Recent advances in the relationship between mental symptoms in postmenopausal women and estrogen fluctuations

BACKGROUND: Estrogen fluctuations during menopause are linked to increased psychiatric symptoms like depression and anxiety. Depression rates in menopausal women are 2-3 times higher than in premenopausal women, primarily due to rapid estrogen changes. Estrogen affects emotional stability by regulating neurotransmitters, adjusting HPA axis sensitivity, and influencing neuroinflammatory and epigenetic pathways. Menopausal hormone therapy (MHT) is a key treatment, stabilizing neurotransmitter systems and HPA axis activity, but requires personalized and evidence-based approaches. OBJECTIVE: This paper aims to systematically summarize the association between estrogen fluctuations and menopausal psychiatric symptoms, elucidate the underlying physiological and molecular mechanisms driving these symptoms, and evaluate the therapeutic potential of MHT, so as to provide a robust theoretical basis for clinical decision-making in menopausal mental health management. METHODS: We performed a thorough review of peer-reviewed studies from medical and psychiatric databases, examining the connections between menopausal estrogen changes, neurotransmitter regulation, HPA axis function, neuroinflammation, epigenetic changes, and the effectiveness and safety of MHT for managing psychiatric symptoms. We prioritized high-quality clinical trials, epidemiological studies, and mechanistic research to ensure reliable evidence. RESULTS: The review highlights that sudden estrogen changes during menopause disrupt serotonin and norepinephrine signaling, alter HPA axis activity, and trigger neuroinflammation and epigenetic changes, increasing the risk of depression and anxiety. Menopausal hormone therapy (MHT) can alleviate these symptoms by restoring neurotransmitter balance and normalizing HPA axis function. However, its effectiveness depends on factors like treatment timing, hormone type, and individual patient characteristics, including medical history and symptom severity. CONCLUSION: Estrogen fluctuation is a significant modifiable risk factor for psychiatric symptoms during menopause, affecting neurotransmitter, endocrine, inflammatory, and epigenetic pathways. Menopausal hormone therapy (MHT) is effective for symptom management when personalized and administered within recommended timeframes. This underscores the importance of assessing estrogen levels and psychiatric symptoms in menopausal women to optimize MHT and enhance mental health outcomes.