The Impact of Late Luteinizing Hormone-Releasing Hormone Agonist Dosing on Testosterone Suppression in Patients with Prostate Cancer: An Analysis of United States Clinical Data

J Urol. 2020 Apr;203(4):743-750. doi: 10.1097/JU.0000000000000577. Epub 2019 Oct 3.


Purpose: We evaluated the timeliness of androgen deprivation therapy dosing, the impact of dosing nonadherence on testosterone, and the frequency of testosterone and prostate specific antigen testing in patients with prostate cancer.

Materials and methods: We retrospectively analyzed the records of 22,860 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonists. Analyses were done using 2 definitions of month, including a 28-day month (late dosing after day 28, 84, 112 or 168) and an extended month (late after day 32, 97, 128 or 194) for 1, 3, 4 and 6-month formulations, respectively. The prevalence of late dosing, associated testosterone values, and the frequency of testosterone and prostate specific antigen testing were assessed. Statistical significance was assessed with the unpaired t-test.

Results: Of the injections 84% and 27% were late for the 28-day and extended month analyses, respectively. For the 28-day month 60% and 29% of injections were late by more than 1 and more than 2 weeks, respectively. Of testosterone values 4% were greater than 50 ng/dl for early/on time injections using both definitions, and 15% and 27% were greater than 50 ng/dl when late, and for the 28-day month and the extended month, respectively. For early/on time vs late injections 22% vs 31% of testosterone values were greater than 20 ng/dl for the 28-day month and 21% vs 43% for the extended month. Mean testosterone was higher when late (49 ng/dl for 28-day month, 79 ng/dl for extended month) vs early/on time (both 21 ng/dl). Of the injections prostate specific antigen measurements were performed in 83% and testosterone assessment was done in only 13%.

Conclusions: Luteinizing hormone-releasing hormone agonists were frequently (84%) administered later than the schedules used in pivotal trials. Nearly half of the late testosterone values for the extended month were greater than 20 ng/dl and mean testosterone was almost double the castration level. Elevated testosterone remained unidentified with infrequent testing.

Keywords: androgens; luteinizing hormone-releasing hormone; prostatic neoplasms; testosterone; treatment adherence and compliance.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Kallikreins / blood
  • Male
  • Medication Adherence / statistics & numerical data*
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Retrospective Studies
  • Testosterone / antagonists & inhibitors*
  • Testosterone / blood
  • Time Factors
  • United States
  • Young Adult


  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen