By Tiffany Kuku

A 2025 paper authored by Tanvi A. Puri and colleagues provides clarity on the non-uniform effects of 17𝛽-estradiol (E2) based menopausal hormone therapy (MHT) on cognition. The study examined baseline data of 7,251 cognitively healthy post-menopausal women (mean age 60.5 ± 10.2 years) from the Canadian Longitudinal Study on Aging (CLSA) dataset. The authors reported that the benefits associated with MHT are dependent on both the mode of administration and the specific cognitive domain being tested.

Transdermal E2 (administered via patches and creams) was associated with significant improvements in episodic memory; a function that relies primarily on the medial temporal lobe. Conversely, orally administered E2 was associated with improvements in prospective memory, which relies on both the frontal and medial temporal lobes. The distinctions in administration are said to induce varied hormone levels, which in turn favor different parts of the memory system and affect cognitive function in different ways. The study also highlighted that an earlier age of menopause was broadly correlated with lower cognitive performance at age of testing. This negative effect was magnified for executive functioning specifically in APOE ε4 carriers and individuals with grand parity (i.e., four or more children), thus indicating an enhanced vulnerability in such groups to earlier hormonal decline.

The results of the study emphasize the differential effects of E2-based MHT depending on the mode of administration and cognitive function. Further, it necessitates the consideration for age of menopause and individualized characteristics in developing therapeutic approaches for cognitive aging in post-menopausal people.

Reference

Puri, T. A., Gravelsins, L. L., Alexander, M. W., McGovern, A. J., Guterman, P. D., Rabin, J. S., Murphy, K. J., Galea, L. A. M. (2025). Association between Menopause Age and Estradiol-Based Hormone Therapy With Cognitive Performance in Cognitively Normal Women in the CLSA. Neurology Journals, 105 (6) e213995. https://doi.org/10.1212/WNL.0000000000213995