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The relevance of gender in Parkinson’s disease: a review

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Abstract

Since the official and systematic inclusion of sex and gender in biomedical research, gender differences have been acknowledged as important determinants of both the susceptibility to develop neurodegenerative diseases in general population and the clinical and therapeutic management of neurodegenerative patients. In this review, we gathered the available evidence on gender differences in Parkinson’s disease (PD) regarding clinical phenotype (including motor and non-motor symptoms), biomarkers, genetics and therapeutic management (including pharmacological and surgical treatment). Finally, we will briefly discuss the role of estrogens in determining such differences. Several data demonstrate that PD in women starts with a more benign phenotype, likely due to the effect of estrogens. However, as the disease progresses, women are at higher risk of developing highly disabling treatment-related complications, such as motor and non-motor fluctuations as well as dyskinesia, compared with men. In addition, women have lower chances of receiving effective treatment for PD as deep brain stimulation. Taken together these findings challenge the definition of a more benign phenotype in women. Still, much work needs to be done to better understand the interaction between gender, genetics and environmental factors in determining the PD risk and clinical features. Improving our understanding in this field may result in implementation of strategies to identify prodromal PD and speed efforts to discern new directions for disease tailored treatment and management.

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Abbreviations

AUC:

Area under the curve

F:

Female

M:

Male

LEDD:

Levodopa equivalent daily dose

NMS:

Non motor symptoms

PD:

Parkinson’s disease

UPDRS-III:

Unified Parkinson’s Disease Rating Scale part III

References

  1. Institute of Medicine Board on Health Sciences Policy, Committee on Understanding the Biology of Sex and Gender Differences. (2001) Exploring the biological contributions to human health: does sex matter? In: Wizemann TM, Pardue M-L (eds) Institute of Medicine, Washington,DC

  2. Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JP (2016) Environmental risk factors and Parkinson’s disease: an umbrella review of meta-analyses. Parkinsonism Relat Disord 23:1–9

    Article  PubMed  Google Scholar 

  3. Mazure CM, Jones DP (2015) Twenty years and still counting: including women as participants and studying sex and gender in biomedical research. BMC Womens Health 15:94

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mazure CM, Swendsen J (2016) Sex differences in Alzheimer’s disease and other dementias. Lancet Neurol 15:451–452

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wooten GF, Currie LJ, Bovbjerg VE, Lee JK, Patrie J (2004) Are men at greater risk for Parkinson’s disease than women? J Neurol Neurosurg Psychiatry 75:637–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Taylor KSM, Cook JA, Counsell CE (2007) Heterogeneity in male to female risk for Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:905–912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Burn DJ (2007) Sex and Parkinson’s disease: a word of difference? J Neurol Neurosurg Psychiatry 78:787

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pringsheim T, Jette N, Frolkis A, Steeves TD (2014) The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 29:1583–1590

    Article  PubMed  Google Scholar 

  9. Moisan F, Kab S, Mohamed F et al (2015) Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J Neurol Neurosurg Psychiatry 87:952–957

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lonneke ML de Lau, Dagmar Verbaan A, Johan Marinus A, van Hilten JJ (2014) Survival in Parkinson’s disease, Relation with motor and non-motor Features, Parkinsonism and Related Disorders 20: 613–616

  11. Pinter B, Diem-Zangerl A, Wenning GK et al (2015) Mortality in Parkinson’s disease: a 38-year follow-up study. Mov Disord 30:266–269

    Article  PubMed  Google Scholar 

  12. Xu J, Gong DD, Man CF, Fan Y (2014) Parkinson’s disease and risk of mortality: meta-analysis and systematic review. Acta Neurol Scand 129:71–79

    Article  CAS  PubMed  Google Scholar 

  13. Haaxma CA, Bloem BR, Borm GF et al (2007) Gender differences in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:819–824

    Article  PubMed  Google Scholar 

  14. Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G (2013) Reproductive factors and clinical features of Parkinson’s disease. Parkinsonism Related Disorders 19:1094–1099

    Article  PubMed  Google Scholar 

  15. Adamson J, Ben-Shlomo Y, Chaturvedi N, Donovan J (2003) Ethnicity, socio-economic position and gender—do they affect reported health-care seeking behaviour? Soc Sci Med 57:895–904

