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Gonadotropin-releasing Hormone Agonists, Orchiectomy, and Risk of Cardiovascular Disease : Semi-ecologic, Nationwide, Population-based Study

Thomsen, Frederik Birkebæk; Sandin, Fredrik; Garmo, Hans; Lissbrant, Ingela Franck; Ahlgren, Göran LU ; Van Hemelrijck, Mieke; Adolfsson, Jan; Robinson, David and Stattin, Pär (2017) In European Urology
Abstract

Background: In observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk. Objective: To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. Design, setting, and participants: Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992-1999 in the Prostate Cancer Database Sweden 3.0. Outcome measurements and statistical analysis: We measured the proportion of men who received GnRH... (More)

Background: In observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk. Objective: To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. Design, setting, and participants: Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992-1999 in the Prostate Cancer Database Sweden 3.0. Outcome measurements and statistical analysis: We measured the proportion of men who received GnRH agonists as primary treatment in 580 experimental units defined by healthcare provider, diagnostic time period, and age at diagnosis. Incident or fatal CVD events in units with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed. Results and limitations: The risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0.93-1.11). Accordingly, there was no difference in the net probability of CVD after GnRH agonist compared to orchiectomy (hazard ratio 1.02, 95% CI 0.96-1.09). The 10-yr crude probability of CVD was 0.56 (95% CI 0.55-0.57) for men on GnRH agonists and 0.52 (95% CI 0.50-0.54) for men treated with orchiectomy. The main limitation was the nonrandom allocation to treatment, with younger men with lower comorbidity and less advanced cancer more likely to receive GnRH agonists. Conclusion: Our data do not support previous observations that GnRH agonists increase the risk of CVD in comparison to orchiectomy. Patient summary: We found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer. We found no difference in the risk of cardiovascular disease or death between gonadotrpin-releasing hormone agonists and orchiectomy as treatments for prostate cancer. Accordingly, no evidence was found in favour of changing the standard hormonal treatment for prostate cancer.

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author
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Androgen deprivation therapy, Cardiovascular risk, Gonadotropin-releasing hormone, Orchiectomy, Prostate cancer, Prostate Cancer Database Sweden (PCBaSe)
in
European Urology
publisher
Elsevier
external identifiers
  • scopus:85023202861
ISSN
0302-2838
DOI
10.1016/j.eururo.2017.06.036
language
English
LU publication?
no
id
482db940-28e9-4a87-b28d-a9eb1a0d4680
date added to LUP
2017-08-22 15:06:57
date last changed
2018-01-07 12:15:41
@article{482db940-28e9-4a87-b28d-a9eb1a0d4680,
  abstract     = {<p>Background: In observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk. Objective: To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. Design, setting, and participants: Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992-1999 in the Prostate Cancer Database Sweden 3.0. Outcome measurements and statistical analysis: We measured the proportion of men who received GnRH agonists as primary treatment in 580 experimental units defined by healthcare provider, diagnostic time period, and age at diagnosis. Incident or fatal CVD events in units with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed. Results and limitations: The risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0.93-1.11). Accordingly, there was no difference in the net probability of CVD after GnRH agonist compared to orchiectomy (hazard ratio 1.02, 95% CI 0.96-1.09). The 10-yr crude probability of CVD was 0.56 (95% CI 0.55-0.57) for men on GnRH agonists and 0.52 (95% CI 0.50-0.54) for men treated with orchiectomy. The main limitation was the nonrandom allocation to treatment, with younger men with lower comorbidity and less advanced cancer more likely to receive GnRH agonists. Conclusion: Our data do not support previous observations that GnRH agonists increase the risk of CVD in comparison to orchiectomy. Patient summary: We found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer. We found no difference in the risk of cardiovascular disease or death between gonadotrpin-releasing hormone agonists and orchiectomy as treatments for prostate cancer. Accordingly, no evidence was found in favour of changing the standard hormonal treatment for prostate cancer.</p>},
  author       = {Thomsen, Frederik Birkebæk and Sandin, Fredrik and Garmo, Hans and Lissbrant, Ingela Franck and Ahlgren, Göran and Van Hemelrijck, Mieke and Adolfsson, Jan and Robinson, David and Stattin, Pär},
  issn         = {0302-2838},
  keyword      = {Androgen deprivation therapy,Cardiovascular risk,Gonadotropin-releasing hormone,Orchiectomy,Prostate cancer,Prostate Cancer Database Sweden (PCBaSe)},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Gonadotropin-releasing Hormone Agonists, Orchiectomy, and Risk of Cardiovascular Disease : Semi-ecologic, Nationwide, Population-based Study},
  url          = {http://dx.doi.org/10.1016/j.eururo.2017.06.036},
  year         = {2017},
}