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NEWS & VIEWS |
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Certain types of androgen deprivation therapy (ADT) for prostate cancer may make men more susceptible to diabetes and heart disease, researchers from Harvard Medical School reported in the Journal of Clinical Oncology (2006;24: 4448–4456). They suggest physicians and patients take this possibility into account when considering therapy with a gonadotropin-releasing hormone (GnRH) agonist.
"Doctors should think twice about prescribing GnRH agonists in situations for which studies have not demonstrated improved survival until we better understand the risks of treatment," study co-author Matthew R. Smith, MD, PhD, Associate Professor of Medicine, said in a statement.
Smith and colleagues conducted an observational study of more than 73,000 Medicare enrollees age 66 years and older diagnosed with locoregional prostate cancer, with a median 4.55 years of follow up. Their aim was to evaluate possible associations of ADT with the incidence of diabetes and heart disease.
Overall, 36.3% of men received a GnRH agonist, and 6.9% underwent bilateral orchiectomy. In men without preexisting diabetes or heart disease, those treated with a GnRH agonist had a significantly higher risk of developing diabetes (Hazard Ratio [HR] 1.44, P < 0.001), coronary heart disease (HR 1.16, P < 0.001), myocardial infarction (HR 1.11, P = 0.03), and sudden cardiac death (HR 1.16, P = 0.004) than men not on hormone therapy. The elevated risk began as soon as 1 to 4 months after treatment and remained elevated among those who continued treatment for longer periods. Men treated with orchiectomy had a significantly higher risk of diabetes (HR 1.34, P < 0.001).
Based on known side effects of GnRH agonists—increased body fat and insulin resistance—these results seem biologically plausible. However, the authors suggest caution in interpreting their results. Because this was an observational study, differences between men who received ADT and those who did not may have contributed to differing outcomes. Also, the researchers did not have information on other oral medications (including antiandrogens); the validity of disease outcomes identified from administrative datasets is difficult to evaluate; and the small number of men who underwent orchiectomy limits conclusions regarding that procedure.
Nevertheless, the findings should give physicians who routinely prescribe these treatments some pause, other experts agree.
"It should make us more cautious in starting men on this therapy, but not preclude starting those who need it," said David Smith, MD, Professor of Internal Medicine and Urology at the University of Michigan, who was not involved in the study.
Smith said men with metastatic disease are obvious candidates for hormone therapy, but he suggested that average patients with newly diagnosed disease usually are not. And deciding how to treat the average patient with biochemical recurrence is difficult, he added.
"I would argue that you really ought to follow PSA trends for some time and only start [ADT] if the PSA rate of rise starts to increase into that logarithmic phase," said Smith, explaining that a PSA rising from 0 to 10 in 10 years may not be of concern, whereas the same rise within 10 months should be.
Both Smith and the study authors agreed that men beginning ADT should be counseled about exercise and weight loss to reduce their risk for diabetes and heart disease.
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