Objective: To deepen into sex-dependent mechanisms of Parkinson’s disease (PD) by analyzing the relationships between reproductive life factors, sex hormones, clinical features, and CSF biomarkers in a cohort of post-menopausal female PD patients.

Background: Epidemiology, clinical and pathophysiological features of PD differ between females and males, suggesting that hormonal factors are key-determinants of the disease [1]. At this regard there are compelling findings from animal models [2], conversely the human-based evidence is still scarce.

Method: The study involved 30 post-menopausal female PD patients afferent to the Neurology Unit of Tor Vergata University Hospital (Rome – Italy). For each subject, demographics and anthropometrics data were recorded. All patients filled a structured ad hoc questionnaire investigating fertile life factors. A complete clinical evaluation, including motor, non-motor and cognitive scores, was coupled to CSF biomarkers assay and blood sex hormones measurement. CSF levels of total α-synuclein (αSyn), amyloid-β-42 (Aβ42), amyloid-β-40 (Aβ40), total tau (t-tau) and phosphorylated-181-p tau (p-tau) were quantified. Aβ42/p-tau, Aβ42/Aβ40 ratios were also calculated. Serum sex hormone levels, including total testosterone, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined.

Results: Longer fertile life span was correlated with less severe motor impairment in terms of H&Y stage. Greater length and higher number of pregnancies were associated with worse clinical impairment, as assessed through UPDRS II, MMSE and MoCA scales. FSH and LH were inversely correlated with both cognitive scores and CSF amyloid-β-42/amyloid-β-40 ratio. Estradiol was inversely associated with the UPDRS-III score.

Conclusion: This study showed how the reproductive life factors and sex hormones can differentially contribute to clinical-pathological features of PD in female patients. Namely, the longer estrogen exposure during fertile life and the higher circulating estradiol levels might have a protective role on motor circuits degeneration, accounting for milder motor impairment. Gonadotropins, instead, might mediate age-dependent amyloidopathy, which in turn is related to synaptopathy and cognitive decline.

References: 1. Cerri S, Mus L, Blandini F. Parkinson’s Disease in Women and Men: What’s the Difference? J. Parkinsons. Dis. (2019).
2. Kompoliti K. Estrogen and Parkinson’s disease. Front. Biosci. (2003).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reproductive-life-factors-and-sex-hormones-in-post-menopausal-female-patients-with-parkinsons-disease/