A recent study published on Nov. 4 in Neurology found that women who had longer reproductive years and those who underwent menopausal hormone therapy exhibited fewer indications of disease in the brain’s small blood vessels during their 70s. The research, which followed 352 Swedish women who underwent brain scans at ages 70 and 75, discovered an association between extended estrogen exposure and the health of brain vessels. However, it is essential to note that the study does not establish a causal relationship between estrogen, birth control pills, or hormone therapy and the observed difference. The study’s observational design means it can only identify correlations, not causation.
Evaluating Brain Scan Results
Cerebral small vessel disease refers to the damage inflicted on the tiny blood vessels deep within the brain, which can increase the risk of stroke, cognitive problems, and dementia. Often, this condition becomes apparent on MRI scans years before symptoms manifest. The researchers, led by senior author Anna Marseglia of Karolinska Institutet in Stockholm, drew their subjects from the Gothenburg H70 Birth Cohort, a long-term study of individuals born in 1944. At the age of 70, all participants were free from cognitive impairment.
To calculate each woman’s reproductive lifespan, the researchers determined the number of years between her first menstrual period and menopause or surgical removal of the ovaries. The average reproductive lifespan was 37 years. Approximately 73% of the women had used birth control pills, and 61% had used or were using menopausal hormone therapy. The MRI scans were scored on a scale of 0 to 4, with each point representing one of four signs of small vessel disease: white matter lesions, microbleeds, lacunes, and moderate to severe enlargement of the spaces surrounding blood vessels.
Correlating Reproductive Years with Brain Health
The study revealed that women with longer reproductive lifespans had 8% lower odds of exhibiting two or more signs of small vessel disease, after adjusting for factors such as education, number of pregnancies, and total months of breastfeeding. A stronger correlation was observed with hormone therapy. In a separate analysis adjusted for education, high blood pressure, and heart disease, women who had undergone hormone therapy had 59% lower odds of having a heavier small vessel disease burden, including fewer microbleeds and enlarged spaces around vessels. Both birth control pills and hormone therapy were associated with healthier white matter structure.
The study also found that longer estrogen exposure was linked to more stable brain changes between ages 70 and 75. According to Marseglia, factors associated with longer estrogen exposure “were associated with fewer signs of cerebral small vessel disease,” although she emphasized that the findings do not establish cause and effect.
The results of this study align with earlier research. A 2023 Neurology study of approximately 9,000 postmenopausal women in the United Kingdom found that greater lifetime hormone exposure, measured by pregnancies and reproductive years, was associated with smaller volumes of white matter damage. While researchers have proposed that estrogen may play a protective role in maintaining blood vessel health, neither study investigated the underlying mechanisms. For women considering hormone therapy in their 40s and 50s, this study provides one data point to consider when evaluating long-term brain health.
Study Limitations and Guidelines
The study has several important limitations. The self-reported hormone use, which occurred long after the fact, may be subject to inaccurate recall. The researchers were unable to measure individual hormone levels over time, and the details regarding pill and hormone therapy types and doses were limited. Additionally, the study’s participants were all cisgender women from Sweden born in the same year, which may limit the applicability of the results to women of different ages, backgrounds, or healthcare systems. Women who underwent hormone therapy may also differ from non-users in ways that affect brain health, such as regular access to medical care. Clinical trials would be necessary to determine whether these hormones directly protect brain vessels.
Current medical guidance remains unchanged. Menopausal hormone therapy should not be used to prevent dementia, and its primary purpose is to alleviate symptoms such as hot flashes and night sweats. Although the FDA removed boxed warnings on heart disease, breast cancer, and probable dementia from menopausal hormone therapy labels, this change did not add dementia prevention as an approved use. Women considering hormone therapy can discuss their age, time since menopause, and medical history with a clinician to weigh the benefits and risks. Brain health can be a part of this conversation, but this study does not provide a reason to start or stop hormone therapy.
Discussing Hormone Therapy with a Clinician
The most effective ways to protect small brain vessels remain the same for everyone. Controlling blood pressure, managing diabetes and cholesterol, avoiding smoking, and engaging in regular physical activity can all reduce the risk of vessel damage. Sudden weakness on one side of the body, trouble speaking, facial drooping, or a severe headache are warning signs of a stroke that require emergency care. Gradual memory changes warrant a medical visit rather than a wait-and-see approach.
Future Research and Study Details
The study was funded by Swedish research councils and foundations focused on dementia and Alzheimer’s disease. Larger studies that track hormone levels across women’s lives are necessary, and further evidence will be reported as it becomes available. The research is currently in preprint form, meaning it has not yet undergone peer review by experts outside the study team.
