A small UCLA Health case series found that 20 menopausal women reported improvements in brain fog and several cognitive symptoms after 12 months of customized estriol and progesterone treatment. The findings add preliminary evidence to research on menopause brain fog, but the uncontrolled study cannot show that the hormone regimen caused the changes.
Key Takeaways
- The study followed 20 menopausal women with a mean age of 53.5 for 12 months.
- Participants received customized oral estriol and progesterone treatment and reported improvements in six cognitive areas, including brain fog and memory.
- The human findings were based on self-reported symptoms measured before treatment and again at 12 months.
- The study had no placebo group, randomization, or untreated comparison group, preventing researchers from establishing causation.
- Researchers called for larger placebo-controlled trials using standardized cognitive testing and brain imaging.
UCLA Study Finds Improvement in Self-Reported Cognitive Symptoms
UCLA researchers reported statistically significant improvements in menopause brain fog and several related cognitive complaints after 20 women received customized estriol and progesterone treatment for 12 months.
Published September 1, 2026, in Scientific Reports, the observational case series included menopausal women with a mean age of 53.5. Participants rated their cognitive symptoms before treatment and again at the end of the 12-month period.
The symptoms assessed included brain fog, concentration, working memory, processing speed, verbal memory, and problem-solving. All six measures improved significantly between baseline and the 12-month assessment, according to the published results.
The findings are notable because cognitive complaints are common during the menopausal transition. A recent perimenopause mental health survey involving more than 2,000 U.S. women also found that respondents frequently described brain fog and sleep disruption as disruptive symptoms. That survey examined women’s experiences rather than the effectiveness of a treatment.
Senior author Dr. Rhonda Voskuhl, a neurologist and member of UCLA Health’s Comprehensive Menopause Center, said the research was motivated by the limited treatment options aimed specifically at cognitive symptoms.
“Women are often told to simply live with brain fog, when in fact there is a neuroscience basis for it,” Voskuhl said.
Treatment Combined Estriol With Progesterone for 12 Months
The 20 participants received oral estriol along with progesterone when clinically appropriate. The treatment schedule and dosage were customized according to factors that included cognitive symptoms, other menopause symptoms, age, and health considerations.
Estriol is one of the body’s naturally occurring estrogens. The researchers focused on it partly because estriol preferentially binds to estrogen receptor beta, or ERβ, a receptor found in the brain that has been studied for its potential role in neuroprotection.
The study differed from research involving estradiol, the estrogen more commonly used in menopausal hormone therapy in the United States. Previous research cited by the study authors has examined estriol in other settings, including women with multiple sclerosis.
Participants completed the Voskuhl Menopause Brain Fog Assessment before starting treatment and after 12 months. The questionnaire asked participants to rate the severity of cognitive symptoms rather than relying on objective neuropsychological tests.
That distinction is important. The study demonstrates that participants reported feeling better across the measured domains, but it does not independently establish corresponding changes on standardized cognitive testing.
Reported Improvements Covered Six Cognitive Areas
After 12 months, participants reported improvements in brain fog, concentration, working memory, processing speed, verbal memory, and problem-solving.
Working memory describes the ability to temporarily hold and use information. Processing speed relates to how quickly information can be understood and acted upon, while verbal memory involves retaining and recalling language-based information.
The study reported statistically significant changes in all six cognitive measures, with reported p-values below 0.001. However, statistical significance within a before-and-after comparison does not determine whether the hormone treatment itself caused those changes.
Other changes occurring during the 12-month period could have influenced participants’ symptoms. Improvements in sleep or vasomotor symptoms such as hot flashes, for example, could indirectly affect concentration and memory.
The researchers acknowledged this possibility. The paper noted that direct and indirect effects of treatment on cognition could occur at the same time.
Mouse Experiments Point to a Possible Biological Mechanism
Alongside the human case series, the researchers conducted experiments involving midlife female mice to investigate how estriol might affect the brain.
In the animal experiments, estriol treatment improved measures of cognitive performance and reduced several changes in the hippocampus associated with estrogen deficiency. The hippocampus plays an important role in learning and memory.
Researchers reported reduced activation of certain glial cells and less synaptic loss in estriol-treated mice. They also studied changes involving ENO1, a protein associated with glucose utilization in astrocytes, and identified a possible pathway involving estrogen receptor beta.
The animal results provide a potential biological explanation for the human findings, but they do not prove that the same mechanisms produced the reported improvements among the women in the study.
The distinction is particularly relevant as researchers continue examining hormones and women’s brain health. Separate research into estrogen therapy and Alzheimer’s markers, for example, has examined associations between estrogen exposure and Alzheimer’s-related brain pathology using a different population, treatment approach, and outcome.
