Taking creatine alongside HRT: what the research says

By The Krevie Team  |  Last reviewed: May 2026

Creatine and hormone therapy (HRT) work through entirely different biological mechanisms — one metabolic, one hormonal — and no pharmacokinetic or pharmacodynamic interaction between them has been identified in the research literature. HRT acts via oestrogen and progesterone receptors. Creatine acts via the ATP-phosphocreatine energy system in muscle and brain cells. These pathways do not overlap biochemically. For that reason, many women on hormone therapy take creatine alongside it without any identified concerns. As with all supplements taken alongside prescribed medication, discussing your full supplement list with your GP is always appropriate.

What hormone therapy is and how it works

Hormone therapy (HT or HRT) is a prescription medical treatment that addresses hormone changes during the menopausal transition by supplementing oestrogen, and in women with an intact uterus, a progestogen to protect the uterine lining. Various formulations exist — oral tablets, transdermal patches, gels, and sprays — and the specific hormones, routes of administration, and doses vary by prescription and clinical indication.

Oestrogen acts by binding to oestrogen receptors (ERα and ERβ) found throughout the body: in reproductive tissue, bone, the cardiovascular system, the central nervous system, and elsewhere. Once bound, oestrogen-receptor complexes influence gene expression, cellular function, and a wide range of physiological processes. Progestogens bind to progesterone receptors with their own distinct receptor-mediated effects.

HRT is a medicine, prescribed and monitored by a GP or specialist. Its mechanism is fundamentally receptor-driven and hormonal in nature. This is what distinguishes it, categorically, from food supplements, which do not act via hormone receptors.

What creatine is and how it works

Creatine is a naturally occurring compound found predominantly in muscle and brain tissue. The body synthesises it from amino acids in the liver, kidneys, and pancreas; additional creatine comes from dietary sources, primarily meat and fish.

Creatine's function is in cellular energy metabolism. It is stored in cells as phosphocreatine (PCr) — a high-energy molecule that rapidly donates its phosphate group to adenosine diphosphate (ADP) to regenerate adenosine triphosphate (ATP), the cell's primary energy currency. This phosphocreatine-ATP cycle operates within milliseconds and is particularly important in tissues with high or fluctuating energy demands: skeletal muscle during physical activity and the brain during cognitive work.

This mechanism has no involvement with oestrogen receptors, progesterone receptors, or the hormonal signalling pathways that HRT acts upon. The creatine transporter (SLC6A8) moves creatine into cells; phosphocreatine conversion involves creatine kinase (CK) enzyme activity. Neither mechanism intersects with the receptor-ligand pharmacology of oestrogen or progestogen.

A narrative review by Smith-Ryan et al. (2021) in Nutrients, examining creatine supplementation across all stages of female life, noted that creatine characteristics vary between males and females — partly due to hormonal influences on creatine kinase activity and creatine synthesis — but that creatine itself does not alter oestrogen levels or exert oestrogenic effects. The review noted that females have 70–80% lower endogenous creatine stores than males and may particularly benefit from supplementation, especially during and after the menopausal transition.

What the research shows

No identified pharmacokinetic interaction

A pharmacokinetic interaction occurs when one compound alters the absorption, distribution, metabolism, or excretion of another. Creatine is metabolised primarily by conversion to creatinine (a waste product excreted in urine), via a non-enzymatic spontaneous conversion. It does not utilise cytochrome P450 liver enzymes — the primary metabolic pathway through which drug-drug interactions commonly occur. HRT formulations — particularly oral oestrogen preparations — are metabolised hepatically via CYP enzymes. Because creatine does not compete for or inhibit these pathways, no pharmacokinetic basis for interaction exists.

No identified pharmacodynamic interaction

A pharmacodynamic interaction occurs when two substances act on the same biological target or pathway and their effects combine or compete. Creatine's mechanism (phosphocreatine-ATP energy buffering) and HRT's mechanism (hormone receptor activation) operate on completely separate biological systems. No receptor-level or pathway-level interaction has been described in the literature.

