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

Marina Romozzi¹Luigi Francesco Iannone²Marcello Silvestro³Giulia Paparella⁴Stefania Scannicchio⁵Stefania Battistini⁵Raffaele Ornello⁶Simona Sacco⁶Federico De Santis⁶Innocenzo RAINERO⁷Andrea Marcinnò⁷Gabriele Sebastianelli⁸Chiara Abagnale⁸Paola Sarchielli⁹Ilenia Corbelli⁹Gloria Vaghi¹⁰Roberto De Icco¹⁰GRAZIA SANCES¹⁰Cristina Tassorelli¹⁰Simona Guerzoni¹¹Flavia Lo Castro¹¹ANTONIO GRANATO¹²Luca Bartole¹²Francesco De Cesaris¹³Andrea Burgalassi¹⁴Giorgio Dalla Volta¹⁵Matteo Cortinovis¹⁵Martino Gentile⁴Paolo Calabresi¹⁶Addolorata Maria Pia Prudenzano⁴Antonio Russo^3*MARINA DE TOMMASO⁴

• ¹Unit of Neurology, Department of Aging, Neurological, Orthopedic and Head and Neck Sciences, Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
• ²Universita degli Studi di Modena e Reggio Emilia, Modena, Italy
• ³Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
• ⁴Universita degli Studi di Bari Aldo Moro, Bari, Italy
• ⁵Universita degli Studi di Siena, Siena, Italy
• ⁶Universita degli Studi dell'Aquila - Polo Coppito, L'Aquila, Italy
• ⁷Universita degli Studi di Torino, Turin, Italy
• ⁸Universita degli Studi di Roma La Sapienza, Rome, Italy
• ⁹Universita degli Studi di Perugia, Perugia, Italy
• ¹⁰Universita di Pavia, Pavia, Italy
• ¹¹Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
• ¹²Universita degli Studi di Trieste, Trieste, Italy
• ¹³Universita degli Studi di Firenze, Florence, Italy
• ¹⁴Azienda Ospedaliero Universitaria Careggi, Florence, Italy
• ¹⁵Universita degli Studi di Brescia, Brescia, Italy
• ¹⁶Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

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.