    Article  PubMed  Google Scholar 

  16. Saunders-Pullman R, Wang C, Stanley K, Bressman SB (2011) Diagnosis and Referral Delay in Women With Parkinson’s Disease. Gend Med 8:209–217

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sato K, Hatano T, Yamashiro K et al (2006) Prognosis of Parkinson’s disease: time to stage III, IV, V, and to motor fluctuations. Mov Disord 21:1384–1395

    Article  PubMed  Google Scholar 

  18. Bjornestad A, Forsaa EB, Pedersen KF, Tysnes OB, Larsen JP, Alves G (2016) Risk and course of motor complications in a population-based incident Parkinson’s disease cohort. Parkinsonism Related Disorders 22:48–53

    Article  PubMed  Google Scholar 

  19. Colombo D, Abbruzzese G, Antonini A et al (2015) The ‘‘Gender Factor’’ in Wearing-Off among Patients with Parkinson’s Disease: a post Hoc analysis of DEEP study. Sci World J 787451

  20. Zappia M, Annesi G, Nicoletti G et al (2005) Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Arch Neurol 62:601–605

    Article  PubMed  Google Scholar 

  21. Sharma JC, Bachmann CG, Linazasoro G (2010) Classifying risk factors for dyskinesia in Parkinson’s disease. Park Relat Disord 16:490–497

    Article  CAS  Google Scholar 

  22. Hassin-Baer S, Molchadski I, Cohen OS et al (2011) Gender effect on time to levodopa-induced dyskinesias. J Neurol 258:2048–2053

    Article  CAS  PubMed  Google Scholar 

  23. Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE (2011) Symptomatology and markers of anxiety disorders in Parkinson’s disease: a cross-sectional study. Mov Disord 26:484–492

    Article  PubMed  Google Scholar 

  24. Leentjens AF, Moonen AJ, Dujardin K (2013) Modeling depression in Parkinson disease: disease-specific and nonspecific risk factors. Neurology 81:1036–1043

    Article  PubMed  PubMed Central  Google Scholar 

  25. Szewczyk-Krolikowski K, Tomlinson P, Nithi K (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 20:99–105

    Article  PubMed  Google Scholar 

  26. Solla P, Cannas A, Ibba FC (2012) Gender differences in motor and non-motor symptoms among Sardinian patients with Parkinson’s disease. J Neurol Sci 323:33–39

    Article  PubMed  Google Scholar 

  27. Martinez-Martin P, Falup Pecurariu C (2012) Gender-related differences in the burden of non-motor symptoms in Parkinson’s disease. J Neurol 259:1639–1647

    Article  PubMed  Google Scholar 

  28. Erro R, Picillo M, Vitale C (2013) Non-motor symptoms in early Parkinson’s disease: a 2-years follow-up study on previously untreated patients. J Neurol Neurosurg Psychiatry 84:14–17

    Article  PubMed  Google Scholar 

  29. Picillo M, Amboni M, Erro R et al (2013) Gender differences in non-motor symptoms in early, drug naïve Parkinson’s disease. J Neurol 260:2849–2855

    Article  PubMed  Google Scholar 

  30. Song Y, Gu Z, An J, Chan P; Chinese Parkinson Study Group (2014) Gender differences on motor and non-motor symptoms of de novo patients with early Parkinson’s disease. Neurol Sci 35:1991–1996

    Article  Google Scholar 

  31. Shen CC, Tsai SJ, Perng CL, Kuo BI, Yang AC (2013) Risk of Parkinson disease after depression: a nationwide population-based study. Neurology 81:1538–1544

    Article  CAS  PubMed  Google Scholar 

  32. Postuma RB, Gagnon JF, Bertrand JA, Génier Marchand D, Montplaisir JY (2015) Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology 84:1104–1113

    Article  PubMed  PubMed Central  Google Scholar 

  33. Picillo M, Pellecchia MT, Erro R et al (2014) The use of University of Pennsylvania Smell Identification Test in the diagnosis of Parkinson’s disease in Italy. Neurol Sci 35:379–3783

