnosed with episodic migraine, and categorized into three distinct groups: 1. women with a regular menstrual cycle, 2. women taking oral contraceptives combining estrogen and progesterone, and 3. postmenopausal women. Three control groups included age-matched women who did not suffer from episodic migraine.

In women with regular menstrual cycles who suffered from migraine, the concentrations of CGRP were significantly higher in both, plasma and tear fluid, during menstruation (a phase of low estrogen levels) in comparison to women without migraine. In addition, in women with regular menstrual cycles who suffered from migraine, the concentration of CGRP was higher only in tear fluid (not in plasma) than in women who suffered from migraine and were taking combined oral contraceptives.

These findings suggest that the relationship between changes in CGRP concentration in plasma and tear fluid and the endogenous sex hormones has been found only in women with regular menstrual cycles who suffered from migraine. 

The authors emphasized that the feasibility of plasma CGRP as a biomarker for migraines remains a matter of debate. However, they stated that analysis of biomaterials that are closer to the trigeminal CGRP source, such as tear fluid, may represent a better and more direct approach. Accordingly, the increased release of CGRP from the trigeminal-vascular system during menstruation could explain the biological predisposition to more frequent, severe, and prolonged migraine attacks during this period.

This article was published in Neurology.

Journal Reference

Raffaelli B. et al. Sex Hormones and Calcitonin Gene-Related Peptide in Women With Migraine: A Cross-sectional, Matched Cohort Study. Neurology. February 22, 2023. (Open Access)  https://n.neurology.org/content/early/2023/02/22/WNL.0000000000207114

 

 

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