Format

Send to

Choose Destination
J Alzheimers Dis. 2014;40(3):563-73. doi: 10.3233/JAD-131994.

Oxidative stress, testosterone, and cognition among Caucasian and Mexican-American men with and without Alzheimer's disease.

Author information

1
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA Center FOR HER, University of North Texas Health Science Center, Fort Worth, TX, USA.
2
Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
3
Department of Psychiatry and Behavioral Health, University of North Texas Health Science Center, Fort Worth, TX, USA Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA.
4
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA.

Abstract

BACKGROUND:

The use of testosterone among aging men has been increasing, but results from studies addressing the effectiveness of testosterone replacement therapy have been equivocal.

OBJECTIVE:

Given our prior pre-clinical studies that reported a major influence of oxidative stress on testosterone's neuroprotective effects, we investigated whether the negative effects of testosterone on brain function were predicted by oxidative load.

METHODS:

In order to test our hypothesis, we determined whether circulating total testosterone and luteinizing hormone correlated with cognition in a subset of the Texas Alzheimer's Research & Care Consortium (TARCC) cohort, consisting of Caucasian (n = 116) and Mexican-American (n = 117) men. We also assessed whether oxidative stress (as indexed by homocysteine levels) modified this relationship between sex hormones and cognition, and whether the levels of two antioxidants, superoxide dismutase-1 and glutathione S-transferase (GST), varied as a function of circulating testosterone.

RESULTS:

In a low oxidative stress environment, testosterone was positively associated with the level of the antioxidant, GST, while no deleterious effects on cognitive function were noted. In contrast, under conditions of high oxidative stress (homocysteine levels >12 μmol/L), testosterone and luteinizing hormone were associated with cognitive impairment, but only among Caucasians. The ethnic difference was attributed to significantly higher GST levels among Mexican-Americans.

CONCLUSION:

While testosterone may be beneficial under conditions of low oxidative stress, testosterone appears to have negative consequences under conditions of elevated oxidative stress, but only in Caucasians. Mexican-Americans, however, were protected from any deleterious effects of testosterone, potentially due to higher levels of endogenous antioxidant defenses such as GST.

KEYWORDS:

Androgens; Mexican American; antioxidants; homocysteine; luteinizing hormone

PMID:
24496073
PMCID:
PMC4219556
DOI:
10.3233/JAD-131994
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for IOS Press Icon for PubMed Central
Loading ...
Support Center