Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study

Disease areas:

• brain

Last updated:

2 July 2025

Author(s):

Ross J. Marriott, Kevin Murray, Leon Flicker, Graeme J. Hankey, Alvin M. Matsumoto, Girish Dwivedi, Leen Antonio, Osvaldo P. Almeida, Shalender Bhasin, Adrian S. Dobs, David J. Handelsman, Robin Haring, Terence W. O'Neill, Claes Ohlsson, Eric S. Orwoll, Dirk Vanderschueren, Gary A. Wittert, Frederick C.W. Wu, Bu B. Yeap

Publish date:

3 January 2022

Journal:

Alzheimer's & Dementia

PubMed ID:

34978125

DOI:

10.1002/alz.12529

Abstract

INTRODUCTION: The association of testosterone concentrations with dementia risk remains uncertain. We examined associations of serum testosterone and sex hormone-binding globulin (SHBG) with incidence of dementia and Alzheimer’s disease.

METHODS: Serum total testosterone and SHBG were measured by immunoassay. The incidence of dementia and Alzheimer’s disease (AD) was recorded. Cox proportional hazards regression was adjusted for age and other variables.

RESULTS: In 159,411 community-dwelling men (median age 61, followed for 7 years), 826 developed dementia, including 288 from AD. Lower total testosterone was associated with a higher incidence of dementia (overall trend: P = .001, lowest vs highest quintile: hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.13-1.81), and AD (P = .017, HR = 1.80, CI = 1.21-2.66). Lower SHBG was associated with a lower incidence of dementia (P < .001, HR = 0.66, CI = 0.51-0.85) and AD (P = .012, HR = 0.53, CI = 0.34-0.84).

DISCUSSION: Lower total testosterone and higher SHBG are independently associated with incident dementia and AD in older men. Additional research is needed to determine causality.