A new study published in the medical journal Neurology has found that a longer reproductive lifespan and a history of using birth control pills or menopausal hormone therapy (HRT) are associated with fewer signs of cerebral small vessel disease and better brain health in older women.
The research, published on Wednesday, November 4, involved 352 women aged 70 who showed no signs of cognitive impairment at the start of the study. Scientists examined reproductive factors linked to lifetime estrogen exposure, calculating each woman's reproductive lifespan as the number of years between her first menstrual period and menopause or surgical removal of the ovaries. On average, the women had a reproductive lifespan of 37 years.
Study Findings on Hormone Use
Of the participants, 73% had used contraceptive pills and 61% had used or were currently using menopausal hormone therapy. The participants underwent MRI brain scans at ages 70 and 75, which were examined for four indicators of cerebral small vessel disease: white matter hyperintensities, microbleeds, lacunes, and moderate to severe enlargement of spaces surrounding blood vessels. Each participant received a score from zero to four, with one point awarded for each sign identified.
After accounting for factors such as education, number of pregnancies, and total months breastfeeding, researchers found that women with a longer reproductive lifespan had 8% lower odds of presenting with two or more signs of cerebral small vessel disease. In a separate analysis that accounted for factors including education, high blood pressure, and heart disease, women who had used or were still using menopausal hormone therapy faced 59% less risk of having a greater small vessel disease "burden," which included fewer microbleeds and enlarged spaces around blood vessels.
Implications for Women's Brain Health
Contraceptive pills and menopausal hormone therapy use were also linked to greater "integrity" of the brain's white matter microstructure, an early marker of healthier brain tissue. Women who had taken oral contraceptives and subsequently received menopausal hormone therapy showed the most favorable vascular brain health, with the lowest amount of cerebral small vessel disease and the healthiest white matter integrity compared with women who had never used hormonal therapies.
Anna Marseglia, PhD, of Karolinska Institutet in Stockholm, Sweden, said: "Women are affected by Alzheimer's disease more often than men. This may be related, in part, to fluctuations in estrogen levels throughout life. Estrogen is known to have protective effects on both neuronal cells and blood vessels in the brain. However, its potential role in women's cerebrovascular health in later life has been largely understudied. Our study found that factors associated with longer estrogen exposure were associated with fewer signs of cerebral small vessel disease and better brain health in older age."
Marseglia added: "What was particularly striking was that the most favorable vascular brain health was observed among women who had used oral contraceptives during their reproductive years and later received menopausal hormone therapy. This suggests that hormonal factors acting across different stages of a woman's life may have cumulative associations with cerebrovascular health in older age. While these findings do not establish cause and effect, they underscore the importance of considering women's reproductive and hormonal history when studying brain aging and dementia risk not only in relation to Alzheimer's disease but also to vascular disease."
Expert Commentary and Limitations
Dr Honorine Lebraud, Senior Partnerships Manager at Alzheimer's Research UK, said: "This study builds on growing evidence that reproductive and hormonal history may play a role in brain health as women age. Researchers found that women who had a longer reproductive lifespan and therefore experienced a longer period of natural oestrogen exposure, from their first period to menopause, tended to show fewer signs of damage to the brain's small blood vessels."
Lebraud continued: "While these findings are interesting, further research is needed to understand these patterns, especially as nearly two-thirds of people with dementia are women. As an observational study, it cannot show that hormone exposure directly improves brain health or reduces dementia risk. For now, our advice remains unchanged. Women should not start or stop taking the contraceptive pill or HRT to reduce their dementia risk based on these findings. Decisions about hormonal treatments should continue to be made with a healthcare professional, based on individual health needs."
The researchers noted limitations of the study, including that hormone exposure was self-reported by participants during data collection interviews, which may not have been entirely accurate. They were also unable to monitor individual hormone levels over time, and there was insufficient detailed information on participants' oral contraceptive and hormone therapy usage.
