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A hormone treatment combining estriol and progesterone was associated with improvements in self-reported brain fog, memory, and other cognitive symptoms among menopausal women in a small UCLA Health study, offering an early signal for symptoms that currently have no FDA-approved treatment specifically targeting them.
The observational case series included 20 women and had no placebo group or randomization, meaning researchers cannot yet determine whether the hormone treatment itself caused the improvements.
Published in Scientific Reports, the study followed the women, who had an average age of 53. Participants underwent an assessment of their cognitive symptoms before beginning treatment, then received a customized regimen of estriol and progesterone for 12 months.
After treatment, participants reported significant reductions in brain fog and improvements in 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,” 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.”
Why Researchers Studied Estriol
Estriol is a naturally occurring form of estrogen produced during pregnancy and has been used in Europe and Asia to treat menopausal symptoms including hot flashes and genitourinary symptoms.
It differs from estradiol, the estrogen most commonly used in hormone therapy in the United States, because it binds primarily to a different estrogen receptor in the brain. Previous research cited by the study authors suggests estriol may help protect brain cells and reduce atrophy in the hippocampus, a region involved in learning and memory.
To explore a potential biological explanation for the findings in women, researchers also studied estriol treatment in midlife female mice. Estriol reduced markers of brain pathology in the hippocampus and improved measures of working and spatial memory.
Promising Results, but Important Limitations
Researchers caution that the findings are preliminary and may not apply to the broader population of women experiencing cognitive symptoms during menopause.
Larger, placebo-controlled clinical trials incorporating brain imaging and standardized cognitive testing are needed to determine whether the treatment can reliably improve menopause-related cognitive symptoms.
The study also includes a disclosure related to the treatment. Voskuhl invented the hormone treatment evaluated in the research, which UCLA patented and licensed to CleopatraRX, the company that markets it as PearlPAK. Voskuhl serves as a medical advisor to the company.
What Nurses Should Know
For nurses caring for women during menopause, the study highlights the importance of taking complaints of brain fog, difficulty concentrating, and memory changes seriously while putting emerging treatment research into context.
The findings suggest estriol and progesterone warrant further investigation for menopause-related cognitive symptoms, but they do not establish the regimen as a proven treatment.
As research into hormone therapy and cognitive health continues, nurses may increasingly encounter patients asking about estriol and other emerging treatments for brain fog. Being able to explain what early findings show, and what they don’t yet establish, can help patients put those results into context.
