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Abstract
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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Footnotes
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.