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EBioMedicine 68 (2021)Contents lists accessible at ScienceDirectEBioMedicinejournal homepage: www.elsevier.com/locate/ebiomResearch paperAtorvastatin induces adrenal androgen downshift in males with prostate cancer: A post Hoc analysis of a pilot adaptive Randomised clinical trialPaavo V.H. Raittinena,, Heimo Syvalab, Teuvo L.J. Tammelab, Merja R. Hakkinenc, Pauliina Ilmonena, Seppo Auriolac, Teemu J. MurtolabaDepartment of Mathematics and Systems Evaluation, Aalto University School of Science, Espoo, 02150, Finland Faculty of Medicine and Overall health Technologies, Tampere University, and Tays Cancer Center, Tampere University Hospital, Finland c College of Pharmacy, University of Eastern Finland, Yliopistonranta 1B, 70210, Kuopio, FinlandbA R T I C L EI N F OA B S T R A C TArticle History: Received 19 February 2021 Revised 21 May 2021 Accepted 26 May 2021 Obtainable on the net xxx Keyword phrases: Prostate cancer Serum adrenal androgens Prostatic tissue adrenal androgens Statins Clinical trialBackground: Prostate cancer (PCa) progression depends on androgen receptor activity. Cholesterol is needed for biosynthesis of all steroid hormones, including androgens. Effect of cholesterol-lowering statins on androgens is unknown. We explored atorvastatin influence on serum and prostatic tissue steroidomic profiles (SP) to expose novel pathways for limiting androgen concentration in guys with PCa. Strategies: This can be a pre-planned post hoc analysis of ESTO-1 pilot randomised, double-blinded, clinical trial. Statin na e men, scheduled for radical prostatectomy resulting from localised PCa, had been randomised 1:1 to utilize everyday 80 mg of atorvastatin or placebo just before the surgery to get a median of 28 days. Participants had been recruited and treated at the Pirkanmaa Hospital District, Tampere, Finland. 108 in the 158 recruited guys were included within the evaluation depending on sample availability for hormone profiling. Serum and prostatic tissue steroid profiles had been determined applying liquid chromatography mass spectrometry. Wilcoxon rank sum test and bootstrap confidence intervals (CI) were applied to analyse the difference among placebo and atorvastatin arms. Findings: Most serum and prostatic steroids, like testosterone and dihydrotestosterone, were not connected with atorvastatin use. On the other hand, atorvastatin use induced serum SP alterations in 11-ketoandrostenedione (placebo 960pM, atorvastatin 617.5pM, p-value 0.0001, median difference -342.five; 95 CI -505.23 -188.98). Within the prostatic tissue, atorvastatin was associated with plausible downshift in 11- ketodihydrotestosterone (placebo 25.0pM in one hundred mg tissue/1 mL saline, atorvastatin 18.5pM in 100 mg tissue/1 mL saline, p-value 0.027, median difference -6.53; 95 CI -12.eight -0.29); nevertheless, this association diminished soon after adjusting for numerous testing. No severe harms have been reported. Interpretation: Atorvastatin was related with adrenal androgen downshift within the serum and possibly within the prostate. The getting warrants additional investigation COX supplier whether or not atorvastatin could increase androgen deprivation therapy efficacy. Funding: Funded by grants from the Finnish Cultural Foundation, Finnish Cancer Society, Academy of Finland, plus the Specialist Responsibility Region with the Tampere University Hospital. Clinicaltrials.gov identifier: NCT01821404. 2021 The Authors. Published by Elsevier B.V. This is an open access short article under the CC BY-NC-ND license (http://creativecommon.