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The Two Faces of Parkinson's: How Men and Women Battle It Differently

In the realm of medical conditions, women frequently bear a greater burden, experiencing higher rates of autoimmune diseases, migraines, and post-traumatic stress, among other ailments. This trend, however, takes an unexpected turn in the case of Parkinson's disease. Surprisingly, men are about 1.5 times more likely than women to develop this progressive neurological disorder, which challenges our understanding of gender disparities in health.

Parkinson's disease is characterised by the gradual loss of dopamine-producing neurons in the substantia nigra region of the brain. This depletion causes more than just a disruption to movement; it extends to cognitive functions and can manifest in symptoms such as slurred speech and depression. The gender gap in Parkinson's disease prevalence is a curious divergence from the typical patterns observed in many other diseases, prompting a deeper exploration into the unique ways this condition affects men and women differently.

As Parkinson's disease progresses, men and women exhibit distinct motor and non-motor symptoms. Women generally experience tremors, recurrent falls, and severe pain syndromes at later stages. These symptoms are often accompanied by reduced rigidity and an increased risk of complications associated with levodopa, a standard Parkinson's disease treatment. In contrast, men with Parkinson's disease are more prone to severe postural issues and greater cognitive decline. Freezing of gait, a debilitating motor complication, tends to develop later in men, who are also at a higher risk for conditions like camptocormia, an abnormal forward flexion of the trunk. The progression and outcome of Parkinson's disease also differ between genders. Women generally have a later onset, slower disease progression, leading to a better overall prognosis compared to men.

The development of Parkinson's disease is multifactorial, involving various genetic and environmental elements. Occupational hazards, particularly in jobs traditionally held by men, may partly explain the higher incidence of Parkinson's disease in males. Industries that involve heavy use of herbicides, pesticides, and solvents have been linked to increased Parkinson's disease risk. For instance, exposure to the herbicide paraquat and the pesticide rotenone is linked to Parkinson's disease. These findings are not only limited to human studies but also observed in animal research, where male animals exposed to certain chemicals displayed a higher risk of developing Parkinson' s-like symptoms. This only explains a proportion of the cases, as most people are not exposed professionally but indirectly through food and other environmental factors.

One prevailing theory suggests that hormonal differences might play a role in Parkinson's disease gender disparity. Oestrogen, for example, is believed to have protective effects against destroying dopamine-producing neurons. While the extent of oestrogen's protective role is still under investigation, it is hypothesised that higher oestrogen levels in women could offer some degree of protection against Parkinson's disease. Men's decline in testosterone during aging might have a role in the progression of Parkinson's disease. However, the evidence is less clear, with studies showing that using testosterone hormonal therapy does not have similar neuroprotective effects as found in oestrogen.

Another biological difference is the amount of alpha-synuclein found in men. Under normal circumstances, alpha-synuclein enables neurons to communicate. However, in patients with Parkinson's disease, exposure to environmental factors and specific genetic mutations can cause the formation of an initial alpha-synuclein clump. The formation of these clumps is toxic to the cells and, over time, causes extensive brain damage. Some genetic mutations render a-Syn more prone to spontaneous self-assembly (e.g., Syn gene duplication increases a-Syn concentrations within neurons, lowering the aggregation barrier). Men have a higher amount of alpha-synuclein, which increases the chance of forming clumps and kickstarting the disease, potentially exacerbating the condition in men.

The distinct experiences of men and women with Parkinson's disease underscore a critical need for gender-specific approaches in both research and treatment. It's clear that the battle against Parkinson's disease isn't just fought on one front; it varies significantly based on gender and is influenced by a tapestry of biological, environmental, and hormonal factors. This understanding opens up new avenues for personalised medicine, where treatments and interventions will be tailored to meet the unique needs of each individual, taking into account their gender-specific risks and responses. The journey ahead for Parkinson's research and care is one of precision and personalisation, guided by a deeper understanding of how the disease uniquely affects men and women.

Dr Victor Dieriks

Group Leader Synuclein Lab

Centre for Brain Research

The University of Auckland, New Zealand

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