title: Androgen deprivation therapy reversibly increases endothelium-dependent vasodilation in men with prostate cancer.
abstract: BACKGROUND
  Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population.
  
  
  RESULTS
  We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 ± 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05).
  
  
  CONCLUSIONS
  In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.
authors.affiliation: Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA (P.L.N., P.L.G., A.H.).
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA (P.J.).
authors.forename: Petr
authors.initials: P
authors.lastname: Jarolim
authors.affiliation: Endocrinology, Brigham and Women's Hospital, Boston, MA (S.B.).
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (J.P.Z., J.M., S.K., J.A.B.).
authors.forename: Jonah P
authors.initials: JP
authors.lastname: Zuflacht
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (J.P.Z., J.M., S.K., J.A.B.).
authors.forename: Jessica
authors.initials: J
authors.lastname: Milian
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (J.P.Z., J.M., S.K., J.A.B.).
authors.forename: Samoneh
authors.initials: S
authors.lastname: Kadivar
authors.affiliation: Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA (P.L.N., P.L.G., A.H.).
authors.forename: Powell L
authors.initials: PL
authors.lastname: Graham
authors.affiliation: Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA (P.L.N., P.L.G., A.H.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Hyatt
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (P.W.K.).
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (J.P.Z., J.M., S.K., J.A.B.).
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Beckman
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D016729:Leuprolide / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; D016729:Leuprolide
keywords: androgen deprivation therapy; endothelial function; inflammation; insulin resistance; prostate cancer