Gender differences in Parkinson's disease: A clinical perspective

Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta‐analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor‐dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross‐sectional. Good‐quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.

[1]  D. Pfaff,et al.  Sex differences in neurological and psychiatric disorders , 2014, Frontiers in Neuroendocrinology.

[2]  L. Abramson,et al.  Development of gender differences in depression: an elaborated cognitive vulnerability-transactional stress theory. , 2001, Psychological bulletin.

[3]  S. Nolen-Hoeksema,et al.  Explaining the gender difference in depressive symptoms. , 1999, Journal of personality and social psychology.

[4]  Gregory F Ball,et al.  Sex Differences in the Brain: The Not So Inconvenient Truth , 2012, The Journal of Neuroscience.

[5]  Z. Wiesenfeld‐Hallin,et al.  Sex differences in pain perception. , 2005, Gender medicine.

[6]  A. Korczyn,et al.  Gender effect on time to levodopa-induced dyskinesias , 2011, Journal of Neurology.

[7]  R. Lipton,et al.  Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy , 2016, Neurology.

[8]  W. Longstreth,et al.  Gender difference in the interaction of smoking and monoamine oxidase B intron 13 genotype in Parkinson's disease. , 2002, Neurotoxicology.

[9]  Z. Mari,et al.  No Sex Differences in Use of Dopaminergic Medication in Early Parkinson Disease in the US and Canada - Baseline Findings of a Multicenter Trial , 2014, PloS one.

[10]  J. J. Lee,et al.  Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease , 2015, Journal of movement disorders.

[11]  D. Aarsland,et al.  Incidence of Parkinson’s disease in Norway: the Norwegian ParkWest study , 2009, Journal of Neurology, Neurosurgery, and Psychiatry.

[12]  G. Wooten,et al.  Are men at greater risk for Parkinson’s disease than women? , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[13]  Murat Emre,et al.  Factors predictive of the development of Levodopa‐induced dyskinesia and wearing‐off in Parkinson's disease , 2013, Movement disorders : official journal of the Movement Disorder Society.

[14]  Bastiaan R Bloem,et al.  Gender differences in Parkinson’s disease , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  Daniel J Schaid,et al.  Risk tables for parkinsonism and Parkinson's disease. , 2002, Journal of clinical epidemiology.

[16]  L. Shulman,et al.  Gender differences in Parkinson's disease. , 2007, Gender medicine.

[17]  R. Uitti,et al.  Gender and the Parkinson’s disease phenotype , 2005, Journal of Neurology.

[18]  D. Inzitari,et al.  Parkinson’s disease and parkinsonism in a longitudinal study , 2000, Neurology.

[19]  A. Friedman,et al.  Reproductive life characteristics in females affected with Parkinson's disease and in healthy control subjects - a comparative study on Polish population. , 2014, Neurologia i neurochirurgia polska.

[20]  John Hardy,et al.  Parkinson's disease , 2009, The Lancet.

[21]  M. T. Pellecchia,et al.  Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients. , 2014, Parkinsonism & related disorders.

[22]  P. Chan,et al.  Gender differences on motor and non-motor symptoms of de novo patients with early Parkinson’s disease , 2014, Neurological Sciences.

[23]  F. Hatz,et al.  Apathy in Parkinson's disease is related to executive function, gender and age but not to depression , 2015, Front. Aging Neurosci..

[24]  I. Tendolkar,et al.  Prevalence of depression in Parkinson's disease: Effects of disease stage, motor subtype and gender , 2011, Journal of the Neurological Sciences.

[25]  Eunju Choi,et al.  Influencing effect of non-motor symptom clusters on quality of life in Parkinson's disease , 2014, Journal of the Neurological Sciences.

[26]  K. Hamberg,et al.  Gender distribution of patients with Parkinson's disease treated with subthalamic deep brain stimulation; a review of the 2000-2009 literature. , 2011, Parkinsonism & related disorders.

[27]  D. Schaid,et al.  Hysterectomy, menopause, and estrogen use preceding Parkinson's disease: An exploratory case‐control study , 2001, Movement disorders : official journal of the Movement Disorder Society.

[28]  K. Marder,et al.  The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. , 1995, American journal of epidemiology.

[29]  Emily W. Gower,et al.  Sex differences in cognition in healthy elderly individuals , 2012, Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition.

[30]  H. Braak,et al.  Staging of Sporadic Parkinson Disease-Related α-Synuclein Pathology: Inter- and Intra-Rater Reliability , 2005, Journal of neuropathology and experimental neurology.

[31]  G. Deuschl,et al.  MDS clinical diagnostic criteria for Parkinson's disease , 2015, Movement disorders : official journal of the Movement Disorder Society.

[32]  H. Engler,et al.  Gender differences in Parkinson's disease symptom profile , 2000, Acta neurologica Scandinavica.

