GnRH agonists' safety profile under FDA review for diabetes, CVD risks

FDA notified providers and patients that they are continuing to review available data suggesting an increase in the risk of diabetes, heart attack, stroke, and sudden death in men treated with gonadotropin-releasing hormone agonists as androgen deprivation therapy for prostate cancer.

Key Points

On May 3, 2010, FDA notified providers and patients that they are continuing to review available data suggesting an increase in the risk of diabetes, heart attack, stroke, and sudden death in men treated with gonadotropin-releasing hormone (GnRH) agonists as androgen deprivation therapy (ADT) for prostate cancer.

GnRH agonists including leuprolide acetate, sold under the brand names Lupron (Abbott), Viadur (Bayer), and Eligard (Sanofi-aventis), goserelin acetate (Zoladex, AstraZeneca), triptorelin pamoate (Trelstar, Watson), histrelin acetate (Vantas, Endo Pharmaceuticals), and nafarelin acetate (Synarel, Pfizer) suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer. Consequently, such agents shrink or slow the growth of prostate tumors.

According to FDA, a number of administrative claims- or registries-based observational studies have "reported small, but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists." Specifically, the agency references 6 studies evaluating patients undergoing ADT to treat prostate cancer versus patients not undergoing this treatment. However, the agency cautions that "these studies have design limitations that make it difficult to confirm a cause and effect relationship."

Patients are being urged not to stop their treatment with GnRH agonists unless told to do so by their provider.

SOURCES

FDA. FDA Drug Safety Communication: Ongoing Safety Review of GnRH Agonists and possible increased risk of diabetes and certain cardiovascular diseases. May 3, 2010. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm209842.htm. Accessed May 10, 2010.

Levine GN, D'Amico AV, Berger P, et al; on behalf of the American Heart Association Council on Clinical Cardiology and Council on Epidemiology and Prevention, the American Cancer Society, and the American Urological Association. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: A science advisory from the American Heart Association, American Cancer Society, and American Urological Association. Circulation. 2010;121:833–840.