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Prostate Cancer Treatment Linked to Increased Risk of Diabetes and Heart Disease

Dec 21, 2009

New research shows that the risk of heart attack, stroke, sudden cardiac death and diabetes in men who underwent androgen deprivation therapy was 20 to 30 percent higher.

More than one in five men who undergo androgen deprivation therapy — a form of castration common after prostate cancer treatment — subsequently develop cardiovascular disease and diabetes they otherwise would not have, according to a new study.

The research, shows that the risk of heart attack, stroke, sudden cardiac death and diabetes in men who underwent ADT was 20 to 30 per cent higher than the risk in men who did not undergo the therapy.

The risks were highest in men taking a class of medications called gonadotropin-releasing hormone (GnRH) agonists, which induce chemical castration, researchers found. These drugs, which are injected by a physician or implanted under the skin every few months, include leuprolide (brand name Lupron) and goserelin (Zoladex).

Men who opted for orchiectomy (surgical removal of the testicles) also had elevated rates of heart disease and diabetes. However, men who took oral androgen agonists after prostate surgery did not have higher rates of disease. The drugs, taken in daily pill form, include flutamide (Euflex) and bicalutamide (Casodex).

Nancy Keating of the division of general internal medicine at Brigham and Women’s Hospital in Boston, MA, and lead author of the new research stated that, “Patients and physicians considering initiation of GnRH agonist treatment for local or regional prostate cancer should factor the potential increased risks of diabetes and cardiovascular disease as they make treatment decisions.”

Her study involved almost 37,443 men who were diagnosed with prostate cancer in the Veterans Health Administration between 2001 and 2005. Over all, 14,597 of the patients (39 percent) underwent androgen deprivation therapy after their initial treatment (radiation, surgery or both) for prostate cancer.

The vast majority of those undergoing ADT, 14,037, were prescribed GnRH agonists. A small number, 308, underwent orchiectomy, and 1,229 were prescribed antiandrogen monotherapy. (The numbers do not add up precisely because some men undergo more than one of the follow-up treatments.)

In an editorial published in the Journal of the National Cancer Institute, Peter Albertsen of the department of surgery at the University of Connecticut Health Center in Farmington, CN, said the new research “offers a rare glimpse into the extent of ADT therapy,” and it should lead both patients and treating physicians to wonder aloud if the benefits of androgen deprivation therapy outweigh the risks.

He noted that the adverse events associated with ADT — heart disease, diabetes, osteoporosis, sexual dysfunction and so on — have been known for decades.

Yet the use of chemical castration has risen steadily, and it is increasingly used in younger men with less severe prostate cancer.

In the new study, almost one-quarter of the men under 55 and more than half the men over 75 received ADT, even though there is no firm evidence that treatment reduces mortality.

“Although the risks associated with androgen deprivation therapy remain incompletely defined, the potential for harm from this treatment underscores the importance of better understanding the benefits,” Dr. Albertsen said.

Prostate cancer is a hormonally fuelled cancer. Cancerous cells feed on testosterone — the principal male sex hormone — and the way to snuff out their spread is to cut off the fuel supply.

Most testosterone (also known as an androgen) is produced in the testicles. So many men, to avoid the risk of recurrence, accept castration — surgical or chemical.

An estimated 500,000 men in North America have undergone androgen deprivation therapy, and their ranks are increasing by 40,000 a year.

Journal of the National Cancer Institute, Dec. 2009