title: Lower testosterone levels with luteinizing hormone-releasing hormone agonist therapy than with surgical castration: new insights attained by mass spectrometry.
abstract: OBJECTIVE
  Androgen deprivation therapy by bilateral orchiectomy (surgical castration) or luteinizing hormone-releasing hormone agonist therapy (medical castration) is recommended for advanced or metastatic prostate cancer. Both methods aim at reducing serum testosterone concentrations to a castrate level which is currently defined as less than 50 ng/dl. The results of previous studies are based on testosterone immunoassays that have insufficient accuracy in the low range. In this study we reevaluated serum testosterone concentrations in men on androgen deprivation therapy using isotope dilution-liquid chromatography-tandem mass spectrometry, an accurate method of measuring testosterone in the castrate range.
  
  
  METHODS
  Subjects underwent surgical castration (34) or received a luteinizing hormone-releasing hormone agonist (32). Serum samples were obtained more than 3 months after surgery or initiation of luteinizing hormone-releasing hormone agonist therapy. Testosterone levels were determined using isotope dilution-liquid chromatography-tandem mass spectrometry. Dihydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and inhibin B levels were determined.
  
  
  RESULTS
  All subjects had serum testosterone values less than 50 ng/dl and 97% had testosterone concentrations less than 20 ng/dl. Medically castrated men had significantly lower testosterone levels (median 4.0 ng/dl, range less than 2.9 to 20.2) than those surgically castrated (median 9.2 ng/dl, range less than 2.9 to 28.8, p <0.001). No difference was found in dehydroepiandrosterone sulfate, androstenedione and sex hormone-binding globulin levels between the groups, whereas inhibin B levels were significantly higher in the luteinizing hormone-releasing hormone agonist treated group.
  
  
  CONCLUSIONS
  Using an accurate technique for testosterone measurement, subjects on luteinizing hormone-releasing hormone agonist therapy had significantly lower testosterone concentrations than men who underwent surgical castration. The clinical relevance of these findings remains to be determined.
authors.affiliation: Department of Urology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Tim M
authors.initials: TM
authors.lastname: van der Sluis
authors.forename: Hong N
authors.initials: HN
authors.lastname: Bui
authors.forename: Eric J H
authors.initials: EJ
authors.lastname: Meuleman
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Heijboer
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: Hartman
authors.forename: Nick
authors.initials: N
authors.lastname: van Adrichem
authors.forename: Egbert
authors.initials: E
authors.lastname: Boevé
authors.forename: Willem
authors.initials: W
authors.lastname: de Ronde
authors.forename: R Jeroen A
authors.initials: RJ
authors.lastname: van Moorselaar
authors.forename: André N
authors.initials: AN
authors.lastname: Vis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000097:blood; D002369:Castration; D002853:Chromatography, Liquid; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000601:surgery / Q000628:therapy*; D012189:Retrospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood*
chemical_list: D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate