Comments on Point:Counterpoint: Estrogen and sex do/do not influence post-exercise indexes of muscle damage, inflammation, and repair.

TO THE EDITOR: Interpretations on the effect of estrogen/sex should be based on direct measures of muscle injury and subsequent repair/regeneration (i.e., improvements in muscle structure and function after injurious exercise). The inclusion of indexes of the inflammatory response (e.g., accumulation of neutrophils and/or macrophages) and inflammation (e.g., edema) into the discussion seems to make interpretations ambiguous (2, 6). We reported that neutrophils and/or macrophages can accumulate in rodent skeletal muscle in the absence of histological and functional signs of injury after either passive stretching, isometric contractions, or concentric contractions (4, 5). These findings support our belief that neutrophil and/or macrophage accumulation in skeletal muscle after exercise should not be used as markers of muscle injury nor repair/regeneration. As mentioned by Tiidus and Enns (6), neutrophils may exacerbate contraction-induced injury, whereas, macrophages appear to aid muscle repair/regeneration. Recent evidence in rodents, however, indicates that neutrophils and/or macrophages also contribute to skeletal muscle hypertrophy (1, 3). Thus neutrophil and/or macrophage accumulation in skeletal muscle is not contingent on the presence of an injury nor does their function in skeletal muscle after exercise appear to be restricted to events that follow an injury. Commonly used measures of edema (e.g., arm circumference, arm volume, and gapping between myofibers) tend to show a high degree of intersubject variability, have a low degree of sensitivity, and have a poor temporal resolution to histological and functional signs of injury and thus, they have limited value when interpreting the influence of estrogen/sex on muscle injury and repair/regeneration.