The findings show that gonadotropin-releasing hormone agonists (GnRH-a), a frequently used treatment for suppressing production of male hormones aimed at slowing the spread of prostate cancer, causes severe drops in bone mass and results in an increased risk of fractures in men.

The researchers led by Dr. Susan Greenspan at the University of Pittsburgh Medical Center (UPMC) and colleagues at Beth Israel Deaconess Medical Center published the research results in the June issue of the Journal of Clinical Endocrinology and Metabolism. The results may require doctors to monitor bone loss in these patients much more closely.

"We were surprised to find that men who were treated with GnRH-a for prostate cancer experienced up to a decade's worth of bone loss within the first year of therapy," senior author Greenspan stated in a press release.

The prostate, found only in men, is a walnut-sized gland located in front of the rectum, at the outlet of the bladder. It contains gland cells that produce some of the seminal fluid, which protects and nourishes sperm cells in semen.

Male hormones stimulate the prostate gland to develop in the fetus. The prostate continues to grow as a man reaches adulthood. It will continue to grow or at least is maintained after it reaches normal size throughout the life of a man as long as male hormones are produced. If male hormones are removed, the prostate gland will not fully develop or will shrink.

GnRH-a works by depriving the body of testosterone, an androgen hormone that increases the growth of prostate tumors. However, testosterone also is essential to maintaining bone mass in men.

While doctors have been using GnRH-a for more than a decade in treating men with late-stage metastatic prostate cancer, they have begun using it more recently in men with earlier-stage disease and for longer periods of time.

"In treating men with this therapy earlier and for longer periods of time, we are putting them in a menopause-equivalent condition and subjecting them to severe osteoporosis -- a disease that may have more serious consequences than early-stage prostate cancer," says Greenspan.

"With close to 200,000 men being diagnosed with prostate cancer each year, we could be facing an enormous increase in the incidence of debilitating bone fractures in men," she says.

In this study, investigators compared bone mineral densities, biochemical markers of bone turnover and body composition in 60 men with prostate cancer -- 19 of whom were on GnRH-a and 41 who were not. They also examined the same markers in 197 healthy men.

While the prostate cancer patients who had not been treated with hormones had bone loss markers that were similar to those of the healthy controls, the scores of men treated with hormones showed marker levels that were up to 17 percent lower than those of untreated men, putting the treated men at a markedly higher risk for fracture.

Treated men also had nearly double the levels of urinary marker for bone absorption, indicating that their bones were disintegrating twice as quickly as the bones of untreated men. In addition, they had significantly lower blood counts and levels of estradiol, a hormone that is needed, along with testosterone, for bone health. Treated men also showed an increase in total body fat and loss of muscle mass.

"Clearly, cutting off testosterone production in men through the administration of GnRH-a has some very serious consequences related to skeletal integrity and overall health," says Greenspan. "This is particularly troubling because the greatest degree of bone loss appears to occur with the initiation of treatment."

Prostate cancer is the second leading cause of cancer death in men in the United States, exceeded only by lung cancer. The American Cancer Society estimates that 31,500 men in the United States will die of prostate cancer during 2001. Prostate cancer accounts for about 11% of male cancer-related deaths.

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