Abstract
The effects of testosterone (T) and estradiol (E(2)) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E(2) on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0+/-8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E(2) were suppressed. In the second phase of the study, either micronized E(2) 1mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E(2) would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E(2)-treated men, exhibited a trend towards improvement in their scores on both the immediate (p=.075) and delayed recall (p=.095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E(2)-treated men on both the immediate (p=.020) and delayed recall (p=.016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E(2) failed to improve short- or long-term verbal memory performance in this sample of older men being treated for prostate cancer.