Men with prostate cancer who receive androgen deprivation therapy are at elevated risk of bone fractures, cardiovascular mortality, and diabetes
Research Activities, December 2009, No. 352
Androgen-deprivation therapy (ADT) is a widely used treatment for men with either localized or advanced prostate cancer. A new review by researchers at the University of Texas Health Sciences Center in Houston has found that the use of ADT increases the chances of bone fracture by 23 percent and cardiovascular mortality by 17 percent. However, in absolute terms, the risk for either remained low. Bone fracture risk rose only from 6.5 per 100 person-years to 7.2 per 100 person-years, while cardiovascular-related mortality risk rose from between 9 and 10 deaths per 1,000 person-years to between 10.5 and 11.7 deaths per 1,000 person-years.
The review scrutinized studies on the major side effects of ADT published between 1966 and 2008. The goal of ADT is to reduce the level of male hormones (androgens) produced mainly by the testicles, which stimulate prostate cancer cells to grow. ADT can take the form either of surgical castration (orchiectomy) or chemical castration with gonadotropin-releasing hormone. It is used as either primary or adjuvant therapy (in combination with radiation) and is effective in alleviating disease-specific symptoms and prolonging survival. Its side effects, in addition to skeletal and cardiovascular complications, include metabolic complications leading to diabetes. On the subject of ADT's effects on bone and cardiovascular-related outcomes, researchers found 683 articles published during the review period, but only 14 were considered rigorous enough to meet the study's inclusion criteria.
The five studies that investigated the risk of fracture as a major side effect of ADT all reported significantly increased risks of overall fracture in patients with prostate cancer who underwent ADT compared with patients who did not undergo ADT. Of the four studies investigating cardiovascular-related mortality, two were randomized clinical trials that reported slightly elevated but nonsignificant increases in cardiovascular mortality related to ADT. The other two studies were retrospective studies, both of which reported significantly increased risks of cardiovascular-related mortality. Also, two studies investigating the risk of diabetes related to ADT found a significant 36 to 39 percent increase in the risk of incident diabetes.
Although the absolute risks of fracture and cardiovascular mortality are low among men treated with ADT, the researchers recommend consideration of preventive treatments, such as the use of bisphosphonates to increase bone density. The study was supported by the Agency for Healthcare Research and Quality (HS16743).
See "Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer," by Lockwood G. Taylor, M.P.H., Steven E. Canfield, M.D., and Xianglin L. Du, M.D., Ph.D., in the June 1, 2009 Cancer 115, pp. 2388-2399.