{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:36:47Z","timestamp":1786977407576,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001466","name":"American Urological Association Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001466","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6\u00a0months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT\u2010associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3\u2010hydroxybutyric acid and ketogenesis. Third, many acyl\u2010carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3\u2010formyl indole (a.k.a. indole\u20103\u2010carboxaldehyde), a microbiota\u2010derived metabolite from the dietary tryptophan. Indole\u20103\u2010carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT\u2010associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT\u2010linked comorbidities and diabetes risk.<\/jats:p>","DOI":"10.1002\/cam4.3016","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T03:41:07Z","timestamp":1585626067000},"page":"3691-3702","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Metabolomic effects of androgen deprivation therapy treatment for prostate cancer"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-903X","authenticated-orcid":false,"given":"Jen\u2010Tsan","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology Center for Genomics and Computational Biology Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pao\u2010Hwa","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Nephrology Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Tolstikov","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taofik","family":"Oyekunle","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Bussberg","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett","family":"Greenwood","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rangaprasad","family":"Sarangarajan","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niven R.","family":"Narain","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Kiebish","sequence":"additional","affiliation":[{"name":"BERG LLC Framingham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Freedland","sequence":"additional","affiliation":[{"name":"Center for Integrated Research in Cancer and Lifestyle Cedars\u2010Sinai Los Angeles CA USA"},{"name":"Durham VA Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2016-000040"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2009.09.004"},{"key":"e_1_2_9_4_1","first-page":"63","article-title":"Androgen deprivation therapy for prostate cancer: long\u2010term safety and patient outcomes","volume":"5","author":"Ahmadi H","year":"2014","journal-title":"Patient Relat Outcome Meas"},{"key":"e_1_2_9_5_1","first-page":"820403","article-title":"The prevalence of cardiac risk factors in men with localized prostate cancer undergoing androgen deprivation therapy in British Columbia","volume":"2015","author":"Davis MK","year":"2015","journal-title":"Canada. 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