Volumetric Sex Differences in Hypothalamic Volume and Associated Subunits Revealed by Automated MRI Segmentation

Abstract Background and purpose: Sex differences in brain structure and function are well documented; however, the impact of these differences on the hypothalamic volume and associated subunits remains underexplored. This study aimed to investigate sex differences in hypothalamic volume and its subregions. Methods: Sixty-six healthy individuals (34 males) with a mean age of 49.42 ± 12.25 years underwent 3T imaging with a 64-channel head coil, using a 3D T1-weighted MPRAGE sequence. Automated segmentation of hypothalamic subregions, including the anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp), was performed to quantify the total volume and 10 subunits using a deep convolutional neural network validated by FreeSurfer v7.4.1, with total intracranial volume (TIV) normalization applied for individual head size variations. Results: Multivariate analysis of covariance (MANCOVA) revealed significant sexual dimorphism (Wilks’ Λ = 0.652, F(10,50) = 2.66, p = 0.011, partial η² = 0.35), with females exhibiting larger adjusted volumes across nearly all subunits. Age showed modest associations with right a-iHyp (p = 0.042), a-sHyp (p = 0.035), supTub (p = 0.049), and the whole right (p = 0.022). These subunits were positively correlated with age. The body mass index, education, handedness, and sex × handedness interactions were not significant (p > 0.05). Conclusions: Our findings suggest that females have larger hypothalamic volumes and that certain subunits exhibit sex-specific differences, emphasizing the importance of considering sex differences in neuroscientific research and clinical practice.