Nutritional Supplementation Combined with Exercise for Musculoskeletal Health in Women: A Systematic Review and Meta-Analysis Evaluating Proteins, Amino Acids, and Creatine across Reproductive Stages

Background: Women experience progressive musculoskeletal deterioration across reproductive stages, with accelerated changes during the menopausal transition.Exercise provides established benefits, but the additive effects of nutritional supplementation strategies, including proteins, amino acids, and related compounds such as creatine, remain uncertain.Previous systematic reviews focused on older adults aged 65 years and above, leaving a knowledge gap regarding women facing unique metabolic challenges related to reproductive hormones.Therefore, this systematic review and meta-analysis was conducted to evaluate whether nutritional supplementation combined with exercise enhances muscle mass, strength, and bone health outcomes in women across reproductive stages, with particular attention to the menopausal transition.Methods: Eight databases were searched from inception to July 2025: CINAHL, ClinicalTrials.gov,Cochrane Central Register of Controlled Trials, Embase, PsycINFO, MEDLINE/PubMed, Scopus, and Web of Science.We included randomized controlled trials examining nutritional supplementation combined with exercise in women across reproductive stages.Interventions comprised whole proteins, amino acids, amino acid derivatives, or protein-derived peptides administered with structured exercise programs.Comparators included exercise alone or a placebo plus exercise.Primary outcomes were muscle mass measures.Secondary outcomes included muscle strength, bone health parameters, body composition, and adverse events.Random-effects meta-analyses calculated Hedges' g with 95% confidence intervals (CIs).Results: Fourteen trials including 763 women across reproductive stages met the inclusion criteria, which evaluated whole-protein supplements (five studies), amino acids and derivatives (six studies), and creatine monohydrate (three studies).The combined intervention showed no significant effects on muscle mass measures: skeletal muscle mass (g=0.065,95% CI: -0.353 to 0.482, p=0.762), appendicular lean mass (g=0.197,95% CI: -0.177 to 0.571, p=0.302), or fat-free mass (g=0.069,95% CI: -0.110 to 0.249, p=0.447).Significant improvements occurred in bench press (g=0.279,95% CI: 0.008 to 0.550, p=0.043) IvyspringInternational Publisher and handgrip strength (g=0.412,95% CI: 0.039 to 0.786, p=0.031).No significant effects emerged for bone mineral content (g=0.195,p=0.421) or bone mineral density (g=0.087,95% CI: -0.129 to 0.303, p=0.430).No increase in adverse events was observed.Conclusions: Current evidence does not support robust additive effects of nutritional supplementation on muscle mass or bone health when combined with exercise in women across reproductive stages.Selective upper-body strength improvements were observed, particularly in studies using creatine supplementation.Exercise alone provides reliable musculoskeletal health benefits.Given the heterogeneity of supplement types examined, future research should employ longer intervention durations (12 months) with site-specific bone measurements and conduct head-to-head comparisons of specific supplement types.