Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach

Area of Science:

• Neuroscience
• Epidemiology
• Genetics

Background:

• Inconsistent findings exist regarding the association between Parkinson's disease (PD) and age at menarche or menopause.
• Mendelian randomization (MR) can mitigate measurement errors in self-reported ages of menarche and menopause.

Purpose of the Study:

• To investigate the association between age at menopause and age at menarche with PD risk using MR.
• To assess potential sex-specific effects on the relationship between menopausal age and PD.

Main Methods:

• Inverse variant-weighted (IVW) MR analysis was performed using genome-wide association study (GWAS) summary data.
• Data included UK Biobank, Danish Parkinson's Disease (PASIDA) study, and Parkinson's Environment and Gene (PEG) study.
• Replication and meta-analysis were conducted using PD consortium summary statistics.

Main Results:

• Each year increase in age at menopause was associated with decreased PD risk in women (OR, 0.84; P=0.03).
• No significant association was found between age at menopause and PD risk in men (OR, 0.98; P=0.71).
• Age at menarche showed no significant association with PD risk (OR, 0.75; P=0.29).

Conclusions:

• A later age at menopause is associated with a reduced risk of Parkinson's disease in women.
• Findings support the hypothesis that sex hormones or factors related to late menopause may offer neuroprotection in PD.
• Further research is warranted to elucidate the mechanisms behind this association.