By Menopause Reviewed Editorial Team | Last reviewed: May 2026
Women describe losing words mid-sentence, misplacing objects in implausible locations, and noticing a mental slowdown that feels different from ordinary tiredness. These reports are not imagined. The SWAN Memory and Cognition substudy, which tracked over 2,300 women longitudinally, found that approximately two-thirds report forgetfulness and memory complaints during perimenopause — and subjective experience is matched by objective measurement: perimenopause is associated with a demonstrable, transient decrement in verbal memory and processing speed.
A 2022 International Menopause Society White Paper by Maki and Jaff characterizes these changes as reliably documented, most often mild, and rooted in the neurobiology of fluctuating estrogen — not in early neurodegeneration. This article reviews the underlying biology, what changes and what doesn't, the treatment evidence, and when symptoms warrant clinical investigation.
The Neurobiology: Why Estrogen Fluctuation Affects the Brain
Estrogen receptors are densely expressed throughout the brain, with particularly high concentrations in the hippocampus and prefrontal cortex — two regions central to verbal memory, working memory, and executive function. Their presence is not incidental: estrogen actively modulates synaptic plasticity, neuronal survival, and the brain's primary energy source.
Research from Roberta Brinton's laboratory, summarized in a 2008 review in Advanced Drug Delivery Reviews, demonstrated that 17β-estradiol (E2) regulates glucose transport into neurons, activates glycolytic enzyme activity, and sustains mitochondrial function — estrogen, in short, helps the brain use glucose efficiently. When it fluctuates during perimenopause, neural energy metabolism is disrupted.
This metabolic consequence has been visualized directly. Lisa Mosconi and colleagues at Weill Cornell Medicine used FDG-PET imaging to study women at different stages of the menopause transition. Their 2021 Scientific Reports study found measurable glucose hypometabolism in frontal and parieto-temporal cortical regions in perimenopausal women compared to premenopausal controls — regions subserving attention, working memory, and verbal processing. A companion 2024 study by the same group used estrogen receptor PET tracers to show that receptor density increases in the hippocampus and frontal cortex during perimenopause, interpreted as a compensatory upregulation as the brain attempts to capture diminishing estrogen. Women with higher receptor density in cognitive regions scored lower on cognitive tests, suggesting the compensation is incomplete.
Neuroinflammation contributes a third mechanism. Estrogen has anti-inflammatory effects in the central nervous system; its decline raises neuroinflammatory markers. Sleep disruption — affecting 20–60% of perimenopausal women — compounds cognitive load through a separate pathway: sleep is required for hippocampal memory consolidation, and fragmentation impairs both encoding and retrieval.
What Changes, and What Doesn't
Greendale and colleagues published the most comprehensive longitudinal analysis in a 2009 paper in Neurology, drawing on 4-year data from 2,362 SWAN participants. Premenopausal and postmenopausal women showed the expected practice-effect improvement on cognitive tests over repeat administrations, but late perimenopausal women did not improve on processing speed or verbal memory delayed recall. The decrement was not a drop below baseline but a failure to gain the practice-related improvement seen in other stages. Critically, improvement rebounded to premenopausal levels in postmenopause, indicating the cognitive difficulties of perimenopause are time-limited for most women.
A 2023 review in Current Psychiatry Reports synthesizing recent longitudinal data confirmed that verbal learning and verbal memory are the domains most reliably affected. Processing speed, attention, and working memory show more modest effects. Higher-order executive functions — strategic planning, abstract reasoning — do not reliably change across the menopause transition. Average performance, while meaningfully lower than a woman's own earlier performance, remains within population-normal limits. Approximately 11–13% of perimenopausal women show clinically significant new-onset cognitive impairment rather than a mild decrement.
The Maki and Jaff 2022 IMS White Paper identifies the factors most strongly linked to objective cognitive difficulties: estrogen fluctuation itself, frequent vasomotor symptoms, sleep disturbance, and depressed mood. These interact — nocturnal hot flashes disrupt sleep, which compounds cognitive impairment, producing effects larger than any single factor in isolation.
Treatment Evidence: What Has Been Tested Rigorously
Hormone Therapy and the Timing Debate
Two landmark randomized controlled trials tested whether initiating estrogen early in the menopause transition would protect cognitive function.
The Kronos Early Estrogen Prevention Study (KEEPS) randomized women within 3 years of menopause to oral conjugated equine estrogens, transdermal estradiol, or placebo for 48 months. The cognitive substudy (KEEPS-Cog), reported in Menopause in 2019, found no treatment-related effects on any of 19 neuropsychological outcomes. A 2024 KEEPS Continuation study in PLOS Medicine, assessing participants roughly 10 years post-trial, confirmed no lasting cognitive benefit or harm.
