Top

Open Access 17-04-2024 | Research Article

Sex-related differences in the clinical presentation of multiple system atrophy

Authors: Fabian Leys, Sabine Eschlböck, Nicole Campese, Philipp Mahlknecht, Marina Peball, Georg Goebel, Victoria Sidoroff, Florian Krismer, Roberta Granata, Stefan Kiechl, Werner Poewe, Klaus Seppi, Gregor K. Wenning, Alessandra Fanciulli

Published in: Clinical Autonomic Research

Abstract

Purpose

To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort.

Methods

The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis.

Results

The literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004).

Conclusion

The available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.

Available only for authorised users

Fanciulli A, Wenning GK (2015) Multiple-system atrophy. N Engl J Med 372(14):1375–1376. https://doi.org/10.1056/NEJMc1501657CrossRefPubMed

Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94(1–3):79–100. https://doi.org/10.1016/0022-510X(89)90219-0CrossRefPubMed

Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J et al (2017) Parkinson disease. Nat Rev Dis Primers 3:17013. https://doi.org/10.1038/nrdp.2017.13CrossRefPubMed

Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences (2001) In: Wizemann TM, Pardue ML (eds) Exploring the biological contributions to human health: does sex matter? National Academies Press, Washington, DC. https://www.ncbi.nlm.nih.gov/books/NBK222288/

Nicoletti A, Baschi R, Cicero CE, Iacono S, Re VL, Luca A et al (2023) Sex and gender differences in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis: a narrative review. Mech Ageing Dev 212:111821. https://doi.org/10.1016/j.mad.2023.111821CrossRefPubMed

Picillo M, Nicoletti A, Fetoni V, Garavaglia B, Barone P, Pellecchia MT (2017) The relevance of gender in Parkinson’s disease: a review. J Neurol 264(8):1583–1607. https://doi.org/10.1007/s00415-016-8384-9CrossRefPubMed

Subramanian I, Mathur S, Oosterbaan A, Flanagan R, Keener AM, Moro E (2022) Unmet needs of women living with Parkinson’s disease: gaps and controversies. Mov Disord 37(3):444–455. https://doi.org/10.1002/mds.28921CrossRefPubMed

Poewe W, Stankovic I, Halliday G, Meissner WG, Wenning GK, Pellecchia MT et al (2022) Multiple system atrophy. Nat Rev Dis Primers 8(1):56. https://doi.org/10.1038/s41572-022-00382-6CrossRefPubMed

Raccagni C, Indelicato E, Sidoroff V, Daniaux M, Bader A, Toth B et al (2021) Female sexual dysfunction in multiple system atrophy: a prospective cohort study. Clin Auton Res 31(6):713–717. https://doi.org/10.1007/s10286-021-00825-2CrossRefPubMedPubMedCentral

10.

Coon EA, Nelson RM, Sletten DM, Suarez MD, Ahlskog JE, Benarroch EE et al (2019) Sex and gender influence symptom manifestation and survival in multiple system atrophy. Auton Neurosci 219:49–52. https://doi.org/10.1016/j.autneu.2019.04.002CrossRefPubMedPubMedCentral

11.

Cuoco S, Picillo M, Cappiello A, Carotenuto I, Erro R, Russillo MC et al (2020) Effects of gender on cognitive and behavioral manifestations in multiple system atrophy. J Neural Transm 127(6):925–934. https://doi.org/10.1007/s00702-020-02169-zCrossRefPubMed

12.

Bailey ES, Hooshmand SJ, Badihian N, Sandroni P, Benarroch EE, Bower JH et al (2023) Sex and gender influence urinary symptoms and management in multiple system atrophy. J Mov Disord 16(2):196–201. https://doi.org/10.14802/jmd.23016CrossRefPubMedPubMedCentral

13.

Graham JG, Oppenheimer DR (1969) Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 32(1):28–34. https://doi.org/10.1136/jnnp.32.1.28CrossRefPubMedPubMedCentral

14.

Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71(9):670–676. https://doi.org/10.1212/01.wnl.0000324625.00404.15CrossRefPubMedPubMedCentral

15.

Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I et al (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 21(2):69–72. https://doi.org/10.1007/s10286-011-0119-5CrossRefPubMed

16.

Rivasi G, Rafanelli M, Mossello E, Brignole M, Ungar A (2020) Drug-related orthostatic hypotension: beyond anti-hypertensive medications. Drugs Aging 37(10):725–738. https://doi.org/10.1007/s40266-020-00796-5CrossRefPubMedPubMedCentral

17.

Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C et al (2004) Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 19(9):1020–1028. https://doi.org/10.1002/mds.20213CrossRefPubMed

18.

Wenning GK, Tison F, Seppi K, Sampaio C, Diem A, Yekhlef F et al (2004) Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord 19(12):1391–1402. https://doi.org/10.1002/mds.20255CrossRefPubMed

19.

Saito Y, Matsuoka Y, Takahashi A, Ohno Y (1994) Survival of patients with multiple system atrophy. Intern Med 33(6):321–325. https://doi.org/10.2169/internalmedicine.33.321CrossRef

20.

Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1994) Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain. 117(Pt 4):835–845. https://doi.org/10.1093/brain/117.4.835CrossRefPubMed

21.

Wenning GK, Ben-Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1995) Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry 58(2):160–166. https://doi.org/10.1136/jnnp.58.2.160CrossRefPubMedPubMedCentral

22.

Tison F, Wenning GK, Volonte MA, Poewe WR, Henry P, Quinn NP (1996) Pain in multiple system atrophy. J Neurol 243(2):153–156. https://doi.org/10.1007/BF02444007CrossRefPubMed

23.

Testa D, Filippini G, Farinotti M, Palazzini E, Caraceni T (1996) Survival in multiple system atrophy: a study of prognostic factors in 59 cases. J Neurol 243(5):401–404. https://doi.org/10.1007/bf00868999CrossRefPubMed

24.

Ben-Shlomo Y, Wenning GK, Tison F, Quinn NP (1997) Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology 48(2):384–393. https://doi.org/10.1212/WNL.48.2.384CrossRefPubMed

25.

Klockgether T, Ludtke R, Kramer B, Abele M, Burk K, Schols L et al (1998) The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain 121(Pt 4):589–600. https://doi.org/10.1093/brain/121.4.589CrossRefPubMed

26.

Testa D, Monza D, Ferrarini M, Soliveri P, Girotti F, Filippini G (2001) Comparison of natural histories of progressive supranuclear palsy and multiple system atrophy. Neurol Sci 22(3):247–251. https://doi.org/10.1007/s100720100005CrossRefPubMed

27.

Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E et al (2002) Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 125(Pt 5):1070–1083. https://doi.org/10.1093/brain/awf117CrossRefPubMed

28.

Seppi K, Yekhlef F, Diem A, Luginger Wolf E, Mueller J, Tison F et al (2005) Progression of parkinsonism in multiple system atrophy. J Neurol 252(1):91–96. https://doi.org/10.1007/s00415-005-0617-2CrossRefPubMed

29.

Yamamoto T, Sakakibara R, Uchiyama T, Liu Z, Ito T, Awa Y et al (2005) When is Onuf’s nucleus involved in multiple system atrophy? A sphincter electromyography study. J Neurol Neurosurg Psychiatry 76(12):1645–1648. https://doi.org/10.1136/jnnp.2004.061036CrossRefPubMedPubMedCentral

30.

Geser F, Wenning GK, Seppi K, Stampfer-Kountchev M, Scherfler C, Sawires M et al (2006) Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG). Mov Disord 21(2):179–186. https://doi.org/10.1002/mds.20678CrossRefPubMed

31.

Williams DR, Watt HC, Lees AJ (2006) Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study. J Neurol Neurosurg Psychiatry 77(4):468–473. https://doi.org/10.1136/jnnp.2005.074070CrossRefPubMedPubMedCentral

32.

Tada M, Onodera O, Ozawa T, Piao YS, Kakita A, Takahashi H et al (2007) Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy. Arch Neurol 64(2):256–260. https://doi.org/10.1001/archneur.64.2.256CrossRefPubMed

33.

Schrag A, Wenning GK, Quinn N, Ben-Shlomo Y (2008) Survival in multiple system atrophy. Mov Disord 23(2):294–296. https://doi.org/10.1002/mds.21839CrossRefPubMed

34.

O’Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton JL et al (2008) Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain 131(Pt 5):1362–1372. https://doi.org/10.1093/brain/awn065CrossRefPubMed

35.

Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ et al (1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163(1):94–98. https://doi.org/10.1016/S0022-510X(98)00304-9CrossRefPubMed

36.