    Article  PubMed  Google Scholar 

  34. Liu R, Umbach DM, Peddada SD, Xu Z, Tröster AI, Huang X, Chen H (2015) Potential sex differences in non motor symptoms in early drug-naive Parkinson disease. Neurology 84:2107–2115

    Article  PubMed  PubMed Central  Google Scholar 

  35. Picillo M, Erro R, Amboni M et al (2014) Gender differences in non-motor symptoms in early Parkinson’s disease: a 2-years follow-up study on previously untreated patients. Parkinsonism Relat Disord 20:850–854

    Article  PubMed  Google Scholar 

  36. Guo X, Song W, Chen K et al (2013) Gender and onset age-related features of non-motor symptoms of patients with Parkinson’s disease—a study from Southwest China. Parkinsonism Relat Disord 19:961–965

    Article  PubMed  Google Scholar 

  37. Picillo M, Palladino R, Moccia M et al (2016) Gender and non motor fluctuations in Parkinson’s disease: a prospective study. Parkinsonism Relat Disord 27:89–92

    Article  PubMed  Google Scholar 

  38. Uc EY, McDermott MP, Marder KS et al (2009) Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort. Neurology 73:1469–1477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Anang JB, Gagnon JF, Bertrand JA et al (2014) Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology 83:1253–1560

    Article  PubMed  PubMed Central  Google Scholar 

  40. Pigott K, Rick J, Xie SX et al (2015) Longitudinal study of normal cognition in Parkinson disease. Neurology 85:1276–1282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cereda E, Cilia R, Klersy C et al (2016) Dementia in Parkinson’s disease: is male gender a risk factor? Parkinsonism Relat Disord 26:67–72

    Article  PubMed  Google Scholar 

  42. Nicoletti A, Vasta R, Mostile G et al (2016) Gender effect on non motor symptoms in parkinson’s disease: are men more at risk? Parkinsonims Relat Disord. doi:10.1016/j.parkreldis.2016.12.008

    Google Scholar 

  43. Brighina L, Prigione A, Begni B et al (2010) Lymphomonocyte alpha-synuclein levels in aging and in Parkinson disease. Neurobiol Aging 31:884–885

    Article  CAS  PubMed  Google Scholar 

  44. Ikeda K, Nakamura Y, Kiyozuka T et al (2011) Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson’s disease: changes linked to disease progression. Neurodegener Dis 8:252–258

    Article  CAS  PubMed  Google Scholar 

  45. Caranci G, Piscopo P, Rivabene R et al (2013) Gender differences in Parkinson’s disease: focus on plasma α-synuclein. J Neural Transm 120:1209–1215

    Article  CAS  PubMed  Google Scholar 

  46. Ho DH, Yi S, Seo H, Son I, Seol W (2014) Increased DJ-1 in urine exosome of Korean males with Parkinson’s disease. Biomed Res Int 704678

  47. Schwarzschild MA, Schwid SR, Marek K et al (2008) Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease. Arch Neurol 265:716–723

    Article  Google Scholar 

  48. Ascherio A, LeWitt PA, Xu K et al (2009) Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol 66:1460–1468

    Article  PubMed  PubMed Central  Google Scholar 

  49. Schwarzschild MA, Marek K, Eberly S et al (2011) Serum urate and probability of dopaminergic deficit in early “Parkinson’s disease”. Mov Disord 26:1864–1868

    Article  PubMed  PubMed Central  Google Scholar 

  50. Jesus S, Pérez I, Cáceres-Redondo MT et al (2013) Low serum uric acid concentration in Parkinson’s disease in southern Spain. Eur J Neurol 20:208–210

    Article  CAS  PubMed  Google Scholar 

  51. McFarland NR, Burdett T, Desjardins CA, Frosch MP, Schwarzschild MA (2013) Postmortem brain levels of urate and precursors in Parkinson’s disease and related disorders. Neurodegener Dis 12:189–198

    Article  CAS  PubMed  Google Scholar 

  52. Gao X, O’Reilly ÉJ, Schwarzschild MA, Ascherio A (2016) Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology 86:520–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Foltynie T, Lewis SG, Goldberg TE et al (2005) The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease. J Neurol 252:833–838

