Estrogen hormone combination may help relieve menopausal brain fog

Many women going through menopause report struggling with memory lapses, trouble concentrating and slower thinking, a set of symptoms often described as "brain fog."

A new study by UCLA Health suggests an estrogen hormone treatment combining estriol and progesterone may help ease these symptoms, offering an early but potentially promising way to address a menopause-related symptom for which there is currently no FDA-approved treatment.

The study, published in the journal Scientific Reports by Nature Portfolio, was an observational case series that followed 20 menopausal women with an average age of 53. The women underwent a baseline assessment for cognitive symptoms prior to treatment and then were treated for 12 months with a customized regimen of estriol and progesterone.

Estriol is a natural form of estrogen that occurs during pregnancy and has been used in Europe and Asia to treat other menopausal symptoms, such as hot flashes and genitourinary symptoms. Estriol differs from estradiol, the most used estrogen hormone therapy in the U.S., by binding primarily to a different estrogen receptor in the brain. Previous research has shown that estriol may play a role in protecting brain cells and reducing brain atrophy in the hippocampus which is responsible for learning and memory.

After the 12-month treatment regimen, the study participants reported significant reduction in brain fog, concentration, working memory, processing speed, verbal memory and problem-solving compared with their symptoms before treatment.

Estrogen plays a well-documented role in protecting the brain, yet there are still no approved type and dose of treatment that specifically targets the cognitive symptoms so many women experience during menopause. Women are often told to simply live with brain fog, when in fact there is a neuroscience basis for it, and potentially a way to address it. That gap in care is what motivated us to look more closely at estriol."

Dr. Rhonda Voskuhl, study's senior author, neurologist and member of the Comprehensive Menopause Center, UCLA Health

To better understand how the hormone treatment might work, the research team also studied estriol treatment in midlife female mice. Estriol reduced markers of brain pathology in the hippocampus, the brain region responsible for learning and memory, and improved the animals' cognitive performance such as working memory and spatial memory.

The study's authors caution that this was a small, preliminary case series without a placebo group or randomization so the findings may not generalize to broader populations. Larger, placebo-controlled clinical trials that include brain imaging and standardized cognitive testing are now warranted to confirm the promising results on cognitive symptoms.