. 2025 Sep 4:16:1649718.

doi: 10.3389/fneur.2025.1649718. eCollection 2025.

Sex differences in the clinical features of 2,841 patients with migraine: a post-hoc, multicenter, cross-sectional study

Marina Romozzi^#^{1

2}, Luigi Francesco Iannone^#^{3

4}, Marcello Silvestro⁵, Giulia Paparella^{6

7}, Stefania Scannicchio⁸, Stefania Battistini⁸, Raffaele Ornello⁹, Simona Sacco⁹, Federico De Santis⁹, Innocenzo Rainero¹⁰, Andrea Marcinnò¹⁰, Gabriele Sebastianelli¹¹, Chiara Abagnale¹¹, Paola Sarchielli¹², Ilenia Corbelli¹², Gloria Vaghi^{13

14}, Roberto De Icco^{13

14}, Grazia Sances¹⁴, Cristina Tassorelli^{13

14}, Simona Guerzoni², Flavia Lo Castro², Antonio Granato¹⁵, Luca Bartole¹⁵, Francesco De Cesaris¹⁶, Andrea Burgalassi¹⁶, Giorgio Dalla Volta¹⁷, Matteo Cortinovis¹⁷, Martino Gentile¹⁸, Paolo Calabresi^{1

2}, Maria Pia Prudenzano¹⁸, Antonio Russo⁵, Marina de Tommaso^{6

7}; RiCe study group

Collaborators, Affiliations

Collaborators

RiCe study group:
Giovanni Rinaldi, Marco Alabiso, Giulia Settembrini, Annalisa Di Dio, Giulia Vigani, Adriana Fallacara, Silvia Grimaldi, Cinzia Tamborino, Gianni Di Fonzo

Affiliations

¹ Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.
² Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
³ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Digital and Predictive Medicine, Pharmacology, Clinical Metabolic Toxicology-Headache Center and Drug Abuse, Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU Policlinico, Modena, Italy.
⁵ Headache Centre, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
⁶ Neurophysiopathology Unit, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
⁷ IRCCS Neuromed, Pozzilli, Italy.
⁸ Neurology and Clinical Neurophysiology Unit, Headache Center, Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
⁹ Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
¹⁰ Headache Center, Department of Neuroscience, University of Torino, Torino, Italy.
¹¹ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Latina, Italy.
¹² Headache Center, Neurologic Clinic, University of Perugia, Perugia, Italy.
¹³ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
¹⁴ Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy.
¹⁵ Clinical Unit of Neurology, Headache Centre, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
¹⁶ Headache Center and Clinical Pharmacology, AOU Careggi, Florence, Italy.
¹⁷ Headache Center of Neurological Unit of Istituto Clinico Città di Brescia, Brescia, Italy.
¹⁸ Headache Center Neurological Clinica "L. Amaducci", AOUC Policlinic, Bari, Italy.

^# Contributed equally.

PMID: 40979206
PMCID: PMC12445143
DOI: 10.3389/fneur.2025.1649718

Sex differences in the clinical features of 2,841 patients with migraine: a post-hoc, multicenter, cross-sectional study

Marina Romozzi et al. Front Neurol. 2025.

. 2025 Sep 4:16:1649718.

doi: 10.3389/fneur.2025.1649718. eCollection 2025.

Authors

Collaborators

RiCe study group:
Giovanni Rinaldi, Marco Alabiso, Giulia Settembrini, Annalisa Di Dio, Giulia Vigani, Adriana Fallacara, Silvia Grimaldi, Cinzia Tamborino, Gianni Di Fonzo

Affiliations

¹ Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.
² Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
³ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Digital and Predictive Medicine, Pharmacology, Clinical Metabolic Toxicology-Headache Center and Drug Abuse, Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU Policlinico, Modena, Italy.
⁵ Headache Centre, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
⁶ Neurophysiopathology Unit, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
⁷ IRCCS Neuromed, Pozzilli, Italy.
⁸ Neurology and Clinical Neurophysiology Unit, Headache Center, Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
⁹ Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
¹⁰ Headache Center, Department of Neuroscience, University of Torino, Torino, Italy.
¹¹ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Latina, Italy.
¹² Headache Center, Neurologic Clinic, University of Perugia, Perugia, Italy.
¹³ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
¹⁴ Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy.
¹⁵ Clinical Unit of Neurology, Headache Centre, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
¹⁶ Headache Center and Clinical Pharmacology, AOU Careggi, Florence, Italy.
¹⁷ Headache Center of Neurological Unit of Istituto Clinico Città di Brescia, Brescia, Italy.
¹⁸ Headache Center Neurological Clinica "L. Amaducci", AOUC Policlinic, Bari, Italy.

