Study finds estrogen-based hormone therapies could protect brain health in older women

Researchers from the University of Kansas have shown a link between reproductive hormone exposure throughout life and brain health in 459 women aged 65 to 80. They discovered older women who had used hormonal birth control in young adulthood were more likely to have larger volumes in brain regions vital to memory, cognition and information processing.

They recently shared their findings in NeuroImage, a peer-reviewed journal.

“It’s showing a protective effect — using estrogen-based hormone therapies was beneficial for the brain in older women,” said co-lead author Amber Watts, professor of psychology at KU and frequent collaborator with KU Alzheimer’s Disease Research Center scientists. “What's unique about this paper is we looked at the use of hormone-based medications both in early adulthood and in midlife, and the use of both of those was associated with brain health in older adult women.”

The KU researcher said evidence suggested it may be the lifetime accumulation of estrogen exposure, first from birth control and later from menopausal hormone therapy, that provides the beneficial effect. So, the KU team examined three possibilities for hormone exposure:

Use of hormonal birth control

Use of menopausal hormone therapy (MHT) during menopause

Natural hormone exposure, estimated by how late menopause occurred.

“A lot of the research work has just looked at menopause hormones specifically and not really looked at what happens earlier in your life,” Watts said. “When your brain is first developing, say in adolescence, there are a lot of hormone changes happening then. People haven't really given much thought to what implications that might have for brain health in the long term.”

Most American women of childbearing age use birth control, according to the Centers for Disease Control.

“I don't think people really stop and think about that,” Watts said. “When they think about taking birth control for the purpose of either regulating their cycles or for contraception, I don't think what people are thinking about is, ‘How will this affect my health later?’”

The KU researcher said the findings should prompt both health care providers and people who take birth control to think about long-term implications.

Women make up nearly two-thirds of Alzheimer's disease patients, according to the Alzheimer’s Association. According to Watts, understanding if reproductive hormones protect the aging brain might eventually inform strategies for reducing dementia risk and improving healthy cognitive aging.

“Estrogen is neuroprotective,” she said. “It’s beneficial for white matter integrity. It helps protect neurons and strengthens neural connections. It is also important for vascular function. One of the things we get wrong about estrogen is people think of estrogen as this thing that has to do with reproduction. But really, estrogen is very important for a lot of different body systems. It’s important for the brain, it's important for the heart, it's important for bone density, and it’s important for the immune system.”

Watts and her co-authors also found women experiencing menopause at a later age — meaning they were exposed to natural ovarian hormones for a longer period — had thicker cortex in multiple brain regions vulnerable to Alzheimer's disease.

The KU researcher said the new evidence in general should support use of hormone therapy during menopause.

“There's been a controversy over hormone therapy use. There was a study back in 2002 called the Women’s Health Initiative, and its results scared everybody out of using estrogen therapy,” Watts said. “For a long time, people stopped prescribing and using those therapies, thinking that it was going to lead to negative outcomes. Since then, there's been a lot of revisiting of those findings and discovering that there were some problems with them and that they didn't apply to everyone.”

The new investigation lines up with Watts’ recent research into hormones and brain health in women, an area that remains under-researched. A related paper by Watts published last year showed birth control and hormone therapy were associated with cognitive outcomes.

“People who underwent early surgical removal of the ovaries definitely benefited from exposure to hormone therapy,” she said.

Going forward, Watts’ team is recruiting for new menopause-related studies. She encouraged women who might be interested in participation to complete a short survey to help determine whether they are eligible.

“It's a topic that women are very excited about, and every time I talk about it, I have a line of people waiting to ask me more questions,” she said. “I think it’s something that people care about.”

REFERENCE:

Robyn A. Honea, Amber Watts, Shannon D. Donofry, Cristina Molina-Hidalgo, Hayley S Ripperger, Sarah L. Aghjayan, Chaeryon Kang, Swathi Gujral, Lauren E. Oberlin, George Grove, Haiqing Huang, Bradley P. Sutton, Jeffrey M. Burns, Eric D. Vidoni, Arthur F. Kramer, Edward McAuley, Charles H. Hillman, Anna L. Marsland, M. Ilyas Kamboh, Kirk I. Erickson, Lifespan exposure to hormone therapies and structural brain morphometry in older women, NeuroImage, Volume 334, 2026, 121974, ISSN 1053-8119, https://doi.org/10.1016/j.neuroimage.2026.121974.