CONCRET-MENOPA trial: no adverse hormonal effects

The CONCRET-MENOPA trial (Forbes, Korovljev, Ostojic et al., 2025), published in the Journal of the American Nutrition Association, was a randomised, double-blind, placebo-controlled trial of creatine HCl supplementation in 36 perimenopausal and menopausal women over eight weeks. The trial reported that all interventions were well tolerated, with no severe adverse effects. Serum lipid profiles were favourably modulated in the 1,500 mg creatine HCl group. No adverse hormonal effects were reported. The medium-dose creatine HCl group (1,500 mg/day) showed improvements in reaction time (6.6% versus 1.2% in placebo, p<0.01) and frontal brain creatine levels (16.4% versus 0.9% in placebo, p<0.01).

While CONCRET-MENOPA did not study women specifically on HRT, the trial enrolled perimenopausal and menopausal women as a population — the population most likely to be on or considering HRT — and observed no adverse effects. The mechanistic independence of creatine's and HRT's pathways means there is no theoretical reason to expect a different safety profile in women on HRT versus those who are not.

Creatine and oestrogen: a metabolic relationship, not a hormonal one

Research has identified that oestrogen influences creatine metabolism. Oestrogen appears to support creatine kinase activity and aspects of creatine synthesis, which is one reason why creatine stores and creatine metabolism may shift during the menopausal transition as oestrogen levels change. The Smith-Ryan et al. (2021) review discussed this in the context of women's creatine metabolism varying across life stages.

This relationship is one-directional in the relevant sense: oestrogen influences creatine metabolism, but creatine supplementation does not influence oestrogen levels. Current evidence does not show that creatine alters endogenous hormone production or receptor sensitivity in healthy women.

This distinction matters for understanding how the two approaches relate. HRT addresses the hormonal dimension of the menopausal transition directly, via receptor-mediated mechanisms. Creatine supplementation addresses cellular energy metabolism — a separate dimension, separately affected by the menopausal transition — via a different mechanism entirely.

How Creatine Companion is used in Krevie

Creatine Companion provides 1,500 mg of creatine hydrochloride per daily serving — one scoop of unflavoured powder per day, taken as a daily food supplement. This dose and form match the CONCRET-MENOPA trial (Forbes et al., 2025), which found significant improvements in reaction time and frontal brain creatine levels over eight weeks in perimenopausal and menopausal women.

Creatine Companion is a food supplement. It is not a medicine, does not act on hormone receptors, and is not intended as an alternative to, or substitute for, any medical treatment including hormone therapy. It is designed to be used alongside whatever medical pathway is right for you — which may or may not include HRT, and is a decision to make with your GP.

If you are currently prescribed HRT and are considering adding creatine or any other food supplement, the practical advice is simple: mention it to your prescribing GP at your next review. This is not because an interaction is expected — the current research suggests there is no basis for one — but because your GP benefits from a complete picture of what you take.

Frequently asked questions

Further reading

• HRT and cognitive changes in perimenopause: what the research does and doesn't show — an overview of the WHIMS, KEEPS, and KEEPS Continuation findings
• Creatine HCl vs creatine monohydrate: why the form matters for women over 40 — solubility, dosing, and the CONCRET-MENOPA trial
• Do you need creatine every day? What the research shows about consistency — how to maintain creatine saturation and why daily dosing matters

References

1. Forbes SC, Korovljev D, Ostojic J, et al. 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). J Am Nutr Assoc. 2026;45(3):199–210. PubMed 40854087
2. Smith-Ryan AE, Cabre HE, Eckerson JM, Candow DG. Creatine Supplementation in Women's Health: A Lifespan Perspective. Nutrients. 2021;13(3):877. PubMed 33800439
3. Rawson ES, Venezia AC. Effects of Creatine Supplementation on Brain Function and Health. Nutrients. 2022;14(5):921. PMC8912287
4. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107–1213. PMID 10893433
5. Candow DG, Forbes SC, Chilibeck PD, et al. Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation. J Clin Med. 2019;8(4):488. PMC6518405