Sex-based differences in hematological values after normalization to body mass or fat-free mass in adults matched for aerobic fitness.

Blood properties influence aerobic exercise performance. While vascular volumes and hemoglobin mass (Hb_mass) are elevated in trained individuals, evidence of sex differences in vascular volumes is equivocal due to inadequate matching of aerobic fitness between males and females. This cross-sectional study aimed to compare hematological values normalized to body mass (BM) and fat-free mass (FFM) between males (n = 45) and females (n = 34) matched for aerobic fitness (V̇O₂max) normalized to FFM (mL∙kg FFM^-1∙min^{- 1}). Data included body composition measured by dual-energy X-ray absorptiometry (DXA), V̇O₂max from an incremental test, and hematological values derived from a CO rebreathe test. Fat mass was unrelated to blood volume (BV; R² = 0.02, P = 0.26) and Hb_mass (R² = 0.03, P = 0.16), while FFM was the strongest predictor of both (R² = 0.75 and R² = 0.83, respectively, P < 0.001). Females exhibited higher FFM-normalized BV (+4%, P < 0.05) and plasma volume (PV) (+14%, P < 0.001) and lower red blood cell volume (RBCV) (-8%, P < 0.001) and Hb_mass (-8%, P < 0.001) compared to males. Positive correlations between aerobic fitness and relative Hb_mass and BV were observed in both sexes when normalized to BM and FFM (0.48 < r < 0.71; P < 0.003). Stepwise multiple regression models, including FFM, V̇O₂max, height, and [Hb], provided accurate predictions of Hb_mass (R² = 0.91) and BV (R² = 0.85). Overall, sex differences persist in relative Hb_mass, BV, PV, and RBCV after matching of aerobic fitness, though relative BV and PV were greater in females. These findings suggest sex-specific strategies in oxygen delivery and/or extraction, and they underscore the importance of carefully selecting normalization practices when assessing sex-based differences in hematological variables.