    Article  CAS  PubMed  Google Scholar 

  54. Gatt AP, Jones EL, Francis PT, Ballard C, Bateman JM (2013) Association of a polymorphism in mitochondrial transcription factor A (TFAM) with Parkinson’s disease dementia but not dementia with Lewy bodies. Neurosci Lett 557:177–180

    Article  CAS  PubMed  Google Scholar 

  55. Gusdon AM, Fang F, Chen J et al (2015) Association of the mt-ND2 5178A/C polymorphism with Parkinson’s disease. Neurosci Lett 587:98–101

    Article  CAS  PubMed  Google Scholar 

  56. Klebe S, Golmard JL, Nalls MA et al (2004) The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson’s disease with a sexual dimorphism. J Neurol Neurosurg Psychiatry 84:666–673

    Article  Google Scholar 

  57. Lin JJ, Yueh KC, Chang CY, Chen CH, Lin SZ (2004) The homozygote AA genotype of the alpha1-antichymotrypsin gene may confer protection against early-onset Parkinson’s disease in women. Parkinsonism Relat Disord 10:469–473

    Article  CAS  PubMed  Google Scholar 

  58. Lin JJ, Chen CH, Yueh KC, Chang CY, Lin SZ (2006) A CD14 monocyte receptor polymorphism and genetic susceptibility to Parkinson’s disease for females. Parkinsonism Relat Disord 12:9–13

    Article  CAS  PubMed  Google Scholar 

  59. Liu RR, Zhou LL, Cheng X et al (2014) CCDC62 variant rs12817488 is associated with the risk of Parkinson’s disease in a Han Chinese population. Eur Neurol 71:77–83

    Article  CAS  PubMed  Google Scholar 

  60. Mariani S, Ventriglia M, Simonelli I et al (2016) Association between sex, systemic iron variation and probability of Parkinson’s disease. Int J Neurosci 126:354–360

    Article  CAS  PubMed  Google Scholar 

  61. Palacios N, Weisskopf M, Simon K, Gao X, Schwarzschild M, Ascherio A (2010) Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson’s disease in men and women. Parkinsonism Relat Disord 16:370–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. San Luciano M, Ozeliusb L, Liptonc RB, Raymonda D, Bressman SB, Saunders-Pullman R (2012) Gender differences in the IL6-174G>C and ESR2 1730G>A polymorphisms and the risk of Parkinson’s disease. Neurosci Lett 506:312–316

    Article  CAS  PubMed  Google Scholar 

  63. Simunovic F, Yi M, Wang Y, Stephens R, Sonntag KC (2010) Evidence for gender-specific transcriptional profiles of Nigral dopamine neurons in Parkinson disease. PLoS ONE 5:e8856

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Yu RL, Guo JF, Wang YQ et al (2015) The single nucleotide polymorphism Rs12817488 is associated with Parkinson’s disease in the Chinese population. J Clin Neurosci 22:1002–1004

    Article  CAS  PubMed  Google Scholar 

  65. Zhang P, Liu L, Huang J et al (2014) Non-SMC condensin I complex, subunit D2 gene polymorphisms are associated with Parkinson’s disease: a Han Chinese study. Genome 57:253–257

    Article  CAS  PubMed  Google Scholar 

  66. Zhao J, Han X, Xue L, Zhu K, Liu H, Xie A (2015) Association of TLR4 gene polymorphisms with sporadic Parkinson’s disease in a Han Chinese population. Neurol Sci 36:1659–1665

    Article  PubMed  Google Scholar 

  67. Agalliu I, San Luciano M, Mirelman A et al (2015) Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson disease: a pooled analysis. JAMA Neurol 72:58–65

    Article  PubMed  PubMed Central  Google Scholar 

  68. Cilia R, Siri C, Rusconi D et al (2014) LRRK2 mutations in Parkinson’s disease: confirmation of a gender effect in the Italian population. Parkinsonism Relat Disord 20:911–914

    Article  PubMed  PubMed Central  Google Scholar 

  69. Clark LN, Wang Y, Karlins E et al (2006) Frequency of LRRK2 mutations in early- and late-onset Parkinson disease. Neurology 67:1786–1791

