Free testosterone and cognitive function: Sex-specific links in adults in the nationwide Korean frailty and aging cohort

Maturitas. 2025 Nov:202:108745. doi: 10.1016/j.maturitas.2025.108745. Epub 2025 Oct 4.

Abstract

Introduction: Previous studies have examined the relationship between endogenous testosterone and cognitive function, but findings have been inconsistent. Additionally, the sex-specific effects of free testosterone (FT) on various cognitive domains in adults who are older, especially within Asian populations, remain under investigation.

Methods: This cross-sectional study involved 2710 Korean adults aged 70-84 participating in the Korean Frailty and Aging Cohort Study. Serum FT levels were measured and categorized into quartiles. Cognitive function was evaluated using the Mini-Mental State Examination - Korean version (MMSE-KC), the Korean version of the CERAD battery, Trail Making Test-A (TMT), Digit Span (DS), Word List Memory test, and the Frontal Assessment Battery (FAB). Multivariable logistic and quantile regression analyses were adjusted for age, education, lifestyle factors, depressive disorder, and physical performance.

Results: In women, lower FT levels were independently linked with impairments in the MMSE-KC, TMT, FAB, and Word List Memory test. Compared with higher FT quartiles, the lowest quartile had significantly increased odds ratios of 1.36, 1.34, 1.39, and 1.52 for these tests, respectively. Pairwise comparisons between quartiles showed that women in the lowest FT quartile performed significantly worse on the MMSE-KC and Word List Memory test than those in the highest quartile. In men, however, no significant associations were identified.

Conclusions: This population-based cross-sectional study of older Korean adults found that lower serum FT levels were independently associated with cognitive impairments across multiple domains in women but not men. These findings highlight FT's potential role in cognitive impairment, particularly among women.

Keywords: Aging; Cognitive function; Free testosterone; Korean cohort; Older persons; Sex differences.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging* / blood
  • Cognition* / physiology
  • Cognitive Dysfunction* / blood
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Frailty* / blood
  • Humans
  • Male
  • Neuropsychological Tests
  • Republic of Korea
  • Sex Factors
  • Testosterone* / blood

Substances

  • Testosterone