Sexual disparities in the incidence and course of MS

Clinical Immunology

Volumn 149, Issue 2, 2013, Pages 201-210

  Bove, Riley ^a   Chitnis, Tanuja ^b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Demyelinating diseases; Disparities; Gender; Genetics; Multiple sclerosis; Sex hormones

Indexed keywords

APOLIPOPROTEIN E4; ESTRIOL; ESTROGEN; GADOLINIUM; GLATIRAMER; INTERFERON; NATALIZUMAB; PROGESTERONE; PROLACTIN; SEX HORMONE; TESTOSTERONE; URIC ACID; VITAMIN D;

ACUTE DISSEMINATED ENCEPHALOMYELITIS; ANDROGEN DEFICIENCY; ATTENTION; BLOOD BRAIN BARRIER; BREAST FEEDING; CLIMACTERIUM; COGNITIVE DEFECT; COORDINATION; CROSS REACTION; DEPTH PERCEPTION; DISABILITY; DISEASE COURSE; DISEASE SEVERITY; EXECUTIVE FUNCTION; FOLLOW UP; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENOTYPE ENVIRONMENT INTERACTION; GRAY MATTER; HORMONE SUBSTITUTION; HUMAN; IMMUNE RESPONSE; INCIDENCE; LIFESTYLE; MEMORY; MENOPAUSE; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; ONSET AGE; OPTIC NEURITIS; ORAL CONTRACEPTIVE USE; PARITY; PATHOGENESIS; PREGNANCY; PRIORITY JOURNAL; PUBERTY; QUALITY OF LIFE; RECURRENCE RISK; REVIEW; SEX DIFFERENCE; SEX RATIO; SEXUAL DYSFUNCTION; SMOKING; SUNLIGHT;

DEMYELINATING DISEASES; DISPARITIES; GENDER; GENETICS; MULTIPLE SCLEROSIS; SEX HORMONES;

FEMALE; GONADAL STEROID HORMONES; HUMANS; MALE; MULTIPLE SCLEROSIS; PREGNANCY; RISK FACTORS; SEX FACTORS;

EID: 84886092999     PISSN: 15216616     EISSN: 15217035     Source Type: Journal    
DOI: 10.1016/j.clim.2013.03.005     Document Type: Review

References (139)

1. Buckley O.E. The status of multiple sclerosis. Ann. N. Y. Acad. Sci. 1954, 58:541-720.
2. Confavreux C., Aimard G., Devic M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 1980, 103:281-300.
3. Grytten N., Glad S.B., Aarseth J.H., Nyland H., Midgard R., Myhr K.M. A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway. Neurology 2006, 66:182-186.
4. Alonso A., Hernan M.A. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008, 71:129-135.
5. Alonso A., Jick S.S., Olek M.J., Hernan M.A. Incidence of multiple sclerosis in the United Kingdom: findings from a population-based cohort. J. Neurol. 2007, 254:1736-1741.
6. Sadovnick A.D. European Charcot Foundation Lecture: the natural history of multiple sclerosis and gender. J. Neurol. Sci. 2009, 286:1-5.
7. Wallin M.T., Culpepper W.J., Coffman P., Pulaski S., Maloni H., Mahan C.M., Haselkorn J.K., Kurtzke J.F. The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service. Brain 2012, 135:1778-1785.
8. Maghzi A.H., Ghazavi H., Ahsan M., Etemadifar M., Mousavi S., Khorvash F., Minagar A. Increasing female preponderance of multiple sclerosis in Isfahan, Iran: a population-based study. Mult. Scler. 2010, 16:359-361.
9. Liu Y., Duan Y., Yu C., Qin W., Chen H., Dong H., Ye J., Butzkueven H., Li K. Clinical isolated syndrome: a 3-year follow-up study in China. Clin. Neurol. Neurosurg. 2011, 113:658-660.
10. Kinnunen E. The incidence of optic neuritis and its prognosis for multiple sclerosis. Acta Neurol. Scand. 1983, 68:371-377.
11. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch. Neurol. 2008, 65:727-732.