^# Contributed equally.

PMID: 40979206
PMCID: PMC12445143
DOI: 10.3389/fneur.2025.1649718

Abstract

Background: Migraine occurs two to three times more frequently in women than in men, exhibiting different clinical characteristics in both sexes. The present study aims to investigate further and extend the findings of sex-specific migraine phenotypes in a large cohort of subjects with migraine enrolled in the "Italian Headache Registry" (RICe).

Methods: This is a post-hoc analysis of prospectively collected data including subjects with episodic (EM) and chronic (CM) migraine, with or without medication-overuse headache (MOH), registered in the RICe database by 24 Italian headache centers. Migraine demographic and clinical characteristics were recorded, including quality and intensity of pain, pain localization at onset, concomitant symptoms, and monthly headache days (MHD).

Results: We included 2,841 migraine subjects (80.0% women; mean age: 45.7 ± 14.3 years; mean MHDs 12.3 ± 9). Among them, 2,087 subjects had EM (73.5%), 754 (26.5%) had CM, and 273 (36.2%) had MOH. When considering individuals with EM and CM as a whole group, women reported higher pain intensity compared to men (NRS scale women [mean 7.6 ± 1.7] vs. men [7.0 ± 2.1], p = 0.006). This difference was also confirmed when comparing intensity categories (severe, moderate/severe, and moderate/mild) (p = 0.020). Moderate/mild attacks occurred more frequently in men than in women (14.9 vs. 7.7%, p = 0.0014). Furthermore, women reported more frequent migraine-associated symptoms such as photophobia/phonophobia (women: 72.7% vs. men: 62.3%, p = 0.006) and nausea/vomiting (women: 44.3% vs. men: 36.0%, p = 0.006). No sex differences were reported in terms of MHDs (p = 0.571) or baseline diagnoses (EM vs. CM, p = 0.269). Focusing on EM individuals, significant sex differences emerged in the summarized intensity categories (p = 0.012), as well as in the percentage of concomitant symptoms, which women more frequently reported.

Conclusion: Women with EM or CM have higher pain intensity and more frequent concomitant migraine symptoms when compared to men. No sex-related differences were found in the frequency of MOH.

Keywords: associated symptoms; gender; headache intensity; migraine; sex.

Copyright © 2025 Romozzi, Iannone, Silvestro, Paparella, Scannicchio, Battistini, Ornello, Sacco, De Santis, Rainero, Marcinnò, Sebastianelli, Abagnale, Sarchielli, Corbelli, Vaghi, De Icco, Sances, Tassorelli, Guerzoni, Castro, Granato, Bartole, De Cesaris, Burgalassi, Volta, Cortinovis, Gentile, Calabresi, Prudenzano, Russo, de Tommaso and the RiCe study group.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

**Figure 2**
Pain features **(A)**, accompanying symptoms **(B)**, and pain intensity in the overall population **(C)**. Percentages are calculated on the total number of males or females, respectively. Values in bold are statistically significant.

**Figure 3**
Pain features **(A)**, accompanying symptoms **(B)**, and pain intensity in subjects with episodic migraine **(C)**. Percentages are calculated on the total number of males or females, respectively. Values in bold are statistically significant.

**Figure 4**
Pain features **(A)**, accompanying symptoms **(B)**, and pain intensity in subjects with chronic migraine **(C)**. Percentages are calculated on the total number of males or females, respectively. Values in bold are statistically significant.

See this image and copyright information in PMC

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Sex differences in the clinical features of 2,841 patients with migraine: a post-hoc, multicenter, cross-sectional study

Collaborators

Affiliations

Sex differences in the clinical features of 2,841 patients with migraine: a post-hoc, multicenter, cross-sectional study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources