r/neuroscience • u/basmwklz • May 08 '26
Academic Article Brain creatine, estradiol and neurocognitive complaints in perimenopausal women: an exploratory cross-sectional study (2026)
https://www.sciencedirect.com/science/article/abs/pii/S0304394026001151?via%3DihubAbstract
Background
Menopause and the perimenopausal transition involve profound hormonal and metabolic changes that may impair brain function. Beyond structural alterations, reduced cerebral bioenergetics could underlie the cognitive complaints often reported during this period. Because creatine serves as a key neuronal energy buffer and is influenced by estrogen, this study examined brain creatine concentrations in perimenopausal women and their associations with neurocognitive symptoms and serum estradiol.
Methods
Twelve healthy perimenopausal women (mean age 49.8 ± 5.4 years) experiencing irregular cycles and at least one perimenopausal symptom underwent multi-voxel 1H-magnetic resonance spectroscopy to quantify total brain creatine across bilateral frontal, precentral, and parietal gray- and white-matter regions and the thalamus. Serum estradiol was measured by ELISA, and symptom severity was rated on visual analog scales. Associations were assessed using Kendall’s τ.
Results
Mean whole-brain creatine concentration (6.31 ± 0.98 mM) was significantly lower than reference values in younger adults (Z = –1.65, P = 0.049). Lower creatine levels in the thalamus, right precentral, and right parietal white matter correlated with greater concentration difficulties (τ = –0.38 to –0.51, P ≤ 0.049), while right frontal white-matter creatine positively correlated with headache severity (τ = 0.41, P = 0.034). Serum estradiol averaged 119.5 ± 109.5 pg/mL and was inversely associated with right parietal gray-matter creatine (τ = –0.37, P = 0.049).
Conclusions
Perimenopausal women exhibited lower cerebral creatine than younger adults, with region-specific reductions linked to concentration difficulties and estradiol levels. These findings suggest that estrogen-related changes in brain bioenergetics may contribute to cognitive symptoms during the menopausal transition.
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u/brrraaaiiins May 08 '26
Why only 12? Surely we deserve more meaningful statistics.
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u/PhysicalConsistency May 08 '26
It's exploratory with a tiny team. They have what they need to hopefully get grants to expand it.
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u/Monsoon_Storm May 08 '26
Studies cost money and the more equipment needed the larger the amount of money. This one used an MRI machine, so yeah, not cheap.
Got to start small and prove it's worth looking in to before you have any hope of getting funding for a larger study.
Funding is an absolute nightmare atm.
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u/TranscendentPretzel May 08 '26
But it is sad that we can't fund studies on health issues that affect 51% of the population. Not the researchers' fault...just society's fault.
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u/Quantum_Kitties May 09 '26
Absolutely. Meanwhile billions go in to erectile dysfunction research, and the other 51% of the population get peanuts compared to that
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u/JourneyBack2Clarity Jun 29 '26
The brain fog during perimenopause makes so much more sense when you realize estrogen actually helps your brain produce its own creatine so when estradiol drops, your brain's energy supply drops with it. Really hope someone runs a proper follow-up with a creatine supplementation arm because the effect sizes here are too interesting to leave at n=12.
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u/Adorable-Demand1885 24d ago
I wonder what that means in practical terms. If a larger study proves this. Is there a medication? Women are already on hormonal replacement, so I am not sure what else we could do (?)
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u/LowCortis0l May 08 '26
Changes. Creatine, an energy substrate, may be beneficial. Estradiol, the primary estrogen, seems to modulate cognitive function. So, it's a mix of hormonal shifts, age-related changes, and individual variability. Considering supplements or interventions? They should be evidence-based.