Women with more years between first period and menopause showed less brain vessel damage at 70

A study of 352 Swedish women born in 1944 found that every additional year between a first period and menopause was associated with roughly 8% lower odds of having two or more signs of small blood vessel disease in the brain at 70. All of the women came from the Gothenburg H70 Birth Cohort Studies and showed no cognitive impairment when they were enrolled. The findings appeared in the journal Neurology on Nov. 4.

Stay ahead on AI: Join 600,000+ professionals who read The Deep View, the daily newsletter that keeps you up to date with artificial intelligence.

Subscribe to The Deep View →

We may earn a commission if you sign up.

Brain imaging is what made the comparison possible. Each participant had an MRI scan at 70, and most had a second at 75, so the researchers could look at how much wear had accumulated in the tiny vessels that feed the brain’s white matter. Small-vessel damage shows up as bright spots and shrunken tissue on those scans, and it is a recognized contributor to stroke and to later memory trouble.

The 8% figure and the reproductive span behind it

The exposure measure was simple arithmetic. Researchers subtracted each woman’s age at her first period from her age at menopause, or at removal of both ovaries, and treated the result as a proxy for lifetime estrogen exposure. Hormone levels themselves were never measured, which is why the authors describe the span as an indirect marker. As ScienceAlert reported, odds of showing two or more small-vessel signs fell by about 8% for each extra year in that span.

Later menopause, not an earlier first period, drove most of the association. In practical terms, the women whose reproductive years ran longest carried a lighter load of vessel damage on their scans than women whose estrogen-producing years ended sooner, and the gap was visible in a group that had no diagnosed cognitive problems at the start.

That pattern fits the biology the team has in mind. Estrogen acts on blood vessel walls and on the brain’s white matter, and a longer window of natural exposure could, in theory, slow the wear that builds up over decades. A Karolinska Institutet news release quotes senior author Anna Marseglia, an assistant professor there, saying that hormonal exposure across different periods of a woman’s life may have cumulative effects on the health of brain blood vessels.

Hormone therapy and the pill in the same cohort

The analysis also looked at medication. Women who had used menopausal hormone therapy showed fewer signs of small-vessel disease and better white matter microstructure, and those who had taken both oral contraceptives and menopausal hormone therapy had the most favorable profile in the Karolinska summary. Among carriers of the APOE-e4 gene variant, a known Alzheimer’s risk factor, hormone therapy was linked to thicker cortex in regions that the disease tends to attack. No such link appeared in non-carriers.

Hormone use was based on what participants reported, and the cohort was too small to separate the effects of timing, dose and formulation. A News-Medical summary of the work makes the same point about the limits of what a single Swedish birth cohort can say.

Limits the researchers place on the data

Giulia Lorenzon, a Yale University neuroscientist and first author, was direct about the boundaries. She said the study is observational, so cause and effect cannot be determined, and that the results cannot be used as a basis for recommending hormone therapy for preventive purposes. The American Academy of Neurology release frames the work the same way, as a reason for further research into estrogen and long-term brain health rather than a treatment signal.

Several limits stack up. The cohort is limited to one country and one birth year, which restricts how far the numbers travel to other populations. Many of the associations weakened or lost statistical significance when the threshold for significance was tightened. Other hormones that fluctuate across a lifetime may also play a part and were not isolated here.

A large review of earlier studies found no strong evidence that menopausal hormone therapy changes dementia risk, and the authors place their result alongside that mixed record instead of against it. The full paper, with the underlying statistics, is listed under its Neurology DOI.

Why a Swedish birth cohort keeps turning up in this research

The H70 studies follow people born in the same year in Gothenburg, repeating examinations as the cohort ages. That design removes much of the noise that comes from comparing people of different generations, because every participant lived through the same decades of medicine, diet and public health. It also means the same women can be re-scanned, which is how a 70 and 75 comparison became available.

The open question is the one the authors themselves raise: whether estrogen exposure causes the protection, or whether women with longer reproductive spans differ in other ways that also shield the brain. Answering it will take studies that measure hormone levels directly and follow women across more countries and birth years, and Marseglia and Lorenzon’s team has not yet reported such a follow-up.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

Stay ahead on AI: Subscribe to The Deep View →

We may earn a commission if you sign up.