12. Swanton J.K., Fernando K.T., Dalton C.M., Miszkiel K.A., Altmann D.R., Plant G.T., Thompson A.J., Miller D.H. Early MRI in optic neuritis: the risk for clinically definite multiple sclerosis. Mult. Scler. 2010, 16:156-165.
13. Lin Y.C., Yen M.Y., Hsu W.M., Lee H.C., Wang A.G. Low conversion rate to multiple sclerosis in idiopathic optic neuritis patients in Taiwan. Jpn. J. Ophthalmol. 2006, 50:170-175.
14. Mamarabadi M., Razjouyan H., Mohammadi F., Moghaddasi M. Assessment of outcome predictors after first attack of optic neuritis. Can. J. Neurol. Sci. 2011, 38:887-895.
15. Kazim S.F., Islam M., Khan M., Hameed B., Shafqat S. Risk of multiple sclerosis after idiopathic optic neuritis in a Pakistani population. Can. J. Neurol. Sci. 2010, 37:258-263.
16. Lebrun C., Le Page E., Kantarci O., Siva A., Pelletier D., Okuda D.T. Impact of pregnancy on conversion to clinically isolated syndrome in a radiologically isolated syndrome cohort. Mult. Scler. 2012, 18:1297-1302.
17. Confavreux C., Compston A. Chapter 4 - the natural history of multiple sclerosis. McAlpine's Multiple Sclerosis 2006, 183-272. Churchill Livingstone, Edinburgh. Fourth edition.
18. Scott T.F., Schramke C.J. Poor recovery after the first two attacks of multiple sclerosis is associated with poor outcome five years later. J. Neurol. Sci. 2010, 292:52-56.
19. Confavreux C., Vukusic S., Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 2003, 126:770-782.
20. Gholipour T., Healy B., Baruch N.F., Weiner H.L., Chitnis T. Demographic and clinical characteristics of malignant multiple sclerosis. Neurology 2011, 76:1996-2001.
21. Bove R.M., Healy B., Augustine A., Musallam A., Gholipour T., Chitnis T. Effect of gender on late-onset multiple sclerosis. Mult. Scler. 2012, 18:1472-1479.
22. Potagas C., Giogkaraki E., Koutsis G., Mandellos D., Tsirempolou E., Sfagos C., Vassilopoulos D. Cognitive impairment in different MS subtypes and clinically isolated syndromes. J. Neurol. Sci. 2008, 267:100-106.
23. Simioni S., Ruffieux C., Kleeberg J., Bruggimann L., du Pasquier R.A., Annoni J.M., Schluep M. Progressive decline of decision-making performances during multiple sclerosis. J. Int. Neuropsychol. Soc. 2009, 15:291-295.
24. Duque B., Sepulcre J., Bejarano B., Samaranch L., Pastor P., Villoslada P. Memory decline evolves independently of disease activity in MS. Mult. Scler. 2008, 14:947-953.
25. Summers M., Fisniku L., Anderson V., Miller D., Cipolotti L., Ron M. Cognitive impairment in relapsing-remitting multiple sclerosis can be predicted by imaging performed several years earlier. Mult. Scler. 2008, 14:197-204.
26. Beatty W.W., Goodkin D.E., Hertsgaard D., Monson N. Clinical and demographic predictors of cognitive performance in multiple sclerosis. Do diagnostic type, disease duration, and disability matter?. Arch. Neurol. 1990, 47:305-308.
27. Beatty W.W., Aupperle R.L. Sex differences in cognitive impairment in multiple sclerosis. Clin. Neuropsychol. 2002, 16:472-480.
28. Benedict R.H., Zivadinov R. Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat. Rev. Neurol. 2011, 7:332-342.
29. Savettieri G., Messina D., Andreoli V., Bonavita S., Caltagirone C., Cittadella R., Farina D., Fazio M.C., Girlanda P., Le Pira F., Liguori M., Lugaresi A., Nocentini U., Reggio A., Salemi G., Tedeschi G., Trojano M., Valentino P., Quattrone A. Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis. J. Neurol. 2004, 251:1208-1214.
30. 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.
