Abstract
OBJECTIVE: The purpose of the study was to conduct a systematic review assessing the impact of pharmacological and non-pharmacological interventions on Relative Energy Deficiency in Sport (REDs). The study design follows a systematic review and meta-analysis. The data sources are CINAHL, MEDLINE, SportDiscus, ERIC, and Embase from inception until July 2025. Eligibility criteria for selecting the studies include the experimental, quasi-experimental, and pre-experimental literature that investigated interventions designed to support the symptoms of REDs. RESULTS: A total of nineteen studies (fifteen non-pharmacological interventions, four pharmacological interventions), with a total of 759 females, were included in the review. Non-pharmacological interventions demonstrated positive benefits on menstrual function recovery, energy availability, fat mass, and body fat percentage. Meta-analyses quantified nutrition intervention benefits on an individual's fat mass (kg), 1.36 (95% CI 0.68, 2.04), and body percentage fat (%), 2.21 (95% CI 1.34, 3.08). It was also possible to identify the impact of non-pharmacological interventions on total triiodothyronine (T3) biomarkers (nmol/L), -2.37 (95% CI -5.57, 0.83). It should be noted, however, that non-pharmacological interventions were limited by quality and certainty assessment, identifying included evidence as low to moderate. Pharmacological interventions demonstrated some positive (at times very strong effect sizes) results for impact on bone mineral density, but conclusions are currently limited by well-powered experimental studies. CONCLUSIONS: The current evidence base favors non-pharmacological management as an initial response for managing REDs. Initial pharmacological management appears to identify limited but potentially (depending on the drug) promising evidence for the impact on bone mineral density; further evidence is required to be more certain about the impact on hormonal profiling and menstrual recovery function. Further research is needed to help develop a greater understanding.