Androgen Deprivation Increases Risks

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It is associated with greater likelihood of diabetes and cardiac events in prostate cancer patients

 

Treatment with a gonadotropin-releasing hormone (GnRH) agonist is associated with increased risks of diabetes, coronary heart disease (CHD), MI, and sudden cardiac death in men with prostate cancer, according to an observational study at Harvard Medical School in Boston.

 

Androgen deprivation therapy with a GnRH agonist or bilateral orchiectomy is a mainstay of treatment in patients with metastatic prostate cancer, but the role of GnRH agonists in those with local or regional cancer has not been completely defined. The adverse physiologic effects of GnRH agonists, including increased fat mass and decreased insulin sensitivity, may be associated with increased risks of diabetes and cardiovascular disease.

 

A group of 73,196 patients aged 66 years or older who were diagnosed with local or regional prostate cancer were followed for up to 10 years (median, 4.55 years). Overall, 36.3% of the men received a GnRH agonist and 6.9% underwent bilateral orchiectomy during follow-up.

 

On average, men receiving GnRH agonists were treated 40% of the time from diagnosis through censoring (the last date for which data were available), and men receiving orchiectomy were on treatment for 76.3% of the time from diagnosis through censoring.

 

After prostate-cancer diagnosis, 5.4% of the men had a MI and 4.5% experienced sudden cardiac death, Nancy L. Keating, MD, and her colleagues reported in the Journal of Clinical Oncology (2006;24:4448-4456). New-onset diabetes developed in 10.9% and CHD developed in 25.3%.

GnRH agonist use was associated with a 44%, 16%, 11%, and 16% increased risk for diabetes, CHD, MI, and sudden cardiac death, respectively, after adjusting for potential confounders, the investigators concluded. The increased risks of diabetes and CHD were evident in men who received GnRH therapy for as few as 1 to 4 months. Orchiectomy was associated with a significant 34% increased adjusted risk of diabetes, but not CHD, MI, or sudden cardiac death.

 

“Decisions about GnRH agonist treatment for local or regional prostate cancer should weight improvements in cancer-specific outcomes against potential increased risks of diabetes and cardiovascular disease,” the authors wrote. “For men who require GnRH agonist therapy, strategies to mitigate modifiable risk factors for diabetes and coronary heart disease may be warranted.”

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