31. Fazekas F., Enzinger C., Wallner-Blazek M., Ropele S., Pluta-Fuerst A., Fuchs S. Gender differences in MRI studies on multiple sclerosis. J. Neurol. Sci. 2009, 286:28-30.
32. Antulov R., Weinstock-Guttman B., Cox J.L., Hussein S., Durfee J., Caiola C., Dwyer M.G., Bergsland N., Abdelrahman N., Stosic M., Hojnacki D., Munschauer F.E., Miletic D., Zivadinov R. Gender-related differences in MS: a study of conventional and nonconventional MRI measures. Mult. Scler. 2009, 15:345-354.
33. Houtchens M.K., Benedict R.H., Killiany R., Sharma J., Jaisani Z., Singh B., Weinstock-Guttman B., Guttmann C.R., Bakshi R. Thalamic atrophy and cognition in multiple sclerosis. Neurology 2007, 69:1213-1223.
34. Till C., Ghassemi R., Aubert-Broche B., Kerbrat A., Collins D.L., Narayanan S., Arnold D.L., Desrocher M., Sled J.G., Banwell B.L. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology 2011, 25:319-332.
35. Schoonheim M.M., Popescu V., Rueda Lopes F.C., Wiebenga O.T., Vrenken H., Douw L., Polman C.H., Geurts J.J., Barkhof F. Subcortical atrophy and cognition: sex effects in multiple sclerosis. Neurology 2012, 79:1754-1761.
36. Schoonheim M.M., Hulst H.E., Landi D., Ciccarelli O., Roosendaal S.D., Sanz-Arigita E.J., Vrenken H., Polman C.H., Stam C.J., Barkhof F., Geurts J.J. Gender-related differences in functional connectivity in multiple sclerosis. Mult. Scler. 2012, 18:164-173.
37. Trojano M., Russo P., Fuiani A., Paolicelli D., Di Monte E., Granieri E., Rosati G., Savettieri G., Comi G., Livrea P. The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis. Mult. Scler. 2006, 12:578-585.
38. Rudick R.A., Kappos L., Kinkel R., Clanet M., Phillips J.T., Herndon R.M., Sandrock A.W., Munschauer F.E. Gender effects on intramuscular interferon beta-1a in relapsing-remitting multiple sclerosis: analysis of 1406 patients. Mult. Scler. 2011, 17:353-360.
39. Randomized controlled trial of interferon- beta-1a in secondary progressive MS: clinical results. Neurology 2001, 56:1496-1504.
40. Wolinsky J.S., Narayana P.A., Johnson K.P. United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates, Multiple Sclerosis Study Group and the MRI Analysis Center. Mult. Scler. 2001, 7:33-41.
41. Wolinsky J.S., Shochat T., Weiss S., Ladkani D. Glatiramer acetate treatment in PPMS: why males appear to respond favorably. J. Neurol. Sci. 2009, 286:92-98.
42. Hutchinson M., Kappos L., Calabresi P.A., Confavreux C., Giovannoni G., Galetta S.L., Havrdova E., Lublin F.D., Miller D.H., O'Connor P.W., Phillips J.T., Polman C.H., Radue E.W., Rudick R.A., Stuart W.H., Wajgt A., Weinstock-Guttman B., Wynn D.R., Lynn F., Panzara M.A. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J. Neurol. 2009, 256:405-415.
43. Paty D.W., Noseworthy J.H., Ebers G.C. Diagnosis of multiple sclerosis. Mult Scler 1997, 48-51. FA Davis Company, Philadelphia, PA. D.W. Paty, G.C. Ebers (Eds.).
44. Ghezzi A. Childhood-juvenile multiple sclerosis: clinical characteristics and treatment. Expert Rev. Neurother. 2005, 5:403-411.
45. Ness J.M., Chabas D., Sadovnick A.D., Pohl D., Banwell B., Weinstock-Guttman B. Clinical features of children and adolescents with multiple sclerosis. Neurology 2007, 68:S37-S45.
46. Chitnis T., Glanz B., Jaffin S., Healy B. Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Mult. Scler. 2009, 15:627-631.