Yamamoto T, Sakakibara R, Uchiyama T, Liu Z, Ito T, Awa Y et al (2009) Questionnaire-based assessment of pelvic organ dysfunction in multiple system atrophy. Mov Disord 24(7):972–978. https://doi.org/10.1002/mds.22332CrossRefPubMed

37.

Köllensperger M, Geser F, Ndayisaba JP, Boesch S, Seppi K, Ostergaard K et al (2010) Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European Multiple System Atrophy Registry. Mov Disord 25(15):2604–2612. https://doi.org/10.1002/mds.23192CrossRefPubMed

38.

Kim HJ, Jeon BS, Lee JY, Yun JY (2011) Survival of Korean patients with multiple system atrophy. Mov Disord 26(5):909–912. https://doi.org/10.1002/mds.23580CrossRefPubMed

39.

Wenning GK, Geser F, Krismer F, Seppi K, Duerr S, Boesch S et al (2013) The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 12(3):264–274. https://doi.org/10.1016/s1474-4422(12)70327-7CrossRefPubMedPubMedCentral

40.

Roncevic D, Palma JA, Martinez J, Goulding N, Norcliffe-Kaufmann L, Kaufmann H (2014) Cerebellar and parkinsonian phenotypes in multiple system atrophy: similarities, differences and survival. J Neural Transm (Vienna) 121(5):507–512. https://doi.org/10.1007/s00702-013-1133-7CrossRefPubMed

41.

Yamamoto T, Sakakibara R, Uchiyama T, Yamaguchi C, Ohno S, Nomura F et al (2014) Time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy. Neurourol Urodyn 33(5):516–523. https://doi.org/10.1002/nau.22441CrossRefPubMed

42.

Figueroa JJ, Singer W, Parsaik A, Benarroch EE, Ahlskog JE, Fealey RD et al (2014) Multiple system atrophy: prognostic indicators of survival. Mov Disord 29(9):1151–1157. https://doi.org/10.1002/mds.25927CrossRefPubMedPubMedCentral

43.

Low PA, Reich SG, Jankovic J, Shults CW, Stern MB, Novak P et al (2015) Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol 14(7):710–719. https://doi.org/10.1016/s1474-4422(15)00058-7CrossRefPubMedPubMedCentral

44.

Coon EA, Sletten DM, Suarez MD, Mandrekar JN, Ahlskog JE, Bower JH et al (2015) Clinical features and autonomic testing predict survival in multiple system atrophy. Brain 138(Pt 12):3623–3631. https://doi.org/10.1093/brain/awv274CrossRefPubMedPubMedCentral

45.

Starhof C, Korbo L, Lassen CF, Winge K, Friis S (2016) Clinical features in a Danish population-based cohort of probable multiple system atrophy patients. Neuroepidemiology 46(4):261–267. https://doi.org/10.1159/000444325CrossRefPubMed

46.

Glasmacher SA, Leigh PN, Saha RA (2017) Predictors of survival in progressive supranuclear palsy and multiple system atrophy: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 88(5):402–411. https://doi.org/10.1136/jnnp-2016-314956CrossRefPubMed

47.

Savica R, Grossardt BR, Bower JH, Ahlskog JE, Boeve BF, Graff-Radford J et al (2017) Survival and causes of death among people with clinically diagnosed synucleinopathies with parkinsonism: a population-based study. JAMA Neurol 74(7):839–846. https://doi.org/10.1001/jamaneurol.2017.0603CrossRefPubMedPubMedCentral

48.

Zhang LY, Cao B, Zou YT, Wei QQ, Ou RW, Zhao B et al (2018) Depression and anxiety in multiple system atrophy. Acta Neurol Scand 137(1):33–37. https://doi.org/10.1111/ane.12804CrossRefPubMed

49.

Zhang L, Cao B, Zou Y, Wei QQ, Ou R, Liu W et al (2018) Causes of death in Chinese patients with multiple system atrophy. Aging Dis 9(1):102–108. https://doi.org/10.14336/ad.2017.0711CrossRefPubMedPubMedCentral

50.

Jecmenica-Lukic MV, Pekmezovic TD, Petrovic IN, Dragasevic NT, Kostić VS (2018) Factors associated with deterioration of health-related quality of life in multiple system atrophy: 1-year follow-up study. Acta Neurol Belg 118(4):589–595. https://doi.org/10.1007/s13760-018-0962-4CrossRefPubMed

51.

