The association between sex hormones and the change in brain-predicted age difference in older women

Jo Wrigglesworth, Ian Harding, Rakibul M. Islam, Phillip G.D. Ward, Robyn L. Woods, Robin J. Bell, John J. McNeil, Elsdon Storey, Gary F. Egan, Anne M. Murray, Ruth E. Trevaks, Stephanie Alison Ward, Susan R. Davis AO, Joanne Ryan

Research output: Contribution to journalArticleResearchpeer-review


Objective: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD). Design: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. Patients: Community-dwelling older women (aged 70+ years). Measurements: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex-hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1-weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. Results: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain-PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p =.04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain-PAD cross-sectionally, nor were any of the examined sex hormones or SHBG associated with brain-PAD longitudinally. Conclusion: No strong evidence of an association between circulating sex hormones and brain-PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.

Original languageEnglish
Pages (from-to)692-699
Number of pages17
JournalClinical Endocrinology
Issue number5
Publication statusPublished - May 2023


  • ageing
  • biomarkers
  • brain
  • hormones
  • magnetic resonance imaging
  • neuroimaging
  • postmenopause

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