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Title: Effect of estradiol on cognition in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial.
Austin Authors: Russell, Nicholas ;Allebone, James;Dandash, Orwa;Hoermann, Rudolf;Cheung, Ada S ;Zajac, Jeffrey D ;Handelsman, David J;Kanaan, Richard A A ;Grossmann, Mathis 
Affiliation: Medicine (University of Melbourne)
Psychiatry (University of Melbourne)
ANZAC Research Institute, University of Sydney and Department of Andrology, Concord Hospital, Sydney, New South Wales, Australia
Issue Date: 12-Feb-2022
Date: 2022
Publication information: Clinical Endocrinology 2022; 97(5): 622-633
Abstract: Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. Randomised trial of transdermal estradiol 0.9mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memory and spatial problem solving over time. Men receiving androgen deprivation therapy (ADT) for prostate cancer. Cognition was assessed by a tablet-based cognitive battery (Cogstate) at baseline, month 1, month 3, and month 6. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. 78 participants were randomised. Baseline mean scores were 21.0 (sd 4.1) for the International Shopping List test (ISL), assessing verbal learning and memory (higher scores better), and 60.4 (sd 19.5) for the Groton Maze Learning test (GML), assessing spatial problem solving (lower scores better). There was no significant difference in performance over time for the estradiol group versus the placebo group for the ISL, mean adjusted difference (MAD) 0.7 (95% CI -1.2 - 2.5), p=0.36, or the GML, MAD -3.2 (95% CI -12.0 - 5.6), p-0.53. There was no significant difference between groups over time in performance in any other cognitive domain, or on depression or anxiety scores. We found no major effects of estradiol on cognition in men with castrate testosterone concentrations. Although the cognitive effects of ADT are debated, this study suggests that any such effects are unlikely to be prevented by administration of estradiol. This article is protected by copyright. All rights reserved.
DOI: 10.1111/cen.14689
ORCID: 0000-0001-5596-6601
Journal: Clinical Endocrinology
PubMed URL: 35150156
PubMed URL:
Type: Journal Article
Subjects: Androgens
Prostatic Neoplasms
Appears in Collections:Journal articles

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