Parkinson's disease in women: A call for improved clinical studies and for comparative effectiveness research

Abstract

The incidence and prevalence of Parkinson's disease (PD) is expected to rise precipitously over the next several decades, as will the associated healthcare related costs. The epidemiology and disease manifestations of PD may differ when comparing women to men. Women are for example less likely to acquire PD, and in several studies have demonstrated a delayed onset of motor symptoms. Women, however, are more likely to experience PD-related complications that may lead to disability (e.g. depression and medication-associated dyskinesia). Further, there are purported differences in the treatment and treatment outcomes in PD men compared to women. Whether estrogen, other hormonal activity, or whether multiple factors underpin these findings remains unknown. Also unknown is whether estrogen itself may represent a therapeutic option for symptomatic PD treatment. This review summarizes what is known about gender differences in epidemiology, clinical features, treatment outcomes (medical and surgical/deep brain stimulation), and social impact among all available PD studies. We offer expert opinion regarding the shortcomings of the current evidence, and we propose a detailed list of studies that will help to clarify important gender related PD questions. Our hope is that this review will spark comparative effectiveness research into improving care and outcomes in women with PD.

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.