[33]  N. Vanacore,et al.  Gender differences in Parkinson’s disease: focus on plasma alpha-synuclein , 2013, Journal of Neural Transmission.

[34]  Ming Yi,et al.  Evidence for Gender-Specific Transcriptional Profiles of Nigral Dopamine Neurons in Parkinson Disease , 2010, PloS one.

[35]  A. Tröster,et al.  Potential sex differences in nonmotor symptoms in early drug-naive Parkinson disease , 2015, Neurology.

[36]  J. Hietala,et al.  Sex differences in striatal presynaptic dopamine synthesis capacity in healthy subjects , 2002, Biological Psychiatry.

[37]  R. Uitti,et al.  Progressive supranuclear palsy: Phenotypic sex differences in a clinical cohort , 2006, Movement disorders : official journal of the Movement Disorder Society.

[38]  M. Kovács,et al.  Impact of Sex on the Nonmotor Symptoms and the Health-Related Quality of Life in Parkinson's Disease , 2016, Parkinson's disease.

[39]  R. Sakakibara,et al.  Time‐dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy , 2013, Neurourology and urodynamics.

[40]  M. Farrer,et al.  A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease , 2009, Journal of Neurology, Neurosurgery & Psychiatry.

[41]  J. Dartigues,et al.  Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[42]  A. Bergareche,et al.  Prevalence of Parkinson’s disease and other types of Parkinsonism , 2004, Journal of Neurology.

[43]  J. Carey,et al.  Sex differences in tracking performance in patients with Parkinson's disease. , 2002, Archives of physical medicine and rehabilitation.

[44]  K. Hamberg,et al.  The decision-making process leading to deep brain stimulation in men and women with parkinson’s disease – an interview study , 2014, BMC Neurology.

[45]  P. Barone,et al.  The “Gender Factor” in Wearing-Off among Patients with Parkinson's Disease: A Post Hoc Analysis of DEEP Study , 2015, TheScientificWorldJournal.

[46]  R. Albin,et al.  Gender differences in cholinergic and dopaminergic deficits in Parkinson disease , 2013, Journal of Neural Transmission.

[47]  R. Zweig,et al.  Sex Differences in Clinical Features of Early, Treated Parkinson’s Disease , 2015, PloS one.

[48]  K. Chaudhuri,et al.  Non-motor symptoms of Parkinson's disease: diagnosis and management , 2006, The Lancet Neurology.

[49]  C. Tanner Epidemiology of Parkinson’s Disease , 1992, Neurologic Clinics.

[50]  Juliessa M Pavon,et al.  Parkinson's disease in women: a call for improved clinical studies and for comparative effectiveness research. , 2010, Maturitas.

[51]  M. Mishina,et al.  Sex Differences in the Pharmacokinetics of Levodopa in Elderly Patients With Parkinson Disease , 2014, Clinical neuropharmacology.

[52]  L. Forsgren,et al.  Incidence of Parkinson's disease and parkinsonism in northern Sweden: A population‐based study , 2010, Movement disorders : official journal of the Movement Disorder Society.

[53]  Anthony Davidson,et al.  Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders. , 2007, Journal of neurosurgery.

[54]  M. Vendette,et al.  Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder , 2009, Neurology.

[55]  S. Chiou Sex-Related Prognostic Predictors for Parkinson Disease Undergoing Subthalamic Stimulation. , 2015, World neurosurgery.

[56]  E. Johansson,et al.  A theoretical model for analysing gender bias in medicine , 2009, International journal for equity in health.

[57]  W. M. Chase,et al.  Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics , 2002, Neurology.

[58]  K. Bertram,et al.  Sex differences in Parkinson’s disease , 2014, Journal of Clinical Neuroscience.

[59]  O. Arrieta,et al.  Female gender but not cigarette smoking delays the onset of Parkinson's disease , 2009, Clinical Neurology and Neurosurgery.

[60]  A. Paganoni,et al.  LRRK2 mutations in Parkinson's disease: Confirmation of a gender effect in the Italian population , 2014, Parkinsonism & related disorders.

[61]  M. Hariz,et al.  Gender differences in disability and health‐related quality of life in patients with Parkinson's disease treated with stereotactic surgery , 2003, Acta neurologica Scandinavica.

[62]  T. Robbins,et al.  The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease , 2005, Journal of Neurology.

[63]  Sex differences in nociceptive withdrawal reflex and pain perception , 2005, Somatosensory & motor research.

[64]  K. Hamberg Gender Bias in Medicine , 2008, Women's health.

[65]  Walter A. Rocca,et al.  Risk factors for Parkinson's disease may differ in men and women: an exploratory study , 2013, Hormones and Behavior.

[66]  E. Dietrichs,et al.  REM sleep behavior disorder in Parkinson's disease--is there a gender difference? , 2013, Parkinsonism & related disorders.

[67]  D. Inzitari,et al.  Parkinson's disease and parkinsonism in a longitudinal study: two-fold higher incidence in men. ILSA Working Group. Italian Longitudinal Study on Aging. , 2000, Neurology.

