Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer

Eur Urol. 2019 Apr;75(4):676-683. doi: 10.1016/j.eururo.2018.11.022. Epub 2018 Nov 26.


Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.

Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n=2078) or GnRH agonists (n=4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5yr before through to 5yr after starting androgen deprivation therapy (ADT).

Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.

Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p<0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-1.44).

Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.

Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

Keywords: Androgen deprivation therapy; Antiandrogen monotherapy; Comorbidity; Gonadotropin-releasing hormone agonists; Prostate cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use*
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Comorbidity
  • Databases, Factual
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Male
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Registries
  • Risk Assessment
  • Risk Factors
  • Sweden / epidemiology
  • Time Factors
  • Treatment Outcome


  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone