Creatine and Menopause: What a New Brain-Creatine Trial Found

A new placebo controlled trial just connected creatine, menopause, and brain function in a way no study had tested before. It gives women in this transition real evidence that a familiar supplement might support mental clarity as estrogen drops.

I spent the past few weeks going through the data behind it. Here is the short version. An 8 week study out of Serbia found that low and moderate doses of creatine raised creatine levels inside the brain's frontal lobe, and the women taking it reported real changes in reaction time, fatigue, and concentration.

Most of what gets written about creatine and women's health focuses on muscle and strength. This trial is different because it measured brain tissue directly, in women specifically in perimenopause and menopause, which is new ground.

That gap matters, because the hormonal shifts happening during this transition are not small. Estrogen touches far more than reproductive health, including how your brain and muscles generate energy day to day.

What the CONCRET-MENOPA Trial Actually Tested

The trial everyone is now citing has a mouthful of a name. Researchers call it CONCRET-MENOPA for short.

A team at the University of Novi Sad in Serbia ran the study, as reported in coverage of the published results. It was an 8 week, randomized, double blind, placebo controlled trial.

The researchers recruited 36 healthy women between the ages of 40 and 60, roughly half perimenopausal and half menopausal. They split the group four ways.

One group took a low dose of 750 milligrams of creatine hydrochloride daily. A second took a medium dose of 1,500 milligrams.

A third took a combined 800 milligram formula, split between creatine hydrochloride and creatine ethyl ester. The fourth group took a placebo.

Notice that none of these doses match the standard 3 to 5 gram daily dose of plain creatine monohydrate most people are used to. That is one of the more interesting parts of this trial, and we will come back to it.

Over those eight weeks, the team tracked computerized cognitive tests, menopause symptom questionnaires, and fatigue assessments. They also ran blood and lipid panels.

A subset of 16 participants had brain imaging too, to measure creatine concentration directly inside brain tissue. That imaging step is what sets this trial apart from most creatine research.

What the Researchers Found in Reaction Time, Fatigue, and Mood

The results landed differently across the three active groups. None of them were subtle.

The medium dose group saw reaction time improve by roughly 6.6 percent. The placebo group slowed down by about 1.2 percent over the same eight weeks.

That same medium dose group also reported a drop in general fatigue of about 14 percent, plus a 48 percent drop in self reported concentration difficulties.

The low dose group reported gains too, in alertness, executive control, and information processing speed. Their reaction times improved 5 to 6 percent, against roughly 1 percent slowing on placebo.

The combined creatine hydrochloride and ethyl ester group reported something different again, close to a 39 percent reduction in anxiety, alongside improved blood lipid markers.

Three different doses, three somewhat different benefit profiles. That pattern alone suggests this is not a one size fits all response, and it is worth watching how larger follow up trials sort it out.

Every active group tolerated the supplement well. There was no weight gain and only minimal side effects across eight weeks, a detail that matters given how often women skip supplements over bloating worries.

Why Brain Creatine Levels Rose on the Scans

The imaging data is the part that makes this trial different from most creatine research before it.

Among the 16 women scanned, the medium dose group showed roughly a 16 percent rise in creatine within right frontal white matter. The placebo group showed under 1 percent change. Smaller increases showed up across all three active groups.

Sergej Ostojic, the researcher who led the trial, told reporters that the size of the effect at such a low dose surprised his own team.

His working theory involves the blood brain barrier. He suspects perimenopause may temporarily change how permeable it is.

Creatine hydrochloride and creatine ethyl ester dissolve and absorb differently than plain creatine monohydrate. Ostojic thinks those forms may be reaching brain tissue through that temporary window more easily than expected.

If that holds up in bigger trials, it would help explain why a 750 milligram dose moved the needle here. For comparison, that is roughly a sixth of a typical daily monohydrate dose.

That is a theory, not a settled mechanism. The researchers were careful to say so themselves.

Why Menopause Changes How Your Body Handles Creatine

None of this happens in a vacuum. Menopause itself is already reshaping how your cells make and use energy.

A 2024 review in Frontiers in Endocrinology lays out how falling estrogen reduces mitochondrial content in skeletal muscle. The same decline shifts energy metabolism in the brain.

That helps explain why so many women notice both muscle and mental changes arriving around the same time. Creatine's whole job in the body is helping cells regenerate ATP, the fuel molecule muscles and neurons both burn, faster than they otherwise could.

There is also a sex specific piece worth naming plainly. Industry researchers quoted in coverage of this trial note that women typically store less creatine in their muscles than men do to begin with.

That lower baseline may be part of why even a low dose produced a measurable effect here. It is also part of why creatine research done mostly on men does not always translate cleanly to women.

None of this means creatine treats or reverses menopause itself, and nobody running this research claimed that it does.

What it does suggest is simpler. The energy support creatine offers may matter more, not less, during this particular stretch of a woman's life.

That is a meaningfully different framing than the usual creatine marketing aimed at young men chasing bigger lifts. The need here is about steady, dependable energy for your brain and your muscles while your body is already working overtime to adjust.

Where This Leaves Creatine Monohydrate

If you already take a creatine supplement, there is a good chance it is monohydrate. This trial does not change that.

Creatine monohydrate is the form backed by the deepest body of research. That includes the 2017 International Society of Sports Nutrition position stand on creatine safety, which reviewed decades of data and found it safe and effective at standard doses for healthy adults.

The CONCRET-MENOPA trial used creatine hydrochloride and creatine ethyl ester instead, at lower doses than monohydrate typically requires. That is genuinely new ground for this life stage, not a reason to switch forms overnight.

A single 8 week trial in 36 women is a promising start, not a verdict. The researchers themselves flagged the small sample size, the short duration, and the reliance on self reported symptoms as real limits.

What it adds is still meaningful. It is evidence that creatine, in some form and even at a modest dose, has a measurable effect on brain chemistry specifically during perimenopause and menopause, a life stage research has mostly skipped.

This is exactly where electrolytes earn their place alongside creatine, rather than as an afterthought. Creatine pulls water into muscle cells to do its job.

Sodium and potassium are what keep that fluid balance working the way it should. That is the whole idea behind pairing the two in TONE, Stacked Fitness Hydration's creatine and electrolyte mix.

Putting This Into Practice During Your Transition

None of this research means you need to overhaul your routine this week.

If you already take creatine monohydrate at the standard 3 to 5 gram daily dose, the ISSN safety data above still applies to you. This trial is not a reason to switch forms.

If you are perimenopausal or menopausal and new to creatine, this is a reasonable, well tolerated place to start. Pairing it with electrolytes helps your body actually use the water creatine pulls into your cells.

Pay attention to the basics that mattered in the trial too. Dose it consistently, every day, rather than on and off.

Drink enough water alongside it, and give it real time. Even the fastest responding group in this study was measured at eight weeks, not eight days.

Track how you actually feel, not just the scale or a workout log. The outcomes that moved most in this trial were reaction time, fatigue, and focus, not body composition.

That is worth remembering if you have tried creatine before and judged it only by the mirror. A supplement built for energy and cognition shows up differently than one built for muscle alone.

If you are managing menopause symptoms beyond energy and focus, talk with your doctor about your full picture before adding anything new. This research points to cognitive performance and energy support, not a treatment for menopause itself.

Further reading

• Ostojic, S. et al. (2025). The Effects of 8-Week Creatine Hydrochloride and Creatine Ethyl Ester Supplementation on Cognition, Clinical Outcomes, and Brain Creatine Levels in Perimenopausal and Menopausal Women (CONCRET-MENOPA), Journal of the American Nutrition Association, via NutraIngredients.
• Psypost (2025). Creatine supplement may enhance brain function during menopause, new research suggests.
• Kreider, R. et al. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation, Journal of the International Society of Sports Nutrition.
• Zhang, C. et al. (2024). Estrogen and metabolic health across the menopause transition, Frontiers in Endocrinology.

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