The role of hormone replacement therapy in the management of perimenopausal mental health symptoms: A narrative review

Abstract Menopause represents a significant physiologic transition in a woman's life, often accompanied by psychological challenges, including depression, anxiety, and cognitive decline. The postmenopausal decline in estrogen levels has been implicated in increased risk of neuropsychiatric disorders and cognitive impairment, with studies highlighting estrogen's neuroprotective and regenerative effects. While hormone replacement therapy (HRT) has been widely used for the relief of vasomotor and physical symptoms of menopause, a definitive consensus on its efficacy in the mitigation and management of mental health symptoms is lacking. This narrative review examines the role of HRT in managing menopausal mental health, evaluating the effects of estrogen‐only therapy, combined estrogen‐progesterone therapy, and alternative hormonal treatments on mood disorders, anxiety, and cognitive function. Findings suggest that estrogen therapy, in particular, transdermal 17β‐estradiol, may have antidepressant effects in perimenopausal women, although its efficacy in postmenopausal depression is less clear. Combined estrogen‐progesterone hormone therapy, while possibly beneficial for mood regulation, may attenuate some cognitive benefits associated with estrogen alone. Additionally, the effects of progesterone remain ambiguous, with synthetic progestins potentially counteracting estrogen's neuroprotective effects. Emerging evidence suggests a possible role for testosterone and selective estrogen receptor modulators in cognitive and mood stabilization, though further research is warranted. Cognitive outcomes associated with HRT appear to be time‐dependent, aligning with the “timing hypothesis”, which posits that early initiation of HRT post‐menopause may confer neuroprotective benefits, whereas late‐life initiation could contribute to an increased risk of dementia. The heterogeneity of findings emphasizes the importance of individualized, carefully considered treatment approaches, underscoring the need for further large‐scale, robust trials to further inform the use of HRT, as appropriate, in menopausal mental health management.