Women who had a longer reproductive period and had used or are using hormone replacement therapy showed fewer signs of damage to the small blood vessels in the brain later in life. This is shown by a study led by Karolinska Institute's researchers, published in the journal Neurology.
In this new study, the researchers examined 352 women from Gothenburg. All were aged 70 with no signs of impaired cognitive functioning. The participants' brains were scanned using magnetic resonance imaging (MRI) at the age of 70 and again five years later.
The researchers also had data on the age at first menstruation and the onset of the menopause, as well as previous use of the contraceptive pill and hormone replacement therapy during the menopause. This was compared with, amongst other things, signs of small-vessel disease – that is, damage to the brain's tiniest blood vessels – the microstructure of the white matter, and the thickness of the cerebral cortex in areas vulnerable to Alzheimer's disease.
A longer reproductive period – that is, the time between the first menstruation and the menopause – was associated with lower small-vessel disease burden in the brain. The use of hormone replacement therapy during the menopause was also associated with less small-vessel disease and a more favourable microstructure in the brain's white matter. Women who had used both the contraceptive pill during their reproductive years and hormone replacement therapy during the menopause showed the most favourable profile for their vascular brain health.
The researchers behind the study note that women not only are more likely than men to develop Alzheimer's disease, a difference that may be partly related to oestrogen fluctuations across the lifespan. The new findings suggest that these hormonal exposures may also influence the health of the brain's 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. The findings suggest that the brain's blood vessels may play an important role in the link between oestrogen and brain ageing," says Anna Marseglia, Assistant Professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, and senior author of the study.
One limitation of the study is that data on hormone use were self-reported, and there was a lack of detailed information on, for example, when treatment began, the dose and the type of treatment.
"Furthermore, the study is an observational study, and we cannot therefore determine cause and effect. The results cannot therefore be used as a basis for recommending hormone therapy for preventive purposes", says first author Giulia Lorenzon, researcher at Yale University and former postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
The study was carried out by researchers at institutions including the Karolinska Institutet, Yale University, the University of Gothenburg, Harvard Medical School and several other international universities. The study was funded by, amongst others, the Swedish Research Council, Forte, the Centre for Innovative Medicine, the Dementia Foundation, the Alzheimer's Foundation and the Karolinska Institutet. The researchers state that there are no conflicts of interest associated with the study.
Publication: "Reproductive lifespan and hormonal therapy in relation to later-life neurovascular health in community-dwelling older women", Giulia Lorenzon, Gemma García-Lluch, Gillian T. Coughlan, Shireen Sindi, Silvia Maioli, Konstantinos Poulakis, Jenna Najar, Rosaleena Mohanty, Lina Rydén, Ernest Privsek, Sara Shams, Rachel Buckley, Eric Westman, Ingmar Skoog, Anna Marseglia, Neurology, online 4 November 2026, doi: 10.1212/WNL.0000000000218706
