title: Prospective study of changes in the metabolomic profiles of men during their first three months of androgen deprivation therapy for prostate cancer.
abstract: OBJECTIVE
  Androgen deprivation therapy (ADT) for prostate cancer causes an increase in fasting insulin and adverse changes in body composition and serum lipid profile. It is unknown what other metabolic alterations are caused by ADT. To better characterize the metabolic effects of ADT, we measured changes in plasma metabolomic profile at baseline and after the first 3 months of therapy.
  
  
  METHODS
  Fasting plasma samples were drawn from 36 subjects at baseline and after 3 months of gonadotropin releasing hormone (GnRH) agonist therapy. Extracted samples were split into equal parts for analysis on the gas chromatography-mass spectrometry and liquid chromatography/tandem mass spectrometry platforms.
  
  
  RESULTS
  Of the 292 identified metabolites, 56 changed significantly (P < 0.05) from baseline to 3 months. Notable changes were grouped as follows: (i) Multiple steroids were lower at 3 months, consistent with the effect of therapy on gonadal androgen synthesis. (ii) Most bile acids and their metabolites were higher during treatment. Cholesterol levels changed very little. (iii) Markers of lipid beta-oxidation (acetyl-carnitines and ketone bodies) and omega-oxidation were lower at 3 months. (iv) Two previously identified biomarkers of insulin resistance (2-hydroxybutyrate and branch chain keto-acid dehydrogenase complex products) were stable to lower at 3 months.
  
  
  CONCLUSIONS
  Unbiased metabolomic analyses revealed expected, novel, and unexpected results. Steroid levels fell, consistent with the effects of ADT. Most bile acids and their metabolites increased during ADT, a novel finding. Biomarkers of lipid metabolism and insulin resistance fell, unexpected given that ADT has been shown to increase fasting insulin.
authors.affiliation: Division of Hematology-Oncology, Massachusetts General Hospital (MGH) Cancer Center, Boston, Massachusetts 02114, USA. psaylor@partners.org
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Saylor
authors.forename: Edward D
authors.initials: ED
authors.lastname: Karoly
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000378:metabolism; D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007333:Insulin Resistance; D016729:Leuprolide / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008297:Male; D055442:Metabolome; D010084:Oxidation-Reduction; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy; D013256:Steroids / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001647:Bile Acids and Salts; D006885:Hydroxybutyrates; D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D016729:Leuprolide; C031570:2-hydroxybutyric acid