- Menopause — the end of a woman’s reproductive years — can bring a range of symptoms, including hot flashes, night sweats, and brain fog.
- Hormone therapy, to boost the levels of hormones that decrease around this time, can help to alleviate these symptoms.
- Now, a study has found that estradiol, a form of estrogen, may improve cognition and memory, but the specific effects vary with the mode of administration.
- Women using transdermal estradiol (patches or gels) showed improvements in episodic memory, and those taking oral estradiol had improved prospective memory.
Menopause signals the end of a woman’s reproductive years, occurring 12 months after the last menstrual period.
During the years leading up to and following menopause many women experience symptoms including hot flashes, night sweats, vaginal dryness, a reduced sex drive, and problems with concentration and memory.
To alleviate symptoms, a woman may take
Now, a study has found that estradiol therapy may not only help with vasomotor symptoms, but could also have beneficial effects on memory.
The study, published in Neurology, the medical journal of the American Academy of Neurology, suggests that transdermal estradiol (patches or gels) has different memory effects than oral estradiol. The researchers found that transdermal estradiol improved recall of past experiences, while oral estradiol improved participants’ ability to remember to do future tasks.
“This study highlights the discrepancies on hormone therapy influence on cognition, the varying effects on the type of estrogen used, the association between when a person goes into menopause impacting cognitive decline supporting early intervention, and how best to counsel patients regarding hormonal therapy and cognition.”
— Sherry Ross, MD, board certified OB/GYN and Women’s Health Expert at Providence Saint John’s Health Center in Santa Monica, CA.
The researchers used data from 7,251 post-menopausal women (who reported their birth sex as female and self-identified as female) in the Canadian Longitudinal Study on Aging (CLSA) in their cross-sectional study. At the start of the study, the women, who had undergone menopause at an average of 50.5 years, were an average of 60.5 years old.
All participants underwent a number of tests of cognitive function. These assessed:
- Episodic memory — the ability to form, store, and recall conscious memories of specific past events
- Prospective memory — the ability to remember to perform a planned action or intention in the future.
- Executive function — mental processes needed for planning and problem solving.
For all the participants, an earlier age of menopause was associated with reduced performance on all three areas of cognitive function.
In total, 6% of the cohort were using estradiol (E2) therapy — 4% transdermal and 2% oral — at the time of testing.
Women using transdermal E2, but not oral E2, performed better on episodic verbal memory (word list recall). Those using oral E2 had better prospective memory (eg. remembering an appointment, or to take a medication), compared with those who had never used E2. Neither therapy had any observed effect on executive function.
Anand Singh, Consultant Gynaecologist at the Cadogan Clinic, London, suggested why the study found no impact on executive function:
“Executive functioning depends on complex networks in the prefrontal cortex, which may be less sensitive to estrogen levels in midlife compared with memory-related regions like the hippocampus. In this cohort, most women were cognitively healthy, leaving limited scope for measurable improvement in executive function.”
“Additionally,” he told Medical News Today, “cognitive benefits may require early or prolonged exposure to menopausal hormone treatment (MHT), and the average duration and timing of therapy in this study may not have been sufficient to produce detectable effects.”
He also suggested that “the tests used for memory are often more sensitive to subtle hormonal influences than those assessing executive function, which could explain the lack of observed effects in this domain.”
Study author Liisa A. M. Galea, PhD, of the Centre for Addiction and Mental Health in Toronto, Canada, suggested why transdermal and oral estradiol might have different effects on memory, telling MNT:
“When we take drugs or hormones orally, they undergo a chemical breakdown in the liver and this can alter how the drugs/hormone work. In the case of estradiol taken orally it converts to a less potent estrogen called estrone. Estrone is not as effective at interacting with the estrogen receptor.”
Estrogen patches vs. pills“We don’t know the reason transdermal estradiol leads to better episodic memory but it could be the number of estrogen receptors in the medial temporal lobe which is the brain region important for episodic memory (and estradiol interacting with them more effectively).”
— Liisa A. M. Galea, PhD
Ross agreed:
“The more stable and efficient transdermal estradiol has benefits of a first-pass metabolism, bypassing the liver, which may also support the area in the brain dependent on memory. Since oral estradiol is metabolized in the liver, estradiol is converted to estrone, which impacts the memory areas of the brain less effectively than transdermal estradiol. The effects of transdermal versus oral estrogen on these areas of the brain ultimately have different effects on cognition.”
Galea emphasized that none of the estradiol therapies were associated with reduced memory.
The authors acknowledged several limitations of the study, including that the women using hormone treatment were predominantly white, and wealthier. The study also focused only on E2s, not any other hormones used for menopause treatment, and did not differentiate between those taking only E2 and those using it together with progestogens. Also, because of its cross-sectional design, the study cannot prove any causative effect.
However, Ross emphasized that memory improvements could be a benefit of hormone therapy for menopause:
“Brain fog and cognitive decline are common symptoms in menopause and with aging. While there are many factors, including lifestyle habits and genetic influences, affecting the decline in cognitive health, hormone therapy may also help to slow cognitive decline in menopause.”
“Estradiol therapy remains a powerful tool for managing menopausal symptoms, but cognitive benefits are modest and domain-specific, and risks vary by formulation, timing and individual patient factors.
Transdermal administration may offer the most promising profile for memory support, but further longitudinal studies are needed to clarify long-term cognitive outcomes.”
— Anand Singh
