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

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

3. 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.

4. 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.

5. 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

6. 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

7. 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.

8. 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)

9. 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

10. 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

11. 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.

12. 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

13. 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

14. 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

15. 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

16. 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.

17. 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

18. 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

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

20. 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

21. Thank you