Combined effects of creatine supplementation in women. A medical review

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Introduction: Creatine plays an essential role in cellular bioenergetics via the creatine kinase/phosphocreatine phosphagen system. Historically, most studies have been conducted in male cohorts. However, contemporary evidence shows considerable sexual dimorphism, characterized by lower baseline endogenous creatine pools in females and by susceptibility to hormonal fluctuations spanning the menstrual cycle and over the lifetime. Objective: The purpose of this medical review is to create current scientific evidence regarding the multi-systemic effects of creatine supplementation in the female organism. Results: In the context of physical exercise, integrating creatine into resistance training (RT) stimulates improvements in dynamic strength, although the hypertrophic potential and accretion of lean body mass (LBM) are lower in females compared to males. A distinct neuroprotective potential has been demonstrated: supplementation increases total creatine concentrations in the frontal lobes, optimizes cognitive function under acute metabolic stress, and effectively supports the pharmacotherapy of major depressive disorder (MDD). In postmenopausal females, combining creatine with exercise is an effective countermeasure against sarcopenia and enhances skeletal structural strength parameters. In gynecology, population data (NHANES) correlate higher dietary creatine intake with regular menstrual cycling, while preclinical models suggest a crucial mediating role for creatine in uterine energetics as well as in protecting the fetus against perinatal hypoxia. Conclusions: Creatine represents a safe, low-cost, and versatile strategy to promote metabolic, skeletal, and neurological health in females across all stages of ontogeny.