Women and Parkinson’s Disease Michelle Fullard, MD, MS University of Colorado Movement Disorders Center

Definitions Sex – biological Gender – social, cultural and personal identification In the medical literature, the two terms are often used interchangeably

Epidemiology Incidence is 1.5-2x higher in men Prevalence is higher in men Women may have a later age of onset Incidence is 1.5 – 2.1 times higher in men.

Risk Factors for Parkinson’s Disease Decreased Risk Increased Risk Smoking Head trauma Coffee intake Pesticide exposure Physical activity Dairy consumption Non-steroidal anti-inflammatory drug use* High urate levels* *NSAIDs decreased risk for men only, may increase risk for women (not significant) High levels of exercise in midlife are associated with lower PD risk, better disease prognosis and lower rates of serious complications [61]. A large international multicenter cohort study on early PD patients showed that higher self-reported activity scores were associated with younger age and male gender. Older patients, especially women, may be particularly vulnerable to inactivity and its compli Men may have more frequent occupational or recreational exposure to risk factors.

Differences in genetic risk factors Not consistent across studies LRRK2 mutation in women Family history of PD more common in women Frequency of family history   Female (1,034) Male (1,489) p value 1st degree 13% 10% 0.058 1st +2nd degree 18% 16% 0.112 1st +2nd +3rd degree 22% 0.017 Cilia Parkinsonism and Related Disorders 2014 Cilia et al. Parkinsonism and Related Disorders 2014

Estrogen Potentially neuroprotective estrogen associated with increased risk of PD Postmenopausal hormone therapy associated with reduced risk of PD in some studies Data supporting a potential protective role of endogenous estrogens come from research indicating that lifetime reduction in estrogen levels (early menopause, fewer pregnancies, hysterectomy=oopherectomy) appears to be a risk factor for the development of PD

Menstruation and Parkinson’s Disease 3-5% of women diagnosed with PD are < 50 years old During menstruation, women may experience Increased symptoms Decreased medication responsiveness Increased OFF time Estrogen levels are lowest during menses Estrogen based hormone replacement therapy may relieve PD symptoms when given in the aerly stages of the disease and decrease the risk of developing PD 3=5% fo women diagnosed with PD are under age 50 They also complain of increased fatigue, cramps and heavier menstrual flow. This can lead to difficulty with self-care issues due to worsening dexterity.

Pregnancy and Parkinson’s disease No differences in fertility compared to those without PD Symptoms worsen in ~ 50% Fetal and maternal outcomes similar to non-PD patients Estriol (in pregnancy) vs estradiol (menstrual form of estrogen)

Menopause and Parkinson’s disease 43% report worsening of symptoms when menses stops Unclear if hormone replacement therapy improves symptoms POETRY trial E. Martignoni et al. Functional Neurology 2003

Sexual Dysfunction in Women Low libido Difficulty achieving orgasm Vaginal dryness Pain with intercourse Treatment options: add lubrication, time intercourse for periods when Parkinson’s symptoms are well controlled, specialist care

Prodromal Parkinson’s Disease Age and sex dependence of predictive values of markers indicating prodromal Parkinson’s disease. Marker-specific positive likelihood ratio (LR1) as referred to by the MDS research criteria for prodromal Parkinson’s disease (PD) and LR1 of markers as observed in the full sample and samples stratified by age and sex are shown. Error bars indicate 95% confidence intervals. Asterisks indicate significant (P < 0.05) marker by age or marker by sex interaction effects in logistic regressions of incident PD cases and PD-free individuals. (*)Statistical trend toward an interaction effect at P < 0.1. For LR-, marker sensitivity and specificity, and results of further nonsignificant markers, see the Supplementary material.

Motor Symptoms at presentation Tremor more common in women More postural instability in women Men have more rigidity and more difficulty with writing and clumsiness. *Some studies show no differences Women are diagnosed two years later Motor progression is similar

Differences in Non-motor Symptoms Women Men Depression Orthostatic hypotension Anxiety Urinary symptoms Constipation, GI symptoms REM Behavior Sleep Disorder Pain Drooling Fatigue Cognitive impairment Sexual dysfunction

Parkinson’s Disease associated cognitive changes Men – deficits in verbal memory tests, executive function and recognition of facial emotions Women – more difficulty with visuospatial cognition

Treatment and Side Effects in Women Dopaminergic medications are similar to men, but lower doses More often prescribed antidepressants and benzodiazepines More susceptible to adverse effects of levodopa Dyskinesias, motor fluctuations and wearing off Time to dyskinesia Estrogen may be partially responsible by interacting with levodopa Women more often prescribed antidepressants and benzodiazepines Men are more likely to receive medication for cognitive impairment or dementia

Deep Brain Stimulation (DBS) Men and women have similar improvement in motor symptoms after DBS. Women have greater improvement in quality of life and disability. Women are less likely to receive DBS than men.

Access to Care Women experience a longer time from…. onset of symptoms to diagnosis onset of symptoms to first visit with a movement disorders specialist Women are less likely to see a neurologist for their care

Care Partners Women are: less likely to have a spouse as primary caregiver. more likely to use a paid caregiver. more likely to attend appointments alone. More likely to be single or widowed

Health Service Use Women had fewer office visits Women were higher uses of home health care, hospice care and skilled nursing facility care

Research Women are underrepresented in Parkinson’s disease research >55% of PD trials since 2010 recruited more than 59% men Without adequate representation in research, it is harder to determine the effectiveness of treatments in women

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