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Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis

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Female gender and hormones have been associated with disease activity in multiple sclerosis (MS). We investigated age at menarche, use of oral contraceptives and pregnancy in relation to progression of disability in relapsing onset and progressive onset MS. We conducted a cross-sectional survey among individuals with MS, registered by the Flemish MS Society in Belgium. A time-to-event analysis and Cox proportional hazard regression were performed with time to Expanded Disability Status Score (EDSS) of 6 (requires a cane) as outcome measure. Hazard ratios for the time from onset and the time from birth were adjusted for age at onset and immunomodulatory treatment. Data on 973 women with definite MS were collected. In the relapsing onset group, women with at least two pregnancies had a reduced risk to reach EDSS 6 compared with nulliparous women. In the progressive onset group, later age at menarche was associated with a reduced risk to reach EDSS 6, whereas oral contraceptive use was associated with a higher risk of reaching EDSS 6. Our study corroborates the association of pregnancies with a reduced progression of disability in relapsing onset MS. In progressive onset MS, a slower progression was found in women with a later onset of menarche and a more rapid progression occurred when women reported the use of oral contraceptives.

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  1. Alonso A, Hernan MA (2008) Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 71(2):129–135. doi:10.1212/01.wnl.0000316802.35974.34

    Article  PubMed  Google Scholar 

  2. Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, Ebers GC (2006) Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 5(11):932–936. doi:10.1016/S1474-4422(06)70581-6

    Article  PubMed  Google Scholar 

  3. Ramagopalan SV, Valdar W, Criscuoli M, DeLuca GC, Dyment DA, Orton SM, Yee IM, Ebers GC, Sadovnick AD (2009) Age of puberty and the risk of multiple sclerosis: a population based study. Eur J Neurol 16(3):342–347. doi:10.1111/j.1468-1331.2008.02431.x

    Article  PubMed  CAS  Google Scholar 

  4. Sloka JS, Pryse-Phillips WE, Stefanelli M (2006) The relation between menarche and the age of first symptoms in a multiple sclerosis cohort. Mult Scler 12(3):333–339

    Article  PubMed  CAS  Google Scholar 

  5. Holmqvist P, Wallberg M, Hammar M, Landtblom AM, Brynhildsen J (2006) Symptoms of multiple sclerosis in women in relation to sex steroid exposure. Maturitas 54(2):149–153. doi:10.1016/j.maturitas.2005.10.003

    Article  PubMed  CAS  Google Scholar 

  6. Poser S, Raun NE, Wikstrom J, Poser W (1979) Pregnancy, oral contraceptives and multiple sclerosis. Acta Neurol Scand 59(2–3):108–118

    PubMed  CAS  Google Scholar 

  7. Holmqvist P, Hammar M, Landtblom AM, Brynhildsen J (2010) Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis. Fertil Steril 10.1016/j.fertnstert.2010.06.045

  8. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T (1998) Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple sclerosis group. N Engl J Med 339(5):285–291. doi:10.1056/NEJM199807303390501

    Article  PubMed  CAS  Google Scholar 

  9. Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR (2002) Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 52(4):421–428. doi:10.1002/ana.10301

    Article  PubMed  CAS  Google Scholar 

  10. Runmarker B, Andersen O (1995) Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis. Brain 118(Pt 1):253–261

    Article  PubMed  Google Scholar 

  11. D’Hooghe MB, Nagels G, Uitdehaag BM (2010) Long-term effects of childbirth in MS. J Neurol Neurosurg Psychiatry 81(1):38–41. doi:10.1136/jnnp.2008.163816

    Article  PubMed  Google Scholar 

  12. Koch M, Uyttenboogaart M, Heersema D, Steen C, De Keyser J (2009) Parity and secondary progression in multiple sclerosis. J Neurol Neurosurg Psychiatry 80(6):676–678. doi:10.1136/jnnp.2008.160911

    Article  PubMed  CAS  Google Scholar 

  13. Lisak RP (2007) Neurodegeneration in multiple sclerosis: defining the problem. Neurology 68(22 Suppl 3):S5–12. doi:10.1212/ (discussion S43-54)

    Google Scholar 

  14. Wilkins A, Scolding N (2008) Protecting axons in multiple sclerosis. Mult Scler 14(8):1013–1025. doi:10.1177/1352458508091370

    Article  PubMed  CAS  Google Scholar 

  15. Thompson AJ, Kermode AG, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, McDonald WI (1990) Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study. BMJ 300(6725):631–634

    Article  PubMed  CAS  Google Scholar 

  16. van Ooteghem P, D’Hooghe MB, Vlietinck R, Carton H (1994) Prevalence of multiple sclerosis in Flanders, Belgium. Neuroepidemiology 13(5):220–225

