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Research paper
Impact of natural menopause on multiple sclerosis: a multicentre study
  1. Damiano Baroncini1,
  2. Pietro Osvaldo Annovazzi2,
  3. Nicola De Rossi3,
  4. Giulia Mallucci4,
  5. Valentina Torri Clerici5,
  6. Simone Tonietti6,
  7. Vittorio Mantero7,
  8. Maria Teresa Ferrò8,
  9. Maria Josè Messina9,
  10. Valeria Barcella10,
  11. Loredana La Mantia11,
  12. Marco Ronzoni12,
  13. Caterina Barrilà12,
  14. Raffaella Clerici13,
  15. Emanuela Laura Susani14,
  16. Maria Letizia Fusco15,
  17. Luca Chiveri16,
  18. Lucia Abate17,
  19. Ottavia Ferraro18,
  20. Ruggero Capra19,
  21. Elena Colombo20,
  22. Paolo Confalonieri21,
  23. Mauro Zaffaroni22
  1. 1 Multiple Sclerosis Centre, Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
  2. 2 Multiple Sclerosis Centre, Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
  3. 3 Multiple Sclerosis Center, Spedali Civili di Brescia, presidio di Montichiari, Brescia, Italy
  4. 4 Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy
  5. 5 Multiple Sclerosis Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
  6. 6 Department of Neurology, ASST Santi Paolo e Carlo - PO San Carlo Borromeo, Milan, Italy
  7. 7 Department of Neurology, ASST Lecco, Lecco, Italy
  8. 8 Neuroimmunology, Multiple Sclerosis Center, Neurological Department, Ospedale Maggiore, Crema, Italy
  9. 9 Department of Neurology, IRCCS Policlinico San Donato, San Donato Milanese (MI), Milan, Italy
  10. 10 USS Malattie Autoimmuni, ASST Papa Giovanni XXIII, Bergamo, Italy
  11. 11 Neurorehabilitation Unit, Fondazione IRCSS Santa Maria Nascente Don Gnocchi, Milano, Italy
  12. 12 Department of Neurology, ASST Rhodense, Ospedale “G. Salvini” - Garbagnate, Garbagnate milanese (MI), Italy
  13. 13 Neurology Unit, Como Hospital, Como, Italy
  14. 14 Neurology and Neuroscience Department, ASST Grande ospedale metropolitano Niguarda, Milano, Italy
  15. 15 Department of Neurology, ASST Monza, Ospedale San Gerardo, Clinica Neurologica, Milan, Italy
  16. 16 Dipartimento di neuroscienze, ASST ovest Milanese, ospedale di Legnano, Legnano, Italy
  17. 17 Neurological Unit, ASST Valtellina e Altolario, Sondrio, Italy
  18. 18 Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
  19. 19 Multiple Sclerosis Centre, Spedali Civili of Brescia, Presidio di Montichiari, Brescia, Italy
  20. 20 Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy
  21. 21 Multiple Sclerosis Center, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy
  22. 22 Multiple Sclerosis Centre, Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
  1. Correspondence to Dr Damiano Baroncini, Gallarate Hospital, ASST Valle Olona, Multiple Sclerosis Centre, Gallarate 21013, Italy; damianobaroncini{at}


Objective To study the effect of natural menopause on multiple sclerosis clinical course.

Methods This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.

Results 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).

Conclusion Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

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  • Contributors DB designed the study, which was reviewed and then approved by all the authors through collegial meetings. POA organised the meetings and the multicentre working group. All the authors enrolled the patients in each centre, collected the data and entered them into a database. DB did the statistical analyses, that were revised by POA, GM and OF. DB drafted the work, that was first revised by MZ and POA, then by all authors. All the authors gave the final approval of the version to be published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests DB received travel grants from Genzyme, Merck and Biogen for participation at national and international congresses; he received speaking honoraria from Sanofi and Novartis, and personal compensation from Almirall for scientific publication. POA received honoraria for lecturing and participation in advisory boards, and/or travel expenses for attending congresses and meetings from Merck, Biogen, Teva, Sanofi- Genzyme, Mylan, Almirall, Roche and Novartis. NDR received speaker honoraria from Biogen Idec, Genzyme, Novartis, Sanofi-Aventis; received funding for participation in advisory board to Novartis and Genzyme-Sanofi and for traveling to scientific meetings from Biogen Idec, teva, Sanofi-Genzyme, Roche, Almirall and NovartisGiulia Mallucci received support to travel to scientific meetings from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis, Teva; received speaker honoraria from Biogen Idec and served on the scientific advisory board for Biogen, Genzyme and Merck SeronoValentina Torri Clerici acted as an Advisory Board member of Novartis and Merck-Serono, received funding for travelling and honoraria for speaking or writing from Teva, Biogen, Genzyme, Merk-Serono and Almirall. She received support for research project by Almirall. Simone Tonietti received honoraria for lecturing from Teva and Sanofi-Genzime, for writing from Teva, for participation in advisory boards from Merck and Biogen and for travel expenses for attending congresses and meetings from Merck, Biogen, Teva, Sanofi-Genzyme and Novartis. MJM received funding for travelling and honoraria for speaking or writing from Genzyme. MR received travel grants for congresses participation from Biogen, Genzyme, Novartis e Merck. He received honoraria for conferences organisation from Biogen. He received honoraria from Merck, Novartis, Biogen for advisory boards participation. VB received speaking honoraria and/or consultant fees from Biogen Idec, Merck Serono, Bayer, Sanofi-Genzyme, Novartis. Vittorio Mantero received honoraria for participation to advisory boards and/or travel expenses for attending congresses and meetings from Merck, Biogen, Teva, Sanofi-Genzyme, Roche and Novartis. PC was a board member of Biogen Idec, received travel grants from Sanofi, Biogen and Merck Serono. RC was consulting fees from Biogen, Teva, Genzyme, Merck Serono, and Novartis. Mauro Zaffaroni received honoraria for lecturing or participation in advisory boards, and financial support for attending congresses from Almirall, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva. Emanuela Susani, Maria Letizia Fusco, Caterina Barrilà, Luca Chiveri, Loredana La Mantia, Maria Teresa Ferrò, Raffaella Clerici, Ottavia Ferraro, Elena Colombo and Lucia Abate have nothing to disclose.

  • Patient consent for publication Not required.

  • Ethics approval Insubria Ethic Committee Approval number 1525 of 14 November 2018.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.

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