Gender differences in the relationships among neurosteroid serum levels, cognitive function, and quality of life

Dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), and pregnenolone are neurosteroids that can be synthesized in the brain. Previous studies have hypothesized that these neurosteroids have antiaging, mood-enhancing, and cognitive-preserving effects; however, these effects may be gender-specific. Therefore, the purpose of this study was to investigate the gender differences in the relationships among neurosteroids (DHEA, DHEA-S, and pregnenolone), cognitive function, and quality of life in healthy individuals.

In this cross-sectional study, we enrolled 47 men (mean age: 32.8 years) and 75 women (mean age: 35.4 years) who had no major physical or psychiatric illnesses and measured their serum DHEA, DHEA-S, and pregnenolone. Furthermore, we evaluated the subjects' cognitive function and quality of life using the Brief Assessment of Cognition in Schizophrenia and the World Health Organization Quality of Life Scale, respectively.

The serum levels of DHEA and DHEA-S demonstrated significant gender differences, even after controlling for age effect. In the male subjects, the DHEA serum levels were positively correlated with three domains of the World Health Organization Quality of Life Scale, including physical health, social relations, and environmental dimensions. Meanwhile, the DHEA-S levels positively correlated with the performance of working memory, and pregnenolone levels had a positive correlation with working memory, verbal fluency, and Brief Assessment of Cognition in Schizophrenia composite score. However, in the female subjects, we observed a correlation only between the serum levels of DHEA-S and working memory.

The findings of our study indicate that neurosteroids play a vital role in cognitive function and quality of life among men but less so among women. Nevertheless, the underlying mechanisms of the gender-specific effect of neurosteroids require further investigation.