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

Abstract

BackgroundDehydroepiandrosterone (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.MethodIn 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.ResultsThe 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.ConclusionThe 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.

A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits

“…The neuroprotection provided by exogenous administration of these hormones extends to males as well. However, it is evident ( Chen et al, 2018 ) that the efficacy of neurosteorids for cognitive function may differ between the genders. Moreover, neurosteroids may be involved in the gender differences found in the susceptibility to schizophrenia ( Huang et al, 2017 ).…”

Neuroactive Steroids and Cognitive Functions in First-Episode Psychosis Patients and Their Healthy Siblings

“…Previous findings in healthy subjects underlined the higher impact of NAS on cognition in men than in women (59). For example, the role of testosterone in cognitive impairment has been discussed in male patients with schizophrenia only (37).…”

Age-trends in Cognitive Function and Quality of Life: Sex Differences in a Community Population in Taiwan

“…A large-scale cohort study in the U.S. suggested that women may have greater cognitive reserve but faster cognitive decline than men, which may contribute to sex differences in late-life dementia [10]. Our previous study, it demonstrated that the correlation between neurosteroids and cognitive function and psychological well-being may differ with sex [11]. Therefore, the uncertain mechanisms of the sexspecific effect on cognition and quality of life warrant further clarification.…”