Timing of hormone replacement therapy may influence Alzheimer’s disease risk, study suggests

The timing of hormone replacement therapy may make a big difference in a woman’s risk of developing Alzheimer’s disease. Starting treatment within five years of menopause may lower the risk by as much as 32%, but delaying it until 65 or later can increase the risk by 38%, according to new research presented at the 150th Annual Meeting of the American Neurological Association (ANA).

In a first-of-its-kind meta-analysis, researchers examined how the timing of hormone replacement therapy influences a woman’s risk of developing Alzheimer’s disease, as well as how the disease progresses once begun. They also included new information regarding how hormone replacement therapy affects brain changes seen on scans or in laboratory tests.

After menopause, natural estrogen levels drop; hormone replacement therapy sustains the benefits of estrogen. That includes helping brain cells communicate with each other, calming inflammation and protecting against damage that can lead to Alzheimer’s disease, researchers believe. Conversely, 10 years or more after menopause, the brain may already have early signs of Alzheimer’s disease, such as protein clumps or reduced blood flow, so adding estrogen may trigger inflammation or stress the brain’s blood vessels, they note.

“Starting hormone replacement therapy early may give the brain some protection, but if a woman already has Alzheimer’s or memory problems, hormone therapy won’t slow them down,” said FNU Vaibhav, MBBS, a student at Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India. “It’s like watering a plant: it helps when the plant is growing, but if it’s already wilting, it might be too late.”

There are various types of hormone replacement therapy for women, including estrogen alone, estrogen and progestin (a synthetic form of progesterone), or estrogen and selective estrogen receptor modulator (SERM). The therapy comes in pill or patch form and is often used to treat menopause symptoms such as hot flashes and sleep disturbances, and may help with heart health and prevent bone loss. Just under 5% of U.S. women use hormone replacement therapy, down from nearly 26% in 1999.

The researchers conducted a meta-analysis of more than 50 clinical trials and observational studies, comparing women who used one of the various forms of hormone replacement therapy after menopause to those who took a placebo or did not receive any treatment. The average age of both groups was 51. They assessed Alzheimer’s disease diagnosis, progression from mild cognitive impairment to dementia and changes to thinking ability and signs in the brain of Alzheimer’s disease, based on blood tests and brain scans.

Their analysis of randomized controlled trials showed the risk of Alzheimer’s disease increased 38% in women who started hormone replacement therapy at age 65 or older, particularly in those whose therapy included progestin.

Based on 45 observational studies of real-world outcomes, they determined that women who started hormone replacement therapy around the time of menopause reduced their risk of Alzheimer’s disease later in life by 22%. Analyzing both randomized controlled trials and observational studies, the researchers determined that those who started therapy within five years of menopause had a 32% lower risk of Alzheimer’s.

“The evidence isn’t strong enough to suggest hormone replacement therapy should be taken to prevent Alzheimer’s. However, if a woman is planning to use it for menopause symptoms, starting soon after menopause might give her brain some protection against Alzheimer’s disease later,” said Dr. Vaibhav. “She should talk to her doctor about stopping it after a few years to avoid raising her risk. And women should not start hormone replacement therapy in their 60s or 70s to protect their brain because it might do more harm than good.”

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