The U.S. Food and Drug Administration (FDA) says it is evaluating whether Gonadotropin-Releasing Hormone (GnRH) Agonists may increase the risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men taking the drugs to treat prostate cancer. These drugs, sold under the brand names Lupron, Zoladex, Trelstar, Viadur, Vantas, Eligard and Synarel, lower male hormone levels to help slow the growth of prostate cancer. That approach is known as Androgen Deprivation Therapy or ADT.
While the agency has not made any conclusions about a possible link between these drugs and the risk of diabetes and cardiovascular disease, there has been concern about that potential for some time. In 2009, Otis W. Brawley, M.D., the Society’s chief medical officer, noted the possibility in an editorial he co-authored in CA: A Cancer Journal for Clinicians, noting that three out of four randomized screening trials showed an increased risk of mortality correlated with screening.
In addition, it is concerning that in the PLCO study, the risk of death from all causes combined appeared to be higher in the screened group than in the control group. This is a weak observation, but it has been observed in 2 previous randomized trials. It raises the possibility that it could be due to a small increased risk of non–prostate cancer death from prostate cancer treatment. It has been reported that hormonal therapies in men with locoregional prostate cancer with gonadotropin–releasing hormone analogs increase the risk of diabetes, cardiovascular disease, and stroke. In the absence of details concerning treatment in these trials, it is not known how many of these men were treated with these drugs, but it needs to be ruled out that treatment may be harmful. This is an unknown that must be the focus of further investigation.
This is an important move by the FDA, since, as noted in a science advisory published in that same journal in February by the American Heart Association, the American Cancer Society, and the American Urological Association, androgen-deprivation therapy (ADT) is a widely used treatment for prostate cancer.
There is a substantial amount of data demonstrating that ADT adversely affects traditional cardiovascular risk factors, including serum lipoproteins, insulin sensitivity, and obesity. Recent studies have reported a relation in patients with prostate cancer between ADT and an increased risk of cardiovascular disease, although different studies both have and have not reported an increased risk of cardiovascular death….The writing group thus believes at this time that it is appropriate to state that there may be a relation between ADT and cardiovascular risk. Future clinical trials of ADT should prospectively assess cardiovascular risk factors before and after ADT is begun and should prospectively monitor patients for adverse cardiovascular events and mortality.
So what’s the bottom line for men concerned about all this? “Patients should feel free to ask their doctors if they should really be getting these drugs,” says Dr. Brawley. “There are men who will clearly benefit from them, even some men with heart disease. But doctors should be careful about indiscriminate use of hormonal therapy.”