Early observational studies suggested that hormone replacement therapy (HRT)  may improve cognitive functioning in postmenopausal women; however, larger studies, including the Women’s Health Initiative, have shown that estrogen replacement therapy started in postmenopausal women (65 years or older) did not enhance cognitive functioning, nor did HRT decrease the risk of dementia.

Taking these disparate findings into consideration, researchers have proposed the hypothesis that there may be a “critical window” such that hormone replacement therapy initiated near the onset of menopause may reduce future risk of developing neurodegenerative disorders and may improve cognition, whereas starting HRT in older women may have no effect on cognitive functioning.  

Exploring this possibility, Carey Gleason, PhD, from the Wisconsin Alzheimer’s Disease Research Center at the University of Wisconsin School of Medicine and Public Health, reviewed data from more recent studies of HRT and cognition, including the Kronos Early Estrogen Prevention Study-Cognitive (KEEPS-Cog) and Affective Study, the Early vs. Late Intervention Trial with Estradiol-Cognitive Endpoints (ELITE-Cog) and the WHI Memory Study-Young (WHIMS-Y).

None of the studies demonstrated any cognitive benefits associated with HRT.  While the KEEPS-Cog study did show that women taking oral conjugated equine estrogens reported improvements in mood and reductions in anxiety symptoms, we still have to contend with the fact that prolonged use of HRT may carry some risk, including increased incidence of stroke, thromboembolic events, and breast cancer.  


Ruta Nonacs, MD PhD


Gleason C. An update on menopausal hormone therapy trials. Presented at: Alzheimer’s Association International Conference; July 22-26, 2018; Chicago.


Reviewed in Hormone therapy not associated with cognitive harm in healthy women (Healio)


Reviewed in HRT Started Close to Menopause Safe for Cognition (MedPage Today)


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