    Article  CAS  PubMed  Google Scholar 

  70. Orr-Urtreger A, Shifrin C, Rozovski U, Rosner S et al (2007) The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect? Neurology 69:1595–1602

    Article  CAS  PubMed  Google Scholar 

  71. Saunders-Pullman R, Stanley K, San Luciano M, Barrett MJ et al (2011) Gender differences in the risk of familial parkinsonism: beyond LRRK2? Neurosci Lett 496:125–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mirelman A, Alcalay RN, Saunders-Pullman R et al (2015) Nonmotor symptoms in healthy Ashkenazi Jewish carriers of the G2019S mutation in the LRRK2 gene. Mov Disord 30:981–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gan-Or Z, Bar-Shira AA, Mirelman A et al (2010) LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease. Neurogenetics 11:121–125

    Article  CAS  PubMed  Google Scholar 

  74. Gan-Or Z, Leblond CS, Mallett V, Orr-Urtreger A, Dion PA, Rouleau G (2015) LRRK2 mutations in Parkinson disease; a sex effect or lack thereof? A meta-analysis. Parkinsonism Relat Disord 21:778–782

    Article  PubMed  Google Scholar 

  75. Lang AE, Lees A (2002) Management of Parkinson’s Disease: an evidence-based review. Mov Disord 17:S1–S166

    Article  Google Scholar 

  76. Ferreira JJ, Katzenschlager R, Bloem BR et al (2013) Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol 20:5–15

    Article  CAS  PubMed  Google Scholar 

  77. Umeh CC, Pérez A, Augustine EF et al (2014) No sex differences in use of dopaminergic medication in early Parkinson disease in the US and Canada—baseline findings of a multicenter trial. PLoS One 9:e112287

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Baba Y, Putzke JD, Whaley NR, Wszolek ZK, Uitti RJ (2005) Gender and the Parkinson’s disease phenotype. J Neurol 252:1201–1205

    Article  PubMed  Google Scholar 

  79. Nyholm D, Karlsson E, Lundberg M, Askmark H (2010) Large differences in levodopa dose requirement in Parkinson’s disease: men use higher doses than women. Eur J Neurol 17:260–266

    Article  CAS  PubMed  Google Scholar 

  80. Lubomski M, Louise Rushworth R, Lee W, Bertram KL, Williams DR (2014) Sex differences in Parkinson’s disease. J Clin Neurosci 21:1503–1506

    Article  PubMed  Google Scholar 

  81. Nyholm D, Constantinescu R, Holmberg B, Dizdar N, Askmark H (2009) Comparison of apomorphine and levodopa infusions in four patients with Parkinson’s disease with symptom fluctuations. Acta Neurol Scand 119:345–348

    Article  CAS  PubMed  Google Scholar 

  82. Sharma JC, Macnamara L, Hasoon M, Vassallo M, Ross I (2006) Cascade of levodopa dose and weight-related dyskinesia in Parkinson’s disease (LD–WD-PD cascade). Parkinsonism Relat Disord 12:499–505

    Article  PubMed  Google Scholar 

  83. Sharma JC, Ross IN, Rascol O, Brooks D (2008) Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight. Eur J Neurol 15:493–496

    Article  CAS  PubMed  Google Scholar 

  84. Kompoliti K, Adler CH, Raman R et al (2002) Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics. Neurology 58:1418–1422

    Article  CAS  PubMed  Google Scholar 

  85. Arabia G, Zappia M, Bosco D et al (2002) Body weight, levodopa pharmacokinetics and dyskinesia in Parkinson’s disease. Neurol Sci 23:S53–S54

    Article  PubMed  Google Scholar 

  86. Kumagai T, Nagayama H, Ota T, Nishiyama Y, Mishina M, Ueda M (2014) Sex differences in the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Clin Neuropharmacol 37:173–176

    Article  CAS  PubMed  Google Scholar 

  87. Martinelli P, Contin M, Scaglione C, Riva R, Albani F, Baruzzi A (2003) Levodopa pharmacokinetics and dyskinesias: are there sex-related differences? Neurol Sci 24:192–193

