title: A prospective analysis of the time to normalization of serum androgens following 6 months of androgen deprivation therapy in patients on a randomized phase III clinical trial using limited hormonal therapy.
abstract: OBJECTIVE
  Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent therapy with gonadotropin-releasing hormone agonists (GnRH-A). While these are largely successful in decreasing testosterone (T) and dihydroxytestosterone (DHT) to castrate levels, discontinuation of such therapy often results in continued suppression of androgens for variable periods of time. We present the largest published series of patients evaluating the timing of T and DHT increase after cessation of GnRH therapy.
  
  
  METHODS
  Serial T and DHT measurements were prospectively obtained every 3 months while on GnRH-A then monthly upon discontinuation of GnRH-A. Analysis of time from the second 3-month GnRH-A administration to T and DHT increase was undertaken.
  
  
  RESULTS
  A total of 80 evaluable patients had a median time to T 50 ng/dl or greater of 12.9 weeks and a median time to T normalization (212 ng/dl or greater) of 16.6 weeks. Low baseline T was associated with a prolonged time to T 212 ng/dl or greater (p = 0.0086) and a similar trend was seen in patients older than 66 years (p = 0.08). There were 62 evaluable patients with a median of 14.9 weeks to DHT 150 pg/ml or greater. There was no association with Gleason score at diagnosis, on study prostate specific antigen, type of prior definitive therapy, or any prior hormonal therapy and time to increase in circulating androgens.
  
  
  CONCLUSIONS
  After 6 months of GnRH-A therapy in these patients, DHT and T levels did not return to normal for a median of 14.9 and 16.6 weeks, respectively.
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. gulleyj@mail.nih.gov
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Jane
authors.initials: J
authors.lastname: Carter
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Gerkamal
authors.initials: G
authors.lastname: Chatta
authors.forename: Maha H
authors.initials: MH
authors.lastname: Hussain
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000627:therapeutic use*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood*; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C013915:boldenone; D016729:Leuprolide