Androgen deprivation may trigger diabetes, CV disease

May 15, 2007

The mainstay of treatment for men with metastatic prostate cancer, gonadotropin-releasing hormone (GnRH) agonists are also the subject of recent studies showing that they raise the risk of such adverse effects as diabetes and cardiovascular disease.

Key Points

Orlando, FL-About one-third of the estimated two million prostate cancer survivors in the United States currently receive hormone therapy in the form of gonadotropin-releasing hormone (GnRH) agonists. The mainstay of treatment for men with metastatic prostate cancer, the drugs are also the subject of recent studies showing that they raise the risk of such adverse effects as diabetes and cardiovascular disease, according to Matthew R. Smith, MD, PhD, associate professor of medicine at Harvard Medical School and director of research in the genitourinary oncology unit at Massachusetts General Hospital Cancer Center, Boston.

"Androgen deprivation therapy with drugs such as Lupron or Zoladex increases weight gain, adversely alters lipids, and decreases insulin sensitivity, resulting in a pre-diabetic condition. This led us to the hypothesis that these metabolic changes will translate into adverse clinical events, such as diabetes or cardiovascular disease," he said in an interview with Urology Times.

Sustaining treatment gains

Awareness of these adverse metabolic changes and the attendant risks goes a long way toward informing the debate and assisting clinical decision making about the timing of hormone therapy in men. Further, in men who require hormone therapy, this knowledge provides an opportunity for physician intervention to prevent the unintended effects of hormone therapy.

"Some practical things can be done," Dr. Smith said. "These unintended effects of hormone therapy make lifestyle modification all the more important for men on hormone therapy. We strongly encourage good nutrition, maintenance of ideal body weight, and exercise for men on hormone therapy and close surveillance for the potential effects of treatment, including osteoporosis, alteration in lipids, and diabetes. These are treatable problems. Our patients on hormone therapy should receive the same careful attention as postmenopausal women receive to manage issues related to menopause.

"One of the common situations is to give hormone therapy to men with rising PSA after prior prostatectomy or radiation therapy for prostate cancer. This is one of the settings where we don't know if there is benefit of early treatment," Dr. Smith pointed out. "By better understanding the harms, we have to ask the question, 'Could we be increasing the risk of death by administering hormone therapy in a setting where we don't know if there is an improvement in cancer-specific survival?'"

Dr. Smith's message to the clinician is that treatment-related cardiovascular disease and diabetes should be considered when assessing the potential risks and benefits of initiating GnRH-agonist treatment. In addition, men initiating GnRH-agonist therapy should be counseled about strategies for reducing the risks of diabetes and cardiovascular disease, he said. "We also need additional research to confirm these observations and better define the scope of the problem."

Dr. Smith is a consultant to Amgen, GTX, Novartis, and Abbott Oncology, and has received research support from Novartis Oncology and Abbott Oncology.