    Article  PubMed  Google Scholar 

  17. Kobelt G (2006) Costs and quality of life for patients with multiple sclerosis in Belgium. Eur J Health Econ 7(Suppl 2):S24–S33. doi:10.1007/s10198-006-0377-7

    PubMed  Google Scholar 

  18. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

    Article  PubMed  CAS  Google Scholar 

  19. Hohol MJ, Orav EJ, Weiner HL (1999) Disease steps in multiple sclerosis: a longitudinal study comparing disease steps and EDSS to evaluate disease progression. Mult Scler 5(5):349–354

    PubMed  CAS  Google Scholar 

  20. Roullet E, Verdier-Taillefer MH, Amarenco P, Gharbi G, Alperovitch A, Marteau R (1993) Pregnancy and multiple sclerosis: a longitudinal study of 125 remittent patients. J Neurol Neurosurg Psychiatry 56(10):1062–1065

    Article  PubMed  CAS  Google Scholar 

  21. Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S (2007) White matter plasticity and enhanced remyelination in the maternal CNS. J Neurosci 27(8):1812–1823. doi:10.1523/JNEUROSCI.4441-06.2007

    Article  PubMed  CAS  Google Scholar 

  22. Blakemore SJ, Burnett S, Dahl RE (2010) The role of puberty in the developing adolescent brain. Hum Brain Mapp 31(6):926–933. doi:10.1002/hbm.21052

    Article  PubMed  Google Scholar 

  23. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2(10):861–863. doi:10.1038/13158

    Article  PubMed  CAS  Google Scholar 

  24. Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Blumenfeld Z (2007) The neuroprotective effect of activin A and B: implication for neurodegenerative diseases. J Neurochem 103(3):962–971. doi:10.1111/j.1471-4159.2007.04785.x

    Article  PubMed  CAS  Google Scholar 

  25. Bentzen J, Flachs EM, Stenager E, Bronnum-Hansen H, Koch-Henriksen N (2010) Prevalence of multiple sclerosis in Denmark 1950–2005. Mult Scler 16(5):520–525. doi:10.1177/1352458510364197

    Article  PubMed  Google Scholar 

  26. Marrie RA, Cutter G, Tyry T, Campagnolo D, Vollmer T (2007) Validation of the NARCOMS registry: diagnosis. Mult Scler 13(6):770–775. doi:10.1177/1352458506075031

    Article  PubMed  CAS  Google Scholar 

  27. Bowen J, Gibbons L, Gianas A, Kraft GH (2001) Self-administered Expanded Disability Status Scale with functional system scores correlates well with a physician-administered test. Mult Scler 7(3):201–206

    PubMed  CAS  Google Scholar 

  28. Ingram G, Colley E, Ben-Shlomo Y, Cossburn M, Hirst CL, Pickersgill TP, Robertson NP (2010) Validity of patient-derived disability and clinical data in multiple sclerosis. Mult Scler 16(4):472–479. doi:10.1177/1352458509358902

    Article  PubMed  CAS  Google Scholar 

  29. Must A, Phillips SM, Naumova EN, Blum M, Harris S, Dawson-Hughes B, Rand WM (2002) Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember? Am J Epidemiol 155(7):672–679

    Article  PubMed  CAS  Google Scholar 

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We thank the Flemish MS Society and all respondents. We are very grateful to A. Van Remoortel and G. Ooms for their continuous support. We thank Raf Roesems for his linguistic assistance. The study is not industry-sponsored. “MS fonds” from the University of Leuven-Melsbroek provided financial support.

Conflict of interest

No conflicts of interests are reported by J De Keyser and P Haentjens. Both MB D’hooghe and G Nagels served as a medical advisory board member, received honoraria from Bayer-Schering, Biogen Idec, Merck-Serono, Novartis and Allergan as part of a consultancy agreement and research support from Sanofi-Aventis. T D’Hooghe is or has been an advisor/consultant/research collaborator to the following pharmaceutical companies: Astellas, Novartis, Merck-Serono, Ferring, Centocor, Pfizer, Ipsen, Schering Plough (previously Organon), Bayer Schering Pharma (before: Schering). He currently holds the Ferring Chair for Reproductive Medicine and the Merck Serono Chair for Reproductive Medicine at Leuven University, Belgium and receives research support from Merck-Serono, Ferring and Schering-Plough companies.

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Correspondence to M. B. D’hooghe.

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D’hooghe, M.B., Haentjens, P., Nagels, G. et al. Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis. J Neurol 259, 855–861 (2012).

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