Migraine and Endometriosis: The FEMININE Study

Официальное название

Investigating the inFluence of EndoMetriosis IN migraINE - FEMININE Study

Обзор

Migraine and endometriosis are common conditions that mainly affect females of reproductive age. Both can cause significant pain and have a strong impact on the quality of life. Increasing evidence suggests that these two conditions often occur together, and that females who have both may experience more severe symptoms than those with only one of them. However, the reasons why migraine and endometriosis are linked are still not well understood. Some biological factors may help explain this connection. One of them is a molecule called calcitonin gene-related peptide (CGRP), which plays an important role in migraine and may also be involved in pain and inflammation in endometriosis. In addition, hormonal changes during the menstrual cycle, especially fluctuations in estrogen levels, may influence symptoms in both conditions. Genetic and epigenetic factors may also contribute to this association. The main hypothesis of this study is that females who have both migraine and endometriosis have a distinct clinical and biological profile compared to females who have only migraine or only endometriosis. In particular, it is expected that differences will be observed in CGRP levels and hormonal patterns across the menstrual cycle. The FEMININE study is a prospective observational study that will follow females over several menstrual cycles. It will include three groups: females with both migraine and endometriosis, females with migraine only, and females with endometriosis only. Participants will record their symptoms in diaries and will provide blood samples at specific times of the menstrual cycle. The main goal of the study is to compare CGRP levels between groups. Additional goals include describing differences in symptoms, menstrual-related migraine, hormonal levels, and selected genetic and epigenetic markers. By improving the understanding of how migraine and endometriosis are related, this study aims to support better diagnosis and more personalized care for females affected by these conditions.

Первичные конечные точки

• Pattern of serum CGRP levels across menstrual phases [Срок оценки: During the first 3 menstrual cycles, up to 6 months if extension is needed]

Вторичные конечные точки (10)

• Migraine frequency [Срок оценки: Baseline through completion of follow-up, up to 6 months]
• Acute medication use [Срок оценки: Baseline through completion of follow-up, up to 6 months]
• Migraine-related disability [Срок оценки: Baseline and end of study, up to 6 months]
• Menstrually related migraine features [Срок оценки: During follow-up, up to 6 months]
• Endometriosis-related quality of life [Срок оценки: Baseline and end of study, up to 6 months]
• Endometriosis-related pain symptoms [Срок оценки: Baseline through completion of follow-up, up to 6 months]
• Serum sex hormone levels [Срок оценки: During predefined menstrual phases across follow-up, up to 6 months]
• Association between CGRP and hormonal levels [Срок оценки: During follow-up, up to 6 months]
• Genetic markers [Срок оценки: Baseline]
• Epigenetic markers [Срок оценки: Baseline]

Критерии участия

Критерии включения

• Adult females (≥18 years old).
• Diagnosis of migraine according to ICHD-3 criteria confirmed by a headache specialist (for MIG-O and MIG-EDM groups).
• Confirmed diagnosis of endometriosis based on clinical symptoms and imaging or surgical criteria according to ESHRE guidelines (for EDM-O and MIG-EDM groups).
• Signed informed consent.

Критерии исключения

• Individuals diagnosed with secondary headache according to the ICHD-3.
• Individuals with a severe disease (e.g., major psychiatric disorder, severe cardiovascular conditions).
• History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months.
• Pregnant or breastfeeding females.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Испания · 1 центр

• Vall d'Hebron University Hospital — Barcelona

Публикации

• Fattori V, Zaninelli TH, Rasquel-Oliveira FS, Heintz OK, Jain A, Sun L, Seshan ML, Peterse D, Lindholm AE, Anchan RM, Verri WA Jr, Rogers MS. Nociceptor-to-macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice. Sci Transl Med. 2024 Nov 6;16(772):eadk8230. doi: 10.1126/scitranslmed.adk8230. Epub 2024 Nov 6. PMID 39504351
• Pasquini B, Seravalli V, Vannuccini S, La Torre F, Geppetti P, Iannone L, Benemei S, Petraglia F. Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhoea. Reprod Biomed Online. 2023 Jul;47(1):71-76. doi: 10.1016/j.rbmo.2023.03.020. Epub 2023 Apr 7. PMID 37202318
• Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P. Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril. 2011 Mar 1;95(3):895-9. doi: 10.1016/j.fertnstert.2010.11.037. Epub 2010 Dec 10. PMID 21145540
• Raffaelli B, Overeem LH, Mecklenburg J, Hofacker MD, Knoth H, Nowak CP, Neeb L, Ebert AD, Sehouli J, Mechsner S, Reuter U. Plasma calcitonin gene-related peptide (CGRP) in migraine and endometriosis during the menstrual cycle. Ann Clin Transl Neurol. 2021 Jun;8(6):1251-1259. doi: 10.1002/acn3.51360. Epub 2021 May 2. PMID 33934575
• Yang MH, Wang PH, Wang SJ, Sun WZ, Oyang YJ, Fuh JL. Women with endometriosis are more likely to suffer from migraines: a population-based study. PLoS One. 2012;7(3):e33941. doi: 10.1371/journal.pone.0033941. Epub 2012 Mar 19. PMID 22442736
• Tietjen GE, Conway A, Utley C, Gunning WT, Herial NA. Migraine is associated with menorrhagia and endometriosis. Headache. 2006 Mar;46(3):422-8. doi: 10.1111/j.1526-4610.2006.00290.x. PMID 16618258
• Lee GJ, Hode V, Georgieva T, Rau J, Dodick DW, Schwedt TJ, Neugebauer V, Porreca F, Navratilova E. Prolactin-induced sensitization of trigeminal nociceptors promotes migraine co-morbidity in endometriosis. Cephalalgia. 2025 Jan;45(1):3331024241313378. doi: 10.1177/03331024241313378. PMID 39814523
• Wu Y, Wang H, Chen S, Lin Y, Xie X, Zhong G, Zhang Q. Migraine Is More Prevalent in Advanced-Stage Endometriosis, Especially When Co-Occuring with Adenomoysis. Front Endocrinol (Lausanne). 2022 Jan 24;12:814474. doi: 10.3389/fendo.2021.814474. eCollection 2021. PMID 35140688

Идентификаторы

NCT: NCT07519343 · FEMININE-2026-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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