The relevance of gender in Parkinson’s disease: a review

Abstract

Since the official and systematic inclusion of sex and gender in biomedical research, gender differences have been acknowledged as important determinants of both the susceptibility to develop neurodegenerative diseases in general population and the clinical and therapeutic management of neurodegenerative patients. In this review, we gathered the available evidence on gender differences in Parkinson's disease (PD) regarding clinical phenotype (including motor and non-motor symptoms), biomarkers, genetics and therapeutic management (including pharmacological and surgical treatment). Finally, we will briefly discuss the role of estrogens in determining such differences. Several data demonstrate that PD in women starts with a more benign phenotype, likely due to the effect of estrogens. However, as the disease progresses, women are at higher risk of developing highly disabling treatment-related complications, such as motor and non-motor fluctuations as well as dyskinesia, compared with men. In addition, women have lower chances of receiving effective treatment for PD as deep brain stimulation. Taken together these findings challenge the definition of a more benign phenotype in women. Still, much work needs to be done to better understand the interaction between gender, genetics and environmental factors in determining the PD risk and clinical features. Improving our understanding in this field may result in implementation of strategies to identify prodromal PD and speed efforts to discern new directions for disease tailored treatment and management.

Comparison of Parkinson’s Disease Patients’ Characteristics by Indication for Deep Brain Stimulation: Men Are More Likely to Have DBS for Tremor

“…8 One potential explanation offered for this finding is that women are more likely to be risk-averse and therefore less likely to undergo a surgical procedure than men. 9 Our finding that men had lower PDQ-39 scores, and therefore better quality of life compared to women at the time of surgery, suggests that for women the risk of surgery was offset by the potential benefit only when their disease-related quality of life was comparatively worse.…”

Sex‐related pattern of intrinsic brain connectivity in drug‐naïve Parkinson's disease patients

“…Epidemiological studies have revealed that male sex is a prominent risk factor for developing Parkinson's disease (PD) . At symptom onset, male PD patients are more likely to present with axial impairment when compared to female patients . Conversely, as the disease progresses, female PD patients seem to be at higher risk to develop treatment‐related motor complications .…”

“…1 At symptom onset, male PD patients are more likely to present with axial impairment when compared to female patients. 2,3 Conversely, as the disease progresses, female PD patients seem to be at higher risk to develop treatment-related motor complications. 4,5 Indeed, it has been shown that prevalence of wearing-off is higher in female than in male PD patients.…”

GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease

“…Consequently, a decline in the release of striatal dopamine (DA) leads to motor manifestations of PD involving resting tremor, bradykinesia, postural instability, and rigidity. Whether there is a sex difference concerning the risk for PD is controversial [2,3,4], but the beneficial effect of estrogen has been well-described in both culture and animal models of PD [5,6,7]. Hormone therapy with estrogens in humans has often been associated with serious side effects, especially after long-term exposure such as for treating breast cancer and blood clots [5].…”