    Article  CAS  PubMed  Google Scholar 

  88. Martinez-Ramirez D, Giugni J, Vedam-Mai V et al (2014) The “brittle response” to Parkinson’s disease medications: characterization and response to deep brain stimulation. PLoS One 9:e94856

    Article  PubMed  PubMed Central  Google Scholar 

  89. Montaurier C, Morio B, Bannier S, Derost P et al (2007) Mechanisms of body weight gain in patients with Parkinson’s disease after subthalamic stimulation. Brain 130:1808–1818

    Article  CAS  PubMed  Google Scholar 

  90. Kleiner-Fisman G, Herzog J, Fisman DN et al (2006) Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord 14:S290–S304

    Article  Google Scholar 

  91. Chan AK, McGovern RA, Brown LT et al (2014) Disparities in access to deep brain stimulation surgery for Parkinson disease: interaction between African American race and Medicaid use. JAMA Neurol 71:291–299

    Article  PubMed  Google Scholar 

  92. Willis AW, Schootman M, Kung N, Wang XY, Perlmutter JS, Racette BA (2014) Disparities in deep brain stimulation surgery among insured elders with Parkinson disease. Neurology 82:163–171

    Article  PubMed  PubMed Central  Google Scholar 

  93. Hariz GM, Nakajima T, Limousin P et al (2011) Gender distribution of patients with Parkinson’s disease treated with subthalamic deep brain stimulation; a review of the 2000-2009 literature. Parkinsonism Relat Disord 17:146–149

    Article  PubMed  Google Scholar 

  94. Hamberg K, Hariz GM (2014) The decision-making process leading to deep brain stimulation in men and women with parkinson’s disease—an interview study. BMC Neurol 14:89

    Article  PubMed  PubMed Central  Google Scholar 

  95. Hariz GM, Lindberg M, Hariz MI, Bergenheim AT (2003) Gender differences in disability and health-related quality of life in patients with Parkinson’s disease treated with stereotactic surgery. Acta Neurol Scand 108:28–37

    Article  PubMed  Google Scholar 

  96. Chandran S, Krishnan S, Rao RM, Sarma SG, Sarma PS, Kishore A (2014) Gender influence on selection and outcome of deep brain stimulation for Parkinson’s disease. Ann Indian Acad Neurol 17:66–70

    Article  PubMed  PubMed Central  Google Scholar 

  97. Hariz GM, Limousin P, Zrinzo L et al (2013) Gender differences in quality of life following subthalamic stimulation for Parkinson’s disease. Acta Neurol Scand 128:281–285

    Article  PubMed  Google Scholar 

  98. Chiou SM (2015) Sex-related prognostic predictors for Parkinson disease undergoing subthalamic stimulation. World Neurosurg 84:906–912

    Article  PubMed  Google Scholar 

  99. Accolla E, Caputo E, Cogiaamanian F et al (2007) Gender differences in patients with Parkinson’s disease treated with subthalamic deep brain stimulation. Mov Disord 22:1150–1156

    Article  PubMed  Google Scholar 

  100. Romito LM, Contarino FM, Albanese A (2010) Transient gender-related effects in Parkinson’s disease patients with subthalamic stimulation. J Neurol 257:603–608

    Article  PubMed  Google Scholar 

  101. Scelzo E, Mehrkens JH, Bötzel K, Krack P et al (2015) Deep brain stimulation during pregnancy and delivery: experience from a series of “DBS Babies”. Front Neurol 6:191

    Article  PubMed  PubMed Central  Google Scholar 

  102. Smith KM, Dahodwala N (2014) Sex differences in Parkinson’s disease and other movement disorders. Exp Neurol 259:44–56

    Article  CAS  PubMed  Google Scholar 

  103. Gillies GE, Pienaar IS, Vohra S, Qamhawi Z (2014) Sex differences in Parkinson’s disease. Front Neuroendocrinol 35:370–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Litim N, Morissette M, Di Paolo T (2016) Neuroactive gonadal drugs for neuroprotection in male and female models of Parkinson’s disease. Neurosci Biobehav Rev 67:79–88

    Article  CAS  PubMed  Google Scholar 

  105. Benedetti MD, Maraganore DM, Bower JH et al (2001) Hysterectomy, menopause, and estrogen use preceding Parkinson’s disease: an exploratory case-control study. Mov Disord 16:830–837

    Article  CAS  PubMed  Google Scholar 

  106. Martignoni E, Nappi RE, Citterio A et al (2002) Parkinson’s disease and reproductive life events. Neurol Sci 23:S85–S86

    Article  PubMed  Google Scholar 

  107. Currie LJ, Harrison MB, Trugman JM, Bennett JP, Wooten GF (2004) Postmenopausal estrogen use affects risk for Parkinson disease. Arch Neurol 61:886–888

    Article  PubMed  Google Scholar 

  108. Ragonese P, D’Amelio M, Salemi G et al (2004) Risk of Parkinson disease in women: effect of reproductive characteristics. Neurology 62:2010–2014

    Article  CAS  PubMed  Google Scholar 

  109. Popat RA, Van Den Eeden SK, Tanner CM et al (2005) Effect of reproductive factors and postmenopausal hormone use on the risk of Parkinson disease. Neurology 65:383–390

    Article  CAS  PubMed  Google Scholar 

  110. Ascherio A, Chen H, Schwarzschild MA, Zhang SM, Colditz GA, Speizer FE (2003) Caffeine, postmenopausal estrogen, and risk of Parkinson’s disease. Neurology 60:790–795

    Article  CAS  PubMed  Google Scholar 

  111. Rocca WA, Bower JH, Maraganore DM et al (2008) Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology 70:200–209

    Article  CAS  PubMed  Google Scholar 

  112. Simon KC, Chen H, Gao X, Schwarzschild MA, Ascherio A (2009) Reproductive factors, exogenous estrogen use, and risk of Parkinson’s disease. Mov Disord 24:1359–1365

    Article  PubMed  PubMed Central  Google Scholar 

  113. Nicoletti A, Nicoletti G, Arabia G et al (2011) Reproductive factors and Parkinson’s disease: a multicenter case-control study. Mov Disord 26:2563–2566

    Article  PubMed  Google Scholar 

  114. Frigerio R, Breteler MM, de Lau LM et al (2007) Number of children and risk of Parkinson’s disease. Mov Disord 22:632–639

    Article  PubMed  Google Scholar 

  115. Rugbjerg K, Christensen J, Tjonneland A, Olsen JH (2013) Exposure to estrogen and women’s risk for Parkinson’s disease: a prospective cohort study in Denmark. Parkinsonism Relat Disord 19:457–460

    Article  PubMed  Google Scholar 

  116. Marder K, Tang MX, Alfaro B et al (1998) Postmenopausal estrogen use and Parkinson’s disease with and without dementia. Neurology 50:1141–1143

    Article  CAS  PubMed  Google Scholar 

  117. Greene N, Lassen CF, Rugbjerg K, Ritz B (2014) Reproductive factors and Parkinson’s disease risk in Danish women. Eur J Neurol 21:1168–1177

    Article  CAS  PubMed  Google Scholar 

  118. Liu R, Baird D, Park Y, Freedman ND et al (2014) Female reproductive factors, menopausal hormone use, and Parkinson’s disease. Mov Disord 29:889–896

    Article  PubMed  Google Scholar 

  119. Gatto NM, Deapen D, Stoyanoff S et al (2014) Lifetime exposure to estrogens and Parkinson’s disease in California teachers. Parkinsonism Relat Disord 20:1149–1156

    Article  CAS  PubMed  Google Scholar 

  120. Gardiner SA, Morrison MF, Mozley PD et al (2004) Pilot study on the effect of estrogen replacement therapy on brain dopamine transporter availability in healthy, postmenopausal women. Am J Geriatr Psychiatry 12:621–630

    Article  PubMed  Google Scholar 

  121. Tsang K, Ho S, Lo S (2000) Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations. Neurology 54:2292–2298

    Article  CAS  PubMed  Google Scholar 

  122. Blanchet PJ, Fang J, Hyland K, Arnold LA, Mouradian MM, Chase TN (1999) Short-term effects of high-dose 17beta-estradiol in postmenopausal PD patients: a crossover study. Neurology 53:91–95

