Abstract
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 ( V̇O2max ) correlates with many physiological outcomes at rest and in response to exercise, differences in V̇O2max between male and female participants may hinder interpretation. Here we revisit decades-old arguments that advocate for matching males and females for V̇O2max normalized to fat-free mass (FFM) when investigating sex differences in the context of exercise. The rationale for using FFM to normalize V̇O2max , 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 V̇O2 . Using a multistudy dataset of males (n = 54) and females (n = 54) matched for V̇O2max per FFM, we illustrate the different approaches to V̇O2max 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 V̇O2max . A group-level difference of less than 5% for V̇O2max 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 V̇O2max to FFM for exercise physiology studies investigating sex differences.