Hormone therapy type may influence postmenopausal cognitive health

The type of estradiol-based hormone therapy taken during and after menopause, such as patches or pills, may be associated with differences in memory performance, according to a study published on August 27, 2025, in Neurology^®, the medical journal of the American Academy of Neurology. The study found when compared to people not taking hormones, those using hormone patches or gels had better episodic memory, the ability to recall past experiences, and those taking hormone pills had better prospective memory, the ability to remember to do future tasks.

The study found associations but did not prove that hormone therapy causes changes in memory.

Hormone therapy is often considered to help manage symptoms of menopause but deciding whether to use it - and which type to use - can be a complex and personal decision. This study highlights that the type of estradiol therapy used may influence cognitive performance differently across various types of memory. Understanding these links could help inform more tailored approaches to maintaining brain health after menopause."

Liisa A. M. Galea, PhD, study author of the Centre for Addiction and Mental Health in Toronto, Canada

The study included 7,251 cognitively healthy postmenopausal participants using data from the Canadian Longitudinal Study of Aging. They had an average age of 61 and reached menopause at an average age of 51.

Participants completed tests that measured different memory and thinking skills. Episodic memory tests assessed their ability to remember words and events. Prospective memory tests measured how well they remembered to do things in the future, such as remembering an appointment later in time. Executive function tests looked at their planning and problem-solving skills.

Participants reported whether they were using estradiol-based hormone therapy, with 4% using transdermal estradiol in the forms of patches or gels applied to the skin or vaginal rings, creams or tablets, and 2% taking it as pills. The remaining 94% of participants did not use hormone therapy.

After adjusting for age, education and vascular risk factors, researchers found that earlier menopause was linked to lower scores across all areas of memory and thinking. For executive function only, the association was strongest in people with four or more children and in those carrying the APOE ε4 gene variant, which increases Alzheimer's disease risk.

Participants who used transdermal estradiol had better scores on episodic memory tests than those who never used hormone therapy, with the average scores of the two groups being a third of a standard deviation apart. Those who took estradiol pills demonstrated better scores on prospective memory than those who never used hormone therapy, with the average scores a third of a standard deviation apart. Neither form of therapy was linked to differences in executive function scores. Across all types of memory tested, neither the number of children nor carrying the APOE ε4 gene variant influenced the findings of estradiol hormone therapies on cognition.

"Our findings suggest that the type of estradiol therapy matters, with different forms linked to different types of memory," Galea said. "While we cannot say hormone therapy causes these effects, it adds to the conversation about how best to support brain health after menopause."

A limitation of the study was most participants were white and had higher incomes, which means the findings may not be the same for people of other racial, ethnic or socioeconomic backgrounds. The data also did not examine how hormone therapy dosage, duration or timing influence cognition.