The Prostate Paradox
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By Ingfei Chen

The Prostate Paradox

Could cancer-fighting hormones do more harm than good?

By Ingfei Chen


The headline on the press release from Harvard Medical School was scary: “Prostate Cancer Treatment Increases Risk of Diabetes and Heart Disease.” That conclusion—from an observational study of hormone therapy—was reported as a clear-cut danger by USA Today and other media. But the research didn’t actually prove a cause-and-effect connection, even the study’s own authors note.

The results, reported Sept. 20, 2006, in the Journal of Clinical Oncology, are preliminary, “a stay-tuned type of finding,” says Barnett Kramer, a medical oncologist at the National Institutes of Health, who wasn’t involved in the research. “This is not something that I would consider definitive,” he cautions.

Harvard investigators scanned Medicare billing records to track more than 73,000 men over age 65 with early prostate cancer that hadn’t yet metastasized to bones or elsewhere. Most patients underwent radiation therapy or prostate surgery, and 36 percent also took injections of hormones—such as Lupron (leuprolide) or Zoladex (goserelin)—to block their production of testosterone, which may feed cancer growth.

For every 1,000 men receiving hormones for a year, eight more cases of diabetes and 11 more cases of heart disease arose than among 1,000 patients not taking the therapy. Even after accounting for differences in age, ethnicity and other factors, the researchers found that long-term hormone use was associated with a 44-percent greater risk of diabetes, and a 16-percent higher risk of heart disease. Such outcomes might explain why prostate cancer patients die more often from non-cancer causes than other men.

The new findings are worrisome because the use of hormones against prostate cancer has jumped sharply in recent decades, according to Nancy Keating, an internist at Brigham and Women’s Hospital in Boston, who led the study. Strong evidence has confirmed that the drugs slow cancer, improve quality of life and decrease bone pain in men with metastatic disease, and in those with early but aggressive “locally advanced” tumors who receive radiation. Keating suggests that these two types of patients, for whom the payoff of hormone treatment is clear, should remain vigilant together with their doctors for signs of diabetes or heart problems, and discuss diet and exercise as ways to aid prevention.

However, a growing number of patients who take hormones don’t have advanced cancer. Increasingly, Keating says, older men with early disease have added the hormone injections to a “watchful waiting” strategy—in which they forgo surgery or radiation, because many prostate tumors grow and spread slowly. (These tumors are unlikely to cause death.) The hormones are also commonly used after surgery or radiation, if blood levels of a tumor marker, prostate-specific antigen, edge upward. For both of these groups, “there’s no data to show that there’s any benefit,” Keating says. Given the new research, she says, such men should think twice about starting hormone therapy, which can also cause problems like osteoporosis and hot flashes.

Still, Kramer warns that conclusions from many observational studies “turn out to be wrong” because hidden biases can skew results. For example, men who see the doctor for regular hormone shots may be more likely to get their blood sugar or cholesterol checked than untreated men. A randomized, controlled clinical trial would be the most direct way to answer whether hormone-replacement therapy sets off diabetes and heart disease, a point that Keating and her colleagues are quick to acknowledge. As Kramer notes, observational studies led to the belief that hormone-replacement therapy protected women from heart disease. Then a randomized trial revealed that the combination of estrogen and progestin actually increased the heart risk. “Those are important lessons,” he says.