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Parkinson’s in Women and Men: recognising the differences

Original article: Parkinson’s Disease in Women and Men: What’s the Difference? Journal of Parkinson’s Disease: 2019

The takeaway

Parkinson’s affects women and men differently. This is reflected both in their different clinical features and progression, as well as in their experience of the condition.

Why is it important?

Factoring gender into research is an essential step toward precision medicine, and developing personalized treatments that work for both women and men.

Background

It has long been known that Parkinson’s affects twice as many men as women. Although women represent a significant proportion of people affected by Parkinson’s, they are less likely to get specialist neurology input compared to men, less likely to have informal caregiver support such as from a spouse or family member, and are also less frequently enrolled in treatment trials (see our linked summary at the bottom of this page). This poses an important problem in terms of underrepresentation. What do we know about the different ways in which Parkinson’s affects women compared to men, and what may underlie these differences?

The details

First, women tend to develop movement symptoms later compared to men, appear to be mostly affected by tremor early on, instability and falls later in the disease, and are more prone to developing complications on levodopa therapy. Women are also more prone to constipation and swallowing problems, as well as visual and spatial difficulties. Other non-motor symptoms disproportionately affecting women include fatigue, depression, and pain, as well as loss of smell and weight decline. Conversely, men appear to be more affected by freezing, often referred to as the most distressing symptom by people with Parkinson’s, postural changes, excessive salivation, and are more prone to developing pathological gambling and hypersexuality.

These important clinical differences necessitate different approaches reflected in tailored medication regimes, psychiatric, dietician, speech and language, and physiotherapy input, and must be taken into account when designing clinical trials. In terms of response to treatments, because of these and other gender differences related to metabolism, women absorb and respond to levodopa more readily, and clear it more slowly than men, suggesting that timing in medication regimes will need to be individually tailored. Women also tend to report greater benefit in terms of quality of life from DBS (deep brain stimulation) compared to men.

The issue of gender is especially important when developing disease modifying approaches to Parkinson’s, as biochemical differences are also present. For example, several studies have highlighted the important role of oestrogen, a female sex hormone, which impacts on how neurons as well as glia, which play a host of roles in inflammation, develop and respond in Parkinson’s. Research has also shown that mitochondria, the powerhouses within neurons, tend to be exposed to lower levels of oxidative stress in women, yet are more vulnerable to excessive levels of calcium compared to mitochondria in men. Findings such as this suggest that different neuroprotective approaches may be suited to women compared to men.

Next steps

The US Parkinson’s Foundation has placed research and care practices that are responsive to the needs of women as well as men firmly on their agenda. The National Institutes of Health have recognised that sex needs to be factored into research studies in Parkinson’s, and the World Health Organisation have also identified women as “a special population in clinical trials” with a “separate ICH (International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) guideline”. These steps now need to be adopted by the clinical and research communities and implemented for the benefit of people with Parkinson’s.

Related work and trials

Cerri, S, Mus, L, Blandini, F. (2019). Parkinson’s Disease in Women and Men: What’s the Difference? Journal of Parkinson’s Disease, vol. 9, no. 3, pp. 501-515.
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