A small UCLA Health case series found improvements in cognitive symptoms after 12 months of estriol and progesterone treatment, but researchers stress that controlled trials are needed
Memory lapses, difficulty concentrating and slower thinking are commonly reported during menopause and often grouped under the term “brain fog.” A preliminary study from UCLA Health suggests that a specific hormone treatment combining estriol and progesterone may help alleviate these cognitive symptoms.
Published in Scientific Reports, the observational case series followed 20 menopausal women with an average age of 53. Participants were assessed before treatment and then received an individually tailored regimen of estriol and progesterone for 12 months.
Improvements reported across several cognitive symptoms
After one year of treatment, participants reported significant improvements compared with their symptoms at baseline. These included reductions in brain fog and difficulties involving concentration, working memory, processing speed, verbal memory and problem-solving.
The findings are notable because there is currently no FDA-approved hormone treatment specifically indicated for menopause-related cognitive symptoms.
“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,” said senior author Dr. Rhonda Voskuhl, a neurologist and member of the Comprehensive Menopause Center at UCLA Health.
“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.”
Estriol differs from commonly used estradiol
Estriol is a naturally occurring form of estrogen that reaches particularly high levels during pregnancy. It has been used in Europe and Asia for menopausal symptoms including hot flashes and genitourinary problems.
The researchers point to differences between estriol and estradiol, the estrogen more commonly used for hormone therapy in the United States. Estriol primarily binds to a different estrogen receptor in the brain, providing one possible avenue for investigating its effects on cognition.
Previous research has suggested that estriol may have neuroprotective properties and could influence the hippocampus, a brain region central to learning and memory.
Mouse experiments support further investigation
Alongside the human case series, the researchers studied estriol treatment in middle-aged female mice. Treatment reduced markers of brain pathology in the hippocampus and improved performance in tests involving working and spatial memory.
The animal findings provide potential biological support for the observations in the women, but they do not establish that estriol produces the same effects in humans.
Small study cannot establish effectiveness
The authors emphasize important limitations. The human study included only 20 participants and had neither a placebo group nor randomization. The reported improvements therefore cannot establish that the hormone treatment itself caused the changes.
Larger randomized, placebo-controlled trials using standardized cognitive testing and brain imaging will be needed to determine whether the results can be replicated and whether the treatment is effective and safe for a broader population.
The study also carries a relevant financial disclosure. The hormone treatment investigated was invented by Voskuhl and is patented by UCLA. UCLA licenses the patent to CleopatraRX, which markets the treatment as PearlPAK, and Voskuhl serves as a medical advisor to the company.
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