Foubert-Samier A, Pavy-Le Traon A, Guillet F, Le-Goff M, Helmer C, Tison F et al (2020) Disease progression and prognostic factors in multiple system atrophy: a prospective cohort study. Neurobiol Dis 139:104813. https://doi.org/10.1016/j.nbd.2020.104813CrossRefPubMed

52.

McCarter SJ, Coon EA, Savica R, St Louis EK, Bower JH, Benarroch EE et al (2020) Lower vitamin B12 level at multiple system atrophy diagnosis is associated with shorter survival. Mov Disord 35(8):1462–1466. https://doi.org/10.1002/mds.28070CrossRefPubMedPubMedCentral

53.

Lin JY, Zhang LY, Cao B, Wei QQ, Ou RW, Hou YB et al (2020) Sleep-related symptoms in multiple system atrophy: determinants and impact on disease severity. Chin Med J (Engl) 134(6):690–698. https://doi.org/10.1097/cm9.0000000000001211CrossRefPubMed

54.

Gurevich T, Merkin L, Rozenberg A, Fisher A, Atanasova Mishkova-Serafimova E, Klepikov D et al (2021) Interrelationships between survival, sex, and blood pressure in patients with multiple system atrophy. Neuroepidemiology 55(1):56–61. https://doi.org/10.1159/000512697CrossRef

55.

Eschlböck S, Kiss G, Krismer F, Fanciulli A, Kaindlstorfer C, Raccagni C et al (2021) Urodynamic evaluation in multiple system atrophy: a retrospective cohort study. Mov Disord Clin Pract 8(7):1052–1060. https://doi.org/10.1002/mdc3.13307CrossRefPubMedPubMedCentral

56.

Wang H, Tang X, Zhou J, Xu Y (2021) Excessive daytime sleepiness is associated with non-motor symptoms of multiple system atrophy: a cross-sectional study in China. Front Neurol 12:798771. https://doi.org/10.3389/fneur.2021.798771CrossRefPubMed

57.

Pavy-Le Traon A, Foubert-Samier A, Ory-Magne F, Fabbri M, Senard JM, Meissner WG et al (2022) Ambulatory blood pressure and drug treatment for orthostatic hypotension as predictors of mortality in patients with multiple system atrophy. Eur J Neurol 29(4):1025–1034. https://doi.org/10.1111/ene.15232CrossRefPubMed

58.

Zhou H, Sun Y, Wei L, Wang X, Jiang Y, Li F et al (2022) Quantitative assessment of oculomotor function by videonystagmography in multiple system atrophy. Clin Neurophysiol 141:15–23. https://doi.org/10.1016/j.clinph.2022.05.019CrossRefPubMed

59.

Xie D, Huang H, Zhao Q, Ning P, Shen Q, Lu H et al (2022) Prevalence and associated factors of frailty and sarcopenia in multiple system atrophy and progressive supranuclear palsy: a cross-sectional study. Neurol Sci 43(11):6329–6337. https://doi.org/10.1007/s10072-022-06296-1CrossRefPubMed

60.

Hu WZ, Cao LX, Yin JH, Zhao XS, Piao YS, Gu WH et al (2022) Non-motor symptoms in multiple system atrophy: a comparative study with Parkinson’s disease and progressive supranuclear palsy. Front Neurol 13:1081219. https://doi.org/10.3389/fneur.2022.1081219CrossRefPubMed

61.

Zhang J, Han J, Shi Z, Zhang J, Zhou Z, Liu J et al (2023) The characteristic of nonmotor symptoms with different phenotypes and onsets in multiple system atrophy patients. J Clin Neurosci 109:1–5. https://doi.org/10.1016/j.jocn.2022.12.012CrossRefPubMed

62.

Altmann CF, Koschel J, Jost WH (2023) Predictors of falls in Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy: a retrospective study. Neurol Neurochir Pol 57(3):297–304. https://doi.org/10.5603/PJNNS.a2023.0036CrossRefPubMed

63.

Fanciulli A, Strano S, Colosimo C, Caltagirone C, Spalletta G, Pontieri FE (2013) The potential prognostic role of cardiovascular autonomic failure in α-synucleinopathies. Eur J Neurol 20(2):231–235. https://doi.org/10.1111/j.1468-1331.2012.03819.xCrossRefPubMed

64.

