Fertility and Sterility
Volume 94, Issue 7 , Pages 2835-2837 , December 2010

Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis

  • Per Holmqvist, M.D.

      Affiliations

    • Division of Womens and Childrens Health, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
    • Clinical Department of Obstetrics and Gynecology, County Hospital Sundsvall, Sweden
    • Corresponding Author InformationReprint requests: Per Holmqvist, M.D., Clinical Department of Obstetrics and Gynecology, County Hospital, SE-85186 Sundsvall, Sweden (FAX: 46-60-181557).
    • ,
  • Mats Hammar, M.D., Ph.D.

      Affiliations

    • Division of Womens and Childrens Health, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
    • ,
  • Anne-Marie Landtblom, M.D., Ph.D.

      Affiliations

    • Division of Neurology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
    • ,
  • Jan Brynhildsen, M.D., Ph.D.

      Affiliations

    • Division of Womens and Childrens Health, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden

Received 9 February 2010 ,Revised 3 June 2010 ,Accepted 16 June 2010.

References 

  1. Correale J, Gilmore W, McMillan M, Li S, McCarthy K, Le T, et al. Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis. J Immunol. 1995;154:2959–2968
  2. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8:579–621
  3. Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 2006;5:932–936
  4. Pozzilli C, Tomassini V, Marinelli F, Paolillo A, Gasperini C, Bastianello S. ‘Gender gap’ in multiple sclerosis: magnetic resonance imaging evidence. Eur J Neurol. 2003;10:95–97
  5. Duquette P, Girard M. Hormonal factors in susceptibility to multiple sclerosis. Curr Opin Neurol Neurosurg. 1993;6:195–201
  6. Bernardi S, Grasso MG, Bertollini R, Orzi F, Fieschi C. The influence of pregnancy on relapses in multiple sclerosis: a cohort study. Acta Neurol Scand. 1991;84:403–406
  7. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998;339:285–291
  8. Damek DM, Shuster EA. Pregnancy and multiple sclerosis. Mayo Clin Proc. 1997;72:977–989
  9. Houtchens MK. Pregnancy and multiple sclerosis. Semin Neurol. 2007;27:434–441
  10. Hutchinson M. Pregnancy in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1993;56:1043–1045
  11. Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004;127:1353–1360
  12. Elenkov IJ, Wilder RL, Bakalov VK, Link AA, Dimitrov MA, Fisher S, et al. IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times. J Clin Endocrinol Metab. 2001;86:4933–4938
  13. Sanchez-Ramon S, Navarro AJ, Aristimuno C, Rodriguez-Mahou M, Bellon JM, Fernandez-Cruz E, et al. Pregnancy-induced expansion of regulatory T-lymphocytes may mediate protection to multiple sclerosis activity. Immunol Lett. 2005;96:195–201
  14. Saraste M, Vaisanen S, Alanen A, Airas L. Clinical and immunologic evaluation of women with multiple sclerosis during and after pregnancy. Gend Med. 2007;4:45–55
  15. Formby B. Immunologic response in pregnancy. Its role in endocrine disorders of pregnancy and influence on the course of maternal autoimmune diseases. Endocrinol Metab Clin North Am. 1995;24:187–205
  16. Pozzilli C, Falaschi P, Mainero C, Martocchia A, D'Urso R, Proietti A, et al. MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns. Neurology. 1999;53:622–624
  17. Bansil S, Lee HJ, Jindal S, Holtz CR, Cook SD. Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis. Acta Neurol Scand. 1999;99:91–94
  18. Ito A, Buenafe AC, Matejuk A, Zamora A, Silverman M, Dwyer J, et al. Estrogen inhibits systemic T cell expression of TNF-alpha and recruitment of TNF-alpha(+) T cells and macrophages into the CNS of mice developing experimental encephalomyelitis. Clin Immunol. 2002;102:275–282
  19. Kim S, Liva SM, Dalal MA, Verity MA, Voskuhl RR. Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology. 1999;52:1230–1238
  20. Morales LB, Loo KK, Liu HB, Peterson C, Tiwari-Woodruff S, Voskuhl RR. Treatment with an estrogen receptor alpha ligand is neuroprotective in experimental autoimmune encephalomyelitis. J Neurosci. 2006;26:6823–6833
  21. Offner H. Neuroimmunoprotective effects of estrogen and derivatives in experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis. J Neurosci Res. 2004;78:603–624
  22. Palaszynski KM, Liu H, Loo KK, Voskuhl RR. Estriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neuroimmunol. 2004;149:84–89
  23. Ito A, Bebo BF, Matejuk A, Zamora A, Silverman M, Fyfe-Johnson A, et al. Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. J Immunol. 2001;167:542–552
  24. Subramanian S, Matejuk A, Zamora A, Vandenbark AA, Offner H. Oral feeding with ethinyl estradiol suppresses and treats experimental autoimmune encephalomyelitis in SJL mice and inhibits the recruitment of inflammatory cells into the central nervous system. J Immunol. 2003;170:1548–1555
  25. Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol. 2002;52:421–428
  26. Hernan MA, Hohol MJ, Olek MJ, Spiegelman D, Ascherio A. Oral contraceptives and the incidence of multiple sclerosis. Neurology. 2000;55:848–854
  27. Thorogood M, Hannaford PC. The influence of oral contraceptives on the risk of multiple sclerosis. Br J Obstet Gynaecol. 1998;105:1296–1299
  28. Alonso A, Jick SS, Olek MJ, Ascherio A, Jick H, Hernan MA. Recent use of oral contraceptives and the risk of multiple sclerosis. Arch Neurol. 2005;62:1362–1365
  29. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–1452
  30. D'Hooghe MB, Nagels G, Uitdehaag BM. Long-term effects of childbirth in MS. J Neurol Neurosurg Psychiatry. 2010;81:38–41

 P.H. has nothing to disclose. M.H. has nothing to disclose. A-M.L. has nothing to disclose. J.B. has nothing to disclose.

PII: S0015-0282(10)00998-2

doi: 10.1016/j.fertnstert.2010.06.045

Fertility and Sterility
Volume 94, Issue 7 , Pages 2835-2837 , December 2010

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