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EBioMedicine 68 (2021)Contents lists available at ScienceDirectEBioMedicinejournal homepage: www.elsevier.com/locate/ebiomResearch paperAtorvastatin induces adrenal androgen downshift in men with prostate cancer: A post Hoc evaluation of a pilot adaptive Randomised KDM3 Storage & Stability 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 Analysis, Aalto University School of Science, Espoo, 02150, Finland Faculty of Medicine and Well being Technology, Tampere University, and Tays Cancer Center, Tampere University Hospital, Finland c School 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 Might 2021 Accepted 26 May well 2021 Readily available on-line xxx Keywords and phrases: Prostate cancer Serum adrenal androgens Prostatic tissue adrenal androgens Statins Clinical trialBackground: Prostate cancer (PCa) progression is dependent upon androgen receptor activity. Cholesterol is needed for biosynthesis of all steroid hormones, which includes androgens. Impact 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. Methods: 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 due to localised PCa, had been randomised 1:1 to use day-to-day 80 mg of atorvastatin or placebo prior to the surgery to get a median of 28 days. Participants had been recruited and treated in the Pirkanmaa Hospital District, Tampere, Finland. 108 with the 158 recruited men had been integrated within the evaluation based on sample availability for hormone profiling. Serum and prostatic tissue steroid profiles were determined working with liquid chromatography mass spectrometry. Wilcoxon rank sum test and bootstrap self-assurance intervals (CI) had been employed to analyse the distinction involving placebo and atorvastatin arms. Findings: Most serum and prostatic steroids, like testosterone and dihydrotestosterone, were not related with atorvastatin use. Nevertheless, atorvastatin use induced serum SP modifications in 11-ketoandrostenedione (placebo 960pM, atorvastatin 617.5pM, p-value 0.0001, median difference -342.5; 95 CI -505.23 -188.98). In the prostatic tissue, atorvastatin was related 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 -12.8 -0.29); nevertheless, this association diminished right after adjusting for numerous testing. No critical harms were reported. Interpretation: Atorvastatin was linked with adrenal androgen downshift inside the serum and possibly within the prostate. The discovering warrants Caspase 4 Formulation additional investigation regardless of whether atorvastatin could enhance androgen deprivation therapy efficacy. Funding: Funded by grants from the Finnish Cultural Foundation, Finnish Cancer Society, Academy of Finland, along with the Professional Responsibility Area of the Tampere University Hospital. Clinicaltrials.gov identifier: NCT01821404. 2021 The Authors. Published by Elsevier B.V. This can be an open access short article under the CC BY-NC-ND license (http://creativecommon.
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