Angelousi A, Girerd N, Benetos A, Frimat L, Gautier S, Weryha G et al (2014) Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis. J Hypertens;32(8):1562–1571; discussion 71. https://doi.org/10.1097/hjh.0000000000000235

65.

Ricci F, De Caterina R, Fedorowski A (2015) Orthostatic hypotension: epidemiology, prognosis, and treatment. J Am Coll Cardiol 66(7):848–860. https://doi.org/10.1016/j.jacc.2015.06.1084CrossRefPubMed

66.

Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS (1992) Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension 19(6 Pt 1):508–519. https://doi.org/10.1161/01.hyp.19.6.508CrossRefPubMed

67.

Alagiakrishnan K, Patel K, Desai RV, Ahmed MB, Fonarow GC, Forman DE et al (2014) Orthostatic hypotension and incident heart failure in community-dwelling older adults. J Gerontol A Biol Sci Med Sci 69(2):223–230. https://doi.org/10.1093/gerona/glt086CrossRefPubMed

68.

Wolters FJ, Mattace-Raso FU, Koudstaal PJ, Hofman A, Ikram MA (2016) Orthostatic hypotension and the long-term risk of dementia: a population-based study. PLoS Med 13(10):e1002143. https://doi.org/10.1371/journal.pmed.1002143CrossRefPubMedPubMedCentral

69.

Méndez AS, Melgarejo JD, Mena LJ, Chávez CA, González AC, Boggia J et al (2018) Risk factors for orthostatic hypotension: differences between elderly men and women. Am J Hypertens 31(7):797–803. https://doi.org/10.1093/ajh/hpy050CrossRefPubMedPubMedCentral

70.

Szewczyk-Krolikowski K, Tomlinson P, Nithi K, Wade-Martins R, Talbot K, Ben-Shlomo Y et al (2014) The influence of age and gender on motor and non-motor features of early Parkinson’s disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort. Parkinsonism Relat Disord 20(1):99–105. https://doi.org/10.1016/j.parkreldis.2013.09.025CrossRefPubMed

71.

Campese N, Goebel G, Leys F, Ndayisaba JP, Eschlboeck S, Eckhardt C et al (2021) Orthostatic hypotension in Parkinson’s disease: do height and weight matter? Mov Disord 36(11):2703–2705. https://doi.org/10.1002/mds.28768CrossRefPubMedPubMedCentral

72.

Bourgeois B, Watts K, Thomas DM, Carmichael O, Hu FB, Heo M et al (2017) Associations between height and blood pressure in the United States population. Medicine 96(50):e9233. https://doi.org/10.1097/md.0000000000009233CrossRefPubMedPubMedCentral

73.

Wells JC (2007) Sexual dimorphism of body composition. Best Pract Res Clin Endocrinol Metab 21(3):415–430. https://doi.org/10.1016/j.beem.2007.04.007CrossRefPubMed

74.

Baker SE, Limberg JK, Ranadive SM, Joyner MJ (2016) Neurovascular control of blood pressure is influenced by aging, sex, and sex hormones. Am J Physiol Regul Integr Comp Physiol 311(6):R1271–R1275. https://doi.org/10.1152/ajpregu.00288.2016CrossRefPubMedPubMedCentral

75.

Fanciulli A, Leys F, Falup-Pecurariu C, Thijs R, Wenning GK (2020) Management of orthostatic hypotension in Parkinson’s disease. J Parkinsons Dis 10(s1):S57–S64. https://doi.org/10.3233/JPD-202036CrossRefPubMedPubMedCentral

76.

Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S et al (2017) The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 264(8):1567–1582. https://doi.org/10.1007/s00415-016-8375-xCrossRefPubMedPubMedCentral

77.

Zhao M, Woodward M, Vaartjes I, Millett ERC, Klipstein-Grobusch K, Hyun K et al (2020) Sex differences in cardiovascular medication prescription in primary care: a systematic review and meta-analysis. J Am Heart Assoc 9(11):e014742. https://doi.org/10.1161/jaha.119.014742CrossRefPubMedPubMedCentral

78.

Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL et al (2023) Heart disease and stroke statistics-2023 update: a report from the American Heart Association. Circulation 147(8):e93–e621. https://doi.org/10.1161/cir.0000000000001123CrossRefPubMed

79.

Fanciulli A, Jordan J, Biaggioni I, Calandra-Buonaura G, Cheshire WP, Cortelli P et al (2018) Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS): endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH). Clin Auton Res 28(4):355–362. https://doi.org/10.1007/s10286-018-0529-8CrossRefPubMedPubMedCentral

80.

