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Title: Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial.
Austin Authors: Russell, Nicholas ;Hoermann, Rudolf;Cheung, Ada S ;Ching, Michael ;Zajac, Jeffrey D ;Handelsman, David J;Grossmann, Mathis 
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Pharmacy Department, Austin Health, Heidelberg, Victoria, Australia
ANZAC Research Institute and Dept of Andrology, Dept of Andrology, Sydney, Australia
Issue Date: 16-Mar-2018 2018
Publication information: European journal of endocrinology 2018; 178(5): 565-576
Abstract: There is increasing recognition that, in men, some biological actions attributed to testosterone (T) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short term biological effects of E2 addback without increasing circulating T. 28-day randomised, placebo-controlled trial Methods: 37 participants were randomised to either 0.9 mg or 1.8 mg of 0.1% E2 gel per day, or matched placebo gel. Fasting morning serum hormones, quality of life questionnaires, and treatment side effects were evaluated at baseline, day 14 and day 28. Hot flush diaries and other biochemical measurements were completed at baseline and study end. Transdermal E2 significantly raised serum E2 from baseline to day 28 compared to placebo in the 0.9mg dose group (median 208 pmol/L; interquartile range 157-332), and in the 1.8mg dose group (median 220 pmol/L; interquartile range 144-660). E2 treatment reduced hot flush frequency and severity as well as beta carboxyl-terminal type 1 collagen telopeptide. In men with castrate levels of E2 and T, daily transdermal E2 0.9-1.8mg increases median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test whether low dose E2 treatment can mitigate ADT-associated adverse effects without E2-related toxicity.
DOI: 10.1530/EJE-17-1072
ORCID: 0000-0001-5257-5525
PubMed URL: 29549104
Type: Journal Article
Appears in Collections:Journal articles

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