Creatine monohydrate is among the most extensively studied dietary supplements,

functioning as a cellular energy substrate that regenerates ATP through the
phosphocreatine system in tissues with high energy demand, including skeletal
muscle and the brain. Its best-established clinical value is the preservation and
accrual of lean body mass, muscle strength, and functional capacity, particularly
when paired with resistance training—benefits that extend to bone health in older
and postmenopausal populations. A growing body of randomized evidence also
points to modest cognitive benefits, most consistently for memory and processing
speed, reflecting creatine’s role in maintaining neuronal energy homeostasis under
metabolic stress such as fatigue or sleep deprivation.
For BHRT providers, creatine is broadly relevant because the hormonal shifts of
menopause and andropause accelerate the loss of muscle mass, strength, and
bone density while contributing to fatigue and cognitive complaints. Creatine
stands on its own clinical merits as a bioenergetic support, complementing
hormone optimization by reinforcing the musculoskeletal and neuronal substrate
on which hormonal signaling acts—without substituting for it. Women store
substantially less endogenous creatine than men and may derive particular benefit
across the lifespan, especially during and after the menopausal transition. During
Brain Health Awareness in July, anchored by World Brain Day, creatine’s role in
cerebral energy metabolism makes it a timely and widely applicable consideration
for hormone-focused patients.
Clinical Note (Dosing): Creatine monohydrate is the most studied and reliable
form. A common approach is 3–5 g daily, which saturates muscle stores over three
to four weeks; an optional loading phase of approximately 0.3 g/kg/day (about 20 g
in divided doses) for five to seven days reaches saturation more quickly before
transitioning to 3–5 g daily. Benefits for muscle and bone are maximized when
combined with resistance training, and select cognitive, older-adult, and
postmenopausal outcomes have been studied at higher doses.
evidence of renal harm in healthy individuals; however, caution and clinical
monitoring are appropriate in patients with pre-existing kidney disease. Clinicians
should note that creatine can modestly raise serum creatinine as a benign
laboratory effect that does not reflect declining renal function, which is relevant
when interpreting routine labs. Transient water retention or mild gastrointestinal
upset may occur with high loading doses and can be minimized using divided or
lower daily doses. Current evidence does not demonstrate meaningful changes in
testosterone or dihydrotestosterone.
Kreider, R. B., Kalman, D. S., Antonio, J., et al. (2017). International Society of Sports Nutrition
position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine.
Journal of the International Society of Sports Nutrition, 14, 18.
Antonio, J., Candow, D. G., Forbes, S. C., et al. (2021). Common questions and misconceptions
about creatine supplementation: What does the scientific evidence really show? Journal of the
International Society of Sports Nutrition, 18(1), 13.
Smith-Ryan, A. E., Cabre, H. E., Eckerson, J. M., & Candow, D. G. (2021). Creatine supplementation
in women’s health: A lifespan perspective. Nutrients, 13(3), 877.
Xu, C., Bi, S., Zhang, W., & Luo, L. (2024). The effects of creatine supplementation on cognitive
function in adults: A systematic review and meta-analysis. Frontiers in Nutrition, 11, 1424972.

Safety Considerations: Creatine monohydrate is well tolerated and carries no

Key References