Palma JA, Redel-Traub G, Porciuncula A, Samaniego-Toro D, Millar Vernetti P, Lui YW et al (2020) The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension. Parkinsonism Relat Disord 75:97–104. https://doi.org/10.1016/j.parkreldis.2020.04.011CrossRefPubMedCentral

81.

Sonnenberg CM, Beekman AT, Deeg DJ, van Tilburg W (2000) Sex differences in late-life depression. Acta Psychiatr Scand 101(4):286–292. https://doi.org/10.1034/j.1600-0447.2000.101004286.xCrossRef

82.

Salk RH, Hyde JS, Abramson LY (2017) Gender differences in depression in representative national samples: meta-analyses of diagnoses and symptoms. Psychol Bull 143(8):783–822. https://doi.org/10.1037/bul0000102CrossRefPubMedCentral

83.

Eid RS, Gobinath AR, Galea LAM (2019) Sex differences in depression: insights from clinical and preclinical studies. Prog Neurobiol 176:86–102. https://doi.org/10.1016/j.pneurobio.2019.01.006CrossRefPubMed

84.

Lv Q, Pan Y, Chen X, Wei J, Wang W, Zhang H et al (2022) Depression in multiple system atrophy: views on pathological, clinical and imaging aspects. Front Psychiatry 13:980371. https://doi.org/10.3389/fpsyt.2022.980371CrossRefPubMedPubMedCentral

85.

Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H et al (2004) Psychotropic drug utilization in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 420:55–64. https://doi.org/10.1111/j.1600-0047.2004.00331.xCrossRef

86.

Kovess-Masfety V, Boyd A, van de Velde S, de Graaf R, Vilagut G, Haro JM et al (2014) Are there gender differences in service use for mental disorders across countries in the European Union? Results from the EU-World Mental Health survey. J Epidemiol Community Health 68(7):649–656. https://doi.org/10.1136/jech-2013-202962CrossRefPubMed

87.

Boyd A, Van de Velde S, Pivette M, Ten Have M, Florescu S, O’Neill S et al (2015) Gender differences in psychotropic use across Europe: results from a large cross-sectional, population-based study. Eur Psychiatry 30(6):778–788. https://doi.org/10.1016/j.eurpsy.2015.05.001CrossRefPubMed

88.

Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero JJ, DeMeo DL et al (2020) Sex and gender: modifiers of health, disease, and medicine. Lancet 396(10250):565–582. https://doi.org/10.1016/s0140-6736(20)31561-0CrossRefPubMedPubMedCentral

89.

Vegeto E, Villa A, Della Torre S, Crippa V, Rusmini P, Cristofani R et al (2020) The role of sex and sex hormones in neurodegenerative diseases. Endocr Rev 41(2):273–319. https://doi.org/10.1210/endrev/bnz005CrossRefPubMed

90.

Hirohata M, Ono K, Morinaga A, Ikeda T, Yamada M (2009) Anti-aggregation and fibril-destabilizing effects of sex hormones on alpha-synuclein fibrils in vitro. Exp Neurol 217(2):434–439. https://doi.org/10.1016/j.expneurol.2009.03.003CrossRefPubMed

91.

Eschlboeck S, Goebel G, Eckhardt C, Fanciulli A, Raccagni C, Boesch S et al (2023) Development and validation of a prognostic model to predict overall survival in multiple system atrophy. Mov Disord Clin Pract 10(9):1368–1376. https://doi.org/10.1002/mdc3.13822CrossRefPubMedPubMedCentral

Title: Sex-related differences in the clinical presentation of multiple system atrophy
Authors: Fabian Leys
Sabine Eschlböck
Nicole Campese
Philipp Mahlknecht
Marina Peball
Georg Goebel
Victoria Sidoroff
Florian Krismer
Roberta Granata
Stefan Kiechl
Werner Poewe
Klaus Seppi
Gregor K. Wenning
Alessandra Fanciulli
Publication date: 17-04-2024
Publisher: Springer Berlin Heidelberg
Published in: Clinical Autonomic Research
Print ISSN: 0959-9851
Electronic ISSN: 1619-1560
DOI: https://doi.org/10.1007/s10286-024-01028-1

At a glance: The STEP trials

Springer Medicine

Sex-related differences in the clinical presentation of multiple system atrophy

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content