Older Age at Menopause Tied to Lower Parkinson’s Risk in Analysis

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by Marisa Wexler |

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Women who are older when going through menopause appear to be at a lower risk of developing Parkinson’s disease, according to a study based on genetic data.

These findings support the idea that certain sex hormones may protect the brain from this disease.

The study, “Increased Menopausal Age Reduces the Risk of Parkinson’s Disease: A Mendelian Randomization Approach,” was published in Movement Disorders.

Parkinson’s is substantially more common in biological males than females, and reasons for this difference are not clear. One proposal is that female sex hormones, especially estrogen, may work to protect cells in the brain from damage.

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If that were the case, it would be expected that a longer time spent between menarche (a person’s first period) and menopause (when menstruation stops) would be associated with a lower risk of Parkinson’s, because estrogen levels tend to be higher during the time of life when a woman is regularly menstruating.

Demonstrating this in scientific studies is difficult, however. This is partly because the factors governing both hormone levels and Parkinson’s risk are complex, and vary markedly person-to-person. Research on the age at menarche and menopause also is complicated by the fact that it often relies on self-reported data, which is prone to inaccuracies because life is messy and memory is fallible.

To circumvent these issues, a team led by scientists at the University of California, Los Angeles, used an approach called Mendelian randomization (MR). This kind of analysis relies on the fact that some genetic variants are associated with traits — specifically here, people with certain genetic variants tend to undergo menopause at earlier or later ages.

While these variants aren’t enough to determine the age at menopause for any person, in a very large population, researchers can use these variants to create groups of individuals who will tend to undergo menopause earlier, and those who will tend to undergo it later, and then make comparisons.

“This is the first study reviewing the association between age at menopause/menarche and PD status using the MR method, which is known to reduce certain biases common in observational studies,” the researchers wrote.

The team conducted MR analysis using data on 1,737 females and 2,430 males (some with Parkinson’s and some without). The data were collected from national databases in the U.S. and in Denmark. All the individuals analyzed were of European ancestry — done to minimize the “noise” in the genetic data, although the researchers acknowledged that this is also a study limitation.

Based on eight previously established genetic variants, the researchers divided patients (of both sexes) into those with a tendency toward earlier or later menopause. MR analyses showed that, among women, an older age at menopause was associated with a significantly lower risk of developing Parkinson’s. No significant association was observed in men (between a hypothetical age at menopause and Parkinson’s).

Further analyses indicated that, for every increased year of age at menopause, the risk of Parkinson’s decreased by roughly 7% among females.

Since this effect was seen among women but not men, the researchers speculated that the difference is likely attributable to sex-specific biological differences in development, like hormone levels. However, they acknowledged that it is impossible to definitively draw cause-and-effect conclusions from this type of analysis, and more research is needed.

“Biological factors related to a later age at menopause — possibly a longer exposure to female sex hormones or other biologic causes of later menopause —might be neuroprotective and prevent or delay a PD [Parkinson’s disease] diagnosis in women,” the team concluded.

Using 19 different genetic variants, the researchers also assessed the effect of age at menarche on Parkinson’s risk. MR showed no significant associations in females or males.

“Based on our findings, there is currently no indication for an association between age at menarche and PD,” the researchers wrote.

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