ReviewParkinson's disease in women: A call for improved clinical studies and for comparative effectiveness research
Introduction
Parkinson's disease (PD) is a progressive neurological condition that occurs due to the loss of dopamine producing brain and degeneration of both motor and non-motor basal ganglia circuitry. Typical manifestations include resting tremor (which is absent in approximately 20%), bradykinesia, rigidity and gait impairment. PD is associated with disability, morbidity, institutionalization, high health care utilization, costs, and even mortality [1], [2], [3], [4], [5], [6]. Although there is no cure for PD, there are medical, behavioral, and surgical treatment modalities, most notably dopamine replacement/agonist therapy and deep brain stimulation, which both have been shown to improve symptoms.
The incidence and prevalence of PD is high and is rising as the population ages [7], [8]. In a diverse sample of New York City residents, the prevalence of PD measured over a 4-year period was 107 per 100,000 persons, and over a 3-year period the average incidence rate was 13 per 100,000 person-years [9]. According to Dorsey et al. [10], the population of PD patients over age 50 in the United States is expected to double to 600,000 by 2030. However, the largest growth is expected to occur in Asian countries, with a population of 5 million PD patients expected in China by 2030. Factors to explain this growth include improved medical care and care access (especially in developing countries) and resultant increased life-expectancy. With improvements in health care also comes increased length of disease duration. Therefore expanding countries are met with the dual threat of increase in incidence and prevalence and subsequent strain on their burgeoning yet unstable health care infrastructures. Awareness of this impending disease burden is critical to shaping treatment strategies and social policies [10].
The epidemiology and disease manifestations of PD appear to differ slightly in men and women. Gender differences in PD are important to consider, given their potential impact on treatment strategies, outcomes, and social planning. This review will examine data on gender differences in incidence, prevalence, and disease characteristics, as well as treatment outcomes and social impact.
The underpinnings of the gender differences in PD are unknown. Some experts have pointed to hormonal levels [11], [12], [13], [14], [15] and others to the deposition of Lewy Bodies in the hypothalamus (part of the degenerative process) [16]. In this review we will highlight what is known about differences between men and women in PD and offer an expert opinion as to what studies need to be done to clarify important remaining questions.
Section snippets
Gender differences in incidence, prevalence and age of onset of PD
There is a greater incidence of PD in men than in women [17], persisting across age groups [17], [18]. In a community-based prospective study performed in Norway the incidence of PD was 1.5 times higher in men compared to women across all age groups [19]. This finding has been replicated in two meta-analyses, which reported similar age-adjusted male:female incidence rate ratios of 1.49 (95% confidence interval (CI) 1.24–1.95, p = 0.031) [20] and 1.46 (95% CI 1.24–1.72, p < 0.001) [21].
Likewise,
Possible gender-based difference in motor symptoms
Some studies have suggested that women with PD tend to have a delay in the onset of certain motor symptoms, compared to men with PD [19]. At presentation, women are more likely than men to exhibit the tremor-dominant PD phenotype, which seems to be associated with a slower deterioration in Unified Parkinson's Disease Rating Scale (UPDRS) scores [23]. One study observed that among patients with PD for greater than 5 years, overall UPDRS motor scores were better in women compared to men [32].
Treatment and management of Parkinson's disease in women
Medical treatment of PD includes levodopa, dopamine agonists, anticholinergics, monoamine oxidase inhibitors, amantadine and several other pharmacologic agents on the market and under study. The treatment impact of sex hormone has been studied in men with PD, who tend to have lower levels of testosterone [52]. However, large treatment trials of testosterone replacement did not improve motor outcomes [53]. Surgical treatments, such as deep brain stimulation and lesion therapy can be effective in
Social impact
Women are likely to experience many complications of PD which have significant impact on their quality of life and their capacity to contribute to and engage in the community. With the aging of the population, society is expected to experience commensurate caregiver and economic burdens associated with PD.
Conclusion
Although epidemiological studies suggest that the incidence and prevalence of PD in women is lower than in men, and that the age of onset is delayed, with the aging population, the number of afflicted women remains very high and is increasing. Moreover, women seem to be at increased risk of experiencing some of the clinical manifestations and complications of PD. Whether estrogen plays a significant role in epidemiologic gender differences, disease characteristics, and management of PD in women
Contributors
J.M. Pavon: Performed literature review, interpreted findings, drafted manuscript, involved in manuscript review and revision; H.E. Whitson: Provided project oversight, performed literature review, interpreted findings, involved in manuscript review and revision; M.S. Okun: Provided expert opinion, involved in manuscript review and revisions.
Conflict of interest
J.M. Pavon and H.E. Whitson: No competing interests; M.S. Okun: Dr. Okun has in the past received honoraria for educational talks for Medtronic. Dr. Okun serves as a consultant and is the National Medical Director for the National Parkinson's Foundation (NPF). Dr. Okun receives research support from NIH, NPF, Parkinson Alliance, and Michael J. Fox Foundation.
Provenance and peer review
Commissioned and externally peer reviewed.
Acknowledgements
Efforts were supported by the National Institute of Health Grant K23-AG032867, grant P30-AG028716, and a grant from the National Parkinson Foundation Center of Excellence.
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2020, Sleep Medicine ReviewsCitation Excerpt :Previous studies suggested that male and female PD patients show a different disease course and differences in non-motor and motor symptoms [110–112]. For non-motor symptoms, female PD patients were more likely to show fatigue, pain, trait anxiety, depression, restless legs, constipation, and higher disability compared with male PD patients [110,111,113–115]. Male PD patients were more likely to show obvious daytime sleepiness, sexual problems, olfaction, and cognitive impairments compared with females [115–117].