Fit for comparison: controlling for cardiorespiratory fitness in exercise physiology studies of sex as a biological variable.

More studies in exercise physiology are investigating sex as a biological variable, but the potential confounding effect of cardiorespiratory fitness is often neglected. As maximal oxygen uptake ( ) correlates with many physiological outcomes at rest and in response to exercise, differences in between male and female participants may hinder interpretation. Here we revisit decades-old arguments that advocate for matching males and females for normalized to fat-free mass (FFM) when investigating sex differences in the context of exercise. The rationale for using FFM to normalize , as opposed to total body mass, is that females, on average, have a greater proportion of body fat than males and body fat does not contribute to . Using a multistudy dataset of males (n = 54) and females (n = 54) matched for per FFM, we illustrate the different approaches to normalization and the effects of poor or incorrect matching on interpretation. Modern assessments of body composition allow for segregation of bone from total FFM and regional measures of body composition; however neither approach seems to be an improvement on whole-body FFM as the normalization factor for . A group-level difference of less than 5% for per unit FFM is a strong starting point for comparisons between males and females, but the allowable difference depends on the extent to which cardiorespiratory fitness influences the variable of interest and other competing study design decisions. Researchers should be encouraged to normalize to FFM for exercise physiology studies investigating sex differences.