47. Gorman M.P., Healy B.C., Polgar-Turcsanyi M., Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch. Neurol. 2009, 66:54-59.
48. Fay A.J., Mowry E.M., Strober J., Waubant E. Relapse severity and recovery in early pediatric multiple sclerosis. Mult. Scler. 2012, 18:1008-1012.
49. Neuteboom R.F., Boon M., Catsman Berrevoets C.E., Vles J.S., Gooskens R.H., Stroink H., Vermeulen R.J., Rotteveel J.J., Ketelslegers I.A., Peeters E., Poll-The B.T., De Rijk-Van Andel J.F., Verrips A., Hintzen R.Q. Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 2008, 71:967-973.
50. Mowry E.M., Pesic M., Grimes B., Deen S., Bacchetti P., Waubant E. Demyelinating events in early multiple sclerosis have inherent severity and recovery. Neurology 2009, 72:602-608.
51. Sri-udomkajorn S., Pongwatcharaporn K. Clinical features and outcome of childhood optic neuritis at Queen Sirikit National Institute of Child Health. J. Med. Assoc. Thai. 2011, 94(Suppl. 3):S189-S194.
52. Banwell B., Bar-Or A., Arnold D.L., Sadovnick D., Narayanan S., McGowan M., O'Mahony J., Magalhaes S., Hanwell H., Vieth R., Tellier R., Vincent T., Disanto G., Ebers G., Wambera K., Connolly M.B., Yager J., Mah J.K., Booth F., Sebire G., Callen D., Meaney B., Dilenge M.E., Lortie A., Pohl D., Doja A., Venketaswaran S., Levin S., Macdonald E.A., Meek D., Wood E., Lowry N., Buckley D., Yim C., Awuku M., Cooper P., Grand'maison F., Baird J.B., Bhan V., Marrie R.A. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol. 2011, 10:436-445.
53. Mowry E.M., Pesic M., Grimes B., Deen S.R., Bacchetti P., Waubant E. Clinical predictors of early second event in patients with clinically isolated syndrome. J. Neurol. 2009, 256:1061-1066.
54. Mowry E.M., Krupp L.B., Milazzo M., Chabas D., Strober J.B., Belman A.L., McDonald J.C., Oksenberg J.R., Bacchetti P., Waubant E. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann. Neurol. 2010, 67:618-624.
55. Krupp L.B., Banwell B., Tenembaum S. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007, 68:S7-S12.
56. Tintore M., Arrambide G. Early onset multiple sclerosis: the role of gender. J. Neurol. Sci. 2009, 286:31-34.
57. Hooge J.P., Redekop W.K. Multiple sclerosis with very late onset. Neurology 1992, 42:1907-1910.
58. Kis B., Rumberg B., Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J. Neurol. 2008, 255:697-702.
59. Tremlett H., Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome?. Neurology 2006, 67:954-959.
60. Noseworthy J., Paty D., Wonnacott T., Feasby T., Ebers G. Multiple sclerosis after age 50. Neurology 1983, 33:1537-1544.
61. Filippi M., Wolinsky J.S., Sormani M.P., Comi G. Enhancement frequency decreases with increasing age in relapsing-remitting multiple sclerosis. Neurology 2001, 56:422-423.
62. Polliack M.L., Barak Y., Achiron A. Late-onset multiple sclerosis. J. Am. Geriatr. Soc. 2001, 49:168-171.
63. Delalande S., De Seze J., Ferriby D., Stojkovic T., Vermersch P. Late onset multiple sclerosis. Rev. Neurol. 2002, 158:1082-1087.
64. Stankoff B., Mrejen S., Tourbah A., Fontaine B., Lyon-Caen O., Lubetzki C., Rosenheim M. Age at onset determines the occurrence of the progressive phase of multiple sclerosis. Neurology 2007, 68:779-781.
65. Chitnis T. The role of CD4 T cells in the pathogenesis of multiple sclerosis. Int. Rev. Neurobiol. 2007, 79:43-72.
66. El-Etr M., Vukusic S., Gignoux L., Durand-Dubief F., Achiti I., Baulieu E.E., Confavreux C. Steroid hormones in multiple sclerosis. J. Neurol. Sci. 2005, 233:49-54.
