Toronto, ON (August 27, 2025) — Estradiol, the most common form of the estrogens used in hormone therapy, may influence different types of memory during the menopausal transition and beyond depending on how it is delivered — through the skin or orally — according to new research led by Dr. Liisa Galea , senior scientist and womenmind Treliving Family Chair in Women’s Mental Health at the Centre for Addiction and Mental Health (CAMH). Published today in the journal Neurology , the study is the first to show that the same hormone can have distinct cognitive effects depending on delivery method — highlighting the need for more personalized approaches to women’s brain health.
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"This is the first study to show that estradiol’s effects on memory vary depending on how it is delivered,” said Dr. Galea. “It also reinforces that cognition is multifaceted, and hormone therapy should be tailored to each woman’s health profile and menopause experience."
The study analyzed data from 7,251 cognitively healthy postmenopausal participants using data from the Canadian Longitudinal Study on Aging, a national research project following Canadians over 20 years to understand how different factors affect health and aging. Participants completed tests measuring episodic memory (recalling past events), prospective memory (remembering to perform future tasks) and executive function (planning and problem-solving). Among participants, 4 per cent used transdermal estradiol (delivered through the skin via patches, gels, or vaginal applications), 2 per cent used oral estradiol pills, and 94 per cent did not use hormone therapy.
The researchers found that the earlier someone experienced menopause, the more it affected cognition across all the areas tested. Transdermal estradiol users demonstrated better episodic memory compared to non-users, while oral estradiol users showed improved prospective memory. This suggests that estradiol’s delivery method impacts different aspects of cognition. Hormone therapy did not appear to affect executive function in either case, and all findings were consistent regardless of the number of children participants had or their genetic risk factors. Notably, estradiol therapy was never associated with poorer cognitive outcomes, reaffirming its potential positive value for women’s brain health in menopause.
