Higher Exposure to Estrogen Has Positive Effects on Brain Health 

New research shows that people with higher cumulative estrogen exposure over their lifetime had greater brain volumes and fewer indicators of brain disease at midlife. 

When researchers examined people’s brain scans, several events that indicate longer estrogen exposure, such as more than 39 reproductive years, a higher number of children and pregnancies, and use of hormone replacement therapy and/or hormone contraceptives, were associated with greater gray matter volume. 

“Previous research has shown that the midlife decline in estrogen that comes with menopause is a driver of brain aging and Alzheimer’s risk in women,” said Lisa Mosconi, PhD, Weill Cornell Medicine. “Our results confirm that, but there’s also good news. Other factors related to women’s reproductive history, such as a longer reproductive span and use of hormonal therapy, appear to offset the effects of menopause. While the age at which menopause starts is determined partly by a person’s genetics, lifestyle and environmental factors like smoking, obesity, and exercise also play a role, and may modify a woman’s risk of brain aging.”

The study evaluated 99 women between 40 years of age and 65 years of age who did not have dementia. They did have risk factors for late-onset Alzheimer’s, such as family history of the disease or the APOE gene that is linked to greater risk. Researchers compared them to 29 men, matched for age, with similar risk factors.
  
Researchers also looked at the relationship between reproductive history with the volume of gray matter in the brain, which is an indicator of brain health, and scores on thinking and memory tests.

For example, for every year longer that a woman was exposed to estrogen in her life, average gray matter volume in certain areas of the brain increased by an average of 1%. People with total reproductive years of 39 years or longer had gray matter volume an average of 5% larger than people with total reproductive years of less than 39 years. 
For each additional child a woman had, gray matter volume in certain areas of the brain increased by an average of 2%. 

This appeared mainly in the temporal cortex, frontal cortex, and precuneus. The results were the same after adjusting for factors such as high blood pressure and smoking. 
  
These data were published in the November 3, 2021, online issue of Neurology, the medical journal of the American Academy of Neurology.