This study from German scientists investigated a difference in the level of calcitonin gene–related peptide (CGRP) during the phases of the menstrual cycle among women who have migraines and women who don’t have migraines. The results have shown that the level of calcitonin gene–related peptide (CGRP) in plasma and tear fluid is related to the endogenous sex steroid levels in women with episodic migraine.
The etiology of migraine is unknown, but, it is well known that neuropeptide CGRP is involved in its pathophysiology. During a migraine attack, CGRP is released from trigeminal afferent nerve fibers, causing vasodilatation and an inflammatory response. People with migraine attacks have a significant increase in plasma levels of CGRP.
The prevalence of migraine is three times higher in females compared to males. Fluctuations in sex hormones play a crucial role in the pathophysiology of the disease. According to “estrogen-withdrawal-hypothesis”, a decrease in plasma estrogen concentrations may trigger migraine attacks.
About the study
The research team examined whether women who have migraine have a higher concentration of the CGRP compared to women who don’t have migraines during the phases of the menstrual cycle. They also investigated whether low levels of endogenous sex steroids due to oral contraceptives (combining estrogen and progesterone) or during menopause change the concentration of CGRP.
This cross-sectional study of matched cohorts included 180 women. The study cohort included three groups of women suffering of episodic migraine: 1. Women with regular menstrual cycle, 2. Women on oral contraceptives combining estrogen and progesterone, 3. Postmenopausal women. Three control groups consisted of age-matched female participants who do not have episodic migraine.
The authors emphasized complex pathophysiological mechanisms behind a migraine attack caused by fluctuation of endogenous steroids. Preclinical data have demonstrated that fluctuation of endogenous steroids can activate the trigeminovascular system and then release CGRP. Estrogen receptors are highly expressed in CGRP-positive neurons in the trigemino-vascular system, and hormonal fluctuations can modulate their excitability. Some recent studies suggest that CGRP is released in phases of low estrogen levels.
The findings showed that women with migraine and regular menstrual cycle had significantly higher levels of the CGRP in plasma and tear fluid during menstruation (phase of low estrogen levels) than women without migraine. In addition, the women with migraine and a regular menstrual cycle had significantly higher CGRP levels in the tear fluid, but not in the plasma during menstruation than women with migraine on combined oral contraception.
These results demonstrated that variation in CGRP level in plasma and tear fluid is related to the endogenous sex steroid levels and presence of migraine in women suffering from episodic migraine.
The authors stated that a feasibility of plasma CGRP as a biomarker of migraine is still under discussion. In contrast, biomaterials closer to the trigeminal CGRP source such as tear fluid may represent a more direct and appropriate approach. The increase in CGRP release from the trigemino-vascular system during menstruation may help to explain the biological predisposition to more frequent, severe, and long-term migraine attacks during this period.
This article was published in the scientific journal Neurology. 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