Chronic testosterone deprivation sensitizes the middle-aged rat brain to damaging effects of testosterone

Levels of the testosterone (T) fall in aging men. Recently, the number of men obtaining testosterone replacement therapy (TRT) has increased dramatically. However, other consequences of aging, such as increased oxidative stress, may result in detrimental effects when combined with TRT, including an increased stroke risk. Whether such a delay would alter the effects of TRT on stroke is not known. We hypothesized that a delay TRT following castration in middle-aged male rats would result in increased oxidative stress and a reduction in the neuroprotective effects of testosterone following stroke. We evaluated the effects of testosterone treatment after short (2 week) and long-term testosterone deprivation (10 weeks) in middle-aged male rats on cerebral ischemia, oxidative stress and cognitive function. Our data suggest testosterone treatment after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia, however in the absence of injury improves cognition. Both effects are regulated by oxidative stress.