title: Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated With Exogenous Testosterone.
abstract: Concern exists that T replacement therapy (TRT) might increase the risk of prostate disease. There are limited data regarding the impact of TRT on prostate androgen concentrations.
  
  
  
  Determine the dose-dependent effects of exogenous T administration on intraprostatic androgen concentrations.
  
  
  
  Twelve-week, double-blinded, randomized, placebo-controlled trial.
  
  
  
  Academic medical center.
  
  
  
  Sixty-two healthy eugonadal men, aged 25-55 years.
  
  
  
  Subjects were randomly assigned to receive injections of acyline, a GnRH antagonist (used to achieve medical castration), every 2 weeks plus transdermal T gel (1.25 g, 2.5 g, 5.0 g, 10 g, or 15 g daily), or placebo injections and transdermal gel for 12 weeks.
  
  
  
  Serum T and dihydrotestosterone (DHT) were measured at baseline and every 2 weeks during treatment. Intraprostatic T and DHT concentrations were assessed from tissue obtained through ultrasound-guided prostate needle biopsies at week 12. Androgens were quantified by liquid chromatography-tandem mass spectrometry.
  
  
  
  51 men completed the study and were included in the analysis. There were no significant adverse events. Exogenous T resulted in a dose-dependent increase in serum T and DHT concentrations (190-770 and 60-180 ng/dL, respectively). Although intraprostatic T differed among dose groups (P = .01), intraprostatic DHT was comparable regardless of T dose (P = .11) and was 10- to 20-fold greater than intraprostatic T.
  
  
  
  In healthy, medically castrate men receiving exogenous T, the total intraprostatic androgen concentration (predominantly DHT) remained stable across serum T concentrations within the physiological range. These findings further our knowledge of the relationship between serum and intraprostatic androgens and suggest that physiological serum T achieved by TRT is unlikely to alter the prostate hormonal milieu.
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Arthi
authors.initials: A
authors.lastname: Thirumalai
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Cooper
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Katya B
authors.initials: KB
authors.lastname: Rubinow
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Marck
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.affiliation: Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
mesh_terms: D000328:Adult; D013196:Dihydrotestosterone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006262:Health; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D009919:Orchiectomy / Q000379:methods; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C109238:acyline