Review Highlights Sex-related Differences In Parkinson’s

Parkinson’s disease (PD) is more common among males, but it tends to progress faster in females. This and other sex-based differences in the neurodegenerative disease were highlighted in a recent review, titled “Parkinson’s Disease in Women and Men: What’s the Difference?” and published in the Journal of Parkinson’s Disease.

The review explains the current state of scientific understanding of how Parkinson’s differs among the biological sexes in a number of regards.

The first of these is motor symptoms, which emerge later in females.

Females are more likely to have tremors as their first presenting symptom, to develop unstable postures, to have reduced rigidity, and to progress to falling. Males, on the other hand, are more likely to develop later gait freezing, and have a higher risk of developing camptocormia — an abnormal flexing of the trunk. An ongoing clinical trial (NCT03573232), sponsored by the Università di Verona in Italy, is evaluating the impact of biological sex on other postural abnormalities.

Non-motor symptoms differ between the sexes as well. Symptoms including fatigue, depression, constipation, pain, excessive sweating, fluctuations in weight, difficulty swallowing, and loss of taste or smell are more common in females, whereas males are more likely to experience cognitive impairment and impulse control disorders, for example, pathological gambling.

Beyond the manifestation of symptoms, the review notes that the mechanisms that cause PD likely differ based on sex. This includes factors ranging from different genes that may be more or less impactful in different sexes, to distinctions in the role of inflammation, to differences in brain cells themselves.

In particular, the review authors highlight the role of sex-related hormones — most notably estrogens — in the development of Parkinson’s.

“Sex hormones act throughout the entire brain of both males and females and sex differences are now highlighted in brain regions and functions not previously considered as subjected to such differences, opening the way to a better understanding of sex-related behavior and functions,” Silvia Cerri, PhD, the head of the laboratory of cellular and molecular neurobiology of the IRCCS Mondino Foundation and co-author of the review, said in a press release.

“Neuroinflammation is an important piece of the pathogenic puzzle of PD,” Cerri added. “Since estrogens have anti-inflammatory properties, their actions throughout the lifespan could partially account for sex-related risk and manifestation of PD.”

Despite these many findings, research into sex-based differences in Parkinson’s is only just beginning to yield clear answers.

“We are still far away from the actual understanding of what underlies such [sex-based] differences,” the researchers said. “Studies in this area are under-represented, both from the clinical and research perspective, especially for females.”

The review’s investigators hope that, by drawing attention to these differences, they can encourage further research in the field. This could have utility not just in understanding how the disease manifests in distinct ways in different people, but also in providing the best possible individualized treatment.

“It is a line that is worth pursuing and will deserve further attention by the scientific community and policy makers,” the authors concluded.