Neither study establishes that hormone therapy prevents dementia.
Study Design Keeps the Findings Preliminary
The most significant limitation is the study’s design.
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All 20 women received treatment. There was no placebo group, no untreated control group, and no random assignment. Researchers therefore cannot determine whether the hormone regimen itself caused the reported improvement.
The small sample also limits how broadly the results can be applied. Twenty participants cannot represent the full population of menopausal women, whose symptoms, health histories, ages, medications, and responses to hormone therapy can vary substantially.
The human portion of the study also relied on participants’ self-reported cognitive symptoms. It did not use standardized neuropsychological testing or brain imaging to objectively measure whether cognitive performance or brain structure changed during treatment.
The authors described the research as preliminary and called for larger placebo-controlled clinical trials that incorporate brain imaging and standardized cognitive testing. Those studies would provide stronger evidence about whether treatment produces measurable cognitive changes.
Study Disclosures Add Context to the Findings
The published research and UCLA Health announcement also disclose financial and intellectual-property interests related to the treatment.
Voskuhl is an inventor on UCLA patents concerning hormone treatment for cognition. UCLA licenses patents related to the treatment to CleopatraRX, and Voskuhl serves as a medical advisor to the company, according to the disclosures.
The disclosure does not determine whether the findings are valid, but it is relevant context when evaluating preliminary research involving a treatment connected to intellectual property held by the investigators’ institution.
Independent replication and larger controlled studies would provide additional evidence about whether the observed results can be reproduced in broader groups of women.
Current Guidance Does Not Establish Estriol as a Cognitive Treatment
The findings do not amount to a recommendation for treating menopause brain fog with estriol.
The U.S. Food and Drug Administration states that there are currently no FDA-approved drugs containing estriol. The agency also advises that menopausal hormone therapy carries potential benefits and risks that depend on an individual’s medical circumstances.
The Menopause Society currently states that hormone therapy is not recommended specifically to improve cognition in women undergoing natural menopause.
Those positions do not contradict the UCLA study. Instead, they reflect the difference between an early observational finding and the level of evidence generally required before a treatment becomes part of clinical recommendations.
The UCLA researchers themselves did not claim that the case series established a standard treatment for cognitive symptoms. Their conclusion was that the findings warrant further investigation.
Larger Clinical Trials Will Test Whether the Results Hold Up
The next step is a larger randomized, placebo-controlled clinical trial.
Such research could compare women receiving the hormone treatment with participants receiving a placebo while using standardized cognitive testing and brain imaging. That design would help researchers separate treatment effects from other factors that could influence symptoms over time.
Larger studies could also determine whether the findings are reproducible across women with different ages, health histories, menopause stages, and symptom profiles.
For menopause brain fog, the current UCLA findings identify a signal worth testing rather than a proven therapeutic effect. The 20 participants reported meaningful improvements after 12 months, but controlled trials will be needed to determine whether estriol and progesterone were responsible for those changes.
Frequently Asked Questions
What is menopause brain fog?
Menopause brain fog refers to cognitive symptoms that can occur during the menopausal transition, including difficulties with concentration, memory, processing information, and thinking clearly. The UCLA study examined menopause brain fog alongside several specific self-reported cognitive domains.
What did the UCLA menopause study find?
The study found that 20 menopausal women reported significant improvements in brain fog, concentration, working memory, processing speed, verbal memory, and problem-solving after 12 months of customized estriol and progesterone treatment. Because there was no placebo or control group, the study cannot establish that the treatment caused those improvements.
What hormone treatment did participants receive?
Participants received customized oral estriol treatment, with progesterone used when clinically appropriate. Dosages and treatment schedules varied according to individual clinical considerations rather than following one identical regimen for every participant.
Does the study prove hormone treatment improves cognition?
No. The research was a 20-person observational case series without randomization, a placebo group, or an untreated comparison group. Larger controlled trials are needed before researchers can determine whether the hormone regimen itself improves cognitive symptoms.
Is estriol FDA-approved for menopause brain fog?
No. The FDA states that there are no FDA-approved drugs containing estriol, and the UCLA findings do not establish estriol as an approved treatment for menopause brain fog. The study authors characterized the results as preliminary and called for additional clinical trials.
Disclaimer
This article is for informational and educational purposes only and is not intended as medical advice, diagnosis, or treatment. Hormone therapy may not be appropriate for everyone, and its potential benefits and risks vary based on individual health history and circumstances. Readers experiencing menopause-related cognitive symptoms should consult a qualified healthcare professional before starting, stopping, or changing any treatment.
