Neurometabolic Alterations in Menopause: A Literature Review and Precision Medicine Perspectives

Authors

Dewi Setiawati¹*, Wachyudi Muchsin², Harun Iskandar², Achmad Harun³

¹Medical and Science Faculty, Universitas Islam Negeri Alauddin Makassar, Indonesia

²Medical Faculty, Hasanuddin University, Makassar, Indonesia

³Medical Faculty, Indonesia Moslem University, Makassar, Indonesia

ABSTRACT

Background: Menopause is increasingly recognized as a neurometabolic transition rather than a purely endocrine event.

Objective: This systematic review examined mechanisms linking estrogen decline to cerebral metabolic dysfunction, neuroimaging biomarkers, and intervention strategies.

Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library databases. From 3,847 records identified, 156 studies involving 89,324 participants were included following PRISMA guidelines.

 Results: Findings revealed 15–25% reductions in cerebral glucose utilization during perimenopause. Timely hormone therapy demonstrated cognitive benefits (effect size d=0.34). Ketogenic dietary interventions showed promising effects (SMD=0.42), alongside structured exercise programs. Novel biomarkers including ATP/PCr ratios and neurofilament light chain demonstrated predictive validity for cognitive decline trajectories.

 Conclusion: These results highlight menopause as a critical neurometabolic inflection point, requiring integrated approaches combining hormone therapy, metabolic interventions, and biomarker-guided monitoring to preserve cognitive function.