Impact of Menopausal Hormone Therapy on Brain Health in Postmenopausal Women, a Pilot Study

Background: The menopause transition and postmenopause are accompanied by a wide range of cognitive, emotional, and physical symptoms that can significantly affect women’s quality of life and brain health. Despite the growing population of menopausal women, menopausal hormone therapy (MHT) remains under-researched in relation to cognitive and emotional well-being. This pilot study evaluated the effects of personalized, continuous MHT on brain health using the validated, multidimensional BrainHealth™ Index (BHI). Methods: Forty-two postmenopausal women completed the BHI at baseline (T1), 6 months (T2), and 12 months (T3). After T1, participants began personalized, titrated MHT with close follow-up at 5 weeks. Thirty-six women from a separate database, matched on age and education, served as controls. Mixed-effects modeling examined main effects of time, group, and the time × group interaction on four measures: the BHI composite and its components—clarity, connectedness, and emotional balance. Results: At T1 (before MHT), the MHT group exhibited significantly lower scores across all BHI indices, indicating greater impairment in cognitive, emotional, and social domains relative to controls. A significant group × time interaction revealed that after starting MHT, the MHT group showed greater improvement from T1 to T2 across all indices compared with the control group. By T2, MHT participants reached scores comparable to controls, and these gains were maintained at T3, with no further group differences in score change. Conclusions: Personalized MHT in this pilot sample of symptomatic postmenopausal women led to improvements in cognitive clarity, emotional well-being, and social connectedness. These preliminary findings suggest that MHT may serve as a whole-person intervention integrating neuroendocrine, cognitive, and emotional domains. Confirmation in larger, randomized controlled trials is needed to evaluate generalizability, adoption of personalized MHT, and the sensitivity of the BHI as a sensitive clinical assessment tool for this population.