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As we all know, the incidence of Parkinson's disease (PD) in men is higher than in women
.
For a long time, the neuroprotective effects of sex hormones have been considered a potential cause of this difference
In observational studies, the relationship between the life-long level of female sex hormones and PD was extensively explored through alternative measures of self-reported menarche age and menopausal age
.
Unfortunately, the research results, including meta-analysis, are inconsistent
Therefore, as the time of menopause increases, women are likely to find it increasingly difficult to accurately recall the time of their last menstrual period: the inconsistency in menopausal age reported in repeated interviews also proves this
.
Misreports and missing values of age at menopause or menarche are unlikely to be random events, and are more likely in case-control studies related to aging, because this information is often collected many years after the transition to menopause occurs
One way to solve these technical problems is through the use of Mendelian randomization (MR) analysis
.
MR analysis is based on the association between genetic variants and exposure, as well as the association between genetic variants and disease states, so that genetic variants serve as instrumental variables
GWAS
After the MR analysis, a replication and meta-analysis was performed using aggregate statistics from a large PD alliance
.
Based on the hypothesis that female hormones may protect dopamine neurons, they assessed whether older menopause or younger menarche are related to a reduction in the risk of women's PD
Based on the hypothesis that female hormones may protect dopamine neurons, they assessed whether older menopause or younger menarche are related to a reduction in the risk of women's PD
In their study, for every one year of menopausal age, women’s risk of PD decreases (odds ratio [OR], 0.
84; 95% confidence interval [CI], 0.
73-0.
Using PD Consortium’s summary statistics for replication, the estimated OR was 0.
94 (95% CI, 0.
90-0.
99; P = 0.
01), while the calculated meta-analysis OR was 0.
93 (95% CI, 0.
89-0.
98; P = 0.
003)
.
There is no indication that there is an association between age at menarche and PD (OR, 0.
75; 95% CI, 0.
44-1.
29; P = 0.
29)
.
75; 95% CI, 0.
44-1.
29; P = 0.
29)
.
The important significance of this study lies in the discovery that the later age of women's menopause is related to the reduced risk of PD, supporting the hypothesis that sex hormones or other factors related to late menopause may have a neuroprotective effect on PD
.
Original source:
Kusters CDJ, Paul KC, Duarte Folle A, et al.
Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach.
Mov Disord.
Published online August 23, 2021:mds.
28760.
doi:10.
1002/mds.
28760
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