67. Gold S.M., Voskuhl R.R. Estrogen treatment in multiple sclerosis. J. Neurol. Sci. 2009, 286:99-103.
68. Gold S.M., Voskuhl R.R. Estrogen and testosterone therapies in multiple sclerosis. Prog. Brain Res. 2009, 175:239-251.
69. Sicotte N.L., Liva S.M., Klutch R., Pfeiffer P., Bouvier S., Odesa S., Wu T.C., Voskuhl R.R. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann. Neurol. 2002, 52:421-428.
70. Liva S.M., Voskuhl R.R. Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J. Immunol. 2001, 167:2060-2067.
71. Ganesan K., Balachandran C., Manohar B.M., Puvanakrishnan R. Comparative studies on the interplay of testosterone, estrogen and progesterone in collagen induced arthritis in rats. Bone 2008, 43:758-765.
72. Panchanathan R., Shen H., Bupp M.G., Gould K.A., Choubey D. Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval. J. Immunol. 2009, 183:7031-7038.
73. Bebo B.F., Zelinka-Vincent E., Adamus G., Amundson D., Vandenbark A.A., Offner H. Gonadal hormones influence the immune response to PLP 139-151 and the clinical course of relapsing experimental autoimmune encephalomyelitis. J. Neuroimmunol. 1998, 84:122-130.
74. Fillmore P.D., Blankenhorn E.P., Zachary J.F., Teuscher C. Adult gonadal hormones selectively regulate sexually dimorphic quantitative traits observed in experimental allergic encephalomyelitis. Am. J. Pathol. 2004, 164:167-175.
75. Ganesan K., Selvam R., Abhirami R., Raju K.V., Manohar B.M., Puvanakrishnan R. Gender differences and protective effects of testosterone in collagen induced arthritis in rats. Rheumatol. Int. 2008, 28:345-353.
76. Palaszynski K.M., Loo K.K., Ashouri J.F., Liu H.B., Voskuhl R.R. Androgens are protective in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J. Neuroimmunol. 2004, 146:144-152.
77. Maccio D.R., Calfa G., Roth G.A. Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis. Neuroimmunomodulation 2005, 12:246-254.
78. Wei T., Lightman S.L. The neuroendocrine axis in patients with multiple sclerosis. Brain 1997, 120(Pt 6):1067-1076.
79. Foster S.C., Daniels C., Bourdette D.N., Bebo B.F. Dysregulation of the hypothalamic-pituitary-gonadal axis in experimental autoimmune encephalomyelitis and multiple sclerosis. J. Neuroimmunol. 2003, 140:78-87.
80. Tomassini V., Onesti E., Mainero C., Giugni E., Paolillo A., Salvetti M., Nicoletti F., Pozzilli C. Sex hormones modulate brain damage in multiple sclerosis: MRI evidence. J. Neurol. Neurosurg. Psychiatry 2005, 76:272-275.
81. Safarinejad M.R. Evaluation of endocrine profile, hypothalamic-pituitary-testis axis and semen quality in multiple sclerosis. J. Neuroendocrinol. 2008, 20:1368-1375.
82. Pines A. Male menopause: is it a real clinical syndrome?. Climacteric 2011, 14:15-17.
83. Sicotte N.L., Giesser B.S., Tandon V., Klutch R., Steiner B., Drain A.E., Shattuck D.W., Hull L., Wang H.J., Elashoff R.M., Swerdloff R.S., Voskuhl R.R. Testosterone treatment in multiple sclerosis: a pilot study. Arch. Neurol. 2007, 64:683-688.
84. Gold S.M., Chalifoux S., Giesser B.S., Voskuhl R.R. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J. Neuroinflammation 2008, 5:32.
85. Ruggieri M., Iannetti P., Polizzi A., Pavone L., Grimaldi L.M. Multiple sclerosis in children under 10years of age. Neurol. Sci. 2004, 25(Suppl. 4):S326-S335.
