Sex differences modulate olfactory bulb volume-function relationships but not olfactory training-induced plasticity

Men typically display larger olfactory bulb (OB) volumes, while women demonstrate superior olfactory performance. Olfactory training (OT) has been shown to induce structural changes in OB, but whether sex influences OT-related plasticity remains unclear. This study aimed to examine how sex differences modulate OB volume-function relationships and OT-related OB neuroplasticity. Participants included 27 women and 11 men with acquired olfactory dysfunction who underwent Sniffin' Sticks Test and T2-weighted MRI before and after a 12-week OT program of twice-daily exposure to four odorants. OB volume was measured by ITK-SNAP. Pooled baseline analysis revealed no significant correlation between OB volume and composite threshold-discrimination-identification (TDI) score. Women showed a significant correlation between baseline OB volume and TDI on both sides (left: r = 0.458, p = 0.016; right: r = 0.413, p = 0.032), whereas no significant associations were observed in men. Following OT, the overall sample showed bilateral OB volume increases (left: mean difference = 4.70 ± 2.16, p = 0.036; right: mean difference = 5.64 ± 1.91, p = 0.005) and improvements in odor discrimination (t = 2.12, p = 0.040) and composite TDI score (t = 2.13, p = 0.040). Men consistently presented larger OB volumes (F(1, 36) = 6.63, p = 0.014), and no sex-by-session interaction effects were observed. It appears that sex can mask cross-sectional associations between OB volume and olfactory performance, supporting sex-aware analysis when interpreting baseline OB morphometry. In contrast, OT elicits comparable OB volume increases across sexes, suggesting a similar pattern of training-induced structural plasticity.