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Depression is a severe psychiatric disorder characterized by high prevalence rates, elevated suicide risks, and significant relapse rates. Women, particularly during the perimenopausal period, are more vulnerable to developing depression. Fluctuations in estrogen levels during perimenopause can heighten a woman's sensitivity to psychosocial stress. Clinical trials have demonstrated the short-term antidepressant efficacy of estradiol in perimenopausal women. However, the precise mechanisms through which estrogen influences mood disorders during perimenopause remain unclear. This review summarizes the risk factors associated with perimenopausal depression (PMD), examines current research on estrogen therapy, and explores the potential mechanisms and related pathological processes involved in estrogen's role in treating depression. Understanding how estrogen mitigates depressive symptoms in perimenopausal women may help reduce the morbidity and mortality associated with PMD while also alleviating its socioeconomic burden.
 
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