Women with a longer reproductive lifespan, defined as the years between their first period and menopause, have a lower burden of cerebral small vessel disease at age 70.
MRI Results in the Gothenburg H70 Birth Cohort
The odds of having two or more signs of cerebral small vessel disease decreased by 8 percent for each additional year of a woman’s reproductive lifespan. All participants were 70 years old when they underwent brain MRI scans to measure markers linked to stroke, cognitive impairment, and dementia. Most participants returned for follow-up imaging at age 75.
The average reproductive lifespan among participants was 37 years, measured from menarche to menopause or the surgical removal of the ovaries.
Menopausal Hormone Therapy Lowers Small Vessel Disease Risk
Women with a history of menopausal hormone therapy had a 59 percent lower risk of a high small vessel disease burden, even after controlling for hypertension, cardiac disease, and socioeconomic background. Within the cohort, 73 percent of women had used oral contraceptives, while 61 percent had used or were using menopausal hormone therapy.
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,
Anna Marseglia, Karolinska Institutet
Hormonal Exposure Across Life Impacts Cerebrovascular Health
Anna Marseglia of the Karolinska Institutet stated that the results suggest hormonal exposure across different periods of a woman’s life may have cumulative effects on cerebrovascular health in later life. She noted that these data indicate a potentially significant function for cerebral blood vessels in the relationship between estrogen levels and the aging process of the brain.
Researchers also evaluated the APOE-ε4 gene variant, finding that favorable associations with small vessel disease and white matter integrity were most pronounced among non-carriers. An editorial published alongside the research by Tracy Madsen, Ph.D., M.D., M.S., an associate professor of emergency medicine at the Larner College of Medicine, connected increased lifetime estrogen exposure to a reduction in cerebrovascular pathology.
Evaluating Observational Research Findings
First author Giulia Lorenzon, PhD, a researcher at Yale University, stated that the results cannot be used as a basis for recommending hormone therapy for preventive purposes because the study is observational. She noted that the benefits and risks of such therapy depend on a patient’s age, time since menopause, medical history, and the type and length of treatment.
Individuals with estrogen-sensitive cancers, a high risk of blood clots, or severe heart disease are generally advised against such therapy. The authors did not track hormone levels throughout life, relying instead on self-reported data subject to recall inaccuracies.