Hormonal disorders in patients with multiple sclerosis Review article
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Published:
Jun 30, 2025
Keywords:
multiple sclerosis, hormonal disorders, thyroid diseases
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Abstract
Multiple sclerosis (SM, sclerosis multiplex) is a chronic, inflammatory, and neurodegenerative disease of the central nervous system with an autoimmune basis. Sex hormones play a significant role from the onset of the disease, influencing its course. On the other hand, thyroid hormone imbalances are more frequently observed in patients with multiple sclerosis, particularly in the course of Hashimoto’s thyroiditis.
SM is more common in women, and sex hormones, particularly estrogen and progesterone, modulate disease activity at various stages of life, including pregnancy and menopause. Hormonal disturbances, such as hyperprolactinemia, menstrual irregularities, and thyroid disease, can influence the course of SM and the immune response. Hormone replacement therapy, estrogens, and oral contraceptives may have a protective effect but require individual evaluation, as hormones significantly impact disease activity, disability progression, and patient quality of life.
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References
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24. Escribano BM, Valdevira ME, Muñoz-Jurado A et al. The Impact of Sex Hormones on Transcranial Magnetic Stimulation Against the Oxidative Stress in the Pathogenesis of Multiple Sclerosis. Biomolecules. 2025; 15(12): 1714.
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26. Da Costa R, Szyper-Kravitz M, Szekanecz Z et al. Ferritin and prolactin levels in multiple sclerosis. Isr Med Assoc J. 2011; 13(2): 91-5.
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28. Golparvar S, Naghavi S, Adibi I. Hyperprolactinemia as a manifestation of multiple sclerosis attack. BMJ Neurol Open. 2025; 7(2): e000971. https://doi.org/10.1136/bmjno-2024-000971.
29. Correale J, Farez MF, Ysrraelit MC. Role of prolactin in B cell regulation in multiple sclerosis. J Neuroimmunol. 2014; 269: 76-86.
30. Zhornitsky S, Yong VW, Weiss S et al. Prolactin in multiple sclerosis. Mult Scler. 2013; 19(1): 15-23.
31. de Carvalho Jennings Pereira WL, Flauzino T, Alfieri DF et al. Prolactin is Not Associated with Disability and Clinical Forms in Patients with Multiple Sclerosis. Neuromolecular Med. 2020; 22(1): 73-80.
32. Dobson R, Giovannoni G. Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis. J Neurol. 2013; 260(5): 1272-85. https://doi.org/10.1007/s00415-012-6790-1.
33. Wawrzyniak S, Rakoca M, Kułakowska A et al. Multiple sclerosis and autoimmune diseases – a case control study. Neurologia i Neurochirurgia Polska. 2023; 57(4): 344-51. https://doi.org/10.5603/PJNNS.a2023.0038.
34. Poursadeghfard M, Mallahzadeh A, Hamidi A et al. Thyroid auto-antibodies in newly diagnosed multiple sclerosis patients: A cross sectional study. Health Sci Rep. 2024; 7(7): e2247. https://doi.org/10.1002/hsr2.2247.
35. Perga S, Martire S, Montarolo F et al. The Footprints of Poly-Autoimmunity: Evidence for Common Biological Factors Involved in Multiple Sclerosis and Hashimoto’s Thyroiditis. Front Immunol. 2018; 9: 311. https://doi.org/10.3389/fimmu.2018.00311.
36. Cui W, Wang B, Shi K et al. Causal relationship between thyroid function and multiple sclerosis: A bidirectional Mendelian randomization study. Medicine (Baltimore). 2024; 103(37): e39709. https://doi.org/10.1097/MD.0000000000039709.
37. Rigoni E, Dorsey R, Malik O et al. Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response. J Clin Endocrinol Metab. 2020; 105(9): dgaa453. https://doi.org/10.1210/clinem/dgaa453.
38. Rashad NM, Amer MG, Reda Ashour WM et al. The pattern of thyroiditis in multiple sclerosis: a cross-sectional study in a tertiary care hospital in Egypt. Egypt J Intern Med. 2020; 32(1): 17. https://doi.org/10.1186/s43162-020-00017-w.
39. Ruchała M, Szczepanek-Parulska E. Objawy neurologiczne w najczęstszych chorobach endokrynologicznych. Neurol Dypl. 2015; 10(6): 34-40.
2. 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.
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. https://doi.org/10.1111/imm.13004.
6. McCombe PA. The role of sex and pregnancy in multiple sclerosis: what do we know and what should we do? Expert Rev Neurother. 2022; 22(5): 377-92. https://doi.org/10.1080/14737175.2022.2060079.
7. Carbone L, Di Girolamo R, Conforti A et al. Ovarian reserve in patients with multiple sclerosis: A systematic review and meta-analysis. Int J Gynaecol Obstet. 2023; 163(1): 11-22. https://doi.org/10.1002/ijgo.14757.
8. Ucciferri CC, Dunn SE. Effect of puberty on the immune system: Relevance to multiple sclerosis. Front Pediatr. 2022; 10: 1059083. https://doi.org/10.3389/fped.2022.1059083.
9. Espinoza-López DA, Huerta-Franco MR, Zermeño-Pöhls F et al. Sex hormones, obstetric and gynecologic characteristics of multiple sclerosis women with and without relapse. Gac Med Mex. 2025; 161(3): 274-79.
10. Kopp TI, Pinborg A, Glazer CH et al. Women with female infertility seeking medically assisted reproduction are not at increased risk of developing multiple sclerosis. Hum Reprod. 2022; 37(6): 1324-33. https://doi.org/10.1093/humrep/deac041.
