Study links hormone use to healthier brains

Anna Marseglia, a neurobiologist at the Karolinska Institute in Stockholm, led a study published Wednesday in the journal Neurology that examined how estrogen exposure affects brain health in older women. The research focused on 352 cognitively healthy women who were 70 years old at the time of assessment.

The study found that women with longer reproductive spans, defined as the period between a first period and menopause, displayed physiological markers of healthier brain aging. Specifically, these women exhibited less damage to small brain blood vessels and better-preserved white matter, which facilitates communication between different brain regions.

A more specific finding emerged regarding external hormone use. Among the participants, those who had used both oral contraceptives and hormone therapy showed the healthiest brain profiles. Marseglia described her personal reaction to these results, stating, “I was personally very excited.” The investigation involved more than a dozen researchers from institutions including Yale University and Harvard Medical School.

The paper does not establish that estrogen caused the observed differences. However, it suggests that external hormone use may extend the period of beneficial estrogen exposure beyond natural menopause. This evidence contributes to a growing reassessment of hormone therapy, a treatment whose risks and benefits have been debated for over two decades.

Prescriptions for hormone therapy in the United States dropped by nearly 40 percent in the year following a 2002 study linking the treatment to increased risks of breast cancer, heart disease, and stroke. Recent medical reviews have since indicated that the age at which women begin treatment influences the balance of these risks and benefits.

Last month, the American College of Obstetricians and Gynecologists issued new guidelines that support hormone therapy as a first-line treatment for menopausal symptoms. The American College of Physicians released similar recommendations on Oct. 5. While these groups recommend the therapy for symptoms like hot flashes and night sweats, they do not yet recommend it specifically for brain protection.

Caroline Just, a neurologist at the Cleveland Clinic, noted that menopause acts as a neurological transition as well as a reproductive one. She pointed to a separate study of more than 2,600 older women published in August in JAMA Network Open, which found that a younger age at menopause was associated with faster cognitive decline. For every five years younger a woman was at menopause, she accumulated about 15 percent more white-matter damage over the following decade.

Researchers are now investigating whether the brain tracks a lifetime total of estrogen exposure. Jill Daniel, a professor of brain science at Tulane University, suggested that a woman’s underlying health status may affect how her brain responds to hormone therapy. Her mouse studies indicate that while hormone therapy improves memory in healthy animals, it can worsen memory in those with high blood pressure or high-fat diets. Marseglia emphasized that while the association is clear, scientists still need to determine which conditions and time windows allow for these potential benefits.