Women who are exposed to estrogen for longer across their lives may have healthier blood vessels in their brains in old age, according to a new study of estrogen and brain aging. The research, published in Neurology on 4 November, looked at 352 healthy women in Sweden, all born in 1944. Each woman had brain scans at 70 and again at 75. A longer reproductive period, the time between a first period and menopause, was linked to fewer signs of damage to the small blood vessels in the brain. The findings add weight to the idea that estrogen and brain aging are connected through the blood vessels that feed the brain. Women develop Alzheimer’s disease more often than men, and scientists have long suspected that sharp changes in estrogen levels across a woman’s life may help explain why.
Estrogen and brain aging: what the study measured
The study drew on the Gothenburg H70 Birth Cohort Studies, which follows people born in Gothenburg in 1944. All 352 women were 70 years old with no signs of impaired thinking when it began. The researchers used MRI scans of the women’s brains at 70 and again five years later, and recorded each woman’s reproductive history, including first period and menopause ages, birth control pill use and hormone therapy use. The team studying estrogen and brain aging, led by neurobiologist Anna Marseglia of the Karolinska Institutet in Sweden, looked for signs of cerebral small vessel disease, a condition in which the tiny blood vessels in the brain become damaged. The damage shows up as small bleeds, white matter changes and enlarged spaces around blood vessels. Each extra year of reproductive period cut a woman’s odds of having two or more signs of small vessel disease at age 70 by about 8 percent. Later menopause, rather than an earlier first period, drove most of that link.
Hormone therapy and the brain’s blood vessels
The study of estrogen and brain aging also looked at hormone therapy. Women who had used hormone replacement therapy during menopause showed fewer signs of small vessel disease and healthier white matter, which carries signals between brain regions. Menopausal hormone therapy users had a 59 percent lower risk of a high burden of small vessel disease, with fewer brain microbleeds and fewer enlarged spaces around blood vessels. Women who had used birth control pills and later received menopausal hormone therapy had the healthiest brain blood vessels. “Our results suggest that hormonal exposure across different periods of a woman’s life may have cumulative effects also on the cerebrovascular health in later life,” Marseglia said. The estrogen and brain aging study also found a link for women who carry the gene variant APOE-e4, which raises Alzheimer’s risk. Among those women, hormone therapy was linked to greater thickness in brain regions that Alzheimer’s tends to affect first. Estrogen is known to protect both nerve cells and blood vessels in the brain, but its role in women’s cerebrovascular health in later life has been little studied.
A separate study points the same way
A second study of estrogen and brain aging, published in the same journal days earlier, reached a similar conclusion from a different angle. Researchers at Stanford University, led by Jennifer L. Bruno, examined records from thousands of older women in two large databases, including the National Alzheimer’s Coordinating Center. They found that estrogen-only hormone therapy during menopause was linked to fewer advanced Alzheimer’s disease changes in brain tissue at death. The hormone therapy group also had lower odds of a clinical dementia diagnosis and better memory test scores. The Stanford study was observational, like the Swedish study, which means it cannot prove that the hormone therapy caused the better brain health. Both studies looked at past records rather than assigning women at random to take hormones or not, so other differences between the groups could explain part of the results.
What estrogen and brain aging research still cannot show
The Swedish study of estrogen and brain aging has limits that its authors state plainly. The data on hormone use were self-reported, and the researchers lacked detailed information on when treatment began, the dose and the type of treatment. The study is observational, so it cannot show cause and effect. Marseglia said the estrogen and brain aging results cannot be used as a basis for recommending hormone therapy for preventive purposes. The study focused on women born in one city in one year, and the findings may not apply to women elsewhere. The authors say clinical trials would be needed to show whether longer estrogen exposure or hormone use directly protects the brain. Swedish research councils and dementia and Alzheimer’s foundations supported the study. The paper appeared in Neurology, the medical journal of the American Academy of Neurology.