Uncovering the Hidden Connections Between PCOS and Alzheimer's Disease: A Two-Sample Mendelian Randomization
Farzaneh Sadat Motafeghi1, Mahdi Akbarzadeh2, Samaneh Talebi3
1Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
International Journal of Endocrinology and Metabolism
|October 17, 2025
Summary
This study found no causal link between Polycystic Ovary Syndrome (PCOS) and Alzheimer's Disease (AD). Genetic predisposition to PCOS does not appear to increase Alzheimer's risk, suggesting other factors may explain observed associations.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Polycystic Ovary Syndrome (PCOS) and Alzheimer's Disease (AD) share overlapping features like metabolic dysfunction and inflammation.
- Observational studies suggest potential links, but confounding factors hinder causal inference.
Purpose of the Study:
- To investigate the potential causal relationship between PCOS and AD.
- Utilize Mendelian randomization (MR) to assess genetic predisposition to PCOS and its effect on AD risk.
Main Methods:
- A two-sample MR analysis was performed using large genome-wide association study (GWAS) summary data.
- Genetic variants for PCOS (10,074 cases, 103,164 controls) and AD (1,036,225 cases, 90,338 controls) of European ancestry were analyzed.
- Inverse variance weighted (IVW) was the primary MR method, supported by MR-Egger, weighted median, and weighted mode analyses, with sensitivity analyses conducted.
Main Results:
- The MR analysis found no significant causal effect of genetically predicted PCOS on AD risk.
- The primary IVW analysis yielded an odds ratio (OR) of 0.967 (P=0.311).
- Refined analyses after outlier removal showed an OR of 0.93 (P=0.057), with consistent results across methods and sensitivity tests.
Conclusions:
- This study provides no evidence for a causal link between genetically predicted PCOS and AD.
- Genetic predisposition to PCOS does not appear to elevate the risk of developing AD.
- Further research is needed to explore alternative explanations for observed associations between PCOS and AD.
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