86. Ramagopalan S.V., Valdar W., Criscuoli M., DeLuca G.C., Dyment D.A., Orton S.M., Yee I.M., Ebers G.C., Sadovnick A.D. Age of puberty and the risk of multiple sclerosis: a population based study. Eur. J. Neurol. 2009, 16:342-347.
87. D'Hooghe M.B., Haentjens P., Nagels G., D'Hooghe T., De Keyser J. Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis. J. Neurol. 2012, 259:855-861.
88. Confavreux C., Hutchinson M., Hours M.M., 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.
89. Vukusic S., Hutchinson M., Hours M., Moreau T., Cortinovis-Tourniaire P., Adeleine P., Confavreux C., G.The Pregnancy In Multiple Sclerosis Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain 2004, 127:1353-1360.
90. Vukusic S., Ionescu I., El-Etr M., Schumacher M., Baulieu E.E., Cornu C., Confavreux C. The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART'MUS) trial: rationale, objectives and state of advancement. J. Neurol. Sci. 2009, 286:114-118.
91. Langer-Gould A., Huang S.M., Gupta R., Leimpeter A.D., Greenwood E., Albers K.B., Van Den Eeden S.K., Nelson L.M. Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch. Neurol. 2009, 66:958-963.
92. Hellwig K., Haghikia A., Rockhoff M., Gold R. Multiple sclerosis and pregnancy: experience from a nationwide database in Germany. Ther. Adv. Neurol. Disord. 2012, 5:247-253.
93. Holmqvist P., Hammar M., Landtblom A.M., Brynhildsen J. Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis. Fertil. Steril. 2010, 94:2835-2837.
94. Kotzamani D., Panou T., Mastorodemos V., Tzagournissakis M., Nikolakaki H., Spanaki C., Plaitakis A. Rising incidence of multiple sclerosis in females associated with urbanization. Neurology 2012, 78:1728-1735.
95. Nielsen N.M., Jorgensen K.T., Stenager E., Jensen A., Pedersen B.V., Hjalgrim H., Kjaer S.K., Frisch M. Reproductive history and risk of multiple sclerosis. Epidemiology 2011, 22:546-552.
96. Ramagopalan S., Yee I., Byrnes J., Guimond C., Ebers G., Sadovnick D. Term pregnancies and the clinical characteristics of multiple sclerosis: a population based study. J. Neurol. Neurosurg. Psychiatry 2012, 83:793-795.
97. Villard-Mackintosh L., Vessey M.P. Oral contraceptives and reproductive factors in multiple sclerosis incidence. Contraception 1993, 47:161-168.
98. Smeltzer S.C. Reproductive decision making in women with multiple sclerosis. J. Neurosci. Nurs. 2002, 34:145-157.
99. Alwan S., Yee I.M., Dybalski M., Guimond C., Dwosh E., Greenwood T.M., Butler R., Sadovnick A.D. Reproductive decision making after the diagnosis of multiple sclerosis (MS). Mult. Scler. 2013, 19:351-358.
100. Portaccio E., Ghezzi A., Hakiki B., Martinelli V., Moiola L., Patti F., La Mantia L., Mancardi G.L., Solaro C., Tola M.R., Pozzilli C., De Giglio L., Totaro R., Lugaresi A., De Luca G., Paolicelli D., Marrosu M.G., Comi G., Trojano M., Amato M.P. Breastfeeding is not related to postpartum relapses in multiple sclerosis. Neurology 2011, 77:145-150.
101. Holmqvist P., Wallberg M., Hammar M., Landtblom A.M., Brynhildsen J. Symptoms of multiple sclerosis in women in relation to sex steroid exposure. Maturitas 2006, 54:149-153.
102. Poser S., Raun N.E., Wikstrom J., Poser W. Pregnancy, oral contraceptives and multiple sclerosis. Acta Neurol. Scand. 1979, 59:108-118.
103. Disanto G., Handel A.E., Ramagopalan S.V. Estrogen-vitamin D interaction in multiple sclerosis. Fertil. Steril. 2011, 95:e3. (author reply e4).
104. Correale J., Ysrraelit M.C., Gaitan M.I. Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects. J. Immunol. 2010, 185:4948-4958.
