New Study Finds Association Between Hormone Replacement Therapy for Menopause and Memory

Results of a study published in Neurology suggest that the type of estradiol-based hormone therapy taken after menopause may be associated with specific domains of memory performance. Researchers found that women who experienced earlier menopause scored lower on cognitive tests overall, but the use of estradiol patches or oral therapy was associated with improved outcomes in certain domains of memory performance: those who used transdermal estradiol patches scored better in episodic memory testing (recall) whereas those who used oral therapy performed better on prospective memory testing (future intentions). The authors caution that these results do not establish a causal relationship between menopause age, menopausal hormone therapy use, and memory.

In the cross-sectional study, researchers analyzed data from 7251 cognitively healthy postmenopausal women participating in the Canadian Longitudinal Study on Aging. Between 2012 and 2015, participants completed assessments of episodic memory, prospective memory, and executive function. Linear regression models adjusted for age, education, vascular risk, and menopause age examined associations with hormone therapy use and cognitive performance.

Key results included the following:

• Earlier menopause was linked to lower scores on all cognitive domains, including episodic memory (β=0.050; P< 0.001), prospective memory (β=0.047; P< 0.001), and executive function (β=0.061; P< 0.001).
• Earlier menopause was associated with lower executive function performance specifically for participants with ≥4 children and carriers of the apolipoprotein E ε4 (APOE ε4) gene variant.
• Participants who used transdermal estradiol therapy showed higher episodic memory scores (95% CI, 0.294 to 0.533) vs those who did not receive hormone therapy (95% CI, 0.196 to 0.247; P=.007; Cohen d=.303).
• Participants who used oral estradiol showed higher prospective memory scores (95% CI, 0.037 to 0.378) vs those who did not receive hormone therapy (95% CI, -0.0359 to 0.009; P=.015; Cohen d=.283).
• Neither route of estradiol administration influenced executive function performance.

Source: Puri TA, Gravelsins LL, Alexander MW, et al. Association between menopause age and estradiol-based hormone therapy with cognitive performance in cognitively normal women in the CLSA. Neurology. 2025;105(6):e213995. doi:10.1212/WNL.0000000000213995