Menopause in woman with multiple sclerosis Review article
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Published:
Dec 31, 2024
Keywords:
multiple sclerosis, menopause, hormone replacement therapy
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Abstract
Multiple sclerosis occurs predominantly in women and sex hormones play an important role during a woman’s reproductive years but also during menopause and the postmenopausal period. Hormonal changes associated with the menopause alter the course of multiple sclerosis (inactivity and observed clinical progression). Symptoms associated with the menopause may overlap or exacerbate neurological symptoms. The use of hormone replacement therapy does not adversely affect the course of the disease, and may alleviate menopausal symptoms.
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References
1. Salpietro V, Polizzi A, Recca G et al. The role of puberty and adolescence in the pathobiology of pediatric multiple sclerosis. Multiple Scler Demyelinating Disorders. 2018; 3: 1-10.
2. Koch-Henriksen N, Magyari M. Apparent changes in the epidemiology and severity of multiple sclerosis. Nat Rev Neurol. 2021; 17: 676-88. https://doi.org/10.1038/s41582-021-00556-y .
3. Rommer PS, Ellenberger D, Hellwig K et al. Relapsing and progressive MS: the sex-specific perspective. Ther Adv Neurol Disord. 2020; 13: 1756286420956495.
4. Ribbons KA, McElduff P, Boz C et al. Male sex is independently associated with faster disability accumulation in relapse onset MS but not in primary progressive MS. PLoS ONE. 2015; 10(6): e0122686.
5. Ysrraelit MC, Correale J. Impact of sex hormones on immune function and multiple sclerosis development. Immunology. 2019; 156(1): 9-22. http://doi.org/10.1111/imm.13004.
6. Confavreux C, Hutchinson M, Hours MM et al. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple Sclerosis Group. N Engl J Med. 1998; 339: 285-91.
7. Bridge F, Butzkueven H, Van der Walt A et al. The impact of menopause on multiple sclerosis. Autoimmun Rev. 2023; 22(8): 103363. http://doi.org/10.1016/j.autrev.2023.103363.
8. MacKenzie-Graham AJ, Rinek GA, Avedisian A et al. Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis. J Neurosci Res. 2012; 90(7): 1310-23. http://doi.org/10.1002/jnr.2301924.
9. Baroncini D, Annovazzi PO, De Rossi N et al. Impact of natural menopause on multiple sclerosis: a multicentre study. J Neurol Neurosurg Psychiatry. 2019; 90: 1201-6.
10. Hall JE. Endocrinology of the Menopause. Endocrinol Metab Clin North Am. 2015; 44(3): 485-96. http://doi.org/10.1016/j.ecl.2015.05.010.
11. Freedman RR. Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med. 2005; 118: 124-30. http://doi.org/10.1016/j.amjmed.2005.09.046.
12. Lorefice L, D’Alterio MN, Firinu D et al. Impact of Menopause in Patients with Multiple Sclerosis: Current Perspectives. Int J Womens Health. 2023; 15: 103-9. http://doi.org/10.2147/IJWH.S334719.
13. Davis SR. Understanding weight gain at menopause. Climacteric. 2012; 15: 419-29. http://doi.org/10.3109/13697137.2012.707385.
14. Pillay CO, Manyonda I. The surgical menopause. Best Pract Res Clin Obstet Gynaecol. 2022; 81: 111-8. http://doi.org/10.1016/j.bpobgyn.2022.03.001.
15. Hsu S, Bove R. Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data. Curr Neurol Neurosci Rep. 2024; 24(1): 1-15. http://doi.org/10.1007/s11910-023-01326-7.
16. Goetzl EJ, Huang MC, Kon J et al. Immunosenescence and inflammaging in the aging process: age-related diseases or longevity? Ageing Res Rev. 2021; 71: 101422.
17. Pawelec G. Immunosenescence and cancer. Biogerontology. 2017 ;18(4): 717-21. http://doi.org/10.1007/s10522-017-9682-z .
18. Campisi J, Robert L. Cell senescence: role in aging and age-related diseases. Aging. 2014; 39: 45-61.
19. Gameiro CM, Romão F, Castelo-Branco C. Menopause and aging: changes in the immune system – a review. Maturitas. 2010; 67(4): 316-20.
20. Bove R, Healy BC, Musallam A et al. Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort. Mult Scler. 2016; 22(7): 935-43. http://doi.org/10.1177/1352458515606211.
21. Silverman HE, Bostrom A, Nylander AN et al. Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis. Neurology. 2025; 104(2): e210228. http://doi.org/10.1212/WNL.0000000000210228.
22. Bove R, Healy BC, Secor E et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015; 4(1): 18-24. http://doi.org/10.1016/j.msard.2014.11.009.
