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Androgen deprivation therapy and cardiac risk: Guidelines are needed, experts say


Publication of a major observational study from Harvard Medical School, Boston, followed within weeks by a science advisory from AUA and other professional organizations, adds further evidence of a link between androgen deprivation therapy and elevated risks of cardiovascular disease and diabetes, although this relationship has not been definitively established.

The data in the Harvard study also hint at the extent to which ADT is being used in men with prostate cancer in the United States and has prompted some experts to say that the time may be ripe to consider establishing U.S. guidelines for the therapy.

"These drugs are associated with risks that may be causal, and we really should think a lot about the indications when we use them," said Nancy L. Keating, MD, MPH, the study's principal author, who is associate professor of medicine and health care policy at Harvard. "And when we use them, we should be aware of the potential side effects and monitor them as recommended by guidelines for cardiovascular risk factors."

The investigators found that GnRH agonists were associated with an increased risk of incident diabetes, coronary heart disease, acute myocardial infarction, and sudden cardiac death (J Natl Cancer Inst 2010; 102:39-46). They also found that ever-use or current use of any ADT was associated with an elevated risk of diabetes. Dr. Keating noted that oral antiandrogen monotherapy was not associated with any risks but cautioned that the numbers of men receiving this treatment were too small to allow conclusions to be drawn.

Data not 'definitive'

"These [overall] data support a reason for concern, but I think the data are not yet definitive. We need data from trials that assess outcomes and right now, we do not have it. But there is enough evidence to cause us to be a little more cautious with the treatment," said Dr. Keating.

The science advisory, which was compiled by the American Heart Association, the American Cancer Society, the American Society for Radiation Oncology, and AUA, reviewed findings from 12 studies. It points out that, while some studies have found an association between ADT and increased cardiovascular risk, other studies have not. An increased risk with ADT was noted in 1% to 6% of the populations in the studies reviewed. The data showed a relationship between ADT, serum lipoproteins, insulin sensitivity, and obesity but did not relate the therapy directly to diabetes, the advisory stated.

"The purpose of this advisory panel was to increase the awareness of urologists and other physicians treating prostate cancer patients and the patients' primary care physicians to the alteration of cardiovascular risks associated with ADT," Arthur I. Sagalowsky, MD, professor of urology and surgery at the University of Texas Southwestern Medical Center in Dallas, told Urology Times. He, along with Dr. Keating, is among the authors of the science advisory, which was published online in CA (Feb. 2, 2010) and Circulation (Feb. 1, 2010).

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