The Impact of Perimenopause on Mood and Cognition: A Review of Neuroendocrine Mechanisms and Treatment Strategies

Abstract

The menopausal transition represents a critical neuroendocrine window during which fluctuating ovarian hormones significantly impact mood and cognition, yet the underlying mechanisms and optimal management strategies remain informatively understood. This review synthesizes current evidence on the neuroendocrine pathways-including hormonal fluctuations, receptor dynamics, and neurotransmitter alterations—that contribute to perimenopausal mood disorders and cognitive decline. It further evaluates both hormonal and non-hormonal interventions, highlighting the need for integrated, personalized treatment approaches to address these complex symptoms. Key topics include the role of estrogen and progesterone in modulating serotonergic and dopaminergic systems, the impact of hypothalamicpituitary- adrenal axis dysregulation, and structural and functional brain changes observed during perimenopause. The review also examines the efficacy of hormone therapy, antidepressants, cognitive behavioral therapy, and complementary treatments such as acupuncture and herbal medicine. Clinical insights are drawn from recent trials assessing transdermal estradiol, micronized progesterone, and traditional formulations, offering a comparative perspective on their benefits and limitations. Additionally, the influence of genetic factors, lifestyle, and psychosocial stressors on symptom severity is discussed, emphasizing the heterogeneity of perimenopausal experiences. The relationship between vasomotor symptoms, sleep disturbances, and cognitive impairment is explored, alongside emerging evidence linking perimenopausal symptoms to long-term neurological risks. Future research should prioritize longitudinal studies to clarify the timing and duration of hormone therapy for cognitive protection and explore the mechanisms of non-hormonal interventions. There is also a critical need to develop biomarker-guided, personalized treatment frameworks that integrate biological, psychological, and social dimensions of perimenopausal health.