23. Ladeira F, Salavisa M, Caetano A et al. The influence of menopause in multiple sclerosis course: a longitudinal cohort study. Eur Neurol. 2018; 80(3-4): 223-7. http://doi.org/10.1159/000496374.
24. Giordano A, Giliberti A, Clarelli F et al. Sex hormone-related factors and the risk of PIRA in women with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2025; 13: jnnp-2024-335547. http://doi.org/10.1136/jnnp-2024-335547.
25. Tansavatdi K, McClain B, Herrington DM. The effects of smoking on estradiol metabolism. Minerva Ginecol. 2004; 56(1): 105-14.
26. Lorefice L, Frau J, Coghe G et al. Assessing the burden of vascular risk factors on brain atrophy in multiple sclerosis: a case- control MRI study. Mult Scler Relat Disord. 2019; 27: 74-78. http://doi.org/10.1016/j.msard.2018.10.011.
27. Bove R, Vaughan T, Chitnis T et al. Women’s experiences of menopause in an online MS cohort: A case series. Mult Scler Relat Disord. 2016; 9: 56-9. http://doi.org/10.1016/j.msard.2016.06.015.
28. Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler. 2014; 20(5): 520-6. http://doi.org/10.1177/1352458513519181.
29. Christianson MS, Mensah VA, Shen W. Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen. Maturitas. 2015; 80(2): 133-9. http://doi.org/10.1016/j.maturitas.2014.11.013.
30. Meyer CE, Smith AW, Padilla-Requerey AA et al. A. Neuroprotection in Cerebral Cortex Induced by the Pregnancy Hormone Estriol. Lab Invest. 2023; 103(8): 100189. http://doi.org/10.1016/j.labinv.2023.100189.
31. Hodis HN, Mack WJ. Menopausal hormone replacement therapy and reduction of all-cause mortality and cardiovascular disease: It is about time and timing. Cancer J. 2022; 28(3): 208-23.
32. Davis SR, Baber RJ. Treating menopause – MHT and beyond. Nat Rev Endocrinol. 2022; 18(8): 490-502. http://doi.org/10.1038/s41574-022-00685-4.
33. Voskuhl RR, Wang H, Wu TC et al. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: A randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016; 15(1): 35-46.
34. Manson JE, Chlebowski RT, Stefanick ML et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013; 310(13): 1353-68. http://doi.org/10.1001/jama.2013.278040.
35. Bove R, Secor E, Chibnik LB et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2014; 82(3): 222-9. http://doi.org/10.1212/WNL.0000000000000033.
36. Vural P, Akgul C, Canbaz M. Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women. Pharmacol Res. 2006; 54(4): 298-302. http://doi.org/10.1016/j.phrs.2006.06.006.
2. Koch-Henriksen N, Magyari M. Apparent changes in the epidemiology and severity of multiple sclerosis. Nat Rev Neurol. 2021; 17: 676-88. https://doi.org/10.1038/s41582-021-00556-y .
3. Rommer PS, Ellenberger D, Hellwig K et al. Relapsing and progressive MS: the sex-specific perspective. Ther Adv Neurol Disord. 2020; 13: 1756286420956495.
4. Ribbons KA, McElduff P, Boz C et al. Male sex is independently associated with faster disability accumulation in relapse onset MS but not in primary progressive MS. PLoS ONE. 2015; 10(6): e0122686.
5. Ysrraelit MC, Correale J. Impact of sex hormones on immune function and multiple sclerosis development. Immunology. 2019; 156(1): 9-22. http://doi.org/10.1111/imm.13004.
6. Confavreux C, Hutchinson M, Hours MM et al. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple Sclerosis Group. N Engl J Med. 1998; 339: 285-91.
7. Bridge F, Butzkueven H, Van der Walt A et al. The impact of menopause on multiple sclerosis. Autoimmun Rev. 2023; 22(8): 103363. http://doi.org/10.1016/j.autrev.2023.103363.
8. MacKenzie-Graham AJ, Rinek GA, Avedisian A et al. Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis. J Neurosci Res. 2012; 90(7): 1310-23. http://doi.org/10.1002/jnr.2301924.
9. Baroncini D, Annovazzi PO, De Rossi N et al. Impact of natural menopause on multiple sclerosis: a multicentre study. J Neurol Neurosurg Psychiatry. 2019; 90: 1201-6.
10. Hall JE. Endocrinology of the Menopause. Endocrinol Metab Clin North Am. 2015; 44(3): 485-96. http://doi.org/10.1016/j.ecl.2015.05.010.
11. Freedman RR. Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med. 2005; 118: 124-30. http://doi.org/10.1016/j.amjmed.2005.09.046.