105. Nashold F.E., Spach K.M., Spanier J.A., Hayes C.E. Estrogen controls vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis by controlling vitamin D3 metabolism and receptor expression. J. Immunol. 2009, 183:3672-3681.
106. Agliardi C., Guerini F.R., Saresella M., Caputo D., Leone M.A., Zanzottera M., Bolognesi E., Marventano I., Barizzone N., Fasano M.E., Al-Daghri N., Clerici M. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. Brain Behav. Immun. 2011, 25:1460-1467.
107. Ramagopalan S.V., Valdar W., Dyment D.A., DeLuca G.C., Yee I.M., Giovannoni G., Ebers G.C., Sadovnick A.D. Association of infectious mononucleosis with multiple sclerosis. A population-based study. Neuroepidemiology 2009, 32:257-262.
108. Ramagopalan S.V., Dyment D.A., Herrera B.M., Criscuoli M., Yee I.M., Sadovnick A.D., Ebers G.C. Clustering of autoimmune disease in families at high risk for multiple sclerosis?. Lancet Neurol. 2007, 6:206-207. (author reply 207).
109. Vlahiotis A., Sedjo R., Cox E.R., Burroughs T.E., Rauchway A., Lich R. Gender differences in self-reported symptom awareness and perceived ability to manage therapy with disease-modifying medication among commercially insured multiple sclerosis patients. J. Manag. Care Pharm. 2010, 16:206-216.
110. Casetta I., Riise T., Wamme Nortvedt M., Economou N.T., De Gennaro R., Fazio P., Cesnik E., Govoni V., Granieri E. Gender differences in health-related quality of life in multiple sclerosis. Mult. Scler. 2009, 15:1339-1346.
111. Fernandez O., Baumstarck-Barrau K., Simeoni M.C., Auquier P. Patient characteristics and determinants of quality of life in an international population with multiple sclerosis: assessment using the MusiQoL and SF-36 questionnaires. Mult. Scler. 2011, 17:1238-1249.
112. Pugliatti M., Riise T., Nortvedt M.W., Carpentras G., Sotgiu M.A., Sotgiu S., Rosati G. Self-perceived physical functioning and health status among fully ambulatory multiple sclerosis patients. J. Neurol. 2008, 255:157-162.
113. Mollaoglu M., Ustun E. Fatigue in multiple sclerosis patients. J. Clin. Nurs. 2009, 18:1231-1238.
114. Hadjimichael O., Kerns R.D., Rizzo M.A., Cutter G., Vollmer T. Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain 2007, 127:35-41.
115. Buchanan R.J., Wang S., Ju H. Gender analyses of nursing home residents with multiple sclerosis. J. Gend. Specif. Med. 2003, 6:35-46.
116. Celik D.B., Poyraz E.C., Bingol A., Idiman E., Ozakbas S., Kaya D. Sexual dysfunction in multiple sclerosis: gender differences. J. Neurol. Sci. 2013, 324:17-20.
117. Marrie R.A., Horwitz R., Cutter G., Tyry T. Cumulative impact of comorbidity on quality of life in MS. Acta Neurol. Scand. 2012, 125:180-186.
118. Nieves J., Cosman F., Herbert J., Shen V., Lindsay R. High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis. Neurology 1994, 44:1687-1692.
119. Grytten Torkildsen N., Lie S.A., Aarseth J.H., Nyland H., Myhr K.M. Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway. Mult. Scler. 2008, 14:1191-1198.
120. Goodin D.S., Reder A.T., Ebers G.C., Cutter G., Kremenchutzky M., Oger J., Langdon D., Rametta M., Beckmann K., DeSimone T.M., Knappertz V. Survival in MS: a randomized cohort study 21years after the start of the pivotal IFNbeta-1b trial. Neurology 2012, 78:1315-1322.
121. Leray E., Morrissey S.P., Yaouanq J., Coustans M., Le Page E., Chaperon J., Edan G. Long-term survival of patients with multiple sclerosis in West France. Mult. Scler. 2007, 13:865-874.
