Testosterone, SHBG and Incident Dementia Risk in Men

Pavankumar Kamat


January 17, 2022


  • Middle-aged and older men with low testosterone levels had an increased risk of incident dementia and Alzheimer’s disease (AD).

  • Men with low sex hormone-binding globulin (SHBG) levels had a lower risk of incident dementia and AD.

  • The associations of testosterone with incident dementia were independent of SHBG levels and vice versa.

Why this matters

  • Findings warrant further interventional studies to investigate the potential causality of the associations and the underlying mechanisms.

Study design

  • A study included 159,411 community-dwelling men (age, 37-73 years) from the UK Biobank.

  • Primary outcome: new diagnosis of dementia from any cause.

  • Funding: Western Australian Health Translation Network and others.

Key results

  • During the follow-up of 7 years, 826 of 159,411 community-dwelling men developed dementia, including 288 from AD.

  • Compared with men with testosterone level in the highest quintile (Q5), those with low total testosterone level in the lowest quintile (Q1) had a higher risk of (adjusted HR [aHR]; 95% CI):

    • incident dementia (1.43; 1.13-1.81; = .001); and

    • AD (1.80; 1.21-2.66; = .017).

  • Compared with men with SHBG level in the highest quintile (Q5), those with low total SHBG level in lowest quintile (Q1) had a lower risk of (aHR; 95% CI):

    • incident dementia (0.66; 0.51-0.85; < .001); and

    • AD (0.53; 0.34-0.84; = .012).


  • Observational design.

  • Data on incident dementia and AD cases were determined using linked hospital admissions and mortality data.

Marriott RJ, Murray K, Flicker L, Hankey GJ, Matsumoto AM, Dwivedi G, Antonio L, Almeida OP, Bhasin S, Dobs AS, Handelsman DJ, Haring R, O'Neill TW, Ohlsson C, Orwoll ES, Vanderschueren D, Wittert GA, Wu FCW, Yeap BB. Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study. Alzheimers Dement. 2022 Jan 03 [Epub ahead of print]. doi: 10.1002/alz.12529. PMID: 34978125 View abstract.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.