12. Lorefice L, D’Alterio MN, Firinu D et al. Impact of Menopause in Patients with Multiple Sclerosis: Current Perspectives. Int J Womens Health. 2023; 15: 103-9. http://doi.org/10.2147/IJWH.S334719.
13. Davis SR. Understanding weight gain at menopause. Climacteric. 2012; 15: 419-29. http://doi.org/10.3109/13697137.2012.707385.
14. Pillay CO, Manyonda I. The surgical menopause. Best Pract Res Clin Obstet Gynaecol. 2022; 81: 111-8. http://doi.org/10.1016/j.bpobgyn.2022.03.001.
15. Hsu S, Bove R. Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data. Curr Neurol Neurosci Rep. 2024; 24(1): 1-15. http://doi.org/10.1007/s11910-023-01326-7.
16. Goetzl EJ, Huang MC, Kon J et al. Immunosenescence and inflammaging in the aging process: age-related diseases or longevity? Ageing Res Rev. 2021; 71: 101422.
17. Pawelec G. Immunosenescence and cancer. Biogerontology. 2017 ;18(4): 717-21. http://doi.org/10.1007/s10522-017-9682-z .
18. Campisi J, Robert L. Cell senescence: role in aging and age-related diseases. Aging. 2014; 39: 45-61.
19. Gameiro CM, Romão F, Castelo-Branco C. Menopause and aging: changes in the immune system – a review. Maturitas. 2010; 67(4): 316-20.
20. Bove R, Healy BC, Musallam A et al. Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort. Mult Scler. 2016; 22(7): 935-43. http://doi.org/10.1177/1352458515606211.
21. Silverman HE, Bostrom A, Nylander AN et al. Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis. Neurology. 2025; 104(2): e210228. http://doi.org/10.1212/WNL.0000000000210228.
22. Bove R, Healy BC, Secor E et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015; 4(1): 18-24. http://doi.org/10.1016/j.msard.2014.11.009.
23. Ladeira F, Salavisa M, Caetano A et al. The influence of menopause in multiple sclerosis course: a longitudinal cohort study. Eur Neurol. 2018; 80(3-4): 223-7. http://doi.org/10.1159/000496374.
24. Giordano A, Giliberti A, Clarelli F et al. Sex hormone-related factors and the risk of PIRA in women with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2025; 13: jnnp-2024-335547. http://doi.org/10.1136/jnnp-2024-335547.
25. Tansavatdi K, McClain B, Herrington DM. The effects of smoking on estradiol metabolism. Minerva Ginecol. 2004; 56(1): 105-14.
26. Lorefice L, Frau J, Coghe G et al. Assessing the burden of vascular risk factors on brain atrophy in multiple sclerosis: a case- control MRI study. Mult Scler Relat Disord. 2019; 27: 74-78. http://doi.org/10.1016/j.msard.2018.10.011.
27. Bove R, Vaughan T, Chitnis T et al. Women’s experiences of menopause in an online MS cohort: A case series. Mult Scler Relat Disord. 2016; 9: 56-9. http://doi.org/10.1016/j.msard.2016.06.015.
28. Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler. 2014; 20(5): 520-6. http://doi.org/10.1177/1352458513519181.
29. Christianson MS, Mensah VA, Shen W. Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen. Maturitas. 2015; 80(2): 133-9. http://doi.org/10.1016/j.maturitas.2014.11.013.
30. Meyer CE, Smith AW, Padilla-Requerey AA et al. A. Neuroprotection in Cerebral Cortex Induced by the Pregnancy Hormone Estriol. Lab Invest. 2023; 103(8): 100189. http://doi.org/10.1016/j.labinv.2023.100189.
31. Hodis HN, Mack WJ. Menopausal hormone replacement therapy and reduction of all-cause mortality and cardiovascular disease: It is about time and timing. Cancer J. 2022; 28(3): 208-23.
32. Davis SR, Baber RJ. Treating menopause – MHT and beyond. Nat Rev Endocrinol. 2022; 18(8): 490-502. http://doi.org/10.1038/s41574-022-00685-4.
33. Voskuhl RR, Wang H, Wu TC et al. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: A randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016; 15(1): 35-46.
34. Manson JE, Chlebowski RT, Stefanick ML et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013; 310(13): 1353-68. http://doi.org/10.1001/jama.2013.278040.
35. Bove R, Secor E, Chibnik LB et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2014; 82(3): 222-9. http://doi.org/10.1212/WNL.0000000000000033.
36. Vural P, Akgul C, Canbaz M. Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women. Pharmacol Res. 2006; 54(4): 298-302. http://doi.org/10.1016/j.phrs.2006.06.006.