{
  "abstract": "Background Accelerated biological ageing has been proposed as a key mechanism influencing disease progression in multiple sclerosis. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, may reflect biological ageing in women and could be associated with disability progression. We aim to evaluate the prognostic implications of AMH levels measured at the first demyelinating event (FDE) suggestive of multiple sclerosis (MS).Methods This retrospective study analysed prospectively collected data from three Spanish neuroimmunology centres (since 1994). It included 365 females aged 20–45 years with serum AMH measured within 2 years of onset. According to AMH tertiles (n, median ng/mL (range)), participants were classified as follows: high (n=121; 4.6 (3.2–17.4)), medium (n=122; 2.1 (1.3–3.2)) and low (n=121; 0.6 (0.01–1.3)). A total of 145 healthy females served as controls. Age-adjusted multivariable linear regression models assessed associations between AMH and baseline clinical, radiological and serum biomarkers. Cox regression models evaluated the risk of Expanded Disability Status Scale 3.0, second relapse, progression independent of relapse activity and relapse-associated worsening.Results At FDE, median (range) age was 32.9 (22.2–44.9) years, follow-up 6.5 years (0.01–29.4) and AMH 2.2 (0.01–17.4); 68% received disease-modifying treatment. AMH levels did not differ between patients and controls and were inversely correlated with chronological age (β −1.21 (95% CI −1.42 to −1.00), p<0.001). After adjustment for chronological age, AMH showed no independent association with clinical, radiological or biomarker measures, or long-term outcomes.Conclusions AMH levels at the time of an FDE suggestive of MS were not associated with baseline activity or long-term outcomes related to relapses or disability. Our findings suggest that the apparent associations between AMH and disease characteristics are largely driven by chronological age, supporting the concept that ovarian reserve primarily reflects biological ageing rather than an independent determinant of MS progression.",
  "authors": [
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Alvaro Cobo-Calvo"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Community of Madrid, Spain"
      ],
      "name": "Juan Pablo Cuello"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain"
      ],
      "name": "Enric Monreal"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain",
        "Neurology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain"
      ],
      "name": "Javier Villacieros-Álvarez"
    },
    {
      "affiliations": [
        "Department of Clinical Biochemistry, Vall d’Hebron University Hospital, Vall d’Hebron University Hospital",
        "Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT), Vall d’Hebron Institut de Recerca",
        "Universitat Autònoma de Barcelona, Barcelona, Spain"
      ],
      "name": "Noelia Díaz-Troyano"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Susana Otero"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Carmen Tur"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Community of Madrid, Spain"
      ],
      "name": "José Manuel García Domínguez"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain"
      ],
      "name": "Lucienne Costa-Frossard"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain"
      ],
      "name": "Susana Sainz de la Maza"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "René Carvajal"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Community of Madrid, Spain"
      ],
      "name": "Carlos José De Miguel Sánchez"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Community of Madrid, Spain"
      ],
      "name": "Haydee Goicochea- Briceño"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Georgina Arrambide"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Community of Madrid, Spain"
      ],
      "name": "María Luisa Martínez-Gines"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Mireia Castillo"
    },
    {
      "affiliations": [
        "Department of Immunology, Hospital Universitario Ramon y Cajal, Madrid, Community of Madrid, Spain"
      ],
      "name": "José Ignacio Fernández Velasco"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Andreu Vilaseca-Jolonch"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Angela Vidal-Jordana"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Helena Ariño"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Luca Bollo"
    },
    {
      "affiliations": [
        "Instituto de investigación Sanitaria del Hospital General Universitario Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain"
      ],
      "name": "Yolanda Higueras"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Joaquín Castilló"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Ingrid Galán"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Luciana Midaglia"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Neus Mongay-Ochoa"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Agustin Pappolla"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Jordi Río"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Breogán Rodríguez-Acevedo"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Ana Zabalza"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Jaume Sastre-Garriga"
    },
    {
      "affiliations": [
        "Instituto de investigación Sanitaria del Hospital General Universitario Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain"
      ],
      "name": "Ariana Meldaña Rivera"
    },
    {
      "affiliations": [
        "Instituto de investigación Sanitaria del Hospital General Universitario Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain"
      ],
      "name": "Irene Ruíz-Pérez"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Hospital General Universitario Gregorio Marañón, Madrid, Spain"
      ],
      "name": "Juan De León-Luis"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Hospital General Universitario Gregorio Marañón, Madrid, Spain"
      ],
      "name": "Virginia Ortega Abad"
    },
    {
      "affiliations": [
        "Department of Immunology, Hospital Universitario Ramon y Cajal, Madrid, Community of Madrid, Spain"
      ],
      "name": "Noelia Villarrubia"
    },
    {
      "affiliations": [
        "Department of Immunology, Hospital Universitario Ramon y Cajal, Madrid, Community of Madrid, Spain"
      ],
      "name": "Alexander Rodero-Romero"
    },
    {
      "affiliations": [
        "Department of Clinical Biochemistry, Hospital Universitario Ramon y Cajal, Madrid, Community of Madrid, Spain"
      ],
      "name": "Ana Gómez Lozano"
    },
    {
      "affiliations": [
        "Department of Clinical Biochemistry, Hospital Universitario Ramon y Cajal, Madrid, Community of Madrid, Spain"
      ],
      "name": "Ignacio Arribas"
    },
    {
      "affiliations": [
        "Department of Clinical Biochemistry, Hospital Universitario Ramon y Cajal, Madrid, Community of Madrid, Spain"
      ],
      "name": "Ana Maria García"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Manuel Comabella"
    },
    {
      "affiliations": [
        "Section of Neuroradiology, Department of Radiology, Vall d’Hebron Institut de Recerca, Vall d’Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Barcelona, Spain"
      ],
      "name": "Álex Rovira"
    },
    {
      "affiliations": [
        "Department of Clinical Biochemistry, Vall d’Hebron University Hospital, Vall d’Hebron University Hospital",
        "Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT), Vall d’Hebron Institut de Recerca",
        "Universitat Autònoma de Barcelona, Barcelona, Spain"
      ],
      "name": "Pilar Reimundo"
    },
    {
      "affiliations": [
        "Unit of Gynecologic Oncology, Department of Gynecology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Melchor Carbonell"
    },
    {
      "affiliations": [
        "Unit of Gynecologic Oncology, Department of Gynecology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Julio Herrero"
    },
    {
      "affiliations": [
        "Unit of Gynecologic Oncology, Department of Gynecology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Elena Carreras"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Xavier Montalban"
    },
    {
      "affiliations": [
        "Department of Clinical Biochemistry, Vall d’Hebron University Hospital, Vall d’Hebron University Hospital",
        "Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT), Vall d’Hebron Institut de Recerca",
        "Universitat Autònoma de Barcelona, Barcelona, Spain"
      ],
      "name": "Roser Ferrer"
    },
    {
      "affiliations": [
        "Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain"
      ],
      "name": "M Luisa Villar"
    },
    {
      "affiliations": [
        "Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Mar Tintore"
    }
  ],
  "title": "Chronological ageing and ovarian reserve in MS: insights from anti-Müllerian hormone and disability progression",
  "uid": "aefeb8f3-98c8-5504-9c57-de1364ec8d50"
}