Women’s History Month: The Role of Hormones in Brain Health Differences

Over the past few decades, the scientific community has shed some light on the vast differences between male and female patient health with an increasing focus on female cardiovascular disease pathology. The reason underlying varying reactions to the same diseases between men and women has been related to the brain, and in particular, sex hormones. Testosterone and estrogen are not only vital to fertility and reproductive functions, but they also play a critical role in brain health, and in particular sex-based risk factors associated with neurodegenerative disease. Emerging research reveals that the brains of males and females are much less different in structure than in how they age as well as the effects aging has on their brain health.

Estrogen and Brain Health

Women account for two-thirds of patients diagnosed with Alzheimer’s disease; they are also twice as likely to experience major depression, three times more likely to be diagnosed with neurodegenerative autoimmune disorders. Although there exists a multitude of factors that contribute to the variations in brain health and cognitive decline between men and women, estrogen is now believed to be one of the primary variables.

“Estradiol, the type of estrogen produced by the ovaries during a woman’s reproductive years, is the most important driver of brain health,” Dr. Kejal Kantarci, director of the Women’s Health Research Center and a radiology professor at Mayo Clinic in Rochester, Minnesota told the American Heart Association. Dr. Kantarci’s research has shown that long-term exposure to estradiol may offer protective benefits. As part of her 2020 study published in Brain Communications, she discovered that women with longer reproductive periods and those with higher numbers of pregnancies were better protected against multiple sclerosis.

Further solidifying previous findings, a study conducted by Lisa Mosconi, director of the Women’s Brain Initiative at Weill Cornell Medicine in New York, revealed that brain energy levels decline by 20% or more during menopause yet there are no observed changes in men of the same age.

Menopausal Transition and Cognitive Function

The menopausal transition, which is characterized by significant decreases in estradiol levels, triggers changes in the brain that may not be apparent until later in life. For instance, prior research has shown that the accumulation of amyloid plaques begins as women transition through menopause as does shrinkage in memory centers, however, cognitive decline may not present for many years. Additionally, the menopausal transition makes women more susceptible to disease as evidence suggests increases in anxiety, depression, multiple sclerosis, and other immune disorders become activated, especially in the case of predisposed patients.

Burgeoning research implicates that the amount of estrogen supplied to the brain may not be as significant as the time at which the hormone levels undergo changes. A 2005 review of clinical trials in postmenopausal women aged 65 and older revealed that these women receiving hormone therapy had an increased risk for dementia and other types of cognitive decline. Meanwhile, a later study found that taking estrogen therapies earlier may protect against cognitive decline and that women exposed longer to natural estrogen had improved cognitive function later in life. 

These findings indicate that the menopausal transition offers a critical window for therapeutic intervention although, further investigation is needed to continue exploring the long-term cognitive implications of hormonal therapies. To better cater to the unique health needs of female patients, clinicians are invited to complete our Women’s Hormones online course taking place from June 7-20, 2021 that will delve into the complexities of women’s hormonal care.