Estrogen and cognitive functioning in men with mild cognitive impairment

Although men do not experience an abrupt cessation of gonadal hormone production at midlife as do women, levels of testosterone (T) decrease gradually with aging. Because estradiol (E-2) arises mainly from the conversion of T in men, the availability of E-2 also decreases with increasing age. In randomized clinical trials, E-2 replacement therapy has been shown to maintain aspects of cognition in postmenopausal women, specifically with regard to verbal memory. The present prospective, randomized, cross-over trial is being undertaken in order to determine whether E-2 will enhance verbal memory in men with Mild Cognitive Impairment (MCI). Men with MCI will randomly receive E-2 or placebo for the first 3 mo of treatment and will then be crossed-over to the other treatment for an additional 3 mo. A battery of neuropsychological tests will be administered at pretreatment and, again, following each 3-mo treatment phase. It is hypothesized that elderly men with MCI will perform better on tests of explicit memory when they are being treated with E-2 compared to their performance under placebo conditions.