Gender Differences in Parkinson's Disease

Parkinson’s disease exhibits clear sex and gender disparities in incidence, presentation and progression. Men are approximately 1.5 times more likely to develop the disorder and often experience earlier onset, more severe motor symptoms and faster functional decline. Women tend to report a higher burden of non-motor manifestations, including mood disturbances, fatigue and quality-of-life impairments, yet they may benefit from endogenous oestrogenic protection. Biological factors such as sex hormones, genetic modifiers and immune responses intersect with gender norms and healthcare access to shape the lived experience of Parkinson’s disease. Recognising these interwoven influences is essential to tailor diagnostics, optimise neuroprotective strategies and deliver gender-sensitive care on a global scale.

Research from Nature Portfolio

In postmenopausal patients, a higher lifetime ratio of oestrogen exposure correlates with greater preservation of striatal dopamine transporter availability, especially in the putamen, and with a slower escalation of levodopa requirements. These findings suggest that endogenous oestrogen may confer neuroprotection on nigrostriatal dopaminergic neurons, offering a rationale for hormone-based therapeutic approaches to attenuate disease progression.

Gender Differences in Parkinson's Disease publication trend

The graph below shows the total number of articles in gender differences in parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Dopaminergic neurons: Neurones that synthesise and release dopamine, a neurotransmitter central to motor control and reward signalling.

Nigrostriatal pathway: The projection from the substantia nigra to the striatum, critical for initiating and regulating movement and preferentially degenerated in Parkinson’s disease.

Dopamine transporter (DAT): A protein that clears dopamine from the synaptic cleft, serving as an indicator of dopaminergic nerve-terminal integrity.

Brain-predicted age difference (Brain-PAD): The discrepancy between chronological age and age estimated from brain imaging, used to detect accelerated neurodegeneration.

Executive function: Higher-order cognitive processes including planning, inhibition and mental flexibility, often compromised in Parkinson’s disease.

References

1. Beneficial effect of estrogen on nigrostriatal dopaminergic neurons in drug-naïve postmenopausal Parkinson’s disease. Scientific Reports (2019).
2. Gender-aware Parkinson’s care: a design-based study of patient perspectives on gender norms and gender-sensitive care. EClinicalMedicine (2023).
3. Differences in brain aging between sexes in Parkinson’s disease. npj Parkinson's Disease (2024).
4. Sex specific cognitive differences in Parkinson disease. npj Parkinson's Disease (2020).