11. Hellwig K, Chen LH, Stancyzk FZ et al. Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome Susceptibility. PLoS One. 2016; 11(3): e0149094. https://doi.org/10.1371/journal.pone.0149094.
12. Otero-Romero S, Carbonell-Mirabent P, Midaglia L et al. Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis. Mult Scler. 2022; 28(6): 950-7. https://doi.org/10.1177/13524585211053001.
13. Pozzilli C, De Giglio L, Barletta VT et al. Oral contraceptives combined with interferon β in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2015; 2(4): e120. https://doi.org/10.1212/NXI.0000000000000120.
14. Zapata LB, Oduyebo T, Whiteman MK et al. Contraceptive use among women with multiple sclerosis: a systematic review. Contraception. 2016; 94(6): 612-20. https://doi.org/10.1016/j.contraception.2016.07.013.
15. 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. https://doi.org/10.1016/j.msard.2016.06.015.
16. 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(11): 1201-6. https://doi.org/10.1136/jnnp-2019-320587.
17. 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. https://doi.org/10.1177/1352458513519181.
18. 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: 74-8. https://doi.org/10.1016/j.msard.2018.10.011.
19. 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. https://doi.org/10.2147/IJWH.S334719.
20. Silverman HE, Bostrom A, Nylander AN et al. Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis. Neurology. 2025; 28; 104(2): e210228. https://doi.org/10.1212/WNL.0000000000210228.
21. Hsu S, Bove R. Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data. Curr Neurol Neurosci Rep. 2024; 24(1): 1-15. https://doi.org/10.1007/s11910-023-01326-7.
22. Davis SR. Understanding weight gain at menopause. Climacteric. 2012; 15: 419-29. https://doi.org/10.3109/13697137.2012.707385.
23. Juutinen L, Ahinko K, Hagman S et al. Immunometabolic profiling in menopausal women with multiple sclerosis: the role of adipokines and hormone therapy. BMJ Neurol Open. 2025; 7(2): e001295.
24. Escribano BM, Valdevira ME, Muñoz-Jurado A et al. The Impact of Sex Hormones on Transcranial Magnetic Stimulation Against the Oxidative Stress in the Pathogenesis of Multiple Sclerosis. Biomolecules. 2025; 15(12): 1714.
25. Alvarez-Sanchez N, Dunn SE. Potential biological contributers to the sex difference in multiple sclerosis progression. Front Immunol. 2023; 14: 1175874. https://doi.org/10.3389/fimmu.2023.1175874.
26. Da Costa R, Szyper-Kravitz M, Szekanecz Z et al. Ferritin and prolactin levels in multiple sclerosis. Isr Med Assoc J. 2011; 13(2): 91-5.
27. Markianos M, Koutsis G, Evangelopoulos ME et al. Serum and cerebrospinal fluid prolactin levels in male and female patients with clinically-isolated syndrome or relapsing-remitting multiple sclerosis. J Neuroendocrinol. 2010; 22: 503-8.
28. Golparvar S, Naghavi S, Adibi I. Hyperprolactinemia as a manifestation of multiple sclerosis attack. BMJ Neurol Open. 2025; 7(2): e000971. https://doi.org/10.1136/bmjno-2024-000971.
29. Correale J, Farez MF, Ysrraelit MC. Role of prolactin in B cell regulation in multiple sclerosis. J Neuroimmunol. 2014; 269: 76-86.
30. Zhornitsky S, Yong VW, Weiss S et al. Prolactin in multiple sclerosis. Mult Scler. 2013; 19(1): 15-23.
31. de Carvalho Jennings Pereira WL, Flauzino T, Alfieri DF et al. Prolactin is Not Associated with Disability and Clinical Forms in Patients with Multiple Sclerosis. Neuromolecular Med. 2020; 22(1): 73-80.
32. Dobson R, Giovannoni G. Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis. J Neurol. 2013; 260(5): 1272-85. https://doi.org/10.1007/s00415-012-6790-1.
33. Wawrzyniak S, Rakoca M, Kułakowska A et al. Multiple sclerosis and autoimmune diseases – a case control study. Neurologia i Neurochirurgia Polska. 2023; 57(4): 344-51. https://doi.org/10.5603/PJNNS.a2023.0038.
34. Poursadeghfard M, Mallahzadeh A, Hamidi A et al. Thyroid auto-antibodies in newly diagnosed multiple sclerosis patients: A cross sectional study. Health Sci Rep. 2024; 7(7): e2247. https://doi.org/10.1002/hsr2.2247.
35. Perga S, Martire S, Montarolo F et al. The Footprints of Poly-Autoimmunity: Evidence for Common Biological Factors Involved in Multiple Sclerosis and Hashimoto’s Thyroiditis. Front Immunol. 2018; 9: 311. https://doi.org/10.3389/fimmu.2018.00311.
36. Cui W, Wang B, Shi K et al. Causal relationship between thyroid function and multiple sclerosis: A bidirectional Mendelian randomization study. Medicine (Baltimore). 2024; 103(37): e39709. https://doi.org/10.1097/MD.0000000000039709.
37. Rigoni E, Dorsey R, Malik O et al. Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response. J Clin Endocrinol Metab. 2020; 105(9): dgaa453. https://doi.org/10.1210/clinem/dgaa453.
38. Rashad NM, Amer MG, Reda Ashour WM et al. The pattern of thyroiditis in multiple sclerosis: a cross-sectional study in a tertiary care hospital in Egypt. Egypt J Intern Med. 2020; 32(1): 17. https://doi.org/10.1186/s43162-020-00017-w.
39. Ruchała M, Szczepanek-Parulska E. Objawy neurologiczne w najczęstszych chorobach endokrynologicznych. Neurol Dypl. 2015; 10(6): 34-40.