Researchers have identified glycerophosphocholine and fatty acid metabolites influencing the timing of menarche and menopause, highlighting key metabolic pathways for female reproductive longevity, according to a Mendelian randomization study.
The study investigated the causal associations between 658 metabolites and age at menarche (AAM) and 684 metabolites and age at natural menopause (ANM). Using data from genome-wide association studies (GWAS) and the ReproGen consortium, the analysis identified 10 candidate metabolites for AAM and 76 for ANM, with 17 showing colocalization. Many of these metabolites belong to the glycerophosphocholine class, including omega-3 fatty acids and phosphatidylcholine.
Pathway analyses and validation in the Avon Longitudinal Study of Parents and Children (ALSPAC) underscored the role of omega and polyunsaturated fatty acids in delaying menopause. Adjusting for body mass index (BMI) revealed that certain metabolites, like lysoPC a C20:4 and PC aa C36:4, retained their significance, suggesting a complex interplay between BMI and metabolic factors.
Colocalization analyses identified 17 metabolites with strong evidence of shared causal variants, implicating genes involved in essential fatty acid metabolism. The study confirmed the directionality of these associations using bidirectional MR analysis and validated the findings in an independent cohort.
These insights suggest that dietary supplementation with omega-3 and polyunsaturated fatty acids could potentially delay menopause, providing a new avenue for therapeutic interventions. The study, published in Genome Medicine, opens the possibility for strategies to manage and extend reproductive lifespan, impacting women's health outcomes.
The authors declared having no competing interests.