Sex differences in global metrics of brain size across the lifespan

Introduction: While global brain volume differences between males and females have been shown to manifest during prenatal life, it is unclear whether global differences remain stable or show variability over the lifespan. Therefore, our goal was to use the existing literature coupled with large-population-based studies to assess age-related differences in effect size estimates of brain size between males and females over the life-span. Methods: We quantified effect size measures (Cohen’s d) of sex differences in terms of head circumference using data drawn from the literature of prenatal (14 weeks to birth) ultrasounds of n = 36,487 uncomplicated healthy births and direct postnatal (0–7 years) head circumference measurements from 85,598 children. The effect size of sex differences of cortical surface area, cortical thickness, and cortical volume were also computed from structural magnetic resonance imaging data from 25,846 healthy individuals aged 5–89 years. Results: Head circumference was consistently larger in males from fetal life through early childhood, with effect sizes typically ranging from ∼0.3 to 0.5 across studies and developmental stages. Males exhibited greater surface area and cortical volume across development, with effect sizes increasing from ∼0.4 at age 5 to ∼1.4 by age 24, after which they remained relatively stable. Cortical thickness showed a female advantage during childhood that diminished by mid-adolescence. Conclusion: The effect size of sex differences in global brain metrics does not remain constant across the lifespan. The underlying mechanisms are likely to involve endocrine and other neurodevelopmental processes. Future studies, especially preclinical and longitudinal studies beginning in the prenatal period may offer insight into the underlying mechanisms and the potential for translation of these findings, assessing the curves in patients with neurodevelopmental disorders.