Migraine and Endometriosis: The FEMININE Study

NCT07519343 | Not Yet Recruiting

• 1 other identifier: FEMININE-2026-01
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Migraine; Endometriosis

Keywords

CGRP

Outcome Measures

Primary Outcomes (1)

• Pattern of serum CGRP levels across menstrual phases

  Serum CGRP levels measured during the periovulatory and perimenstrual phases and compared among females with comorbid migraine and endometriosis, migraine only, and endometriosis only.

  During the first 3 menstrual cycles, up to 6 months if extension is needed

Secondary Outcomes (10)

• Migraine frequency

  Baseline through completion of follow-up, up to 6 months

• Acute medication use

  Baseline through completion of follow-up, up to 6 months

• Migraine-related disability

  Baseline and end of study, up to 6 months

• Menstrually related migraine features

  During follow-up, up to 6 months

• Endometriosis-related quality of life

  Baseline and end of study, up to 6 months

Study Arms (3)

Migraine and Endometriosis (MIG-EDM)

Females with a diagnosis of both migraine (ICHD-3 criteria) and endometriosis (ESHRE criteria)

Migraine Only (MIG-O)

Females with a diagnosis of migraine (ICHD-3 criteria) and no history of endometriosis.

Endometriosis Only (EDM-O)

Females with a diagnosis of endometriosis (ESHRE criteria) and no history of migraine.

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participants of female sex assigned at birth with reproductive potential
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from prospectively maintained clinical databases at Vall d'Hebron University Hospital (Headache Unit and Gynecology Unit) and from outpatient clinics specialized in migraine and endometriosis. The study population consists of adult females of reproductive age with a diagnosis of migraine, endometriosis, or both, who are receiving routine clinical care at a tertiary referral center.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Tietjen GE, Bushnell CD, Herial NA, Utley C, White L, Hafeez F. Endometriosis is associated with prevalence of comorbid conditions in migraine. Headache. 2007 Jul-Aug;47(7):1069-78. doi: 10.1111/j.1526-4610.2007.00784.x.

  PMID: 17635599 BACKGROUND

• Aegidius KL, Zwart JA, Hagen K, Dyb G, Holmen TL, Stovner LJ. Increased headache prevalence in female adolescents and adult women with early menarche. The Head-HUNT Studies. Eur J Neurol. 2011 Feb;18(2):321-328. doi: 10.1111/j.1468-1331.2010.03143.x.

  PMID: 20636369 BACKGROUND

• Miller JA, Missmer SA, Vitonis AF, Sarda V, Laufer MR, DiVasta AD. Prevalence of migraines in adolescents with endometriosis. Fertil Steril. 2018 Apr;109(4):685-690. doi: 10.1016/j.fertnstert.2017.12.016. Epub 2018 Mar 28.

  PMID: 29605402 BACKGROUND

• Selntigia A, Exacoustos C, Ortoleva C, Russo C, Monaco G, Martire FG, Rizzo G, Della-Morte D, Mercuri NB, Albanese M. Correlation between endometriosis and migraine features: Results from a prospective case-control study. Cephalalgia. 2024 Mar;44(3):3331024241235210. doi: 10.1177/03331024241235210.

  PMID: 38436302 BACKGROUND

• Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019 Nov;37(4):631-649. doi: 10.1016/j.ncl.2019.06.001. Epub 2019 Aug 27.

  PMID: 31563224 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders; Endometriosis

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Patricia Pozo-Rosich, Professor

CONTACT

+34 934 89 30 00; patricia.pozo@vallhebron.cat

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 9, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)