Timing of menopause could influence a woman’s risk for Alzheimer’s disease

By Denise Mann Health Day Reporter

TUESDAY, April 4, 2023 (HealthDay News) — Women are known to be at greater risk of developing Alzheimer’s disease than men, and now a new brain scan study suggests that the timing of menopause and the use of Hormone replacement therapy may play a role in this increased risk.

“Female sex, early age at menopause, and later use of hormone therapy were all associated with higher levels of tau in the brain,” said the study’s first author. Gillian Coughlan, a researcher at Massachusetts General Hospital in Boston. Beta-amyloid plaques and tau tangles are hallmarks of Alzheimer’s disease.

“This finding, if replicated, is clinically significant because higher levels of tau in the brain generally predict [mental] decline in the coming years,” Coughlan noted.

The study was not designed to say how, or even if, early menopause or delayed hormone therapy after menopause caused higher levels of tau in the brain, just that they seemed to travel together.

For the study, 193 women and 99 men underwent positron emission tomography (PET) scans to examine beta-amyloid and tau levels in seven brain regions. None of the people in the study showed signs of thinking decline.

The women in the study had higher levels of tau than the men, especially when they also had high levels of beta-amyloid.

Women aged 40 to 45 when they entered menopause had higher tau levels on their PET scans, suggesting that longer lifetime exposure to estrogen may protect against the disease. Alzheimers.

During menopause, levels of estrogen, a female sex hormone, drop dramatically. Tau levels were highest in regions of the brain close to its memory center and implicated in the progression of Alzheimer’s disease, the study showed.

Early or premature menopause only occurs in up to 10% of women. “This proportion of the female population may need to be considered an at-risk group if the results are replicated,” Coughlan said.

Women who started taking hormone therapy more than five years after menopause had higher levels of tau in the brain, the new study found.

Hormone replacement therapy fell out of favor after the Women’s Health Initiative study was stopped in 2002 because hormone therapy was shown to increase the risk of stroke and breast and brain cancer. ovary. But short-term use of hormone therapy is now considered safe for some women who have severe menopausal symptoms, such as hot flashes and night sweats. Another part of this landmark study found that the use of hormone replacement therapy increased the risk of dementia in women aged 65 and older, which is consistent with the findings of the new study.

Women who took hormone replacement therapy within five years of the onset of menopause did not have higher tau levels. “Hormone replacement therapy may only pose a risk to long-term cognition if started several years after the onset of menopause,” Coughlan said.

Alzheimer’s disease runs in certain families and is largely due to the presence of the APOE4 gene. “Whether or not the presence of this gene influences the association between menopause, hormone therapy, and Alzheimer’s disease is under investigation,” Coughlan added.

Findings need to be replicated in a larger group of women, the corresponding author added Rachel Buckley. She is an assistant professor of neurology at Massachusetts General Hospital/Harvard Medical School in Boston.

“Our data certainly supports the findings of the Women’s Health Initiative which suggest that giving hormone therapy to women after a long postmenopausal period may increase the risk of Alzheimer’s disease,” Buckley said. “There’s certainly a case to be made for hormone therapy to help short-term symptoms, but women should definitely consult their doctor to see if their situation supports longer-term use.”

Experts point out that timing can be key when it comes to using hormone replacement therapy after menopause.

“The current study expands our understanding of the interplay between female gender, Alzheimer’s disease and menopause, and how hormone therapies may contribute to these relationships,” said Dr. Kejal Kantarcidirector of the Women’s Health Research Center and associate director of the Alzheimer’s Disease Research Center at Mayo Clinic in Rochester, Minn.

The influence of hormone replacement therapy on tau was limited to women who started hormone therapy five years after menopause.

“Hormone treatments started early during the menopausal transition did not impact tau deposition and are considered safe,” Kantarci said.

Yuko Haradirector of prevention and aging at the Alzheimer’s Drug Discovery Foundation in New York, agreed.

“The findings are consistent with existing literature suggesting that starting hormone therapy several years after menopause may be harmful to cognitive health,” Hara said.

Still, it’s too early to draw firm conclusions about how hormone replacement therapy after menopause affects Alzheimer’s disease risk, she said. “For a more definitive answer, we need amyloid and tau PET imaging data from randomized controlled trials that test hormone therapy versus placebo in women within a specific time window of menopause,” said Hara added.

Such studies are ongoing, she said.

“The decision whether or not to take hormone replacement therapy should be made with your healthcare provider to maximize benefits such as menopausal symptom relief while minimizing risks,” Hara said.

SOURCES: Gillian Coughlan, PhD, fellow, neurology, Massachusetts General Hospital, Boston; Rachel Buckley, PhD, assistant professor, neurology, Massachusetts General Hospital/Harvard Medical School, Boston; Kejal Kantarci, MD, director, Women’s Health Research Center, and associate director, Alzheimer’s Disease Research Center, Mayo Clinic, Rochester, Minn.; Yuko Hara, PhD, director, prevention and aging, Alzheimer’s Drug Discovery Foundation, New York; JAMA NeurologyApril 3, 2023, online

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