GnRH Agonists Associated With Higher Adverse Effect Risk vs Orchiectomy

Gonadotropin-releasing hormone agonist (GnRHa) therapy is associated with increased risks of numerous clinically relevant adverse events compared with orchiectomy, a study published in JAMA Oncology has shown.1

Although androgen deprivation therapy (ADT) via orchiectomy is equally efficacious as medical castration in treating prostate cancer, the adverse effect profile of both ADT modalities has never been compared. Therefore, researchers sought to evaluate the adverse effects of GnRHa compared with bilateral orchiectomy in a Medicare population.

For the study, researchers analyzed data from 3295 men age 66 years or older with metastatic prostate cancer included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that patients who received a bilateral orchiectomy had significantly reduced risks of experiencing any fractures (HR, 0.77; 95% CI: 0.62-0.94; P=.01), peripheral arterial disease (HR, 0.65; 95% CI: 0.49-0.87; P=.004), and cardiac-related complications (HR, 0.74; 95% CI: 0.58-0.94; P=.01) compared with patients with GnRHa therapy. In contrast, there were no statistically significant differences for diabetes and cognitive disorders between the 2 groups.

Researchers found that in patients treated with GnRHa for 35 months or more, there was an elevated risk for fractures (HR, 1.80), peripheral arterial disease (HR, 2.25), venous thromboembolism (HR, 1.52), cardiac-related complications (HR, 1.69), and diabetes mellitus (HR, 1.88) (P≤.01 for all) compared with being treated with orchiectomy.

In regard to costs, the study demonstrated that at 12 months after prostate cancer diagnosis, the median total expenditure was not significantly different between medical castration and surgical castration.


1. Sun M, Choueriri TK, Hamnvik O-P, et al. Comparison of gonadotropin-releasing hormone agonists and orchiectomy: effects of androgen-deprivation therapy [published online ahead of print December 23, 2015]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.4917.

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