[68]  G. Hariz,et al.  Gender distribution in surgery for Parkinson's disease. , 2000, Parkinsonism & related disorders.

[69]  A. Ramasamy,et al.  Widespread sex differences in gene expression and splicing in the adult human brain , 2013, Nature Communications.

[70]  M. S. Luciano,et al.  Gender differences in the risk of familial parkinsonism: Beyond LRRK2? , 2011, Neuroscience Letters.

[71]  J. Trojanowski,et al.  Clinical and biochemical differences in patients having Parkinson disease with vs without GBA mutations. , 2013, JAMA neurology.

[72]  K. Nie,et al.  Sex differences in cognition among Chinese people with Parkinson’s disease , 2015, Journal of Clinical Neuroscience.

[73]  A. Cronin-Golomb,et al.  Gender differences in Parkinson's disease: Clinical characteristics and cognition , 2010, Movement disorders : official journal of the Movement Disorder Society.

[74]  A. Hofman,et al.  Incidence of parkinsonism and Parkinson disease in a general population , 2004, Neurology.

[75]  M. T. Pellecchia,et al.  Gender and non motor fluctuations in Parkinson's disease: A prospective study. , 2016, Parkinsonism & related disorders.

[76]  Lorene M Nelson,et al.  Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. , 2003, American journal of epidemiology.

[77]  N. Scott,et al.  Age-, and gender-specific incidence of vascular parkinsonism, progressive supranuclear palsy, and parkinsonian-type multiple system atrophy in North East Scotland: the PINE study. , 2014, Parkinsonism & related disorders.

[78]  T. Robbins,et al.  Review Personality, Addiction, Dopamine: Insights from Parkinson's Disease Table 1. Possible Site of Striatal Dopamine Dysfunction Causing Different Motor and Cognitive Symptoms in Parkinson's Disease , 2022 .

[79]  Y. Ben-Shlomo,et al.  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. , 2014, Parkinsonism & Related Disorders.

[80]  J. Schulz,et al.  Evidence for gender differences in cognition, emotion and quality of life in Parkinson's disease? , 2014, Aging and disease.

[81]  S. Galea,et al.  Participation rates in epidemiologic studies. , 2007, Annals of epidemiology.

[82]  A. Lang,et al.  Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. , 2010, Archives of neurology.

[83]  M. T. Pellecchia,et al.  Gender differences in non-motor symptoms in early, drug naïve Parkinson’s disease , 2013, Journal of Neurology.

[84]  D. Aarsland,et al.  Gender-related differences in the burden of non-motor symptoms in Parkinson’s disease , 2012, Journal of Neurology.

[85]  Wei Song,et al.  Gender and onset age-related features of non-motor symptoms of patients with Parkinson's disease--a study from Southwest China. , 2013, Parkinsonism & related disorders.

[86]  T. Vahlberg,et al.  Effects of dopamine agonist dose and gender on the prognosis of impulse control disorders in Parkinson's disease. , 2012, Parkinsonism & related disorders.

[87]  Nir Giladi,et al.  Quality of life and gender identity in Parkinson’s disease , 2005, Journal of Neural Transmission.

[88]  K. Hamberg,et al.  Gender differences in quality of life following subthalamic stimulation for Parkinson's disease , 2013, Acta neurologica Scandinavica.

[89]  G. Rouleau,et al.  LRRK2 mutations in Parkinson disease; a sex effect or lack thereof? A meta-analysis. , 2015, Parkinsonism & related disorders.

[90]  A. Rajput,et al.  Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson's disease , 2013 .

[91]  A. Nicoletti,et al.  Prevalence of Parkinson's disease: a door-to-door survey in rural Bolivia. , 2003, Parkinsonism & related disorders.

[92]  A. Friedman,et al.  Prolactin and sex hormones levels in males with Parkinson's disease , 2015, Acta neurologica Scandinavica.

[93]  R. Lipton,et al.  Female advantage in verbal memory , 2016, Neurology.

[94]  G Foffani,et al.  Gender‐related differences in the human subthalamic area: a local field potential study , 2006, European Journal of Neuroscience.

[95]  Xiang Gao,et al.  Prospective study of plasma urate and risk of Parkinson disease in men and women , 2016, Neurology.

[96]  M. Frosch,et al.  Effects of gender on nigral gene expression and parkinson disease , 2007, Neurobiology of Disease.

[97]  Sara Marceglia,et al.  Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulation , 2007, Movement disorders : official journal of the Movement Disorder Society.

[98]  R. Walker,et al.  Gender differences in 1-year survival rates after weight loss in people with idiopathic Parkinson's disease. , 2012, International journal of palliative nursing.

[99]  F. Marrosu,et al.  Gender differences in motor and non-motor symptoms among Sardinian patients with Parkinson's disease , 2012, Journal of the Neurological Sciences.