Neurological Disorders

Sex and Gender Differences in Parkinsonâ??s Disease and the Conclusions We Should Draw

Abstract

Marita F. Thiel* and Wolfgang H. Jost

Studies in recent years suggest that in Parkinson’s disease there is a distinction between the sexes. As a preliminary step we examined the data of 100 male and 100 female Parkinson’s patients from a dedicated Parkinson’s hospital. On the one hand, we found significant differences in their levodopa dose equivalent: This was distinctly lower for the female patients, whereas depression occurred more frequently in the female group. On the other hand, data on serum values for vitamin B12 and vitamin D as well as on the results of the test for orthostatic dysregulation and a sonographic examination of residual urine failed to show any significant differences. Our literature search revealed differences in the extent of motor and non-motor symptoms as well as in subjectively reported quality of life. These results however do have some discrepancies that will have to be clarified in future studies. For years now, the lower incidences in the female patients have suggested the possible relevance of estrogen. Precisely because women are less frequently afflicted, a possible neuroprotective role of estrogen has been discussed. In this respect the duration of estrogenic exposition, that is, the earlier or later occurrence of menopause, might be playing a role here. More recent work has also highlighted the function of the RORA receptor (retinoic acid receptor-related orphan receptor alpha). A neuroprotective function has been attributed to this receptor which is found in the pars compacta of the substantia nigra. Because its expression is subject to control from sex hormones, it might play a role in neurodegenerative diseases. Genetic studies also offer highly promising aspects: Parkinson’s disease in women is more often associated with an altered variant of the gene coding for glucocerebrosidase (GBA) as well as the LRRK2 gene (leucine-rich repeat kinase 2). Further subgroups may also be significant here. The current study data thus reveals different perspectives on Parkinson’s disease in men and women. Final clarification needs further work in the future.