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.
"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.
Dr. Galea added: "There's clearly a lot more we need to understand about how different estrogens can support the brain health of older women. To truly personalize care, we need a better sense of when, how, and for whom it is optimal to use these hormones to support memory. This will be a key area of future exploration."
She also emphasized the lack of investment in women’s brain health research. "Only six to seven per cent of health research grants from Canada’s largest health granting agency address women’s health issues but mostly focused on pregnancy — with just 0.18 per cent across 15 years on menopause," she said. "Women’s brain health remains understudied, underfunded, and overgeneralized. We urgently need more evidence to support women in midlife and beyond. That is why I am thrilled that, with new funding from Wellcome Leap, we are developing an Alzheimer’s disease prediction tool specifically for women, leveraging machine learning and big data."
About the Centre for Addiction and Mental Health (CAMH)
The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and addiction teaching hospital and a world leading research centre in this field. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental illness and addiction. CAMH is fully affiliated with the University of Toronto and is a Pan American Health Organization/World Health Organization Collaborating Centre. For more information, please visit camh.ca
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