TY - JOUR
T1 - Oxidative stress, testosterone, and cognition among caucasian and mexican-american men with and without alzheimer's disease
AU - Cunningham, Rebecca L.
AU - Singh, Meharvan
AU - O'Bryant, Sid E.
AU - Hall, James R.
AU - Barber, Robert C.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Androgens
KW - Mexican American
KW - antioxidants
KW - homocysteine
KW - luteinizing hormone
UR - http://www.scopus.com/inward/record.url?scp=84901943724&partnerID=8YFLogxK
U2 - 10.3233/JAD-131994
DO - 10.3233/JAD-131994
M3 - Article
C2 - 24496073
AN - SCOPUS:84901943724
SN - 1387-2877
VL - 40
SP - 563
EP - 573
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 3
ER -