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While the benefits of physical activity are numerous, the female athlete triad poses a significant health risk to young athletes. Emerging research links the triad to endothelial dysfunction — a sentinel event in cardiovascular disease — suggesting that this complex interplay of metabolic and endocrine factors may be described more accurately as a tetrad. Effective treatment of the triad/tetrad requires a multidisciplinary approach. Emphasis must be placed on prevention, recognition, and treatment of triad for the promotion of healthy nutritional and activity profiles in female athletes across their lifespans.