    Article  CAS  PubMed  Google Scholar 

  123. Parkinson Study Group POETRY Investigators (2011) A randomized pilot trial of estrogen replacement therapy in post-menopausal women with Parkinson’s disease. Parkinsonism Relat Disord 17:757–760

    Article  Google Scholar 

  124. Nicoletti A et al (2007) Hormonal replacement therapy in women with Parkinson disease and levodopa-induced dyskinesia: a crossover trial. Clin Neuropharmacol 30:276–280

    Article  CAS  PubMed  Google Scholar 

  125. Strijks E, Kremer JA, Horstink MW (1999) Effects of female sex steroids on Parkinson’s disease in postmenopausal women. Clin Neuropharmacol 22:93–97

    Article  CAS  PubMed  Google Scholar 

  126. Voskuhl RR, Wang H, Wu TC et al (2016) Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol 15:35–46

    Article  CAS  PubMed  Google Scholar 

  127. Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333

    Article  CAS  PubMed  Google Scholar 

  128. Picillo M, Fasano A (2015) How much does sex matter in Parkinson disease? Neurology 84:2102–2104

    Article  PubMed  Google Scholar 

  129. Augustine EF, Pérez A, Dhall R et al (2015) Sex differences in clinical features of early, treated Parkinson’s disease. PLoS One 10:e0133002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Fengler S, Roeske S, Heber I et al (2016) Verbal memory declines more in female patients with Parkinson’s disease: the importance of gender-corrected normative data. Psychol Med 46:2275–2286

    Article  CAS  PubMed  Google Scholar 

  131. Gao L, Nie K, Tang H et al (2015) Sex differences in cognition among Chinese people with Parkinson’s disease. J Clin Neurosci 22:488–492

    Article  PubMed  Google Scholar 

  132. Scott B, Borgman A, Engler H, Johnels B, Aquilonius SM (2000) Gender differences in Parkinson’s disease symptom profile. Acta Neurol Scand 102:37–43

    Article  CAS  PubMed  Google Scholar 

  133. Wee N, Kandiah N, Acharyya S, Chander RJ, Ng A, Au WL, Tan LC (2016) Baseline predictors of worsening apathy in Parkinson’s disease: a prospective longitudinal study. Parkinsonism Relat Disord 23:95–98

    Article  PubMed  Google Scholar 

  134. Jain S, Ton TG, Boudreau RM et al (2011) The risk of Parkinson disease associated with urate in a community-based cohort of older adults. Neuroepidemiology 36:223–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Lyons KE, Hubble JP, Tröster AI, Pahwa R, Koller WC (1998) Gender differences in Parkinson’s disease. Clin Neuropharmacol 21:118–121

    CAS  PubMed  Google Scholar 

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Acknowledgements

This review was designed after the authors have been involved in a talk about “Gender differences in movement disorders” during the last meeting of the Italian LIMPE-DISMOV Academy held in Bari on May 4–6, 2016.

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Authors and Affiliations

  1. Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Salerno, 84131, Italy

    Marina Picillo, Paolo Barone & Maria Teresa Pellecchia

  2. Section of Neurosciences, Department GF Ingrassia, University of Catania, Catania, Italy

    Alessandra Nicoletti

  3. Neurologia Fatebenefratelli-ASST Fatebenefratelli Sacco, Milan, Italy

    Vincenza Fetoni

  4. Molecular Neurogenetics Unit, IRCCS Foundation Neurological Institute “Carlo Besta”, Milan, Italy

    Barbara Garavaglia

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  1. Marina Picillo
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  2. Alessandra Nicoletti
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  3. Vincenza Fetoni
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  4. Barbara Garavaglia
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  5. Paolo Barone
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  6. Maria Teresa Pellecchia
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Correspondence to Marina Picillo.

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Picillo, M., Nicoletti, A., Fetoni, V. et al. The relevance of gender in Parkinson’s disease: a review. J Neurol 264, 1583–1607 (2017). https://doi.org/10.1007/s00415-016-8384-9

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  • DOI: https://doi.org/10.1007/s00415-016-8384-9

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