The Early versus Late Intervention Trial with Estradiol (ELITE) randomized 567 women to 17β-estradiol or placebo stratified by time since menopause (within 6 years versus 10 or more years). The cognitive substudy (ELITE-Cog), published in Neurology in 2016, found no differences in verbal memory, executive functions, or global cognition — and no interaction by timing group. The critical-window hypothesis was not supported for cognitive outcomes.
The 2022 Menopause Society position statement reflects this: hormone therapy is not indicated to treat cognitive symptoms or prevent cognitive decline. HRT remains appropriate for vasomotor symptoms and sleep disruption — and symptom relief may indirectly benefit cognition — but cognitive protection is not an established independent indication.
Exercise
Aerobic and resistance exercise have a more consistent cognitive evidence base than any pharmacological intervention. Exercise increases cerebral blood flow, induces hippocampal BDNF expression, reduces neuroinflammation, and improves sleep architecture.
A 2024 study in Behavioral Sciences examined aerobic exercise effects on executive function in perimenopausal women using an emotional Stroop task. Perimenopausal women showed significantly improved reaction times following aerobic exercise, and the improvement was larger than that seen in younger controls — suggesting particular cognitive sensitivity to exercise in this population. A 2025 pilot RCT in Innovation in Aging followed 35 perimenopausal and early postmenopausal women through a 9-month, twice-weekly resistance training program and found significant improvement in cognitive flexibility on the NIH Toolbox compared to a waitlist control group. Both are small trials, but they align with broader evidence and the WHO recommendation of 150 minutes of moderate-intensity aerobic activity per week.
Sleep: CBT-I as First-Line Intervention
Given the causal relationship between sleep deprivation and verbal learning and memory deficits, treating menopausal insomnia is one of the most direct available levers for cognitive symptoms.
The MS-FLASH multi-arm RCT enrolled 546 peri- and postmenopausal women with insomnia and significant vasomotor symptoms, comparing six interventions. Cognitive behavioral therapy for insomnia (CBT-I) produced the largest reduction in insomnia severity from baseline (−5.2 points, 95% CI −7.0 to −3.4), outperforming aerobic exercise, yoga, omega-3 supplementation, escitalopram, and estradiol. A 2024 scoping review in Life confirmed that CBT-I consistently improves sleep quality in menopausal women with benefits maintained at 6-month follow-up, supporting its use as a first-line intervention ahead of pharmacological sleep aids.
Omega-3 Fatty Acids (EPA/DHA)
A 2025 review in Post Reproductive Health synthesized evidence for EPA and DHA in brain health during the menopause transition. DHA is a structural component of neuronal membranes; EPA has central anti-inflammatory actions. The review found substantial preclinical and epidemiological support, plus RCT data showing episodic and working memory improvement in adults with low habitual fish intake consuming 1.4 g EPA+DHA daily for 6 months. Evidence in menopausal women specifically remains limited — indicative of benefit, not yet definitive — but safety profiles are favorable and cardiovascular benefits well-established.
Iron and B12 Screening
Heavy or irregular perimenopausal bleeding creates a window of iron insufficiency even without formal anemia. A 2025 cross-sectional study from the University of Oklahoma, published in Nutrients, found that higher serum ferritin correlated with better accuracy, faster reaction times, and better performance across multiple cognitive domains — and that below-expected iron levels impaired cognition even without frank iron deficiency anemia. A companion Nutrients review provided a rationale for screening and correcting iron insufficiency in perimenopausal women with cognitive symptoms.
Vitamin B12 insufficiency independently causes cognitive impairment and is more common in women over 40, those on plant-based diets, and users of proton pump inhibitors or metformin. B12 is inexpensive to test and straightforward to correct, and it belongs in any cognitive symptom evaluation.
A Note on Cognitive Peptides
Among compounds studied preclinically for cognitive and neuroprotective applications, two synthetic peptides developed in Russia — Semax and Selank — have attracted interest in the nootropics community. Semax is a synthetic analog of ACTH(4–10) with documented effects on BDNF and trkB expression in the rat hippocampus (2006, Brain Research); Russian clinical data, not published in Western peer-reviewed journals, report attention and short-term memory improvements in healthy subjects. Selank, derived from the immune peptide tuftsin, has been studied in Russian preclinical models for anxiolytic effects via GABAergic and serotonergic modulation (2016, Frontiers in Pharmacology). Neither has completed Western RCTs, neither has been studied specifically in perimenopausal women, and neither is FDA-approved for any indication. The preclinical biology is mechanistically plausible; the evidence base does not yet support clinical characterization of efficacy or safety.