title: Effect of androgen suppression compared with androgen receptor blockade on arterial stiffness in men with prostate cancer.
abstract: Endogenous testosterone and estradiol are thought to be cardio-protective in men. We wanted to determine the effects of 2 different anti-androgen therapies on arterial stiffness as one suppresses (goserelin--a gonadotrophin-releasing hormone analog) while the other increases (bicalutamide--an androgen receptor blocker) both testosterone and estradiol. We conducted a randomized trial on 43 men (mean age, 71.2 +/- 6.2 years) with localized prostate cancer. They received either goserelin or bicalutamide for 24 weeks. Carotid-femoral (C-F) and carotid-radial (C-R) pulse wave velocities (PWVs) were measured. Twenty age- and disease-matched men with prostate cancer on no active treatment were studied in a similar manner. After 12 weeks of goserelin, radial artery PWV increased significantly from baseline and a nonsignificant increase was observed in femoral PWV (change from baseline radial: +1.4 m/s, P = .002, femoral: +0.9 m/s, P = .127) Both PWV measures increased significantly with bicalutamide (change from baseline radial: +0.8, femoral: +0.9 m/s, P <or= .049). PWV increased further after 24 weeks with goserelin (change from baseline radial: +1.7, femoral: +1.3 m/s, P <or= .049 for both) but not bicalutamide (change from baseline radial: +0.4, femoral: +0.4 m/s, P not significant [NS]); however, comparison of changes between the 2 drugs were not significantly different at either 12 or 24 weeks (P >or= .967 at 12 weeks and P >or= .07 at 24 weeks). The untreated men studied in parallel showed no changes at 12 or 24 weeks in either PWV measure. Anti-androgen treatment in men might increase large artery stiffness, an adverse cardiovascular risk factor; however, the effect was not maintained with testosterone receptor blockade, in the longer term, but tended to be sustained with suppression therapy. This could relate to the different sex hormone effects of the 2 therapies.
authors.affiliation: Department of Medicine for the Elderly, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom. fdockery@doctors.org.uk
authors.forename: Frances
authors.initials: F
authors.lastname: Dockery
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bulpitt
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Agarwal
authors.forename: Clare
authors.initials: C
authors.lastname: Vernon
authors.forename: Chakravarthi
authors.initials: C
authors.lastname: Rajkumar
mesh_terms: D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000627:therapeutic use*; D002339:Carotid Arteries; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011673:Pulsatile Flow / Q000187:drug effects*; D011944:Receptors, Androgen; D014105:Tosyl Compounds / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide