TESTOSTERONE REPLACEMENT THERAPY: ONE SIZE FITS ALL?

Testosterone replacement therapy (TRT) has been used to improve libido and overall well-being in men. Recently, there has been a rise in off-label TRT to treat diminished libido in women. Current studies from our laboratory have shown that testosterone is linked with cognition and memory in aging men. However, the relationship is murkier when associating cognitive impairment with testosterone in aging women. A key component of aging is oxidative stress (OS). Previous studies by our laboratory have shown that OS and the male sex hormone, testosterone, have a significant impact on neuronal viability, and subsequently cognition. An analysis of plasma biomarker proteins for OS (homocysteine) and testosterone was conducted on 177 Mexican-American women, 185 Caucasian women, 117 Mexican-American men, and 116 Caucasian men with a mean age of 72 from the Texas Alzheimer’s Research and Care Consortium (TARCC) to determine their role on memory and cognitive impairment. Participants were stratified according to their OS status (Low OS 12 mol/L of homocysteine). Participants were diagnosed as cognitively intact, mild cognitive impairment, or Alzheimer’s disease. Our results show that OS was significantly higher in men relative to women. Under a low oxidative stress environment, testosterone did not have a significant impact on memory or cognitive impairment, regardless of ethnicity or gender. However, in a high OS environment, testosterone significantly improved memory function and decreased cognitive impairment in Mexican-American men. Further, testosterone had a negative impact in Caucasian men, in which testosterone increased cognitive impairment. Testosterone had no effect on memory or cognitive impairment in women, irrespective of ethnicity. Collectively, the data support the hypotheses that: 1) testosterone mediates cognitive impairment in Caucasian men with high OS, 2) TRT therapy may be a viable option for Mexican-American men and, 3) testosterone does not alter memory or cognitive impairment in women. Therefore, the use of TRT should be tailored to an individual with respect to ethnicity and gender. Purpose (a): Testosterone replacement therapy (TRT) has been used to improve libido and overall well-being in men. Recently, there has been a rise in off-label TRT to treat diminished libido in women. Current studies from our laboratory have shown that testosterone is linked with cognition and memory in aging men. However, the relationship is murkier when associating cognitive impairment with testosterone in aging women. A key component of aging is oxidative stress (OS). Previous studies by our laboratory have shown that OS and the male sex hormone, testosterone, have a significant impact on neuronal viability, and subsequently cognition. Methods (b): An analysis of plasma biomarker proteins for OS (homocysteine) and testosterone was conducted on 177 Mexican-American women, 185 Caucasian women, 117 Mexican-American men, and 116 Caucasian men with a mean age of 72 from the Texas Alzheimer’s Research and Care Consortium (TARCC) to determine their role on memory and cognitive impairment. Participants were stratified according to their OS status (Low OS < 12 mol/L and High OS >12 mol/L of homocysteine). Participants were diagnosed as cognitively intact, mild cognitive impairment, or Alzheimer’s disease. Results (c): Our results show that OS was significantly higher in men relative to women. Under a low oxidative stress environment, testosterone did not have a significant impact on memory or cognitive impairment, regardless of ethnicity or gender. However, in a high OS environment, testosterone significantly improved memory function and decreased cognitive impairment in Mexican-American men. Furthermore, testosterone had a negative impact in Caucasian men, in which testosterone increased cognitive impairment. Testosterone had no effect on memory or cognitive impairment in women, irrespective of ethnicity. Conclusions (d): Collectively, the data support the hypotheses that: 1) testosterone mediates cognitive impairment in Caucasian men with high OS, 2) TRT therapy may be a viable option for Mexican-American men and, 3) testosterone does not alter memory or cognitive impairment in women. Therefore, the use of TRT should be tailored to an individual with respect to ethnicity and gender.