122. Ragonese P., Aridon P., Mazzola M.A., Callari G., Palmeri B., Famoso G., Terruso V., Salemi G., D'Amelio M., Savettieri G. Multiple sclerosis survival: a population-based study in Sicily. Eur. J. Neurol. 2010, 17:391-397.
123. Sumelahti M.L., Tienari P.J., Wikstrom J., Salminen T.M., Hakama M. Survival of multiple sclerosis in Finland between 1964 and 1993. Mult. Scler. 2002, 8:350-355.
124. Alonso A., Cook S.D., Maghzi A.H., Divani A.A. A case-control study of risk factors for multiple sclerosis in Iran. Mult. Scler. 2011, 17:550-555.
125. Rodriguez Regal A., del Campo Amigo M., Paz-Esquete J., Martinez Feijoo A., Cebrian E., Suarez Gil P., Mourino M.A. A case-control study of the influence of the smoking behaviour in multiple sclerosis. Neurologia 2009, 24:177-180.
126. Burton R.C., Ferguson P., Gray M., Hall J., Hayes M., Smart Y.C. Effects of age, gender, and cigarette smoking on human immunoregulatory T-cell subsets: establishment of normal ranges and comparison with patients with colorectal cancer and multiple sclerosis. Diagn. Immunol. 1983, 1:216-223.
127. Palacios N., Alonso A., Bronnum-Hansen H., Ascherio A. Smoking and increased risk of multiple sclerosis: parallel trends in the sex ratio reinforce the evidence. Ann. Epidemiol. 2011, 21:536-542.
128. Kragt J., van Amerongen B., Killestein J., Dijkstra C., Uitdehaag B., Polman C., Lips P. Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult. Scler. 2009, 15:9-15.
129. Zoccolella S., Tortorella C., Iaffaldano P., Direnzo V., D'Onghia M., Luciannatelli E., Paolicelli D., Livrea P., Trojano M. Low serum urate levels are associated to female gender in multiple sclerosis patients. PLoS One 2012, 7:e40608.
130. Spach K.M., Hayes C.E. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J. Immunol. 2005, 175:4119-4126.
131. Munger K.L., Chitnis T., Ascherio A. Body size and risk of MS in two cohorts of US women. Neurology 2009, 73:1543-1550.
132. Hedstrom A.K., Olsson T., Alfredsson L. High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Mult. Scler. 2012, 18:1334-1336.
133. Marrie R.A., Horwitz R.I., Cutter G., Tyry T., Vollmer T. Association between comorbidity and clinical characteristics of MS. Acta Neurol. Scand. 2011, 124:135-141.
134. Turer C.B., Lin H., Flores G. Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics 2013, 131:e152-e161.
135. Nielsen T.R., Pedersen M., Rostgaard K., Frisch M., Hjalgrim H. Correlations between Epstein-Barr virus antibody levels and risk factors for multiple sclerosis in healthy individuals. Mult. Scler. 2007, 13:420-423.
136. Ramagopalan S.V., Byrnes J.K., Dyment D.A., Guimond C., Handunnetthi L., Disanto G., Yee I.M., Ebers G.C., Sadovnick A.D. Parent-of-origin of HLA-DRB1*1501 and age of onset of multiple sclerosis. J. Hum. Genet. 2009, 54:547-549.
137. Hensiek A.E., Sawcer S.J., Feakes R., Deans J., Mander A., Akesson E., Roxburgh R., Coraddu F., Smith S., Compston D.A. HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2002, 72:184-187.
138. Chao M.J., Ramagopalan S.V., Herrera B.M., Orton S.M., Handunnetthi L., Lincoln M.R., Dyment D.A., Sadovnick A.D., Ebers G.C. MHC transmission: insights into gender bias in MS susceptibility. Neurology 2011, 76:242-246.
139. Chao M.J., Ramagopalan S.V., Herrera B.M., Lincoln M.R., Dyment D.A., Sadovnick A.D., Ebers G.C. Epigenetics in multiple sclerosis susceptibility: difference in transgenerational risk localizes to the major histocompatibility complex. Hum. Mol. Genet. 2009, 18:261-266.